Measuring Resistance to Change at the Within-Session Level

ERIC Educational Resources Information Center

Tonneau, Francois; Rios, Americo; Cabrera, Felipe

2006-01-01

Resistance to change is often studied by measuring response rate in various components of a multiple schedule. Response rate in each component is normalized (that is, divided by its baseline level) and then log-transformed. Differential resistance to change is demonstrated if the normalized, log-transformed response rate in one component decreases…

Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

PubMed

Jacobson, Ira M; Washington, Mary K; Buti, Maria; Thompson, Alexander; Afdhal, Nezam; Flisiak, Robert; Akarca, Ulus Salih; Tchernev, Konstantin G; Flaherty, John F; Aguilar Schall, Raul; Myers, Robert P; Subramanian, G Mani; McHutchison, John G; Younossi, Zobair; Marcellin, Patrick; Patel, Keyur

2017-07-01

Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P = .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P = .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P = .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov registration numbers: NCT00117676 and NCT00116805. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

PubMed

Sokup, Alina; Góralczyk, Barbara; Góralczyk, Krzysztof; Rość, Danuta

2012-02-01

To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. Prospective postpregnancy cohort study. Polish university hospitals. Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. All women were studied 2-24 months (mean 12 ± 10 months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels. Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83 mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high-sensitivity C-reactive protein and triglyceride/high-density lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E-selectin was independently associated with triglyceride levels. Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2-24 months after an index pregnancy. Normalization of triglycerides should be included in preventive therapy after a pregnancy complicated by gestational diabetes. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Levels of uric acid may predict the future development of pulmonary hypertension in systemic lupus erythematosus: a seven-year follow-up study.

PubMed

Castillo-Martínez, D; Marroquín-Fabián, E; Lozada-Navarro, A C; Mora-Ramírez, M; Juárez, M; Sánchez-Muñoz, F; Vargas-Barrón, J; Sandoval, J; Amezcua-Guerra, L M

2016-01-01

The objective of this paper is to assess whether pulmonary hypertension (PH) may be detected at one point in time or longitudinally predicted by serum uric acid (sUA) levels in systemic lupus erythematosus (SLE). We conducted a post-hoc analysis of a long-term followed cohort of Mexican SLE patients. Echocardiography-based definitions of PH by the ESC/ERS/ISHLT and its associations with clinical and laboratory data on enrollment were studied. Especially, the impact that sUA levels at baseline may have on the future development of PH in patients with normal pulmonary artery systolic pressure (PASP) was explored. Out of the 156 SLE patients originally enrolled in the cohort, 44 met the inclusion criteria for the present study and were grouped as having (n =10) or not having (n = 34) PH. At baseline, sUA levels of 5.83 ± 1.79 and 5.82 ± 1.97 mg/dl (p = ns) were found in patients with and without PH, respectively. No association between PASP and other markers was found. In patients with normal PASP, the presence of sUA ≥ 7 mg/dl at baseline predicted future development of PH (relative risk 8.5, 1.0009 to 72; p = 0.04). In SLE, sUA levels at one point in time are useless to detect PH. However, steady hyperuricemia may predict the future development of PH in patients with normal PASP at baseline. © The Author(s) 2015.

Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy.

PubMed

Verstovsek, Srdan; Harrison, Claire N; Kiladjian, Jean-Jacques; Miller, Carole; Naim, Ahmad B; Paranagama, Dilan C; Habr, Dany; Vannucchi, Alessandro M

2017-05-01

Polycythemia vera (PV) is characterized by erythropoiesis and JAK2-activating mutations, with increased risks of morbidity and mortality. Most patients with PV are iron deficient, and treatment often includes hematocrit control with phlebotomy, which may exacerbate iron deficiency-associated complications. The phase 3 RESPONSE trial evaluated the JAK1/JAK2 inhibitor ruxolitinib (n=110) versus best available therapy (BAT; n=112) in patients with PV who were hydroxyurea-resistant/intolerant. Ruxolitinib was superior to BAT for hematocrit control, reduction in splenomegaly, and blood count normalization. This exploratory analysis, the first to evaluate iron status in a prospective study of patients with PV, investigated ruxolitinib effects on 7 serum iron markers and iron deficiency-related patient-reported outcomes (PRO). Among patients with evidence of baseline iron deficiency, ruxolitinib was associated with normalization of iron marker levels, compared with lesser improvement with BAT. Iron levels remained stable in ruxolitinib patients with normal iron levels at baseline. Regardless of baseline iron status, treatment with ruxolitinib was associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity, although improvements were generally greater among patients with baseline iron deficiency. The improvements in iron deficiency markers and PROs observed with ruxolitinib are suggestive of clinical benefits that warrant further exploration. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Effect of Prolonged Glucosamine Usage on HbA1c Levels and New-Onset Diabetes Mellitus in Overweight and Obese Middle-Aged Women.

PubMed

Gommans, Yvonne M M; Runhaar, Jos; Jacobs, Marloes L; Bierma-Zeinstra, Sita M A

2017-06-01

The aim of the present study was to evaluate the effect of a 2.5-year glucosamine sulfate intervention on hemoglobin A1c (HbA1c) levels and the incidence of new-onset diabetes mellitus over 6.5 years in middle-aged women with a body mass index ≥27 kg/m 2 . In total, 407 women were randomized into either oral crystalline glucosamine sulfate or placebo. At baseline, 1 year, 2.5 years, and 6.5 years, a blood sample for the HbA1c level was drawn and questionnaires were taken. After 6.5 years there were missing data for some variables, therefore, multiple imputation was used. With the imputed data, a generalized estimating equation was performed to analyze the effect of glucosamine sulfate usage over 6.5 years. Finally, these analyses were rerun for the 2 subgroups of participants with and without high HbA1c level (≥42 mmol/mol) at baseline. There was no significant effect of a 2.5-year glucosamine sulfate intervention on mean HbA1c level or on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years. The subgroup analyses of participants with and without high HbA1c level at baseline were also not statistically significant. However, participants with a high HbA1c level at baseline had higher odds ratios compared with the participants with a normal HbA1c at baseline. There was no effect of glucosamine sulfate on mean HbA1c level nor on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years, especially in participants with a normal HbA1c level at baseline. Copyright © 2016 Elsevier Inc. All rights reserved.

Statin-related aminotransferase elevation according to baseline aminotransferases level in real practice in Korea.

PubMed

Kim, H-S; Lee, S H; Kim, H; Lee, S-H; Cho, J H; Lee, H; Yim, H W; Kim, S-H; Choi, I-Y; Yoon, K-H; Kim, J H

2016-06-01

Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables. © 2016 The Authors. Journal of Clinical Pharmacy and Therapeutics Published by John Wiley & Sons Ltd.

A 12-month phase 3 study of pasireotide in Cushing's disease.

PubMed

Colao, Annamaria; Petersenn, Stephan; Newell-Price, John; Findling, James W; Gu, Feng; Maldonado, Mario; Schoenherr, Ulrike; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M K

2012-03-08

Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 μg (82 patients) or 900 μg (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 μg twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. Twelve of the 82 patients in the 600-μg group and 21 of the 80 patients in the 900-μg group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose-lowering medication was initiated in 74 of 162 patients. The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

40 CFR 80.45 - Complex emissions model.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCW% = Percentage change in winter VOC emissions from baseline levels (8) Phase II total VOC emissions... its domain Phase I = The years 1995-1999 Phase II = Year 2000 and beyond (b) Weightings and baselines... appropriate pollutant and Phase: Table 1—Normal and Higher Emitter Weightings for Exhaust Emissions Phase I...

Influence of insulin on beta-endorphin plasma levels in obese and normal weight subjects.

PubMed

Brunani, A; Pincelli, A I; Pasqualinotto, L; Tibaldi, A; Baldi, G; Scacchi, M; Fatti, L M; Cavagnini, F

1996-08-01

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2). Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Postprocedural pain in shoulder arthrography: differences between using preservative-free normal saline and normal saline with benzyl alcohol as an intraarticular contrast diluent.

PubMed

Storey, Troy F; Gilbride, George; Clifford, Kelly

2014-11-01

The purpose of this study was to prospectively evaluate the effect of benzyl alcohol, a common preservative in normal saline, on postprocedural pain after intraarticular injection for direct shoulder MR arthrography. From April 2011 through January 2013, 138 patients underwent direct shoulder MR arthrography. Using the Wong-Baker Faces Pain Scale, patients were asked to report their shoulder pain level immediately before and immediately after the procedure and then were contacted by telephone 6, 24, and 48 hours after the procedure. Fourteen patients did not receive the prescribed amount of contrast agent for diagnostic reasons or did not complete follow-up. Sixty-two patients received an intraarticular solution including preservative-free normal saline (control group) and 62 patients received an intraarticular solution including normal saline with 0.9% benzyl alcohol as a contrast diluent (test group). Patients were randomized as to which intraarticular diluent they received. Fluoroscopic and MR images were reviewed for extracapsular contrast agent administration or extravasation, full-thickness rotator cuff tears, and adhesive capsulitis. The effect of preservative versus control on pain level was estimated with multiple regression, which included time after procedure as the covariate and accounted for repeated measures over patients. Pain scale scores were significantly (p = 0.0382) higher (0.79 units; 95% CI, 0.034-1.154) with benzyl alcohol preservative compared with control (saline). In both study arms, the pain scale scores decreased slightly after the procedure, increased by roughly 1 unit over baseline for the test group and 0.3 unit over baseline for the control group by 6 hours after the procedure, were 0.50 unit over baseline for the test group and 0.12 unit over baseline for the control group at 24 hours, then fell to be slightly greater than baseline at 48 hours with benzyl alcohol and slightly less than baseline without benzyl alcohol. These trends over time were highly significant (p < 0.0001). Shoulder arthrography is often associated with postprocedural discomfort that begins immediately after the procedure and resolves by 48 hours. There is significantly increased patient discomfort at 6 and 48 hours when using normal saline preserved with benzyl alcohol as a diluent compared with using normal saline without preservative as a diluent.

Processing Science of Epoxy Resin Composites

DTIC Science & Technology

1984-01-15

3 2.2 LAMINATE FABRICATION 30 2.2.1 Baseline Laminate Fabrication 30 2.2.2 Large Laminate Fabrication 36 2.3 DIFFUSIVITY AND SOLUBILITY...Thick Laminate 42 28 Baseline Cure Cycle With Specimen Advancement Levels 45 29 Composite Panel Fabrication 47 30 Composite Panel Fabrication 48 31...first change was the elimination of the different 1 resin formulations and concentration on the normal or baseline 5208/T300 prepreg as produced by

Normal peer models and autistic children's learning.

PubMed Central

Egel, A L; Richman, G S; Koegel, R L

1981-01-01

Present research and legislation regarding mainstreaming autistic children into normal classrooms have raised the importance of studying whether autistic children can benefit from observing normal peer models. The present investigation systematically assessed whether autistic children's learning of discrimination tasks could be improved if they observed normal children perform the tasks correctly. In the context of a multiple baseline design, four autistic children worked on five discrimination tasks that their teachers reported were posing difficulty. Throughout the baseline condition the children evidenced very low levels of correct responding on all five tasks. In the subsequent treatment condition, when normal peers modeled correct responses, the autistic children's correct responding increased dramatically. In each case, the peer modeling procedure produced rapid achievement of the acquisition which was maintained after the peer models were removed. These results are discussed in relation to issues concerning observational learning and in relation to the implications for mainstreaming autistic children into normal classrooms. PMID:7216930

Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Jiangxia; Wang, Mei-Cheng; Moghekar, Abhay; Miller, Michael I; Albert, Marilyn

2017-12-01

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of baseline body mass index status on glucose lowering and weight change during sitagliptin treatment for type 2 diabetics.

PubMed

Chen, Jung-Fu; Chang, Chih-Min; Kuo, Ming-Chun; Tung, Shih-Chen; Tsao, Cheng-Feng; Tsai, Chia-Jen

2016-10-01

This study was designed to evaluate the efficacy of sitagliptin in Taiwanese diabetic subjects with different baseline BMI status. This was a single-center, hospital-based, retrospective chart review in subjects (n=1874) with type 2 diabetes who received sitagliptin. Subjects were classified into subgroups depending upon their baseline BMI by Taiwan national weight classification: normal (BMI<24kg/m(2)) (n=504), overweight (BMI: 24-27kg/m(2)) (n=615), and obese (BMI⩾27kg/m(2)) (n=755). Changes in HbA1c and weight were evaluated over a 12month treatment period. For all three groups, the HbA1c levels declined over the first three months by about 8%, and subsequently plateaued for the next nine months. Obese subjects were slower in reducing HbA1c compared with normal and overweight subjects (P<0.05), but at nine months the reduction was similar across groups. Mean body weight increased over the first nine months of sitagliptin therapy in subjects with normal BMI (57.12-58.30kg), but there was no change in mean body weight in the overweight group. After three months the obese groups had significantly greater loss in body weight compared with the normal group. Baseline BMI status may influence the reduction of HbA1c levels within the first six months of sitagliptin therapy and affect weight change after three months. Being obese was associated with an initial lag in HbA1c reduction and greater weight loss compared with normal and overweight subjects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controls.

PubMed

Croonenberghs, Jan; Verkerk, Robert; Scharpe, Simon; Deboutte, Dirk; Maes, Michael

2005-03-25

Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) may play a role in the pathophysiology of autistic disorder. This study examines the whole blood concentrations of 5-HT and 5-hydroxy-indoleacetic acid (5-HIAA) in baseline conditions and during a challenge with L-5-OH-tryptophane (5-HTP; 4 mg/kg in non enteric-coated tablets), the precursor of 5-HT, in a study group of 18 male, post-pubertal, Caucasian autistic patients (age 13-19 y.; I.Q.>55) and 20 matched healthy volunteers. In baseline conditions, no significant differences in 5-HT or 5-HIAA levels could be found between autistic youngsters and normal controls. 5-HTP administration significantly increased the levels of 5-HT in autistic youngsters but not in normal controls. Following 5-HTP challenge the 5-HT levels were significantly higher in autistic patients than in healthy volunteers. After challenge with 5-HTP, no significant differences were found in the concentrations of 5-HIAA or the test substance between autistic youngsters and normal controls. Differences in the peripheral metabolism of 5-HT which may not be observed in baseline conditions but which became clear after loading with 5-HTP, suggest that an increased synthesis of 5-HT from its precursor 5-HTP might be a one factor responsible for differences in the serotonergic system between autistic post-pubertal youngsters and normal controls.

Standardization of plasma vitellogenin level for surveying environmental estrogen pollution using the Japanese common goby Acanthogobius flavimanus.

PubMed

Song, Jing; Nagae, Masaki; Soyano, Kiyoshi

2018-07-01

Field surveys of the impact of environmental estrogen (EE) pollution in aquatic wildlife have been conducted using vitellogenin (VTG) as a biomarker to evaluate the influence of EE. However, a standard baseline of VTG level that can be used to evaluate EE pollution has not been fully determined. To the best of our knowledge, the present study is the first to determine the standard baseline VTG level for evaluating the biological effects of EE pollution using the Japanese common goby (Acanthogobius flavimanus) as the target model fish. Plasma VTG and estradiol-17β (E 2 ) levels associated with the reproductive cycle of wild goby inhabiting an unpolluted environment were measured. Mean plasma VTG and E 2 levels exhibited similar changes, increasing in the yolk vesicle stage and peaking in the tertiary yolk stage in females. However, plasma VTG and E 2 levels showed no significant changes in males, remaining at low levels throughout the reproductive cycle. The highest VTG levels in females and males were 1.6 mg ml -1 and 124.87 ng ml -1 , respectively. These results indicate that the baseline level (normal level) in males was approximately 130 ng ml -1 at most. We concluded that the threshold between normal and abnormal levels with a 10% risk rate was 150 ng ml -1 in the wild male goby. Plasma VTG levels in males captured from Nagasaki Harbor were higher than the threshold in each reproductive developmental stage, indicating the possibility of EE pollution at this site. The biological standard baseline for VTG established in this study is useful for assessing EE pollution in natural waters. Copyright © 2018 John Wiley & Sons, Ltd.

Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.

PubMed

Findling, James W; Fleseriu, Maria; Newell-Price, John; Petersenn, Stephan; Pivonello, Rosario; Kandra, Albert; Pedroncelli, Alberto M; Biller, Beverly M K

2016-11-01

Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.

Evaluation of nutrient status after laparoscopic sleeve gastrectomy 1, 3, and 5 years after surgery.

PubMed

Saif, Taha; Strain, Gladys W; Dakin, Gregory; Gagner, Michel; Costa, Ricardo; Pomp, Alfons

2012-01-01

Laparoscopic sleeve gastrectomy evolved as a primary bariatric procedure with little information on its nutritional effects. Our objective was to assess the longer term micronutrient and vitamin status after laparoscopic sleeve gastrectomy at a university hospital. Measurements of ferritin, iron, total iron binding capacity, hemoglobin, hematocrit, parathyroid hormone, albumin, calcium, magnesium, phosphorus, zinc, folate, and vitamins A, B1, B12, and D were obtained at baseline and 1, 3, and 5 years after surgery. Two-sample t tests with multiple adjusted comparisons and Fisher's exact test were used to determine deficiency. A total of 82 patients (67% women), with a mean age of 46.4 years and a baseline body mass index 55.7 kg/m2 were included in the present study (35 at 1, 27 at 3, and 30 at 5 years postoperatively). The percentage of excess body mass index loss was 58.5% at year 1 in 35 patients, 63.1% at year 3 in 27 patients, and 46.1% at year 5 in 30 patients. The parathyroid hormone level decreased from 75.0 to 49.6 ng/mL in year 1 to 40.7 ng/mL in year 3. The year 5 levels increased to 99.6 ng/mL. The mean vitamin D level increased from 23.6 ng/mL to 35.0, 32.1 and 34.8 at years 1, 3, and 5 (P = .05 for baseline to year 1). The vitamin D level was less than normal in 42% of the patients at year 5. After normalization from baseline, by year 5, parathyroid hormone had increased in 58.3% of patients. At year 5, vitamin B1 was less than normal in 30.8% of patients, and hemoglobin and hematocrit were less than normal in for 28.6% and 25% of patients, respectively. Finally, 28.9% of patients reported taking supplements in year 1, 42.9% in year 3, and 63.3% in year 5. The other variables were not significantly different. Laparoscopic sleeve gastrectomy resulted in health improvements through year 3. At year 5, the nutrient levels had reverted toward the baseline values. These observations provide focus for necessary clinical monitoring. Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis.

PubMed

Gurrin, Lyle C; Osborne, Nicholas J; Constantine, Clare C; McLaren, Christine E; English, Dallas R; Gertig, Dorota M; Delatycki, Martin B; Southey, Melissa C; Hopper, John L; Giles, Graham G; Anderson, Gregory J; Olynyk, John K; Powell, Laurie W; Allen, Katrina J

2008-12-01

There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in individuals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF >1000 microg/L. For males with SF 300-1000 microg/L at baseline, the predicted probability of progressing to SF >1000 microg/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, <15% were predicted to develop SF >1000 microg/L if left untreated. The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS >95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.

IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

PubMed

Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

2018-05-04

Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

Associations of I148M variant in PNPLA3 gene with plasma ALT levels during 2-year follow-up in normal weight and overweight children: the PANIC Study.

PubMed

Viitasalo, A; Pihlajamaki, J; Lindi, V; Atalay, M; Kaminska, D; Joro, R; Lakka, T A

2015-04-01

PNPLA3 I148M polymorphism (rs738409) has been strongly associated with liver fat content and plasma alanine aminotransferase (ALT) levels in obese adults and children, but little is known about these relationships in normal weight individuals. We studied the associations and interactions of overweight and the PNPLA3 I148M polymorphism with plasma ALT levels during 2-year follow-up in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years examined at baseline and 419 children re-examined after 2-year follow-up. Altogether, 58 (12%) of 481 children at baseline and 71 (17%) of 419 children after 2-year follow-up were overweight. We assessed plasma ALT levels and other cardiometabolic risk factors and genotyped the PNPLA3 I148M polymorphism. Being overweight and carrying PNPLA3 148M allele were associated with increased ALT levels at baseline (P = 0.002; P = 0.033) and after 2-year follow-up (P < 0.001; P = 0.001). Being overweight (P < 0.001) and carrying PNPLA3 148M allele (P = 0.001) were also associated with increase in ALT levels during 2-year follow-up. PNPLA3 148M allele carriers had increased ALT levels at baseline (P = 0.024 for interaction) and after 2-year follow-up (P = 0.002 for interaction) as well as a larger increase in ALT levels during 2-year follow-up (P = 0.002 for interaction) if they were overweight but not if they were normal weight. Further adjustment for clinical puberty, dietary factors, physical activity or sedentary behaviour had little or no effect on these associations. PNPLA3 148M allele carriers had higher plasma ALT levels and larger increase in ALT levels during follow-up than non-carriers only among overweight children. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

AGM-88E Advanced Anti-Radiation Guided Missile (AGM-88E AARGM)

DTIC Science & Technology

2015-12-01

0.0 0.0 Acq O&M 0.0 0.0 -- 0.0 0.0 0.0 0.0 Total 1528.5 1661.1 N/A 2107.4 1861.4 2026.2 2663.7 1 APB Breach Confidence Level Confidence Level of...normal conditions, encountering average levels of technical, schedule, and programmatic risk and external interference. Based on the rigor in methods...SAR Baseline to Current SAR Baseline (TY $M) Initial PAUC Development Estimate Changes PAUC Production Estimate Econ Qty Sch Eng Est Oth Spt Total

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Mei-Cheng; Moghekar, Abhay R; O'Brien, Richard J; Selnes, Ola A; Albert, Marilyn S

2016-06-01

Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aβ and tau or Aβ and phosphorylated tau (p-tau): stage 0 (high Aβ and low tau), stage 1 (low Aβ and low tau), stage 2 (low Aβ and high tau), and suspected non-AD pathology (SNAP) (high Aβ and high tau). The data presented herein were collected between August 1995 and August 2014. An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aβ and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (β ≤ -0.06 for all and P ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The APOE ε4 genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.

Presbycusis, sociocusis, and nosocusis

NASA Technical Reports Server (NTRS)

1984-01-01

The establishment of a baseline of normal hearing is investigated through the examination of pure tone hearing level surveys and variables such as age, sociocusis, sex, race, and otological disorders. Mathematical formulae used to predict hearing levels in industrial and nonindustrial surveys is included.

Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

PubMed

Li, Ge; Mayer, Cynthia L; Morelli, Daniel; Millard, Steven P; Raskind, Wendy H; Petrie, Eric C; Cherrier, Monique; Fagan, Anne M; Raskind, Murray A; Peskind, Elaine R

2017-09-19

To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42 , total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status. Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42 , total tau, and p-tau 181 , respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 ( p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.

Eldecalcitol normalizes bone turnover markers regardless of their pre-treatment levels.

PubMed

Shiraki, Masataka; Saito, Hitoshi; Matsumoto, Toshio

2012-09-01

Three-year treatment with eldecalcitol has been shown to improve lumbar and total hip bone mineral density (BMD), decrease bone turnover markers, and lower the incidences of vertebral and wrist fractures in patients with osteoporosis more than with treatment with alfacalcidol under vitamin D repletion. The purpose of this study was to determine whether there was a risk of eldecalcitol causing severely suppressed bone turnover in osteoporosis patients with low pre-treatment levels of bone turnover markers. Post-hoc analysis was conducted on the data from a 3-year, randomized, double-blind, active-comparator, clinical trial of eldecalcitol versus alfacalcidol under vitamin D repletion conducted in Japan. Enrolled patients with baseline measurements of bone turnover markers were stratified into tertiles according to their pre-treatment levels of serum bone-specific alkaline phosphatase, serum procollagen type I N-terminal propeptide, or urinary collagen-N-telopeptide. Eldecalcitol treatment rapidly reduced bone turnover markers, and kept them within the normal range. However, in the patients whose baseline values for bone turnover were low, eldecalcitol treatment did not further reduce bone turnover markers during the 3-year treatment period. Further long-term observation may be required to reach the conclusion. CLINICALTRIALS.GOV NUMBER: NCT00144456. Eldecalcitol normalizes, but does not overly suppress, bone turnover regardless of baseline levels of bone turnover markers. Thus, it is unlikely that eldecalcitol treatment will increase the risk of severely suppressed bone turnover and therefore deterioration of bone quality, at least for a treatment duration of 3 years.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E M; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E; Farooqui, Mohammed Z; Notkins, Abner L; Wiestner, Adrian; Aue, Georg

2015-11-05

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330.

Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Sun, Clare; Tian, Xin; Lee, Yuh Shan; Gunti, Sreenivasulu; Lipsky, Andrew; Herman, Sarah E. M.; Salem, Dalia; Stetler-Stevenson, Maryalice; Yuan, Constance; Kardava, Lela; Moir, Susan; Maric, Irina; Valdez, Janet; Soto, Susan; Marti, Gerald E.; Farooqui, Mohammed Z.; Notkins, Abner L.; Aue, Georg

2015-01-01

Chronic lymphocytic leukemia (CLL) is characterized by immune dysregulation, often including hypogammaglobulinemia, which contributes to a high rate of infections and morbidity. Ibrutinib, a covalent inhibitor of Bruton tyrosine kinase (BTK), inhibits B-cell receptor signaling and is an effective, US Food and Drug Administration (FDA)-approved treatment of CLL. Inactivating germline mutations in BTK cause a severe B-cell defect and agammaglobulinemia. Therefore, we assessed the impact of ibrutinib on immunoglobulin levels, normal B cells, and infection rate in patients with CLL treated with single-agent ibrutinib on a phase 2 investigator-initiated trial. Consistent with previous reports, immunoglobulin G (IgG) levels remained stable during the first 6 months on treatment, but decreased thereafter. In contrast, there were a transient increase in IgM and a sustained increase in IgA (median increase 45% at 12 months, P < .0001). To distinguish the effects on clonal B cells from normal B cells, we measured serum free light chains (FLCs). In κ-clonal CLL cases, clonal (κ) FLCs were elevated at baseline and normalized by 6 months. Nonclonal (λ) FLCs, which were often depressed at baseline, increased, suggesting the recovery of normal B cells. Consistently, we observed normal B-cell precursors in the bone marrow and an increase in normal B-cell numbers in the peripheral blood. Patients with superior immune reconstitution, as defined by an increase in serum IgA of ≥50% from baseline to 12 months, had a significantly lower rate of infections (P = .03). These data indicate that ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL. This trial was registered at www.clinicaltrials.gov as #NCT015007330. PMID:26337493

Factor VIII in Acute Cerebral Ischemia Pilot Study: Biomarker in Patients With Large Vessel Occlusion?

PubMed

Navalkele, Digvijaya; Boehme, Amelia; Albright, Karen; Leissinger, Cindy; Schluter, Laurie; Freeman, Melissa; Drury, Stacy; Khoury, Ramy El; Beasley, T Mark; Martin-Schild, Sheryl

2018-01-01

We conducted a prospective serial laboratory cohort study to assess the correlation of factor VIII (FVIII) levels in response to thrombolysis in patients with large vessel occlusion (LVO) and acute ischemic stroke (AIS). Patients with AIS with anterior circulation LVO were eligible for enrollment if treated within 4.5 hours from last seen normal with intravenous tissue plasminogen activator (tPA). Patients (n = 29) had a mean age of 71 years and median National Institute of Health Stroke Scale of 14. Baseline pre-tPA FVIII was not significantly correlated with clot burden score (-0.147, P = .447) or vessel recanalization (-0.133, P = .499). Median FVIII decreased significantly from baseline to 6 hours post-tPA (282% to 161%, P = .002), but delta in FVIII level did not correlate with vessel recanalization (0.013, P = .948). There was no difference between median FVIII level at baseline and 90 days post-AIS. FVIII level decreased significantly after tPA, but baseline FVIII level and early change in FVIII level were not significant predictors of clot burden, vessel recanalization after thrombolysis, or symptomatic hemorrhage.

Effects of a beta-adrenergic blocking agent timolol on intra ocular pressure responses induced by stimulation of cervical sympathetic nerve in the cat.

PubMed

Naito, A; Izumi, H; Karita, K; Tamai, M

2001-12-01

We clarified whether the intraocular pressure (IOP) response elicited by stimulation of the cervical sympathetic nerve (CSN) is influenced by changes in the baseline of IOP level and by beta-adrenergic blockade. The CSN was stimulated electrically for 30 seconds (10 V, 0.1-100 Hz, 2 milliseconds pulse duration) in urethane (100 mg/kg i.v.)-chloralose (50 mg/kg i.v.)-anesthetized, paralyzed cats. The IOP was monitored manometrically, and a controlled saline infusion was delivered into the anterior chamber to gradually increase IOP. CSN stimulation was delivered at the various baseline IOP levels so obtained. When required, a beta-adrenergic blocker timolol (2%) was delivered into the conjunctival cul-de-sac. The normal IOP in our cats was 25+/-3 mmHg. This value decreased transiently on CSN stimulation. The amplitude of this IOP response depended on stimulus frequency and the pre-stimulus baseline IOP level. Topical administration of timolol increased the IOP response to CSN stimulation at a given baseline level. These results suggest that beta-adrenergic blockade increases the alpha-adrenergic mediated-IOP reduction elicited by CSN stimulation at given baseline IOP level.

Tumor type M2 pyruvate kinase expression in advanced breast cancer.

PubMed

Lüftner, D; Mesterharm, J; Akrivakis, C; Geppert, R; Petrides, P E; Wernecke, K D; Possinger, K

2000-01-01

Recently, a high validity correlation of the tumor M2 pyruvate kinase (Tu M2-PK) isoenzyme in comparison to standard tumor markers has been demonstrated in solid tumors. We investigated this marker in 67 patients with advanced breast cancer (ABC) in comparison to healthy controls. Plasma Tu M2-PK was measured using an ELISA assay (ScheBo Tech, Giessen, Germany) while serum CA27.29 was determined using a chemiluminescent immunoassay (Bayer Diagnostics, Tarrytown, USA). In a ROC analysis, the cut-off to discriminate patients from controls was established at 15 U/ml for Tu M2-PK (specificity 85%; positive predictive value 81%) and 30 U/ml for CA27.29 (specificity 91%; positive predictive value 92%). Median ABC baseline levels (ranges) in patients with ABC for Tu M2-PK and CA27.29 were 12.8 U/ml (4.8-252,495) and 130 U/ml (13.3-8130), respectively. Response assessment was done in 45 chemotherapy courses of 38 pts. In 13 out of 19 blocks (68.4%) with PD (progressive disease), an elevated level of Tu M2-PK at baseline or in the follow-up was found. In 17 out of 20 blocks (85%) with SD (stable disease), the Tu M2-PK level was normal at baseline or normalised within 4 weeks of treatment. All 6 patients with disease remission had a normal baseline Tu M2-PK level or the levels decreased promptly. Tu M2-PK gives additional information about ABC, indicating disease activity and sensitivity to chemotherapy while CA27.29 reflects tumor burden.

Genetic and environmental relationships of metabolic and weight phenotypes to metabolic syndrome and diabetes: the healthy twin study.

PubMed

Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

2015-02-01

We aimed to examine the relationships, including genetic and environmental correlations, between metabolic and weight phenotypes and factors related to diabetes and metabolic syndrome. Participants of the Healthy Twin Study without diabetes (n=2687; 895 monozygotic and 204 dizygotic twins, and 1588 nontwin family members; mean age, 42.5±13.1 years) were stratified according to body mass index (BMI) (<25 vs. ≥25 kg/m(2)) and metabolic syndrome categories at baseline. The metabolic traits, namely diabetes and metabolic syndrome, metabolic syndrome components, glycated hemoglobin (HbA1c) level, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed after 2.5±2.1 years. In a multivariate-adjusted model, those who had metabolic syndrome or overweight phenotypes at baseline were more likely to have higher HbA1C and HOMA-IR levels and abnormal metabolic syndrome components at follow-up as compared to the metabolically healthy normal weight subgroup. The incidence of diabetes was 4.4-fold higher in the metabolically unhealthy but normal weight individuals and 3.3-fold higher in the metabolically unhealthy and overweight individuals as compared with the metabolically healthy normal weight individuals. The heritability of the metabolic syndrome/weight phenotypes was 0.40±0.03. Significant genetic and environmental correlations were observed between the metabolic syndrome/weight phenotypes at baseline and the metabolic traits at follow-up, except for incident diabetes, which only had a significant common genetic sharing with the baseline phenotypes. The genetic and environmental relationships between the metabolic and weight phenotypes at baseline and the metabolic traits at follow-up suggest pleiotropic genetic mechanisms and the crucial role of lifestyle and behavioral factors.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity

PubMed Central

Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2015-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18–30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. PMID:26316585

Dacarbazine with or without oblimersen (a Bcl-2 antisense oligonucleotide) in chemotherapy-naive patients with advanced melanoma and low-normal serum lactate dehydrogenase: 'The AGENDA trial'.

PubMed

Bedikian, Agop Y; Garbe, Claus; Conry, Robert; Lebbe, Celeste; Grob, Jean J

2014-06-01

In a previous large randomized, open-label study, retrospective subset analysis revealed that the addition of the Bcl-2 antisense oligonucleotide oblimersen to dacarbazine (Dac) significantly improved overall survival, progression-free survival, and the response rate in chemotherapy-naive patients with advanced melanoma and normal baseline serum lactate dehydrogenase (LDH) levels. To confirm and expand on this observation, we conducted a prospective double-blind, placebo-controlled study to determine whether oblimersen augmented the efficacy of Dac in advanced melanoma patients with low-normal baseline LDH levels. A total of 314 chemotherapy-naive patients were randomly assigned to receive Dac (1000 mg/m(2)) preceded by a 5-day continuous intravenous infusion of either oblimersen sodium (7 mg/kg/day) or placebo every 21 days for less than eight cycles. Co-primary efficacy endpoints were overall survival and progression-free survival. Response and progression of the disease were assessed by independent blinded review of computed tomography scan images. No difference in overall nor progression-free survival was observed between the Dac-oblimersen and Dac-placebo groups. Although the overall (17.2 vs. 12.1%) and durable (10.8 vs. 7.6%) response rates numerically favored Dac-oblimersen over Dac-placebo, they did not differ significantly (P=0.19 and 0.32, respectively). The incidence of hematologic adverse events, particularly thrombocytopenia and neutropenia, was higher in the Dac-oblimersen group than in the Dac-placebo group. Withdrawals from the study because of treatment-related adverse events were low (i.e. <2.5%) in both groups. The addition of oblimersen to Dac did not significantly improve overall survival nor progression-free survival in patients with advanced melanoma and low-normal levels of LDH at baseline.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined formore » each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.« less

Physical activity and cognitive trajectories in cognitively normal adults: the adult children study.

PubMed

Pizzie, Rachel; Hindman, Halley; Roe, Catherine M; Head, Denise; Grant, Elizabeth; Morris, John C; Hassenstab, Jason J

2014-01-01

Increased physical activity may protect against cognitive decline, the primary symptom of Alzheimer disease. In this study, we examined the relationship between physical activity and trajectories of cognitive functioning over serial assessments. Cognitively normal (Clinical Dementia Rating 0) middle-aged and older adults (N=173; mean age, 60.7 ± 7.8 y) completed a self-report measure of physical activity and a battery of standard neuropsychological tests assessing processing speed, attention, executive functioning, and verbal memory. At baseline, individuals with higher physical activity levels performed better on tests of episodic memory and visuospatial functioning. Over subsequent follow-up visits, higher physical activity was associated with small performance gains on executive functioning and working memory tasks in participants with one or more copies of the apolipoprotein ε4 allele (APOE4). In APOE4 noncarriers, slopes of cognitive performance over time were not related to baseline physical activity. Our results suggest that cognitively normal older adults who report higher levels of physical activity may have slightly better cognitive performance, but the potential cognitive benefits of higher levels of physical activity over time may be most evident in individuals at genetic risk for Alzheimer disease.

Sickle Cell Vaso-occlusive Crisis Induces the Release of Circulating Serum Heat Shock Protein-70

PubMed Central

Adewoye, Adeboye H.; Klings, Elizabeth S.; Farber, Harrison W.; Palaima, Elizabeth; Bausero, Maria A.; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H.; Asea, Alexzander

2006-01-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P < 0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P < 0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD. PMID:15726596

Sickle cell vaso-occlusive crisis induces the release of circulating serum heat shock protein-70.

PubMed

Adewoye, Adeboye H; Klings, Elizabeth S; Farber, Harrison W; Palaima, Elizabeth; Bausero, Maria A; McMahon, Lillian; Odhiambo, Adam; Surinder, Safaya; Yoder, Mark; Steinberg, Martin H; Asea, Alexzander

2005-03-01

Inflammation may play an important role in the pathophysiology of sickle cell disease (SCD), and recent studies have identified the 70-kDa heat shock protein (Hsp70) as an important mediator of inflammatory responses. Here we demonstrate a significant increase in circulating serum Hsp70 level in SCD during vaso-occlusive crisis (VOC) as compared with baseline steady-state levels (P <0.05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD.

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

PubMed

Thébaut, Alice; Nemeth, Antal; Le Mouhaër, Jeannie; Scheenstra, René; Baumann, Ulrich; Koot, Bart; Gottrand, Fredéric; Houwen, Roderick; Monard, Laure; de Micheaux, Sylvie Lafaye; Habes, Dalila; Jacquemin, Emmanuel

2016-12-01

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus.

PubMed

Shlomai, Amir; Kariv, Revital; Leshno, Moshe; Beth-or, Anat; Sheinberg, Bracha; Halpern, Zamir

2010-10-01

Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Do extra compulsory physical education lessons mean more physically active children--findings from the childhood health, activity, and motor performance school study Denmark (The CHAMPS-study DK).

PubMed

Møller, Niels Christian; Tarp, Jakob; Kamelarczyk, Eva Friis; Brønd, Jan Christian; Klakk, Heidi; Wedderkopp, Niels

2014-09-24

Primarily, this study aims to examine whether children attending sports schools are more active than their counterpart attending normal schools. Secondary, the study aims to examine if physical activity (PA) levels in specific domains differ across school types. Finally, potential modifications by status of overweight/obesity and poor cardio-respiratory fitness are examined. Participants were from the first part of the CHAMPS-study DK, which included approximately 1200 children attending the 0th - 6th grade. At the sports schools, the mandatory physical education (PE) program was increased from 2 to 6 weekly lessons over a 3-year period. Children attending normal schools were offered the standard 2 PE lessons. PA was assessed at two different occasions with the GT3X ActiGraph accelerometer, once during winter in 2009/10 and once during summer/fall in 2010. Leisure time organized sports participation was quantified by SMS track. Based on baseline values in 2008, we generated a high-BMI and a low-cardio-respiratory fitness for age and sex group variable. There were no significant differences in PA levels during total time, PE, or recess between children attending sports schools and normal schools, respectively. However, children, especially boys, attending sports schools were more active during school time than children attending normal schools (girls: β=51, p=0.065; boys: β=113, p<0.001). However, in the leisure time during weekdays children who attended sports schools were less active (girls: β=-41, p=0.004; boys: β=-72, p<0.001) and less involved in leisure time organized sports participation (girls: β=-0.4, p=0.016; boys: β=-0.2, p=0.236) than children who attended normal schools. Examination of modification by baseline status of overweight/obesity and low cardio-respiratory fitness indicated that during PE low fit girls in particular were more active at sports schools. No differences were revealed in overall PA levels between children attending sports schools and normal schools. Sports schools children were more active than normal schools children during school time, but less active during leisure time. In girls, less organized sports participation at least partly explained the observed differences in PA levels during leisure time across school types. Baseline status of cardio-respiratory fitness modified school type differences in PA levels during PE in girls.

Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis.

PubMed

Cai, Xiaoling; Yang, Wenjia; Gao, Xueying; Zhou, Lingli; Han, Xueyao; Ji, Linong

2016-01-01

The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs). Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015. 227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), -1.39%) compared to obese patients (WMD, -0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, -0.99%) compared to obese patients (WMD, -1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.94%) that was comparable that in overweight (WMD, -0.72%) and obese patients (WMD, -0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, -1.04%) that was comparable with that in overweight (WMD, -1.02%) and obese patients (WMD, -0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.93%) that was comparable with that in overweight (WMD, -0.66%) and obese patients (WMD, -0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline. In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline.

Baseline Body Mass Index and the Efficacy of Hypoglycemic Treatment in Type 2 Diabetes: A Meta-Analysis

PubMed Central

Cai, Xiaoling; Yang, Wenjia; Gao, Xueying; Zhou, Lingli; Han, Xueyao; Ji, Linong

2016-01-01

Aim The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs). Methods Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015. Results 227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), −1.39%) compared to obese patients (WMD, −0.77%)(p<0.05). Treatment with metformin in overweight patients resulted in a comparable change in the HbA1c levels (WMD, −0.99%) compared to obese patients (WMD, −1.06%)(p>0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.94%) that was comparable that in overweight (WMD, −0.72%) and obese patients (WMD, −0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, −1.04%) that was comparable with that in overweight (WMD, −1.02%) and obese patients (WMD, −0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, −0.93%) that was comparable with that in overweight (WMD, −0.66%) and obese patients (WMD, −0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline. Conclusion In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline. PMID:27935975

High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

PubMed

Miodownik, Chanoch; Lerner, Vladimir; Vishne, Tali; Sela, Ben-Ami; Levine, Joseph

2007-01-01

Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

The impact of acute aerobic exercise on chitinase 3-like protein 1 and intelectin-1 expression in obesity.

PubMed

Huang, Chun-Jung; Slusher, Aaron L; Whitehurst, Michael; Wells, Marie; Maharaj, Arun; Shibata, Yoshimi

2016-01-01

Chitinase 3-like 1 (CHI3L1) and intelectin 1 (ITLN-1) recognize microbial N-acetylglucosamine polymer and galactofuranosyl carbohydrates, respectively. Both lectins are highly abundant in plasma and seem to play pro- and anti-inflammatory roles, respectively, in obesity and inflammatory-related illnesses. The aim of this study was to examine whether plasma levels of these lectins in obese subjects are useful for monitoring inflammatory conditions immediately influenced by acute aerobic exercise. Plasma interleukin-6, a pro-inflammatory cytokine, was also examined. Twenty-two (11 obese and 11 normal-weight) healthy subjects, ages 18-30 years, were recruited to perform a 30 min bout of acute aerobic exercise at 75% VO2max. We confirmed higher baseline levels of plasma CHI3L1, but lower ITLN-1, in obese subjects than in normal-weight subjects. The baseline levels of CHI3L1 were negatively correlated with cardiorespiratory fitness (relative VO2max). However, when controlled for BMI, the relationship between baseline level of CHI3L1 and relative VO2max was no longer observed. While acute aerobic exercise elicited an elevation in these parameters, we found a lower ITLN-1 response in obese subjects compared to normal-weight subjects. Our study clearly indicates that acute aerobic exercise elicits a pro-inflammatory response (e.g. CHI3L1) with a lower anti-inflammatory effect (e.g. ITLN-1) in obese individuals. Furthermore, these lectins could be predictors of outcome of exercise interventions in obesity-associated inflammation. © 2015 by the Society for Experimental Biology and Medicine.

Health-related quality-of-life parameters as independent prognostic factors in advanced or metastatic bladder cancer.

PubMed

Roychowdhury, D F; Hayden, A; Liepa, A M

2003-02-15

This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox's proportional hazards model. Factors with individual prognostic value (P <.05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.

Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

PubMed Central

Kester, Maartje I.; Teunissen, Charlotte E.; Crimmins, Daniel L.; Herries, Elizabeth M.; Ladenson, Jack. H.; Scheltens, Philip; van der Flier, Wiesje M.; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

2015-01-01

IMPORTANCE Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic–based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. MAIN OUTCOME AND MEASURE Levels of NGRN in CSF samples. RESULTS Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with Aβ42. Baseline CSF levels of NGRN were also higher in patients with MCI who progressed to AD (median level, 2842 pg/mL [interquartile range, 1882-3950 pg/mL]) compared with those with stable MCI (median level, 1752 pg/mL [interquartile range, 1024-2438 pg/mL]) (P = .004), and they were predictive of progression from MCI to AD (hazard ratio, 1.8 [95% CI, 1.1-2.9]; stratified by tertiles). Linear mixed-model analyses demonstrated that within-person levels of NGRN increased over time in cognitively normal participants (mean [SE] level, 90 [45] pg/mL per year; P < .05) but not in patients with MCI or AD. CONCLUSIONS AND RELEVANCE Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss. PMID:26366630

Joint association of physical activity and overweight with subsequent psychotropic medication: a register-linked follow-up study among employees.

PubMed

Loponen, Tiina; Lallukka, Tea; Holstila, Ansku; Lahti, Jouni

2015-10-03

Physical activity level and overweight have shown associations with mental health problems but it is not known whether the risk of mental health problems due to overweight varies by physical activity. We examined joint association of physical activity and overweight with subsequent psychotropic medication among 40-60-year-old employees. The questionnaire survey data were derived from Helsinki Health Study baseline postal questionnaires in 2000-02 among employees of the City of Helsinki aged 40-60 years (n = 8960, response rate 67%). Baseline survey data were linked with prospective register data on prescribed psychotropic medication (ATC-codes N05 and N06, except N06D) among those with written consent (74%) for such linkage. The analyses included 6169 responders (78% women, corresponding to the target population). We divided participants into six groups according to their baseline self-reported body mass index and leisure-time physical activity using physically highly active normal-weight participants as a reference group. We used Cox regression analysis adjusted for age, gender, psychotropic medication prior to baseline, and socioeconomic position, marital status, working conditions, limiting long-standing illness, alcohol use, and smoking. At baseline, 49% were overweight and 23% were physically inactive. After adjusting for age and gender, inactive normal-weight (hazard ratio (HR) 1.3, 95% CI 1.1-1.5), moderately active overweight (HR 1.3, 95% CI 1.1-1.5) and inactive overweight (HR 1.4, 95% CI 1.2-1.6) had higher risk for any psychotropic medication compared with group of highly active normal-weight. After adjusting for prior medication, only the inactive overweight group had higher risk (HR 1.4, 95% CI 1.2-1.6). Other covariates made but a minor contribution to the examined associations. For antidepressants the associations were somewhat stronger than for sedatives. Both normal-weight and physical activity help prevent psychotropic medication but physical activity dominates the association over normal-weight.

Functional Impairment and Changes in Depression Subtypes for Women in STAR*D: A Latent Transition Analysis

PubMed Central

Rothschild, Anthony J.; Lapane, Kate L.

2016-01-01

Abstract Objective: To characterize the association between functional impairment and major depression subtypes at baseline and to characterize changes in subtypes by functional impairment level in women receiving citalopram in level 1 of the Sequenced Treatment Alternatives to Relieve Depression trial. Method: Women who completed baseline and week 12 study visits were included. Items from the self-reported Quick Inventory of Depressive Symptomatology were used to define the latent depression subtypes. The Work and Social Adjustment Scale was used to classify baseline functional impairment. A latent transition analysis model provided estimates of the prevalence of subtype membership and transition probabilities by functional impairment level. Results: Of the 755 women included, 69% had major functional impairment at baseline. Regardless of functional impairment level, the subtypes were differentiated by depression severity, appetite changes, psychomotor disturbances, and insomnia. Sixty-seven percent of women with normal/significant functional impairment and 60% of women with major impairment were likely to transition to a symptom resolution subtype at week 12. Women with baseline major impairment who were in the severe with psychomotor agitation subtype at the beginning of the study were least likely to transition to the symptom resolution subtype (4% chance). Conclusions: Functional impairment level was related to both the baseline depression subtype and the likelihood of moving to a different subtype. These results underscore the need to incorporate not only depression symptoms but also functioning in the assessment and treatment of depression. PMID:26488110

Effect of obesity on acute hemostatic responses to live-fire training drills.

PubMed

Smith, Denise L; Horn, Gavin P; Petruzzello, Steven J; Freund, Gregory G; Woods, Jeffrey A; Cook, Marc D; Goldstein, Eric; Fernhall, Bo

2014-12-01

The objective of this study was to evaluate the impact of obesity and firefighting activities on coagulation and fibrinolytic activity in relatively young, apparently healthy firefighters. Firefighters performed simulated firefighting activities for 18 minutes in a live-fire training structure. Blood samples were obtained at baseline, before firefighting, and within a few minutes of completing the activity. Nearly all markers of coagulation and fibrinolytic activity increased immediately after firefighting with an overall shift toward a procoagulatory profile. Obese firefighters exhibited lower levels of tissue plasminogen activator activity (0.98 vs 0.63 IU/ml) and higher levels of plasminogen activator inhibitor-1 activity (2.2 vs 4.5 ng/ml) at baseline compared with normal-weight firefighters, suggesting that fibrinolytic activity was lower in obese firefighters. There were few interactions between body mass index and firefighting activity, thus our findings suggest that obese firefighters did not exhibit a greater procoagulatory response to live firefighting compared with normal-weight firefighters. Acute live firefighting produced increases in both fibrinolytic and coagulatory responses; although obesity was associated with a reduced fibrinolytic profile at baseline, the changes produced by acute firefighting were similar in obese and nonobese firefighters. Copyright © 2014 Elsevier Inc. All rights reserved.

Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

PubMed

Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

1983-04-01

In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.

A low calorie morning meal prevents the decline of hepatic glycogen stores: a pilot in vivo (13)C magnetic resonance study.

PubMed

Bawden, S J; Stephenson, M C; Ciampi, E; Hunter, K; Marciani, L; Spiller, R C; Aithal, G P; Morris, P G; Macdonald, I A; Gowland, P A

2014-09-01

Previous studies have reported a meal-induced rise in hepatic glycogen stores from baseline levels following a fast and it is generally assumed that glycogen levels rise steadily following meals throughout the day. However, measurements are normally taken in conditions that are not typical of the Western breakfast, which is relatively carbohydrate rich with a lower calorific content than most experimental test meals. As such, little is known about the normal metabolic response to a realistic, low calorie morning meal. Therefore, the aim of this pilot study was to evaluate the effects of a low dose oral glucose intake on hepatic glycogen levels following an overnight fast in healthy subjects. Glycogen levels were monitored in vivo using (13)C Magnetic Resonance Spectroscopy at baseline and hourly for 4 hours following either a 50 g glucose drink (773 kJ) or a control drink (0 kJ) given over two different visits. During the control visit hepatic glycogen levels decreased throughout the experiment with statistically significant decreases from baseline at 190 minutes (P < 0.05) and 250 minutes (P < 0.05). By contrast, the low dose glucose intake maintained glycogen concentrations with no significant decrease from baseline over 4 hours. A comparison between visits revealed that mean glycogen concentrations were significantly greater during the glucose visit (control visit, AUC = 218 ± 39 mol L(-1) min(-1); glucose visit, AUC = 305 ± 49 mol L(-1) min(-1); P < 0.05). Liver volume decreased significantly from baseline at 180 minutes (P < 0.05) post consumption in both groups, with no significant difference found between visits. Gastric content volumes were significantly higher for the glucose visit immediately following consumption (P < 0.001) and at 60 minutes (P = 0.007) indicating slower gastric emptying for the glucose compared with the control. In conclusion, following an overnight fast, a low dose oral glucose challenge prevents a reduction in hepatic glycogen content but does not increase it above fasted levels.

Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.

PubMed

Galinowski, A; Castelnau, C; Spreux-Varoquaux, O; Bourdel, M C; Olie, J P; Loo, H; Poirier, M F

2000-11-01

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

PubMed

Furst, Daniel E; Kay, Jonathan; Wasko, Mary Chester; Keystone, Edward; Kavanaugh, Arthur; Deodhar, Atul; Murphy, Frederick T; Magnus, Jeanette H; Hsia, Elizabeth C; Hsu, Benjamin; Xu, Stephen; Rahman, Mahboob U; Doyle, Mittie K

2013-10-01

To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.

Mis-segmentation in voxel-based morphometry due to a signal intensity change in the putamen.

PubMed

Goto, Masami; Abe, Osamu; Miyati, Tosiaki; Aoki, Shigeki; Gomi, Tsutomu; Takeda, Tohoru

2017-12-01

The aims of this study were to demonstrate an association between changes in the signal intensity of the putamen on three-dimensional T1-weighted magnetic resonance images (3D-T1WI) and mis-segmentation, using the voxel-based morphometry (VBM) 8 toolbox. The sagittal 3D-T1WIs of 22 healthy volunteers were obtained for VBM analysis using the 1.5-T MR scanner. We prepared five levels of 3D-T1WI signal intensity (baseline, same level, background level, low level, and high level) in regions of interest containing the putamen. Groups of smoothed, spatially normalized tissue images were compared to the baseline group using a paired t test. The baseline was compared to the other four levels. In all comparisons, significant volume changes were observed around and outside the area that included the signal intensity change. The present study demonstrated an association between a change in the signal intensity of the putamen on 3D-T1WI and changed volume in segmented tissue images.

Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-Blind, Randomized, Placebo-Controlled DESCARTES Study.

PubMed

Blom, Dirk J; Djedjos, C Stephen; Monsalvo, Maria Laura; Bridges, Ian; Wasserman, Scott M; Scott, Rob; Roth, Eli

2015-09-25

Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels. To determine the effects of evolocumab on vitamin E and steroid hormone levels. After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L. As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01516879. © 2015 American Heart Association, Inc.

Effects of myofascial release after high-intensity exercise: a randomized clinical trial.

PubMed

Arroyo-Morales, Manuel; Olea, Nicolas; Martinez, Manuel; Moreno-Lorenzo, Carmen; Díaz-Rodríguez, Lourdes; Hidalgo-Lozano, Amparo

2008-03-01

The usefulness of massage as a recovery method after high-intensity exercise has yet to be established. We aimed to investigate the effects of whole-body massage on heart rate variability (HRV) and blood pressure (BP) after repeated high-intensity cycling exercise under controlled and standardized pretest conditions. The study included 62 healthy active individuals. After baseline measurements, the subjects performed standardized warm-up exercises followed by three 30-second Wingate tests. After completing the exercise protocol, the subjects were randomly assigned to a massage (myofascial release) or placebo (sham treatment with disconnected ultrasound and magnetotherapy equipment) group for a 40-minute recovery period. Holter recording and BP measurements were taken after exercise protocol and after the intervention. After the exercise protocol, both groups showed a significant decrease in normal-to-normal interval, HRV index, diastolic BP (P > .001), and low-frequency domain values (P = .006). After the recovery period, HRV index (P = .42) and high-frequency (HF) (P = .94) values were similar to baseline levels in the massage group, whereas the HRV index tended (P = .05) to be lower and the HF was significantly (P < .01) lower vs baseline values in the placebo group, which also showed a tendency (P = .06) for HF to be lower than after the exercise. Likewise, diastolic BP returned to baseline levels in the massage group (P = .45) but remained lower in the placebo group (P = .02). Myofascial release massage favors the recovery of HRV and diastolic BP after high-intensity exercise (3 Wingate tests) to preexercise levels.

Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease.

PubMed

Peng, Sui; Xiong, Li-shou; Xiao, Ying-lian; Wang, An-jiang; Lin, Jin-kun; Hu, Pin-jin; Chen, Min-hu

2010-08-05

The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease (GERD) on proton-pump inhibitor (PPI) therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients. GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH+ group did not. Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% (52/58) of symptom-free patients and 67% (12/18) of symptom-persistent patients achieved esophageal pH normalization after therapy (P = 0.030). The mean post-therapy gastric nocturnal percent time of pH < 4.0 was significantly higher in pH+ group than that in pH- group (P < 0.001) after therapy. The multivariate regression analysis identified hiatus hernia (P < 0.001) and persistent reflux symptom (P = 0.004) were two independent factors predicting the low post-therapy esophageal pH level. Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse. Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men.

PubMed

Kenny, Anne M; Biskup, Bradley; Robbins, Bertha; Marcella, Glenn; Burleson, Joseph A

2003-12-01

To study the effects of vitamin D supplementation in healthier populations of men. : Randomized, controlled trial. General clinical research center. Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.

Thyroid hormone levels and incident chronic kidney disease in euthyroid individuals: the Kangbuk Samsung Health Study.

PubMed

Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo

2014-10-01

Overt and subclinical hypothyroidism are associated with higher levels of serum creatinine and with increased risk of chronic kidney disease (CKD). The prospective association between thyroid hormones and kidney function in euthyroid individuals,however, is largely unexplored. We conducted a prospective cohort study in 104 633 South Korean men and women who were free of CKD and proteinuria at baseline and had normal thyroid hormone levels and no history of thyroid disease or cancer. At each annual or biennial follow-up visit, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by radioimmunoassay. The study outcome was incident CKD, defined as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. After a median follow-up of 3.5 years, 1032 participants developed incident CKD.There was a positive association between high-normal levels of TSH and increased risk of incident CKD. In fully-adjusted models including baseline eGFR, the hazard ratio comparing the highest vs the lowest quintiles of TSH was 1.26 [95% confidence interval (CI) 1.02 to 1.55; P for linear trend=0.03]. In spline models, FT3 levels below 3 pg/ml were also associated with increased risk of incident CKD. There was no association between FT4 levels and CKD. In a large cohort of euthyroid men and women, high levels of TSH and low levels of FT3, even within the normal range, were modestly associated with an increased risk of incident CKD.

Impact of body fat percentage change on future diabetes in subjects with normal glucose tolerance.

PubMed

Zhao, Tianxue; Lin, Ziwei; Zhu, Hui; Wang, Chen; Jia, Weiping

2017-12-01

The aim of the work was to determine the effect of body fat change on risk of diabetes in normal glucose tolerance (NGT) population. A total of 1,857 NGT subjects were included and followed up for an average period of 44.57 months. Body fat percentage (BF%) was measured by bioelectrical impedance analysis. Subjects were grouped based on the BF% and/or body mass index (BMI) state. Among all subjects, 28 developed diabetes after follow-up. Compared with subjects with stable normal BF% (control), subjects who became obesity at follow-up were defects in insulin secretion and had a higher risk of developing diabetes (7.102, 95% confidence intervals [CI] 1.740-28.993), while no difference in diabetic risk could be viewed between subjects with abnormal BF% at baseline but normal at the end of follow-up and control subjects after adjustment of confounding factors. Moreover, compared with those keeping normal BF% and BMI both at baseline and follow-up, subjects who had normal BMI at baseline and follow-up, but abnormal BF% at baseline or/and follow-up still had a higher risk to develop diabetes (4.790, 95% CI 1.061-21.621), while those with normal BF% at baseline and follow-up, but abnormal BMI at baseline or/and follow-up had not. Subjects from normal BF% at baseline to obese at follow-up are associated with an increased risk of diabetes. Maintaining normal body fat is more relevant than BMI in preventing diabetes. © 2017 IUBMB Life, 69(12):947-955, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Anterior cingulate cortex and cerebellar hemisphere neurometabolite changes in depression treatment: A 1H magnetic resonance spectroscopy study.

PubMed

Chen, Li-Ping; Dai, Hai-Yang; Dai, Zhuo-Zhi; Xu, Chong-Tao; Wu, Ren-Hua

2014-05-01

We utilized single-voxel 1H magnetic resonance spectroscopy to determine biochemical abnormalities related to major depressive disorder (MDD) in the bilateral dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), and cerebellar hemisphere before and after antidepressant treatment. Fifteen adult MDD patients and 15 age- and sex-matched healthy controls were involved. Magnetic resonance spectroscopy of the brain was conducted in all subjects at the beginning of the study and the depressed subjects were reassessed after 8 weeks of antidepressant treatment. At baseline, N-acetyl aspartate (NAA), total glutamine plus glutamate (Glx) and myo-inositol (MI) levels in the bilateral ACC were significantly lower in MDD patients than in controls (P < 0.05/3). MI in the bilateral cerebellar hemisphere were also decreased in patients compared with controls. After the treatment, the lower NAA, Glx and MI in ACC were normalized in MDD patients and the NAA and Glx increased compared to baseline values. The MI levels in the bilateral cerebellar hemisphere were also normalized in patients. MI and choline levels in the right cerebellar hemisphere were elevated compared to those at baseline. Our study suggests that metabolic abnormalities in the ACC and cerebellar hemisphere are implicated in MDD. Antidepressants may alter the local metabolic abnormalities in these areas. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Cumulative increased risk of incident type 2 diabetes mellitus with increasing triglyceride glucose index in normal-weight people: The Rural Chinese Cohort Study.

PubMed

Zhang, Ming; Wang, Bingyuan; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Wang, Chongjian; Li, Linlin; Zhang, Lu; Ren, Yongcheng; Zhao, Yang; Zhou, Junmei; Han, Chengyi; Zhao, Jingzhi; Hu, Dongsheng

2017-03-01

Risk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China. We included data from 5706 people with normal body mass index (BMI) (18.5-23.9 kg/m 2 ) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure-response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2]. Risk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20-5.11], 3.77 [1.83-7.79], and 5.30 [2.21-12.71], P trend  < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22-6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index. Risk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

Arterial stiffness parameters associated with vitamin D deficiency and supplementation in patients with normal cardiac functions.

PubMed

Sünbül, Murat; Çinçin, Altuğ; Bozbay, Mehmet; Mammadov, Ceyhun; Ataş, Halil; Özşenel, Ekmel Burak; Sarı, İbrahim; Başaran, Yelda

2016-06-01

Arterial stiffness parameters including pulse wave velocity (PWV) and augmentation index (AIx) are associated with increased risk of cardiovascular disease. A close relationship has been demonstrated between vitamin D deficiency and cardiovascular disease. The aim of the present study was to investigate effects of vitamin D deficiency and supplementation on arterial stiffness parameters in patients with normal cardiac functions. Study population consisted of 45 patients with vitamin D deficiency and normal cardiac functions. Median age (interquartile range) was 45.0 (12.00) years, and 33 patients were female. Patients were treated with oral administration of vitamin D3. Arterial stiffness parameters were evaluated using Mobil-O-Graph arteriograph system, which detected signals from the brachial artery before and after treatment. Vitamin D levels significantly increased after treatment (9.0 [6.00] nmol/L vs 29.0 [11.50] nmol/L, p<0.001). No significant difference was observed among conventional echocardiographic parameters before or after treatment. Post-treatment PVW and AIx were significantly lower than baseline measurements (6.8 [1.55] m/s vs 6.4 [1.30] m/s, p<0.001 and 23.0 [22.00]% vs 31.0 [14.50]%, p<0.001, respectively). Baseline vitamin D levels significantly correlated with PWV (r=-0.352, p=0.018). Post-treatment vitamin D levels also significantly correlated with post-treatment PWV (r=-0.442, p=0.002) and AIx (r=-0.419, p=0.004). Multivariate linear regression analysis revealed no independent predictor of baseline log-transformed PWV. Vitamin D supplementation has beneficial effects on arterial stiffness. Arterial stiffness parameters may aid in the assessment of cardiovascular risk in patients with vitamin D deficiency.

Crustal deformation at very long baseline interferometry sites due to seasonal air-mass and ground water variations

NASA Technical Reports Server (NTRS)

Stolz, A.; Larden, D. R.

1980-01-01

The seasonal deformation normal to the Earth's surface was calculated at stations involved or interested in very long baseline interferometry (VLBI) geodesy and at hypothetical sites in Australia and Brazil using global atmospheric pressure data, values for groundwater storage, and load Love numbers deduced from current Earth models. It was found that the annual range of deformation approached the centimeter level measuring potential of the VLBI technqiue at Greenbank, Haystack, and the Brazil site.

Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

PubMed

Veltri, Flora; Kleynen, Pierre; Grabczan, Lidia; Salajan, Alexandra; Rozenberg, Serge; Pepersack, Thierry; Poppe, Kris

2018-02-01

In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off < and ≥2.5 mIU/L). Tobacco use was associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08-1.74); P  = 0.009. FT4 levels were inversely correlated with age and BMI (rho = -0.096 and -0.089; P  < 0.001 and 0.001 respectively) and positively correlated with ferritin levels (rho = 0.097; P  < 0.001). Postpartum haemorrhage (>500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P  = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies. © 2018 European Society of Endocrinology.

The effect of ubiquinone and combined antioxidant therapy on oxidative stress markers in non-proliferative diabetic retinopathy: A phase IIa, randomized, double-blind, and placebo-controlled study.

PubMed

Rodríguez-Carrizalez, Adolfo Daniel; Castellanos-González, José Alberto; Martínez-Romero, Esaú César; Miller-Arrevillaga, Guillermo; Pacheco-Moisés, Fermín Paul; Román-Pintos, Luis Miguel; Miranda-Díaz, Alejandra Guillermina

2016-07-01

Objective To evaluate the effect of ubiquinone (Coenzyme Q10) and combined antioxidant therapy (CAT) on oxidative stress markers in non-proliferative diabetic retinopathy (NPDR) under clinical management. Study design In a randomized, double-blind, phase IIa, placebo-controlled, clinical trial, three study groups were formed and administered medications as follows: Group 1, Coenzyme Q10; Group 2, CAT; and Group 3, placebo. Methods Serum levels of the products of lipid peroxidation (LPO) and nitrites/nitrates, as markers of oxidative/nitrosative stress, were measured. As antioxidants, the total antioxidant capacity (TAC), catalase activity, and glutathione peroxidase (GPx) activity were measured. Results Baseline serum levels of LPO and nitrites/nitrates were significantly elevated in the three groups vs. healthy group (P < 0.0001), while final levels in the Coenzyme Q10 and CAT groups were decreased vs. normal levels (P < 0.0001). The baseline TAC was consumed in the three groups (P < 0.0001), while final results in the Coenzyme Q10 and CAT groups improved (P < 0.0001). Baseline catalase activity was increased in all groups vs. normal values (P < 0.001), while final levels in the Coenzyme Q10 (P < 0.001) and CAT groups (P < 0.0001) were decreased. GPx behaved similarly to catalase and improved in the final results (P < 0.0001). Discussion Adjunctive antioxidant treatment for 6 months was effective and safe for improving the oxidative stress in NPDR.

Effect of dietary aspartame on plasma concentrations of phenylalanine and tyrosine in normal and homozygous phenylketonuric patients.

PubMed

Mackey, S A; Berlin, C M

1992-07-01

Six normal subjects each ingested a single 12-oz can of a diet cola (Diet Coke) providing 184 mg aspartame (APM), of which 104 mg is phenylalanine (Phe), and, on another occasion, a single 12-oz can of regular cola (Coke Classic). Neither cola significantly affected plasma concentrations of Phe or tyrosine over the three-hour postingestion study period. Each of five homozygous phenylketonuric (PKU) subjects (ages 11, 16, 17, 21, and 23 years) ingested a single 12-oz can of the same diet cola. In these five subjects (three with classic PKU and two with hyperphenylalinemia), the increase in plasma Phe concentrations varied from 0.26 mg/dL to 1.77 mg/dL two or three hours after ingestion (baseline levels, 5.04 to 17.2 mg/dL). Tyrosine concentrations did not differ significantly from baseline levels. The data indicate that ingestion of dietary Phe, as supplied in a single can of diet cola, is readily handled in both normal and PKU subjects. The small increases in plasma Phe concentrations in the homozygous PKU patients are not considered clinically significant.

A genetic study of dehydroepiandrosterone sulfate measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

PubMed

An, P; Rice, T; Gagnon, J; Hong, Y; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2000-03-01

Familial aggregation and possible major gene effects were evaluated for the baseline serum dehydroepiandrosterone sulfate (DHEAS) level and the change in DHEAS in response to a 20-week exercise training program in a sample of 481 individuals from 99 Caucasian families who were sedentary at baseline and who participated in the HERITAGE Family Study. Baseline DHEAS levels were not normally distributed, and were therefore logarithmically transformed and adjusted for the effects of age and sex prior to genetic analysis. The DHEAS response to training was computed as the simple difference, post-training minus baseline, and was adjusted for the baseline DHEAS level, age, and sex. Maximal (genetic and familial environmental) heritabilities (using a familial correlation model) reached 58% and 30% for the baseline and the response to training, respectively. Our estimate for the baseline is generally in agreement with previous reports, suggesting that the magnitude of the familial effect underlying this phenotype in these sedentary families is similar to that in the general population. However, segregation analysis showed no evidence for a multifactorial familial component in data for either the baseline or the response to training. Rather, a major additive gene controlling the baseline was found. For the response to training in the complete sample, transmission of the major effect from parents to offspring was ambiguous, but in a subset of 56 "responsive" families (with at least 1 family member whose response to training was greater than 1 standard deviation) this major effect was Mendelian in nature. The putative major genes accounted for 50% and 33% of the variance for the baseline and the response to training, respectively. The novel finding in this study is that the baseline DHEAS level and the change in DHEAS in response to training may be influenced by major gene effects.

A Statistical Simulation Approach to Safe Life Fatigue Analysis of Redundant Metallic Components

NASA Technical Reports Server (NTRS)

Matthews, William T.; Neal, Donald M.

1997-01-01

This paper introduces a dual active load path fail-safe fatigue design concept analyzed by Monte Carlo simulation. The concept utilizes the inherent fatigue life differences between selected pairs of components for an active dual path system, enhanced by a stress level bias in one component. The design is applied to a baseline design; a safe life fatigue problem studied in an American Helicopter Society (AHS) round robin. The dual active path design is compared with a two-element standby fail-safe system and the baseline design for life at specified reliability levels and weight. The sensitivity of life estimates for both the baseline and fail-safe designs was examined by considering normal and Weibull distribution laws and coefficient of variation levels. Results showed that the biased dual path system lifetimes, for both the first element failure and residual life, were much greater than for standby systems. The sensitivity of the residual life-weight relationship was not excessive at reliability levels up to R = 0.9999 and the weight penalty was small. The sensitivity of life estimates increases dramatically at higher reliability levels.

Troponin T elevation after permanent pacemaker implantation.

PubMed

Chen, Xueying; Yu, Ziqing; Bai, Jin; Hu, Shulan; Wang, Wei; Qin, Shengmei; Wang, Jingfeng; Sun, Zhe; Su, Yangang; Ge, Junbo

2017-08-01

The objective of the study is to study the incidence, significance, and factors associated with cardiac troponin T (CTNT) elevation after pacemaker implantation. Three hundred seventy-four patients (104 single-chamber pacemakers or ICD, 243 dual-chamber pacemakers, and 27 cardiac resynchronization therapy/cardiac resynchronization therapy defibrillator) who had normal levels of CTNT at baseline and underwent implantation of a permanent pacemaker system were included in this study. Serum levels of CTNT were measured at baseline, 6 and 24 h after the implantation procedure. The median of CTNT levels increased from 0.012 ng/mL at baseline to 0.032 and 0.019 ng/mL at 6 and 24 h after the procedure, respectively (all p < 0.0001). Elevated CTNT levels were noted in 208 patients (55.6%) at 6 h after the implantation, among which 29 patients (7.8%) had CTNT levels exceeding the range of minimal myocardial damage (>0.09 ng/mL). After 1-year follow-up, the incidence of complications including dislodgement of the lead, pocket infection, pneumothorax, hemothorax, and vein thrombus and cardiac outcomes including hospitalization of heart failure, coronary artery disease, arrhythmia, and cardiovascular mortality was not significantly different between the normal and elevated CTNT groups at 6 h after the procedure. By logistic regression analysis, gender, N-terminal pro-B type natriuretic peptide (NT-pro-BNP) at baseline, left ventricular ejection fractions (LVEF), estimated glomerular filtration rate (eGFR), and fluoroscopy time were independently associated with CTNT elevation after adjusted for age, pacemaker types, right ventricle lead location (RVA or RVOT), heart function, and left ventricular end systolic dimension. Pacemaker implantation was found to be accompanied with CTNT elevation in 55.6% of the patients at 6 h after the procedure, and its kinetics were fast, which might not be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, gender, NT-pro-BNP at baseline, LVEF, eGFR, and fluoroscopy time were found to be independent predictors of CTNT elevation.

The effects of gum arabic oral treatment on the metabolic profile of chronic renal failure patients under regular haemodialysis in Central Sudan.

PubMed

Ali, Adil Ahmed; Ali, Khalid Eltom; Fadlalla, Abd Eigani; Khalid, Khalid Eltahir

2008-01-10

This study aimed at assessing the effect of gum arabic (Acacia senegal) oral treatment on the metabolic profile of chronic renal failure (CRF) patients. A total of 36 CRF patients (under regular haemodialysis) and 10 normal subjects participated in this study. The patients were randomly allocated into three groups-group A: 12 CRF patients under low-protein diet (LPD) (<40 g day(-1)) and gum arabic (50 g day(-1)) treatment; group B: 14 CRF patients under LPD and gum arabic, iron (ferrous sulphate, 200 mg day(-1)) and folic acid (5 mg day(-1)) treatment; group C (control group): 10 CRF patients under LPD and iron and folic acid treatment and group D: 10 normal volunteers (on normal diet) under daily dose of 50 g gum arabic. Each of the above treatments was continued for three consecutive months. Blood samples were collected from each subject before treatment and twice per month "pre-dialysis" for 3 months. Biochemical parameters measured were: serum urea, serum creatinine, serum uric acid, serum calcium and serum phosphorus. By the end of the 3 months of treatment, serum urea levels significantly decreased by 31.2 and 44.18% for group A and B, respectively, compared with the baseline (0.01 < p < 0.001) and control group (p < 0.05). Serum creatinine levels significantly decreased in the groups of gum users (A, B and D) by 9.94, 12.65 and 11.7%, respectively, compared with the control group (p < 0.001). There was a significant decrease (p < 0.05) in serum uric acid levels by 14 and 19.9% for group A and B, respectively, compared with the baseline. Serum calcium levels increased by 12.64, 15.75 and 8.75% for group A, B and D, respectively, and these increases were significantly different (0.05 < p < 0.001) from baseline and control group for groups A and B. Serum phosphorus levels significantly decreased by 22.54% for group A, 17.69% for group B and 7.71% for group D, compared with the baseline (0.05 < p < 0.001). From this study, we conclude that oral administration of gum arabic could conceivably alleviate adverse effects of CRF.

Growth hormone secretory pattern and response to treatment in children with short stature followed to adult height.

PubMed

Radetti, Giorgio; Buzi, Fabio; Cassar, Walburga; Paganini, Claudio; Stacul, Elisabetta; Maghnie, Mohamad

2003-07-01

To compare the relative utility of GH stimulation tests and assays of spontaneous GH secretion as predictors of change in height standard deviation score at the end of GH treatment in children with short stature. We retrospectively studied 116 children (67 boys and 49 girls) with subnormal growth rates and short stature, defined as a height of more than 2SD below the mean for age and sex. The patients were classified according to their pattern of findings on baseline pharmacological GH stimulation tests and a 12-h assay of nocturnal spontaneous GH secretion. Twenty-eight patients (24%) had normal hormone levels by both methods (group I); 14 (12%) had normal levels by stimulation tests but subnormal levels by the physiological assay (group II); 48 (41%) had subnormal levels on pharmacological stimulation, with normal physiologic levels (group III); and 26 (22%) had subnormal levels by both methods (group IV). All children in groups II and IV, and 27 in group III, designated IIIb, were treated with recombinant GH at 0.7 U (0.23 mg/kg) of body weight per week. GH secretory patterns were related to final height SD scores and other growth parameters, after the patients had attained their adult stature 6.7 +/- 2.2 years (SD) after GH evaluation. The five groups were similar with respect to mean baseline height SD scores for chronological as well as bone age. Whether assessed as absolute or parentally adjusted (relative) values, mean gains in height SD scores were significantly greater in treated patients with physiological hormone deficiency (groups II and IV) than in those with normal hormone levels (group I, untreated controls). Relative height gains were 1.03 +/- 1.45 cm (6.6 +/- 9.28 cm) and 1.85 +/- 1.21 cm (SDS; 11.8 +/- 7.74 cm) in groups II and IV respectively, compared with only 0.11 +/- 0.42 cm (0.7 +/- 2.68 cm) in group I (P < 0.01 and P < 0.001). GH treatment failed to improve either the absolute or parentally adjusted final height of patients with GH deficiency by stimulation tests but normal levels by physiological assay. Long-term administration of GH to short children with normal spontaneous GH secretion is not associated with an appreciable increase in adult height.

The efficacy of vitamin C supplementation on reducing total serum cholesterol in human subjects: a review and analysis of 51 experimental trials

PubMed Central

McRae, Marc P.

2006-01-01

Abstract Objective Observational studies in humans have shown an inverse relationship between plasma vitamin C concentration and total serum cholesterol. However, experimental studies have shown inconsistent results regarding the ability of vitamin C to reduce total serum cholesterol. Methods Published reports of trials studying the effects of vitamin C on serum lipids were identified by a search of Medline from 1966 to 2004. Data from 51 experimental studies comprising of 1666 pooled subjects were selected for analysis. Results A very strong negative association was observed between baseline total serum cholesterol and the percent change in cholesterol (r = −0.585, p<0.001). When subjects were divided into 4 groups based on their baseline total serum cholesterol levels, the following weighted mean percent changes in cholesterol from baseline were observed: normal cholesterol (<199mg/dl): 0.91±6.8% (n=508); borderline high cholesterol (200–239mg/dl): 3.90±5.78% (n=605); high cholesterol (240–279mg/dl): 11.40±7.96% (n=300); severe cholesterol (>280mg/dl): 14.30±8.36% (n=253). A significant inverse relationship was found between the baseline plasma vitamin C concentrations and mean percent change in total cholesterol from baseline (r = −0.500, p<0.005). It was also observed that the high and severe baseline cholesterol groups possessed lower baseline plasma vitamin C concentrations than those in the normal cholesterol groups (0.79 and 0.55 versus 1.24 mg/dl respectively). Conclusion This finding strengthens the hypothesis that the cholesterol lowering and cardio-protective benefit of vitamin C supplementation may be in its ability to elevate plasma vitamin C concentrations in those patients who initially possess lower than normal vitamin C plasma concentrations. PMID:19674666

CSF biomarkers of Alzheimer disease

PubMed Central

Fagan, Anne M.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.

2013-01-01

Objectives: To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Aβ42, and ptau181/Aβ42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Methods: Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Results: Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. Conclusions: CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples. PMID:24212387

CSF biomarkers of Alzheimer disease: "noncognitive" outcomes.

PubMed

Roe, Catherine M; Fagan, Anne M; Grant, Elizabeth A; Holtzman, David M; Morris, John C

2013-12-03

To test whether CSF Alzheimer disease biomarkers (β-amyloid 42 [Aβ42], tau, phosphorylated tau at threonine 181 [ptau181], tau/Aβ42, and ptau181/Aβ42) predict future decline in noncognitive outcomes among individuals cognitively normal at baseline. Longitudinal data from participants (N = 430) who donated CSF within 1 year of a clinical assessment indicating normal cognition and were aged 50 years or older were analyzed. Mixed linear models were used to test whether baseline biomarker values predicted future decline in function (instrumental activities of daily living), weight, behavior, and mood. Clinical Dementia Rating Sum of Boxes and Mini-Mental State Examination scores were also examined. Abnormal levels of each biomarker were related to greater impairment with time in behavior (p < 0.035) and mood (p < 0.012) symptoms, and more difficulties with independent activities of daily living (p < 0.012). However, biomarker levels were unrelated to weight change with time (p > 0.115). As expected, abnormal biomarker values also predicted more rapidly changing Mini-Mental State Examination (p < 0.041) and Clinical Dementia Rating Sum of Boxes (p < 0.001) scores compared with normal values. CSF biomarkers among cognitively normal individuals are associated with future decline in some, but not all, noncognitive Alzheimer disease symptoms studied. Additional work is needed to determine the extent to which these findings generalize to other samples.

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.

PubMed

Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M; Benzinger, Tammie L S; Grant, Elizabeth A; Holtzman, David M; Morris, John C; Roe, Catherine M

2016-01-01

The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood. We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis

PubMed Central

Ishikawa, Koji; Nagai, Takashi; Sakamoto, Keizo; Ohara, Kenji; Eguro, Takeshi; Ito, Hiroshi; Toyoshima, Yoichi; Kokaze, Akatsuki; Toyone, Tomoaki; Inagaki, Katsunori

2016-01-01

Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium. PMID:27980413

Vitamin D Levels and Lipid Response to Atorvastatin

PubMed Central

Pérez-Castrillón, José Luis; Abad Manteca, Laura; Vega, Gemma; del Pino Montes, Javier; de Luis, Daniel; Dueňas Laita, Antonio

2010-01-01

Adequate vitamin D levels are necessary for good vascular health. 1,25-dihydroxycholecalciferol activates CYP3A4, an enzyme of the cytochrome P450 system, which metabolizes atorvastatin to its main metabolites. The objective of this study was to evaluate the response of cholesterol and triglycerides to atorvastatin according to vitamin D levels. Sixty-three patients with acute myocardial infarction treated with low and high doses of atorvastatin were included. Levels of total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol were measured at baseline and at 12 months of follow-up. Baseline levels of 25-hydroxyvitamin D (25-OHD) were classified as deficient (<30 nmol/L), insufficient (30–50 nmol/L), and normal (>50 nmol/L). In patients with 25-OHD <30 nmol/L, there were no significant changes in levels of total cholesterol (173 ± 47 mg/dL versus 164 ± 51 mg/dL), triglycerides (151 ± 49 mg/dL versus 177 ± 94 mg/dL), and LDL cholesterol (111 ± 48 mg/dL versus 92 45 ± mg/dL); whereas patients with insufficient (30–50 nmol/L) and normal vitamin D (>50 nmol/L) had a good response to atorvastatin. We suggest that vitamin D concentrations >30 nmol/L may be required for atorvastatin to reduce lipid levels in patients with acute myocardial infarction. PMID:20016682

Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism.

PubMed

Caronia, Lisa M; Dwyer, Andrew A; Hayden, Douglas; Amati, Francesca; Pitteloud, Nelly; Hayes, Frances J

2013-02-01

This study examines the physiological impact of a glucose load on serum testosterone (T) levels in men with varying glucose tolerance (GT). Cross-sectional study. 74 men (19-74 years, mean 51·4 ± 1·4 years) underwent a standard 75-g oral glucose tolerance test with blood sampling at 0, 30, 60, 90 and 120 min. Fasting serum glucose, insulin, total T (and calculated free T), LH, SHBG, leptin and cortisol were measured. 57% of the men had normal GT, 30% had impaired GT and 13% had newly diagnosed type 2 diabetes. Glucose ingestion was associated with a 25% decrease in mean T levels (delta = -4·2 ± 0·3 nm, P < 0·0001). T levels remained suppressed at 120 min compared with baseline (13·7 ± 0·6 vs 16·5 ± 0·7 nm, P < 0·0001) and did not differ across GT or BMI. Of the 66 men with normal T levels at baseline, 10 (15%) had levels that decreased to the hypogonadal range (<9·7 nm) at one or more time points. SHBG, LH and cortisol levels were unchanged. Leptin levels decreased from baseline at all time points (P < 0·0001). Glucose ingestion induces a significant reduction in total and free T levels in men, which is similar across the spectrum of glucose tolerance. This decrease in T appears to be because of a direct testicular defect, but the absence of compensatory changes in LH suggests an additional central component. Men found to have low nonfasting T levels should be re-evaluated in the fasting state. © 2012 Blackwell Publishing Ltd.

Prolactin as a Marker of Successful Catheterization during IPSS in Patients with ACTH-Dependent Cushing's Syndrome

PubMed Central

Sharma, S. T.; Raff, H.

2011-01-01

Context: Anomalous venous drainage can lead to false-negative inferior petrosal sinus sampling (IPSS) results. Baseline inferior petrosal sinus to peripheral (IPS/P) prolactin ratio higher than 1.8 ipsilateral to the highest ACTH ratio has been proposed to verify successful catheterization. Prolactin-normalized ACTH IPS/P ratios may differentiate Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Objective: Our objective was to examine the utility of prolactin measurement during IPSS. Design, Setting, and Participants: We conducted a retrospective analysis of prolactin levels in basal and CRH-stimulated IPSS samples in ACTH-dependent Cushing's syndrome (2007–2010). Results: Twenty-five of 29 patients had a pathologically proven diagnosis (17 CD and eight EAS). IPSS results were partitioned into true positive for CD (n = 16), true negative (n = 7), false negative (n = 1), and false positive (n = 1). Prolactin IPS/P ratio suggested successful IPSS in eight of 11 with abnormal venograms. Baseline prolactin IPS/P ratio was helpful in two patients with abnormal venograms and false-negative (catheterization unsuccessful) or true-negative (catheterization successful) IPSS results; the normalized ratio correctly diagnosed their disease. Normalized ACTH IPS/P ratio was at least 1.3 in all with CD, but prolactin IPS/P ratios were misleadingly low in two. One patient with cyclic EAS had a false-positive IPSS when eucortisolemic (baseline prolactin IPS/P = 1.7; normalized ratio = 5.6). All other EAS patients had normalized ratios no higher than 0.7. Conclusion: Prolactin measurement and evaluation of the venogram can improve diagnostic accuracy when IPSS results suggest EAS but is not necessary with positive IPSS results. Confirmation of hypercortisolemia remains a prerequisite for IPSS. A normalized ratio of 0.7–1.3 was not diagnostic. PMID:22031511

Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype.

PubMed

Pomara, Nunzio; Willoughby, Lisa M; Hashim, Audrey; Sershen, Henry; Sidtis, John J; Wesnes, Keith; Greenblatt, David J; Lajtha, Abel

2004-07-01

The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.

Three Toxic Heavy Metals in Open-Angle Glaucoma with Low-Teen and High-Teen Intraocular Pressure: A Cross-Sectional Study from South Korea.

PubMed

Lee, Si Hyung; Kang, Eun Min; Kim, Gyu Ah; Kwak, Seung Woo; Kim, Joon Mo; Bae, Hyoung Won; Seong, Gong Je; Kim, Chan Yun

2016-01-01

To investigate the association between heavy metal levels and open-angle glaucoma (OAG) with low- and high-teen baseline intraocular pressure (IOP) using a population-based study design. This cross-sectional study included 5,198 participants older than 19 years of age who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2012 and had blood heavy metal levels available. The OAG with normal baseline IOP (IOP ≤ 21 mmHg) subjects were stratified into low-teen OAG (baseline IOP ≤ 15 mmHg) and high-teen OAG (15 mmHg < baseline IOP ≤ 21 mmHg), and the association between blood lead, mercury, and cadmium levels and glaucoma prevalence was assessed for low- and high-teen OAG. The adjusted geometric mean of blood cadmium levels was significantly higher in subjects with low-teen OAG than that of the non-glaucomatous group (P = 0.028), whereas there were no significant differences in blood lead and mercury levels. After adjusting for potential confounders, the low-teen OAG was positively associated with log-transformed blood cadmium levels (OR, 1.41; 95% confidence interval (CI), 1.03-1.93; P = 0.026). For high-teen OAG, log-transformed blood levels of the three heavy metals were not associated with disease prevalence. The association between log-transformed blood cadmium levels and low-teen OAG was significant only in men (OR, 1.65; 95% CI, 1.10-2.48; P = 0.016), and not in women (OR, 1.10; 95% CI, 0.66-1.85; P = 0.709). The results of this study suggest that cadmium toxicity could play a role in glaucoma pathogenesis, particularly in men and in OAG with low-teen baseline IOP.

Longitudinal change of biomarkers in cognitive decline.

PubMed

Lo, Raymond Y; Hubbard, Alan E; Shaw, Leslie M; Trojanowski, John Q; Petersen, Ronald C; Aisen, Paul S; Weiner, Michael W; Jagust, William J

2011-10-01

To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Cohort study. The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

Upregulating Apoptotic Signaling in Neurofibromatosis

DTIC Science & Technology

2009-09-01

Schwannoma) cells that are NF1 deficient cells were used. Rat pheochromocytoma PC12 cells were selected as a control, in which Ras signaling is normal. The...Down and Detection kit. The baseline level of GTP bound Ras was detected in PC12 cells (rat pheochromocytoma ) in which Ras signaling is intact. In

The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study.

PubMed

Wang, Haoyu; Liu, Aihua; Zhou, Yingying; Xiao, Yue; Yan, Yumeng; Zhao, Tong; Gong, Xun; Pang, Tianxiao; Fan, Chenling; Zhao, Jiajun; Teng, Weiping; Shan, Zhongyan; Lai, Yaxin

2017-09-01

Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

PubMed Central

Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

2015-01-01

Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

Burosumab Therapy in Children with X-Linked Hypophosphatemia.

PubMed

Carpenter, Thomas O; Whyte, Michael P; Imel, Erik A; Boot, Annemieke M; Högler, Wolfgang; Linglart, Agnès; Padidela, Raja; Van't Hoff, William; Mao, Meng; Chen, Chao-Yin; Skrinar, Alison; Kakkis, Emil; San Martin, Javier; Portale, Anthony A

2018-05-24

X-linked hypophosphatemia is characterized by increased secretion of fibroblast growth factor 23 (FGF-23), which leads to hypophosphatemia and consequently rickets, osteomalacia, and skeletal deformities. We investigated burosumab, a monoclonal antibody that targets FGF-23, in patients with X-linked hypophosphatemia. In an open-label, phase 2 trial, we randomly assigned 52 children with X-linked hypophosphatemia, in a 1:1 ratio, to receive subcutaneous burosumab either every 2 weeks or every 4 weeks; the dose was adjusted to achieve a serum phosphorus level at the low end of the normal range. The primary end point was the change from baseline to weeks 40 and 64 in the Thacher rickets severity total score (ranging from 0 to 10, with higher scores indicating greater disease severity). In addition, the Radiographic Global Impression of Change was used to evaluate rachitic changes from baseline to week 40 and to week 64. Additional end points were changes in pharmacodynamic markers, linear growth, physical ability, and patient-reported outcomes and the incidence of adverse events. The mean Thacher rickets severity total score decreased from 1.9 at baseline to 0.8 at week 40 with every-2-week dosing and from 1.7 at baseline to 1.1 at week 40 with every-4-week dosing (P<0.001 for both comparisons); these improvements persisted at week 64. The mean serum phosphorus level increased after the first dose in both groups, and more than half the patients in both groups had levels within the normal range (3.2 to 6.1 mg per deciliter [1.0 to 2.0 mmol per liter]) by week 6. Stable serum phosphorus levels were maintained through week 64 with every-2-week dosing. Renal tubular phosphate reabsorption increased from baseline in both groups, with an overall mean increase of 0.98 mg per deciliter (0.32 mmol per liter). The mean dose of burosumab at week 40 was 0.98 mg per kilogram of body weight with every-2-week dosing and 1.50 mg per kilogram with every-4-week dosing. Across both groups, the mean serum alkaline phosphatase level decreased from 459 U per liter at baseline to 369 U per liter at week 64. The mean standing-height z score increased in both groups, with greater improvement seen at all time points with every-2-week dosing (an increase from baseline of 0.19 at week 64) than with every-4-week dosing (an increase from baseline of 0.12 at week 64). Physical ability improved and pain decreased. Nearly all the adverse events were mild or moderate in severity. In children with X-linked hypophosphatemia, treatment with burosumab improved renal tubular phosphate reabsorption, serum phosphorus levels, linear growth, and physical function and reduced pain and the severity of rickets. (Funded by Ultragenyx Pharmaceutical and Kyowa Hakko Kirin; ClinicalTrials.gov number, NCT02163577 ; EudraCT number, 2014-000406-35 ).

Prefrontal and Striatal Gamma-Aminobutyric Acid Levels and the Effect of Antipsychotic Treatment in First-Episode Psychosis Patients.

PubMed

de la Fuente-Sandoval, Camilo; Reyes-Madrigal, Francisco; Mao, Xiangling; León-Ortiz, Pablo; Rodríguez-Mayoral, Oscar; Jung-Cook, Helgi; Solís-Vivanco, Rodolfo; Graff-Guerrero, Ariel; Shungu, Dikoma C

2018-03-15

Abnormally elevated levels of gamma-aminobutyric acid (GABA) in the medial prefrontal cortex (mPFC) have been reported in antipsychotic-free patients with schizophrenia. Whether such GABA elevations are also present in other brain regions and persist after antipsychotic treatment has not been previously investigated. Twenty-eight antipsychotic-naïve patients with first-episode psychosis (FEP) and 18 healthy control subjects completed the study. Following baseline proton magnetic resonance spectroscopy scans targeting the mPFC and a second region, the dorsal caudate, patients with FEP were treated with oral risperidone for 4 weeks at an initial dose of 1 mg/day that was titrated as necessary based on clinical judgment. After the 4-week treatment period, both groups were brought back to undergo outcome magnetic resonance spectroscopy scans, which were identical to the scans conducted at baseline. At baseline, higher GABA levels were found both in the mPFC and in the dorsal caudate of patients with FEP compared with healthy control subjects. Following 4 weeks of antipsychotic treatment, GABA levels in patients with FEP decreased relative to baseline in the mPFC, but decreased only at the trend level relative to baseline in the dorsal caudate. For either brain region, GABA levels at 4 weeks or posttreatment did not differ between patients with FEP and healthy control subjects. The results of the present study documented elevations of GABA levels both in the mPFC and, for the first time, in the dorsal caudate of antipsychotic-naïve patients with FEP, which normalized in both regions following 4 weeks of antipsychotic treatment. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Macular auto-fluorescence is a follow-up parameter for cystoids macular edema.

PubMed

Zhang, XinYuan; Gong, XiaoHong; Wang, YanHong; Wang, NingLi

2015-08-01

This study aimed to evaluate if macular autofluorescence (MAF) is a valuable, non-invasive follow-up parameter for cystoid macular edema. A total of 71 eyes (71 cases) with cystoid macular edema (CME) were included in the study. Macular pigment (MP) was evaluated using HRA2 (infrared) IF and FA models. The density of MP was graded into three categories: without, partial, and normal amount of MP. A comparison was made between the baseline (before the first administration) level and at the fourth month, following three consecutive intravitreal lucentis injections every month. The morphology and distribution of MAF, and the density and distribution of MP were regarded as the main outcome measures. At the baseline visit, all eyes with CME had petaloid/irregular-shaped MAF in the macular area (100%). No MAF was detected in the control eyes (0). There was significant difference in MAF between the CME and normal groups (P=0.000). At the fourth monthly visit, normal levels of MP density without MAF was detected in 68 eyes (95.8%) with the best corrected spectacular visual acuity increasing to at least 1 line accordingly. We conclude that macular MAF can be used as a follow-up parameter for patients with CME. MP and MAF can indirectly reflect the fovea cone function.

Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

PubMed

Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

2015-01-01

Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (p<0.05). Obese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

[Effect of supplementation with a single dose of vitamin D in children with cerebral palsy. Preliminary randomised controlled study].

PubMed

Le Roy, Catalina; Meier, Martina; Witting, Scarlett; Pérez-Bravo, Francisco; Solano, Carlos; Castillo-Durán, Carlos

2015-01-01

Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients. To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP. Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group. Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bed-ridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient+deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P=.07). A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Baseline markers of inflammation are associated with progression to macroalbuminuria in type 1 diabetic subjects.

PubMed

Lopes-Virella, Maria F; Baker, Nathaniel L; Hunt, Kelly J; Cleary, Patricia A; Klein, Richard; Virella, Gabriel

2013-08-01

The current study aimed to determine in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications cohort whether or not abnormal levels of markers of inflammation and endothelial dysfunction measured in samples collected at DCCT baseline were able to predict the development of macroalbuminuria. Levels of inflammation and endothelial cell dysfunction biomarkers were measured in 1,237 of 1,441 patients enrolled in the DCCT study who were both free of albuminuria and cardiovascular disease at baseline. To test the association of log-transformed biomarkers with albuminuria, generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, micro-, and macroalbuminuria were the outcomes of interest. In the logistic regression models adjusted by DCCT treatment assignment, baseline albumin excretion rate, and use of ACE/angiotensin receptor blocker drugs, one unit increase in the standardized levels of soluble E-selectin (sE-selectin) was associated with an 87% increase in the odds to develop macroalbuminuria and one unit increase in the levels of interleukin-6 (IL-6), plasminogen activator inhibitor 1 (PAI-1; total and active), and soluble tumor necrosis factor receptors (TNFR)-1 and -2 lead to a 30-50% increase in the odds to develop macroalbuminuria. Following adjustment for DCCT baseline retinopathy status, age, sex, HbA1c, and duration of diabetes, significant associations remained for sE-selectin and TNFR-1 and -2 but not for IL-6 or PAI-1. Our study indicates that high levels of inflammatory markers, mainly E-selectin and sTNRF-1 and -2, are important predictors of macroalbuminuria in patients with type 1 diabetes.

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

PubMed Central

Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

PubMed

Rush, Gavin; O'Donovan, Aoife; Nagle, Laura; Conway, Catherine; McCrohan, AnnMaria; O'Farrelly, Cliona; Lucey, James V; Malone, Kevin M

2016-11-15

Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-β changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

A longitudinal investigation of parenting stress in caregivers of children with retinoblastoma.

PubMed

Willard, Victoria W; Qaddoumi, Ibrahim; Zhang, Hui; Huang, Lu; Russell, Kathryn M; Brennan, Rachel; Wilson, Matthew W; Rodriguez-Galindo, Carlos; Phipps, Sean

2017-04-01

Retinoblastoma is typically diagnosed in young children and may present unique parenting challenges. Qualitative research suggests that parents experience distress related to the initial diagnosis and treatment that subsequently resolves. The objectives were to systematically assess parenting stress over time in parents of young children with retinoblastoma and to examine associations between parenting stress and child outcomes. Parents of children with retinoblastoma completed the Parenting Stress Index (PSI) during serial psychological assessments scheduled based on the child's age (6 months to 5 years). Caregivers of 92 patients (85.9% mothers) completed the assessments. Child outcomes included developmental functioning and parent-reported adaptive functioning. At baseline and age 5, all subscales on the PSI were within normal limits, and most were significantly below normative means (i.e., demonstrating low levels of stress). All domains remained relatively stable over time. Associations between parenting stress and child outcomes were much stronger at age 5 than at baseline. Child-directed parenting stress was a small but significant contributor to declines in child functioning over time. Parents of children with retinoblastoma report normal levels of parenting stress while their children are young. However, baseline parenting stress appears to contribute to changes in child functioning over time. Future studies should assess illness-related aspects of adjustment to further understand the parenting experience of young children with cancer and/or having a visually impaired child. © 2016 Wiley Periodicals, Inc.

Reversibility of Vasalgel™ male contraceptive in a rabbit model.

PubMed

Waller, Donald; Bolick, David; Lissner, Elaine; Premanandan, Christopher; Gamerman, Gary

2017-01-01

Development of a non-hormonal long-acting reversible contraceptive for men could have a significant impact on reducing unintended pregnancies. Vasalgel™ is a high molecular weight polymer consisting of styrene-alt-maleic acid (SMA) dissolved in dimethyl sulfoxide being developed as a reversible male contraceptive device. It forms a hydrogel when implanted into the vasa deferentia, which prevents the passage of sperm. Previous studies in the rabbit have proven its efficacy, durability and rapid onset. This study evaluates the capacity to restore sperm concentrations in ejaculates after a reversal procedure. Sodium bicarbonate was injected into the vasa deferentia after fourteen months of azoospermia following the injection of two device variations (Vasalgel 100 and Vasalgel 80). Semen samples were then collected for six months and sperm characteristics were compared to baseline levels. Samples of vasa deferentia were obtained for histological examination. Spermatozoa were present in all subject ejaculates after the reversal procedure. Sperm concentration and sperm motility were similar to baseline levels after reversal, while sperm forward progression was significantly lower and normal acrosomes were not observed. Forward progression percentages increased linearly during six months of semen collection, however, normal acrosomes were not observed at the conclusion of the study. Histologically, several vasa deferentia were clear of the device and contained an intact epithelial lining. A smaller proportion of tissues contained residual test material. A secondary intraluminal inflammatory response was seen occasionally in the tissues containing residual material. There was no difference between the two device variations for studied parameters. Vasalgel's prevention of sperm transport for 14 months was reversed through an intravasal injection of sodium bicarbonate. Post-reversal sperm concentrations and motility returned to baseline levels during the six-month follow up. Residual material in the vas lumen or compromised epididymal and vas deferens function may be resulting in reduced forward progression and loss of acrosomes during transit through the vas. Reduced forward progression and the lack of normal acrosomes strongly suggest impaired sperm function.

Long-term changes in body weight are associated with changes in blood pressure levels.

PubMed

Markus, M R P; Ittermann, T; Baumeister, S E; Troitzsch, P; Schipf, S; Lorbeer, R; Aumannn, N; Wallaschofski, H; Dörr, M; Rettig, R; Völzke, H

2015-03-01

Hypertension and obesity are highly prevalent in Western societies. We investigated the associations of changes in body weight with changes in blood pressure and with incident hypertension, incident cardiovascular events, or incident normalization of blood pressure in patients who were hypertensive at baseline, over a 5-year period. Data of men and women aged 20-81 years of the Study of Health in Pomerania were used. Changes in body weight were related to changes in blood pressure by linear regression (n = 1875) adjusted for cofounders. Incident hypertension, incident cardiovascular events, or incident blood pressure normalization in patients who were hypertensive at baseline were investigated using Poisson regression (n = 3280) models. A change of 1 kg in body weight was positively associated with a change of 0.45 mm Hg (95% confidence interval (CI): 0.34-0.55 mm Hg) in systolic blood pressure, 0.32 mm Hg (95% CI: 0.25-0.38 mm Hg) in diastolic blood pressure, and 0.36 mm Hg (95% CI: 0.29-0.43 mm Hg) in mean arterial pressure (all p-values <0.001). A 5% weight loss reduced the relative risk (RR) of incident hypertension (RRs 0.84 (95% CI: 0.79-0.89)) and incident cardiovascular events (RRs 0.81 (95% CI: 0.68-0.98)) and increased the chance of incident blood pressure normalization in patients who were hypertensive at baseline by 15% (95% CI: 7-23%). Absolute and relative changes in body weight are positively associated with changes in blood pressure levels and also affect the risk of cardiovascular events. Copyright © 2014 Elsevier B.V. All rights reserved.

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis from the EXCEL Trial.

PubMed

Redfors, Björn; Chen, Shmuel; Crowley, Aaron; Ben-Yehuda, Ori; Gersh, Bernard J; Lembo, Nicholas J; Brown, W Morris; Banning, Adrian P; Taggart, David P; Serruys, Patrick W; Kappetein, Arie Pieter; Sabik, Joseph F; Stone, Gregg W

2018-04-17

Background -Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main (LM) CAD. Methods -The EXCEL trial randomized patients with LMCAD and low or intermediate SYNTAX scores to PCI with everolimus-eluting stents versus CABG. The primary endpoint was the composite of all-cause death, myocardial infarction (MI) or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. Results -BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower LVEF than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary endpoint (18.6% vs. 11.7%, adjusted HR 1.62, 95% CI 1.16-2.28, P=0.005), and higher mortality (11.5% vs. 3.9%, adjusted HR 2.49, 95% CI 1.48-4.19, P=0.0006), both from cardiovascular and non-cardiovascular causes. In contrast, there were no significant differences in the risks of MI, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction (P interaction =0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite endpoint at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG 1.54, 95% CI 0.96-2.47) versus normal BNP (adjusted HR 0.74, 95% CI 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable (P interaction =0.002). Conclusions -In the EXCEL trial, elevated baseline BNP levels in patients with LMCAD undergoing revascularization were independently associated with long-term mortality but not non-fatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI vs. CABG for revascularization of LMCAD may be conditioned by the baseline BNP level. Clinical Trial Registration -URL: http://www.clinicaltrials.gov. Unique identifier: NCT01205776.

Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-01

Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

Ringers lactate vs Normal saline for children with acute diarrhea and severe dehydration- a double blind randomized controlled trial.

PubMed

Mahajan, Vidushi; Sajan, Shiv Saini; Sharma, Amit; Kaur, Jasbinder

2012-12-01

WHO recommends Ringers lactate (RL) and Normal Saline (NS) for rapid intravenous rehydration in childhood diarrhea and severe dehydration. We compared these two fluids for improvement in pH over baseline during rapid intravenous rehydration in children with acute diarrhea. Double-blind randomized controlled trial Pediatric emergency facilities at a tertiary-care referral hospital. Children with acute diarrhea and severe dehydration received either RL (RL-group) or NS (NS-group), 100 mL/kg over three or six hours. Children were reassessed after three or six hours. Rapid rehydration was repeated if severe dehydration persisted. Blood gas was done at baseline and repeated after signs of severe dehydration disappeared. Primary outcome was change in pH from baseline. Secondary outcomes included changes in serum electrolytes, bicarbonate levels, and base-deficit from baseline; mortality, duration of hospital stay, and fluids requirement. Twenty two children, 11 each were randomized to the two study groups. At primary end point (disappearance of signs of severe dehydration), the improvement in pH from baseline was not significant in RL-group [from 7.17 (0.11) to 7.28 (0.09)] as compared to NS-group [7.09 (0.11) to 7.21 (0.09)], P=0.17 (after adjusting for baseline serum Na/ Cl). Among this limited sample size, children in RL group required less fluids [median 310 vs 530 mL/kg, P=0.01] and had shorter median hospital stay [38 vs 51 hours, P=0.03]. There was no difference in improvement in pH over baseline between RL and NS among children with acute diarrhea and severe dehydration.

Adrenocorticotrophic Hormone Levels in Ground Based Studies

NASA Technical Reports Server (NTRS)

Campbell, B. O.

1972-01-01

Baseline values of immunoreactive ACTH were established in the normal healthy adult. Normal levels of ACTH secretion were determined for both the male and the female in circulating plasma and serum. The data obtained in these studies are particularly significant in that the sampling was carefully controlled; only healthy employed individuals of both sexes were tested in a routine work situation that would not be considered conducive to stress. It has been found that alterations in the classically described circadian rhythm of ACTH secretion can occur when activities (such as work/rest cycles) are imposed on the individual studied. These changes can be demonstrated even when there is no appreciable change noted in the rhythm of hydrocortisone secretion.

Foot shape and its effect on functioning in Royal Australian Air Force recruits. Part 1: Prospective cohort study.

PubMed

Esterman, Adrian; Pilotto, Louis

2005-07-01

To determine whether foot shape (flat, normal, or cavus feet) affects functioning among military recruits. A total of 230 Royal Australian Air Force recruits embarking on a 10-week basic training course took part in a prospective cohort study of foot shape and its effect on functioning. Recruits were divided into three groups based on their foot shape, i.e., flat feet (n = 22), normal feet (n = 139), and cavus feet (n = 44), with the diagnosis being made from the arch index measured from their footprints. The groups were assessed at baseline and week 8. Outcome measures included pain, injury, foot health, and quality of life. There were no significant differences in outcome measures at baseline. At the end of the trial, foot shape was not related to injury. The flat feet group had significantly poorer subjective physical health than did the normal feet group (p = 0.001). This study provides high-level evidence that foot shape has little impact on pain, injury, and functioning among military recruits.

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

PubMed

Baumgartner, Christine; da Costa, Bruno R; Collet, Tinh-Hai; Feller, Martin; Floriani, Carmen; Bauer, Douglas C; Cappola, Anne R; Heckbert, Susan R; Ceresini, Graziano; Gussekloo, Jacobijn; den Elzen, Wendy P J; Peeters, Robin P; Luben, Robert; Völzke, Henry; Dörr, Marcus; Walsh, John P; Bremner, Alexandra; Iacoviello, Massimo; Macfarlane, Peter; Heeringa, Jan; Stott, David J; Westendorp, Rudi G J; Khaw, Kay-Tee; Magnani, Jared W; Aujesky, Drahomir; Rodondi, Nicolas

2017-11-28

Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF. © 2017 American Heart Association, Inc.

Individual differences in normal body temperature: longitudinal big data analysis of patient records.

PubMed

Obermeyer, Ziad; Samra, Jasmeet K; Mullainathan, Sendhil

2017-12-13

To estimate individual level body temperature and to correlate it with other measures of physiology and health. Observational cohort study. Outpatient clinics of a large academic hospital, 2009-14. 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (-0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: -0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg 2 , P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Individuals' baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Individual differences in normal body temperature: longitudinal big data analysis of patient records

PubMed Central

Samra, Jasmeet K; Mullainathan, Sendhil

2017-01-01

Abstract Objective To estimate individual level body temperature and to correlate it with other measures of physiology and health. Design Observational cohort study. Setting Outpatient clinics of a large academic hospital, 2009-14. Participants 35 488 patients who neither received a diagnosis for infections nor were prescribed antibiotics, in whom temperature was expected to be within normal limits. Main outcome measures Baseline temperatures at individual level, estimated using random effects regression and controlling for ambient conditions at the time of measurement, body site, and time factors. Baseline temperatures were correlated with demographics, medical comorbidities, vital signs, and subsequent one year mortality. Results In a diverse cohort of 35 488 patients (mean age 52.9 years, 64% women, 41% non-white race) with 243 506 temperature measurements, mean temperature was 36.6°C (95% range 35.7-37.3°C, 99% range 35.3-37.7°C). Several demographic factors were linked to individual level temperature, with older people the coolest (–0.021°C for every decade, P<0.001) and African-American women the hottest (versus white men: 0.052°C, P<0.001). Several comorbidities were linked to lower temperature (eg, hypothyroidism: –0.013°C, P=0.01) or higher temperature (eg, cancer: 0.020, P<0.001), as were physiological measurements (eg, body mass index: 0.002 per m/kg2, P<0.001). Overall, measured factors collectively explained only 8.2% of individual temperature variation. Despite this, unexplained temperature variation was a significant predictor of subsequent mortality: controlling for all measured factors, an increase of 0.149°C (1 SD of individual temperature in the data) was linked to 8.4% higher one year mortality (P=0.014). Conclusions Individuals’ baseline temperatures showed meaningful variation that was not due solely to measurement error or environmental factors. Baseline temperatures correlated with demographics, comorbid conditions, and physiology, but these factors explained only a small part of individual temperature variation. Unexplained variation in baseline temperature, however, strongly predicted mortality. PMID:29237616

Reduction in labile plasma iron during treatment with deferasirox, a once-daily oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia

PubMed Central

Daar, Shahina; Pathare, Anil; Nick, Hanspeter; Kriemler-Krahn, Ulrike; Hmissi, Abdel; Habr, Dany; Taher, Ali

2009-01-01

This subgroup analysis evaluated the effect of once-daily oral deferasirox on labile plasma iron (LPI) levels in patients from the prospective, 1-yr, multicentre ESCALATOR study. Mean baseline liver iron concentration and median serum ferritin levels were 28.6 ± 10.3 mg Fe/g dry weight and 6334 ng/mL respectively, indicating high iron burden despite prior chelation therapy. Baseline LPI levels (0.98 ± 0.82 μmol/L) decreased significantly to 0.12 ± 0.16 μmol/L, 2 h after first deferasirox dose (P=0.0006). Reductions from pre- to post-deferasirox administration were also observed at all other time points. Compared to baseline, there was a significant reduction in preadministration LPI that reached the normal range at week 4 and throughout the remainder of the study (P≤0.02). Pharmacokinetic analysis demonstrated an inverse relationship between preadministration LPI levels and trough deferasirox plasma concentrations. Once-daily dosing with deferasirox ≥20 mg/kg/d provided sustained reduction in LPI levels in these heavily iron-overloaded patients, suggesting 24-h protection from LPI. Deferasirox may therefore reduce unregulated tissue iron loading and prevent further end-organ damage. PMID:19191863

Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database.

PubMed

Bushe, Chris J; Slooff, Cees J; Haddad, Peter M; Karagianis, Jamie L

2013-04-01

The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m²), overweight (25-30 kg/m²) and obese (>30 kg/m²). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.

Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

PubMed

Arenas, Ivan A; Navas-Acien, Ana; Ergui, Ian; Lamas, Gervasio A

2017-10-01

Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Glucose-6-phosphate dehydrogenase deficiency and reduced haemoglobin levels in African children with severe malaria.

PubMed

Nguetse, Christian N; Meyer, Christian G; Adegnika, Ayola Akim; Agbenyega, Tsiri; Ogutu, Bernhards R; Kremsner, Peter G; Velavan, Thirumalaisamy P

2016-07-07

Extensive studies investigating the role of host genetic factors during malaria associate glucose-6-phosphate dehydrogenase deficiency with relative protection. G6PD deficiency had been reported to associate with anti-malarial drug induced with haemolytic anaemia. A total of 301 Gabonese, Ghanaian, and Kenyan children aged 6-120 months with severe malaria recruited in a multicentre trial on artesunate were included in this sub-study. G6PD normal (type B), heterozygous (type A(+)) and deficient (type A(-)) genotypes were determined by direct sequencing of the common African mutations G202A and A376G. Furthermore, multivariate analyses were executed to associate possible contributions of G6PD deficiency with baseline haemoglobin levels, parasitaemia and with severe malarial anaemia. Two hundred and seventy-eight children (132 females and 146 males) were successfully genotyped for G6PD variants. The overall prevalence of G6PD deficiency was 13 % [36/278; 3 % (4/132) female homozygous and 22 % (32/146) male hemizygous], 14 % (40/278) children were female heterozygous while 73 % (202/278) were G6PD normal [67 % (88/132) females and 78 % (114/146) males] individuals. Multivariate regression revealed a significant association of moderately and severely deficient G6PD genotypes with haemoglobin levels according to the baseline data (p < 0.0001; G6PD heterozygous: p < 0.0001; G6PD deficient: p = 0.009), but not with severe malarial anaemia (p = 0.66). No association of G6PD genotypes with baseline parasitaemia. In this study, moderately (type A(+)) and severely (type A(-)) G6PD deficiency showed significant association with lower haemoglobin concentrations at baseline in African children with severe malaria without leading to severe malarial anaemia. In addition, there was no association of G6PD variant types with parasite densities on admission.

Effect of acute intraocular pressure elevation on the minimum rim width in normal, ocular hypertensive and glaucoma eyes.

PubMed

Sharma, Sourabh; Tun, Tin A; Baskaran, Mani; Atalay, Eray; Thakku, Sri Gowtham; Liang, Zhang; Milea, Dan; Strouthidis, Nicholas G; Aung, Tin; Girard, Michael Ja

2018-01-01

To estimate and compare changes in the Bruch's membrane opening-minimum rim width (BMO-MRW) and area in normal, ocular hypertensive and glaucoma eyes following acute elevations in intraocular pressure (IOP). The optic nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and 53 with primary glaucoma) were imaged using Spectral-domain optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and ONH was rescanned with OCT. In each OCT volume, BMO-MRW and area were calculated and at each IOP increment. The baseline MRW was significantly smaller in glaucoma subjects (174.3±54.3 µm) compared with normal (287.4±42.2 µm, p<0.001) and OHT subjects (255.4±45.3 µm, p<0.001). MRW of glaucoma subjects was significantly thinner at the first and second IOP elevations than that at baseline (both p<0.01), but no significant change was noted in normal and OHT subjects. There was no significant change of BMO area at acute IOP elevations from baseline in all diagnoses (all p>0.05). Acute IOP elevation leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma subjects only without changing ONH size. This suggests that the neural and connective tissues at ONH level in glaucoma subjects are more susceptible to acute IOP episodes than OHT or normal controls. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An Investigation of Stimulant Effects on the EEG of Children With Attention-Deficit/Hyperactivity Disorder.

PubMed

Clarke, Adam R; Barry, Robert J; Baker, Iris E; McCarthy, Rory; Selikowitz, Mark

2017-07-01

Stimulant medications are the most commonly prescribed treatment for Attention-Deficit/Hyperactivity Disorder (AD/HD). These medications result in a normalization of the EEG. However, past research has found that complete normalization of the EEG is not always achieved. One reason for this may be that studies have used different medications interchangeably, or groups of subjects on different stimulants. This study investigated whether methylphenidate and dexamphetamine produce different levels of normalization of the EEG in children with AD/HD. Three groups of 20 boys participated in this study. There were 2 groups with a diagnosis of AD/HD; one group, good responders to methylphenidate, and the second, good responders to dexamphetamine. The third group was a normal control group. Baseline EEGs were recorded using an eyes-closed resting condition, and analyzed for total power and relative delta, theta, alpha, and beta. Subjects were placed on a 6-month trial of methylphenidate or dexamphetamine, after which a second EEG was recorded. At baseline, the children with AD/HD had elevated relative theta, less relative alpha and beta compared with controls. Baseline differences were found between the two medication groups, with the dexamphetamine group having greater EEG abnormalities than the methylphenidate group. The results indicate that good responders to methylphenidate and dexamphetamine have different EEG profiles when assessed before medication, and these differences may represent different underlying central nervous system deficits. The 2 medications were found to result in substantial normalization of the EEG, with no significant differences in EEG changes occurring between the 2 medications. This indicates that the degree of pretreatment EEG abnormality was the major factor contributing to the degree of normalization of the EEG. As good responders to the 2 medications appear to have different central nervous system abnormalities, it is recommended that stimulant medications be treated independently and not used interchangeably in research and treatment of AD/HD.

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. PMID:21670386

Predictors of activity limitation in people with gout: a prospective study.

PubMed

Stewart, Sarah; Rome, Keith; Eason, Alastair; House, Meaghan E; Horne, Anne; Doyle, Anthony J; Knight, Julie; Taylor, William J; Dalbeth, Nicola

2018-04-21

The objective of the study was to determine clinical factors associated with activity limitation and predictors of a change in activity limitation after 1 year in people with gout. Two hundred ninety-five participants with gout (disease duration < 10 years) attended a baseline assessment which included medical and disease-specific history, pain visual analog score and plain radiographs scored for erosion and narrowing. Activity limitation was assessed using the Health Assessment Questionnaire-II (HAQ-II). After 1 year, participants were invited to complete a further HAQ-II; follow-up questionnaires were available for 182 participants. Fully saturated and stepwise regression analyses were used to determine associations between baseline characteristics and HAQ-II at baseline and 1 year, and to determine predictors of worsening HAQ-II in those with normal baseline scores. Median (range) baseline HAQ-II was 0.20 (0-2.50) and 0.20 (0-2.80) after 1 year of follow-up. Pain score was the strongest independent predictor of baseline HAQ-II, followed by radiographic narrowing score, type 2 diabetes, swollen joint count, BMI, age and urate (model R 2  = 0.51, P < 0.001). Baseline HAQ-II was the strongest predictor of change in HAQ-II at 1 year, followed by tender joint count (model R 2  = 0.19, P < 0.001). Of those with HAQ-II scores of 0 at baseline (n = 59, 32% of those with follow-up data), most did not progress (n = 52, 88%); however, baseline pain score, type 2 diabetes and flare frequency were significant predictors of worsening HAQ-II in this group (R 2  = 0.34, P < 0.001). People with gout experience a wide range of activity limitation, and levels of activity limitation are, on average, stable over a 1-year period. Baseline pain scores are strongly associated with activity limitation and predict development of activity limitation in those with normal HAQ-II scores at baseline.

Association Between Neighborhood Supermarket Presence and Glycated Hemoglobin Levels Among Patients With Type 2 Diabetes Mellitus.

PubMed

Zhang, Y Tara; Mujahid, Mahasin S; Laraia, Barbara A; Warton, E Margaret; Blanchard, Samuel D; Moffet, Howard H; Downing, Janelle; Karter, Andrew J

2017-06-15

We estimated associations between neighborhood supermarket gain or loss and glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients from the Kaiser Permanente Northern California Diabetes Registry (n = 434,806 person-years; 2007-2010). Annual clinical measures were linked to metrics from a geographic information system for each patient's address of longest residence. We estimated the association between change in supermarket presence (gain, loss, or no change) and change in HbA1c value, adjusting for individual- and area-level attributes and according to baseline glycemic control (near normal, <6.5%; good, 6.5%-7.9%; moderate, 8.0%-8.9%; and poor, ≥9.0%). Supermarket loss was associated with worse HbA1c trajectories for those with good, moderate, and poor glycemic control at baseline, while supermarket gain was associated with marginally better HbA1c outcomes only among patients with near normal HbA1c values at baseline. Patients with the poorest baseline HbA1c values (≥9.0%) had the worst associated changes in glycemic control following either supermarket loss or gain. Differences were not clinically meaningful relative to no change in supermarket presence. For patients with type 2 diabetes mellitus, gaining neighborhood supermarket presence did not benefit glycemic control in a substantive way. The significance of supermarket changes on health depends on a complex interaction of resident, neighborhood, and store characteristics. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain-Derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study

PubMed Central

Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.

2014-01-01

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367

Association between physical exercise, body mass index, and risk of fibromyalgia: longitudinal data from the Norwegian Nord-Trøndelag Health Study.

PubMed

Mork, Paul J; Vasseljen, Ottar; Nilsen, Tom I L

2010-05-01

To examine the association between leisure time physical exercise, body mass index (BMI), and risk of fibromyalgia (FM). A longitudinal study with baseline assessment of physical exercise (frequency, duration, and intensity) and BMI was used to explore the risk of having FM at 11-year followup in a large, unselected female population (n = 15,990) without FM or physical impairments at baseline. At followup, 380 cases of incident FM were reported. A weak dose-response association was found between level of physical exercise and risk of FM (for trend, P = 0.13) where women who reported the highest exercise level had a relative risk (RR) of 0.77 (95% confidence interval [95% CI] 0.55-1.07). BMI was an independent risk factor for FM (for trend, P < 0.001), and overweight or obese women (BMI > or =25.0 kg/m(2)) had a 60-70% higher risk compared with women with normal weight (BMI 18.5-24.9 kg/m(2)). Overweight or obese women who exercised > or =1 hour per week had an RR of 1.72 (95% CI 1.07-2.76) compared with normal-weight women with a similar activity level, whereas the risk was >2-fold higher for overweight or obese women who were either inactive (RR 2.09, 95% CI 1.36-3.21) or exercised <1 hour per week (RR 2.19, 95% CI 1.39-3.46). Being overweight or obese was associated with an increased risk of FM, especially among women who also reported low levels of physical exercise. Community-based measures aimed at reducing the incidence of FM should emphasize the importance of regular exercise and the maintenance of normal body weight.

The effect of weight loss and treatment with metformin on serum vaspin levels in women with polycystic ovary syndrome.

PubMed

Koiou, Ekaterini; Tziomalos, Konstantinos; Dinas, Konstantinos; Katsikis, Ilias; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Kandaraki, Eleni A; Panidis, Dimitrios

2011-01-01

Many patients with polycystic ovary syndrome (PCOS) have insulin resistance, obesity (mostly visceral) and glucose intolerance, conditions associated with abnormalities in the production of vaspin, a novel adipokine that appears to preserve insulin sensitivity and glucose tolerance. The aim of the study was to assess serum vaspin levels in PCOS and the effects on vaspin levels of metformin or of weight loss. We studied 79 patients with PCOS and 50 healthy female volunteers. Normal weight patients with PCOS (n=25) were treated with metformin 850 mg bid for 6 months. Overweight/obese patients with PCOS (n=54) were prescribed a normal-protein, energy-restricted diet for 6 months; half of them were also given orlistat 120 mg tid and the rest were given sibutramine 10 mg qd. At baseline and after 6 months, serum vaspin levels and anthropometric, metabolic and hormonal features of PCOS were determined. Overall, patients with PCOS had higher vaspin levels than controls (p=0.021). Normal weight patients with PCOS had higher vaspin levels than normal weight controls (p=0.043). Vaspin levels were non-significantly higher in overweight/obese patients with PCOS than in overweight/obese controls. In normal weight patients with PCOS, metformin reduced vaspin levels non-significantly. In overweight/obese patients with PCOS, diet plus orlistat or sibutramine did not affect vaspin levels. Vaspin levels were independently correlated with body mass index in women with PCOS (p=0.001) and with waist circumference in controls (p=0.015). In conclusion, serum vaspin levels are elevated in PCOS but neither a small weight loss nor metformin affect vaspin levels significantly.

The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

PubMed

Pincelli, A I; Brunani, A; Scacchi, M; Dubini, A; Borsotti, R; Tibaldi, A; Pasqualinotto, L; Maestri, E; Cavagnini, F

2001-01-01

The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. These data indicate that circulating concentrations of TNF-alpha do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin resistance at tissue level. Copyright 2001 S. Karger AG, Basel

Transcriptional responses of the rat vasopressin gene to acute and repeated acute osmotic stress.

PubMed

Zemo, David A; McCabe, Joseph T

2002-09-01

To determine the impact of hypertonic saline administration upon rat arginine vasopressin (AVP) gene transcription in supraoptic nucleus neurons, a probe complementary to the first intron (AVP1) of AVP was used to measure changes in AVP heteronuclear RNA (hnRNA) levels. Animals that received hypertonic saline had increases in AVP1 after 15 and 30 min, with a return to baseline levels by 180 min. In a double injection paradigm, animals were given an injection of normal or hypertonic saline followed 180 min later by a second injection of normal or hypertonic saline and sacrificed 30 min later. When both injections were hypertonic saline (H-H), AVP1 levels were greater than levels seen after a single hypertonic saline injection, or after an injection of normal saline followed by a second injection of hypertonic saline (N-H). This study shows acute, repeated exposure to hypertonic saline causes a robust increase in vasopressin gene transcription. Since a second hyperosmotic stimulus is known to increase neuronal firing rate and activity, our results suggest that a correlation exists with intracellular mechanisms regulating vasopressin gene transcription.

ERBB3: A potential serum biomarker for early detection and therapeutic target for devil facial tumour 1 (DFT1)

PubMed Central

Kunde, Dale A.; Taylor, Robyn L.; Pyecroft, Stephen B.; Sohal, Sukhwinder Singh; Snow, Elizabeth T.

2017-01-01

Devil Facial Tumour 1 (DFT1) is one of two transmissible neoplasms of Tasmanian devils (Sarcophilus harrisii) predominantly affecting their facial regions. DFT1’s cellular origin is that of Schwann cell lineage where lesions are evident macroscopically late in the disease. Conversely, the pre-clinical timeframe from cellular transmission to appearance of DFT1 remains uncertain demonstrating the importance of an effective pre-clinical biomarker. We show that ERBB3, a marker expressed normally by the developing neural crest and Schwann cells, is immunohistohemically expressed by DFT1, therefore the potential of ERBB3 as a biomarker was explored. Under the hypothesis that serum ERBB3 levels may increase as DFT1 invades local and distant tissues our pilot study determined serum ERBB3 levels in normal Tasmanian devils and Tasmanian devils with DFT1. Compared to the baseline serum ERBB3 levels in unaffected Tasmanian devils, Tasmanian devils with DFT1 showed significant elevation of serum ERBB3 levels. Interestingly Tasmanian devils with cutaneous lymphoma (CL) also showed elevation of serum ERBB3 levels when compared to the baseline serum levels of Tasmanian devils without DFT1. Thus, elevated serum ERBB3 levels in otherwise healthy looking devils could predict possible DFT1 or CL in captive or wild devil populations and would have implications on the management, welfare and survival of Tasmanian devils. ERBB3 is also a therapeutic target and therefore the potential exists to consider modes of administration that may eradicate DFT1 from the wild. PMID:28591206

Adequate intake of potassium does not cause hyperkalemia in hypertensive individuals taking medications that antagonize the renin angiotensin aldosterone system.

PubMed

Malta, Daniela; Arcand, JoAnne; Ravindran, Anju; Floras, Vanessa; Allard, Johane P; Newton, Gary E

2016-10-01

Reduced potassium excretion caused by angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) may increase the risk of hyperkalemia (serum potassium concentration >5 mmol/L) in the setting of increased potassium intake. The purpose of this study was to assess the effect of increasing dietary potassium on serum potassium concentration in hypertensive individuals with normal renal function treated with an ACEi or ARB. We hypothesized that an increase in dietary potassium would not provoke hyperkalemia in this population despite treatment with either an ACEi or ARB. We conducted a controlled, parallel-design clinical trial in 20 hypertensive subjects with normal renal function treated with an ACEi or ARB, with random assignment to a usual diet or a high-potassium diet (HKD). Fruit and vegetable intake was used to increase potassium intake. Serum potassium concentration, 3-d food records, and 24-h urine collections were completed at baseline and 4 wk. In the usual-diet group there were no statistically significant differences for potassium excretion, intake, or serum levels at end of study compared with baseline. The HKD group had significant differences in urinary potassium excretion (83 ± 26 mmol/d at baseline compared with 109 ± 35 mmol/d at 4 wk, P = 0.01) and dietary potassium intake (3775 ± 1189 mg/d at baseline compared with 5212 ± 1295 mg/d at 4 wk, P = 0.02). Despite increased potassium intake in the HKD group, serum potassium concentrations did not significantly increase from baseline at midpoint or end of study (4.1 ± 0.6, 4.3 ± 0.3, and 4.2 ± 0.4 mmol/L, respectively). This study demonstrates that an increase in dietary potassium over a 4-wk period is safe in hypertensive subjects who have normal renal function and are receiving ACEi and/or ARB therapy. This trial was registered at www.clinicaltrials.gov as NCT02759367. © 2016 American Society for Nutrition.

A low glycemic index staple diet reduces postprandial glucose values in Asian women with gestational diabetes mellitus.

PubMed

Hu, Zhi-Geng; Tan, Rong-Shao; Jin, Di; Li, Wei; Zhou, Xiao-Yan

2014-12-01

A low glycemic index (GI) diet is beneficial for glucose control in patients with diabetes mellitus. This study aimed to investigate the influence of a low-GI diet on postprandial glucose levels in women with gestational diabetes mellitus (GDM). Pregnant women with GDM were randomized to receive a normal diabetic control diet or a low-GI staple diet for 5 days. A low-GI staple food was used to replace rice in lunch and dinner for the low-GI staple diet group, whereas the total energy and carbohydrate levels remained equal in both groups. Fasting and postprandial glucose levels were determined daily. A total of 140 pregnant women with GDM were included in the study, including 66 in the low-GI staple diet group and 74 in the normal diabetic diet control group. No differences existed in baseline characteristics between the 2 groups (all P > 0.05). After dietary intervention, glucose levels were significantly reduced in the low-GI staple diet group (all P < 0.01) and the control group (all P < 0.008). Postintervention glucose values after breakfast, lunch, and dinner were significantly reduced in the treatment group compared with those in the control group (all P < 0.05). The percentage changes from baseline of all glucose values were significantly greater in the treatment group than in the control group (all P < 0.05). A low-GI staple diet significantly reduces postprandial glucose levels in women with GDM.

Coffee consumption and the incidence of type 2 diabetes in men and women with normal glucose tolerance: The Strong Heart Study

PubMed Central

Zhang, Ying; Lee, Elisa T.; Cowan, Linda D.; Fabsitz, Richard R.; Howard, Barbara V.

2009-01-01

Background and aims It was reported that high coffee consumption was related to decreased diabetes risk. The aim of this study is to examine the association between coffee consumption and the incidence of type 2 diabetes in persons with normal glucose tolerance in a population with a high incidence and prevalence of diabetes. Methods and results In a prospective cohort study, information about daily coffee consumption was collected at the baseline examination (1989-1992) in a population-based sample of American Indian men and women 45-74 years of age. Participants with normal glucose tolerance (N=1141) at the baseline examination were followed for an average of 7.6 years. The incidence of diabetes was compared across the categories of daily coffee consumption. The hazard ratios of diabetes related to coffee consumption were calculated using Cox proportional hazards models, adjusted for potential confounders. Levels of coffee consumption were positively related to levels of current smoking and inversely related to body mass index, waist circumference, female gender, and hypertension. Compared to those who did not drink coffee, participants who drank 12 or more cups of coffee daily had 67% less risk of developing diabetes during the follow-up (hazard ratio: 0.33, 95% confidence interval: 0.13, 0.81). Conclusion In this population, a high level of coffee consumption was associated with a reduced risk of deterioration of glucose metabolism over an average 7.6 years of follow-up. More work is needed to understand whether there is a plausible biological mechanism for this observation. PMID:20171062

Combined oral contraceptives and body weight: do oral contraceptives cause weight gain? A primate model.

PubMed

Edelman, A; Jensen, J T; Bulechowsky, M; Cameron, J

2011-02-01

The aim of this study was to determine if oral contraceptive (OC) use affects body weight, body composition and metabolism in primates. Reproductive-age female rhesus monkeys of normal and obese BMI were studied to document baseline weight stability, then treated continuously with an OC (dosed to achieve equivalent human serum levels for a 30 µg ethinyl estradiol/150 µg levonorgestrel preparation) for 237 days. Monkeys were monitored for changes in body weight, levels of physical activity (measured by a triaxial Actical accelerometer), food/caloric intake, percent body fat (dual energy X-ray absorptiometry, DEXA) and metabolism (24 h metabolic rate and serum metabolic substrate and hormone concentrations). All 10 monkeys completed the study protocol with no adverse events. While body weight (-0.73% change) and percent body fat (-1.78% change) of the normal BMI group did not significantly decrease from baseline, obese monkeys showed a significant decrease in body weight (-8.58% change, P < 0.01) and percent body fat (-12.13% change P = 0.02) with OC treatment. In both the obese (P = 0.03) and the normal BMI (P = 0.01) groups, there was a significant increase in basal metabolic rate with OC use. No changes were seen in food intake, activity level or % lean muscle mass with OC use for either BMI-based group. Overall, OC use appears to cause a slight increase in basal metabolic rate in female monkeys, leading to a decrease in body weight and percent body fat in obese individuals.

Study design and baseline findings from the progression of ocular findings (PROOF) natural history study of dry eye.

PubMed

McDonnell, Peter J; Pflugfelder, Stephen C; Stern, Michael E; Hardten, David R; Conway, Taryn; Villanueva, Linda; Hollander, David A

2017-12-28

The aim of this research is to initiate a 5-year natural history study of dry eye disease (DED) using objectively assessed and patient-reported outcomes, to explore the hypothesis that DED is a progressive condition that has substantive and measurable impacts not only on the ocular surface, but on quality of life and visual functioning. Our objective for this report is to examine the baseline data. A multicenter, prospective, controlled, observational study of Level 2 (mild-to-moderate) DED patients based on International Task Force Delphi Panel severity grading, and controls, documented baseline measures (including tear film biomarkers and quality of life). Tear cytokine concentrations were also measured in the tear film. Patients were using artificial tears as needed. Two hundred seventeen DED patients and 67 gender- and age-matched controls were enrolled. A majority were females and Caucasian and groups did not differ significantly in terms of gender, race, or age. Differences between DED and matched controls, at baseline, included mean scores for Ocular Surface Disease Index (31.7 vs 4.1, P < 0.0001), Schirmer test (5.7 vs 15.3 mm, P < 0.0001), corneal staining (1.4 vs 0.2, P < 0.0001), conjunctival staining (1.4 vs 0.3, P < 0.0001), and tear break-up time (5.7 vs 8.5 s, P < 0.0001). Tear cytokines levels were determined and included interferon-γ, interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α, epidermal growth factor, IL-13, IL-17, IL-1α, and inducible protein-10. The mean levels of IL-8 and IL-6 were slightly higher in the DED group at baseline. Blurred vision was reported as moderate/severe/very severe at baseline in 57.6% of DED patients vs.10.5% of normal controls (P < 0.0001). DED patients reported greater reductions in work and non-work productivity, as well as greater need for visits to ophthalmologists during the prior year. In this report of the baseline findings of a 5-year natural history study of DED, a striking disease burden is observed with regard to blurred vision, productivity, and visits to eye care practitioners in mild to moderate DED patients compared to normal subjects of similar ages and genders. ClinicalTrials.gov NCT00833235 on January 30, 2009.

C-Reactive Protein and Resistance Exercise in Community Dwelling Old Adults.

PubMed

Ramel, A; Geirsdottir, O G; Jonsson, P V; Thorsdottiri, I

2015-08-01

C-reactive protein (CRP), an acute phase reactant, has been associated with atherosclerosis and has also been discussed as a target for intervention. The effects of resistance exercise on CRP are currently not clear. The present analysis investigated the response of CRP to resistance exercise in old adults. Intervention study. Community. Old Icelandic adults (N = 235, 73.7 ± 5.7 years, 58.2% female). Twelve-week resistance exercise program (3 times/week; 3 sets, 6-8 repetitions at 75-80% of the 1-repetition maximum) designed to increase strength and muscle mass of major muscle groups. C-reactive protein (CRP). Mean CRP levels were 7.1 ± 4.6 mg/dL at baseline, thirty-six (15.6%) subjects had abnormally high CRP (>10 mg/L) values at baseline. After the resistance exercise program the overall changes in CRP were minor and not significant. However, CRP decreased considerably in participants with high CRP at baseline (-4.28 ± 9.41 mg/L; P = 0.015) but increased slightly in participants with normal CRP (0.81 ± 4.58 mg/L, P = 0.021). Our study shows that the concentrations of circulating CRP decreased considerably after a 12-week resistance exercise program in participants with abnormally high CRP at baseline, possibly reducing thus risk for future disease. CRP changed little in participants with normal CRP at the start of the study.

Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

PubMed

Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

2015-01-01

We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters.

PubMed

Maslow, Bat-Sheva L; Davis, Stephanie; Engmann, Lawrence; Nulsen, John C; Benadiva, Claudio A

2016-09-01

This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Müllerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters.

Association of Fetal Heart Rate Baseline Change and Neonatal Outcomes.

PubMed

Yang, Michael; Stout, Molly J; López, Julia D; Colvin, Ryan; Macones, George A; Cahill, Alison G

2017-07-01

Objective  The objective of this study was to describe the incidence of baseline change within normal range during labor and its prediction of neonatal outcomes. Materials and Methods  This was a prospective cohort of singleton, nonanomalous, term neonates with continuous electronic fetal monitoring and normal baseline fetal heart rate throughout the last 2 hours of labor. We determined baseline in 10-minute segments using Eunice Kennedy Shriver National Institute of Child Health and Human Development criteria. We evaluated baseline changes of ≥ 20 and ≥ 30 bpm for association with acidemia (umbilical cord arterial pH ≤ 7.10) and neonatal intensive care unit (NICU) admission. Finally, we performed a sensitivity analysis of normal neonates, excluding those with acidemia, NICU admission, or 5-minute Apgar < 4. Results  Among all neonates ( n  = 3,021), 1,267 (41.9%) had change ≥ 20 bpm; 272 (9.0%) had ≥ 30 bpm. Among normal neonates ( n  = 2,939), 1,221 (41.5%) had change ≥20 bpm. Acidemia was not associated with baseline change of any direction or magnitude. NICU admission was associated with decrease ≥ 20 bpm (adjusted odds ratio [aOR]: 2.93; 95% confidence interval [CI]: 1.19 - 7.21) or any direction ≥ 20 bpm (aOR: 4.06; 95% CI: 1.46-11.29). For decrease ≥ 20 bpm, sensitivity and specificity were 40.0 and 81.7%; for any direction ≥ 20 bpm, 75.0 and 58.3%. Conclusion  Changes of normal baseline are common in term labor and poorly predict morbidity, regardless of direction or magnitude. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

PubMed

Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong

2018-01-01

We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

Delay and trace fear conditioning in C57BL/6 and DBA/2 mice: issues of measurement and performance.

PubMed

Tipps, Megan E; Raybuck, Jonathan D; Buck, Kari J; Lattal, K Matthew

2014-08-01

Strain comparison studies have been critical to the identification of novel genetic and molecular mechanisms in learning and memory. However, even within a single learning paradigm, the behavioral data for the same strain can vary greatly, making it difficult to form meaningful conclusions at both the behavioral and cellular level. In fear conditioning, there is a high level of variability across reports, especially regarding responses to the conditioned stimulus (CS). Here, we compare C57BL/6 and DBA/2 mice using delay fear conditioning, trace fear conditioning, and a nonassociative condition. Our data highlight both the significant strain differences apparent in these fear conditioning paradigms and the significant differences in conditioning type within each strain. We then compare our data to an extensive literature review of delay and trace fear conditioning in these two strains. Finally, we apply a number of commonly used baseline normalization approaches to compare how they alter the reported differences. Our findings highlight three major sources of variability in the fear conditioning literature: CS duration, number of CS presentations, and data normalization to baseline measures. © 2014 Tipps et al.; Published by Cold Spring Harbor Laboratory Press.

HIV proviral DNA associated with decreased neuropsychological function.

PubMed

Shiramizu, Bruce; Paul, Robert; Williams, Andrew; Shikuma, Cecilia; Watters, Michael; Grove, John; Valcour, Victor

2007-01-01

The authors previously found a strong association between elevated HIV proviral DNA (HIV DNA) and a diagnosis of HIV-1-associated dementia (HAD) vs. normal cognition. It is unclear whether HIV DNA globally affects the diagnosis of HAD or whether the effect is limited to individual neuropsychological deficits. This exploratory study examined baseline HIV DNA and its association with individual neuropsychological deficits. HIV DNA was significantly associated with baseline neuropsychological deficits independent of age, ethnicity, IQ, and plasma HIV-1 RNA levels. However, HIV DNA did not predict future changes in neuropsychological deficits. The data suggest that HIV DNA and neuropsychological deficits may co-vary over time.

Changes in Fasting Plasma Glucose Levels with Ribavirin and Pegylated Interferon Treatment in Normal and Impaired Glucose Tolerant Patients with Chronic Hepatitis C

PubMed Central

Sarasombath, Ongkarn; Suwantarat, Nuntra; Tice, Alan D

2012-01-01

Background Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). Methods A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. Results The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. Conclusions In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding. PMID:22737650

The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

PubMed Central

Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2014-01-01

Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones

PubMed Central

Shak, Joshua R.; Roper, Jatin; Perez-Perez, Guillermo I.; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A.; Ren, Christine

2013-01-01

Background We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. Methods Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. Results Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p<0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p<0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p>0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. Conclusions LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term. PMID:18408980

The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones.

PubMed

Shak, Joshua R; Roper, Jatin; Perez-Perez, Guillermo I; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A; Ren, Christine; Blaser, Martin J

2008-09-01

We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p < 0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p < 0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p > 0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term.

Systemic inflammatory responses in progressing periodontitis during pregnancy in a baboon model

PubMed Central

Ebersole, J L; Steffen, M J; Holt, S C; Kesavalu, L; Chu, L; Cappelli, D

2010-01-01

This study tested the hypothesis that pregnant female baboons exhibit increased levels of various inflammatory mediators in serum resulting from ligature-induced periodontitis, and that these profiles would relate to periodontal disease severity/extent in the animals. The animals were sampled at baseline (B), mid-pregnancy (MP; two quadrants ligated) and at delivery (D; four quadrants ligated). All baboons developed increased plaque, gingival inflammation and bleeding, pocket depths and attachment loss following placement of the ligatures. By MP, both prostaglandin E2 (PGE2) and bactericidal permeability inducing factor (BPI) were greater than baseline, while increased levels of interleukin (IL)-6 occurred in the experimental animals by the time of delivery. IL-8, MCP-1 and LBP all decreased from baseline through the ligation phase of the study. Stratification of the animals by baseline clinical presentation demonstrated that PGE2, LBP, IL-8 and MCP-1 levels were altered throughout the ligation interval, irrespective of baseline clinical values. IL-6, IL-8 and LBP were significantly lower in the subset of animals that demonstrated the least clinical response to ligation, indicative of progressing periodontal disease. PGE2, macrophage chemotactic protein (MCP)-1, regulated upon activation, normal T cell expressed and secreted (RANTES) and LBP were decreased in the most diseased subset of animals at delivery. Systemic antibody responses to Fusobacterium nucleatum, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Campylobacter rectus were associated most frequently with variations in inflammatory mediator levels. These results provide a profile of systemic inflammatory mediators during ligature-induced periodontitis in pregnant baboons. The relationship of the oral clinical parameters to systemic inflammatory responses is consistent with a contribution to adverse pregnancy outcomes in a subset of the animals. PMID:21070210

Mood changes in cognitively normal older adults are linked to Alzheimer’s disease biomarker levels

PubMed Central

Babulal, Ganesh M.; Ghoshal, Nupur; Head, Denise; Vernon, Elizabeth K.; Holtzman, David M.; Benzinger, Tammie L. S.; Fagan, Anne M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Objectives To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, ptau181/Aβ42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Setting Knight Alzheimer’s Disease Research Center (ADRC) at Washington University (WU). Participants Participants, 65 year of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. Measurements CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory Questionnaire (NPI-Q). Results Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p >0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < .05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning Conclusion Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults. PMID:27426238

Serum C-reactive protein in patients undergoing elective shoulder arthroplasty. Prospective study.

PubMed

Torrens, Carlos; Santana, Fernando; Marí, Raquel; Puig, Lluis; Alier, Albert

2017-09-01

The objective of the study was to determine the normalization curve of the serum C-reactive protein (CRP) in elective shoulder arthroplasty. A prospective study including 58 consecutive patients who had undergone elective shoulder arthroplasty. Forty-one patients had received a Reverse Shoulder Arthroplasty, 13 a Total Shoulder Arthroplasty and 4 a Hemiarthroplasty. Based on a pilot study, blood samples to determine CRP values were obtained at baseline (1 h before surgery), on the 1st, 2nd, 6th, 8th and 14th postoperative days. All the patients included presented no postoperative complications during inpatient stay or any re-admission during the three months after surgery. Mean CRP values showed a rapid increase on the 1st postoperative day (7-fold higher than the baseline in cuff tear arthropathy, 11-fold higher in primary osteoarthritis, 1-fold higher in acute fracture) and reached a peak on the 2nd postoperative day (14-fold higher than the baseline in cuff tear arthropathy, 24-fold higher in primary osteoarthritis and 2-fold higher in acute fracture). After the 2nd postoperative day CRP values began to slowly decrease reaching the normal range in the 14th postoperative day. Serum CRP levels after elective shoulder arthroplasty rapidly increase to reach a maximum peak after the 2nd surgery day and then slowly decrease to return to normality on the 14th day. Knowing the normalization curve of CRP can be a helpful tool to help in the diagnosis of acute infections in elective shoulder arthroplasty. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels.

PubMed

Babulal, Ganesh M; Ghoshal, Nupur; Head, Denise; Vernon, Elizabeth K; Holtzman, David M; Benzinger, Tammie L S; Fagan, Anne M; Morris, John C; Roe, Catherine M

2016-11-01

To evaluate whether cerebrospinal fluid (CSF) and PET Pittsburgh Compound B (PiB) biomarkers of underlying Alzheimer disease (AD) pathology (β-amyloid 42 [Aβ 42 ], tau, phosphorylated tau 181 [ptau 181 ], tau/Aβ 42 , ptau 181 /Aβ 42 and mean cortical binding potential [MCBP] for PET-PiB) predict changes in mood in cognitively normal older adults. Knight Alzheimer's Disease Research Center (ADRC) at Washington University (WU). Participants, 65 years of age or older, were enrolled from longitudinal studies at the WU Knight ADRC. CSF, PET-PiB biomarkers, Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE), Profile of Mood States-Short Form (POMS-SF), the Geriatric Depression Scale (GDS), and Neuropsychiatric Inventory Questionnaire (NPI-Q). Data from 118 participants at baseline and 66 participants at one-year follow-up were analyzed. CSF and PET biomarkers were not associated cross-sectionally with any mood disturbances at baseline (p > 0.05). Changes in mood as indicated by the total mood disturbance score on the POMS-SF, selected POMS-SF subscales, GDS, and NPI-Q scores from baseline to one-year follow-up were associated with (p < 0.05) CSF and PET-PiB biomarkers. There was no statistically significant decline in cognitive functioning. Generally, higher values of CSF and PET-PiB biomarkers are associated with more changes in mood in cognitively normal older adults. Further work is needed to understand the temporal development of mood changes over several years during the phase of preclinical AD. Evaluating mood as a noncognitive outcome may provide further insight into the development of preclinical AD in cognitively normal older adults. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Orthostatic intolerance and the postural tachycardia syndrome: genetic and environment pathophysiologies. Neurolab Autonomic Team

NASA Technical Reports Server (NTRS)

Robertson, D.; Shannon, J. R.; Biaggioni, I.; Ertl, A. C.; Diedrich, A.; Carson, R.; Furlan, R.; Jacob, G.; Jordan, J.

2000-01-01

Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.

[Serum potassium levels and long-term mortality in the elderly with hypertension].

PubMed

Heras Benito, M; Fernández-Reyes, M J; Guerrero Díaz, M T; Muñoz Pascual, A

There is increasing evidence that small variations within the normal range (3.5-5mEq/L) of potassium are associated with mortality. To determine whether there is an association between serum potassium level (sK) and mortality in a cohort of elderly hypertensive patients. A retrospective, observational study was conducted on patients who had sK levels available in a period of clinical stability during their recruitment between January and April 2006 and followed-up for 10 years. The study obtained a total of 62 stable patients, with a mean age of 82.19±6 years (range 69-97), with 74.2% women, 33.9% diabetics, 20.3% with a history of heart failure, Ischaemic heart disease was observed in 19.4% and 44.3% received Angiotensin Converting Enzyme (ACE) inhibitors. An analysis was performed on the mortality rate during the 10 year period. The statistics were performed using the SPSS15.0 package. There were 49 deaths. The sK had a normal distribution. Baseline mean sK levels and median were 4.45±0.5mEq/L (range 3.1-5.5 mEq/L). Baseline sK levels were significantly higher in diabetic patients and patients on ACE inhibitors. The patients that died had higher sK levels (4.53±0.49mEq/L versus 4.14±0.40mEq/L, P=.011). Survival estimated using Kaplan Meier showed that patients with sK levels higher than the median and P75 had higher mortality. In our study, sK levels greater than 4.45mEq/L were associated with mortality. When selecting antihypertensive treatment in hypertensive elderly patients,, the use of ACE inhibitors should be assessed individually, with close monitoring at sK levels and try to keep them in the lower limit of the normal range (<4.45 mEq/L). Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Habitat quality affects stress responses and survival in a bird wintering under extremely low ambient temperatures

NASA Astrophysics Data System (ADS)

Cīrule, Dina; Krama, Tatjana; Krams, Ronalds; Elferts, Didzis; Kaasik, Ants; Rantala, Markus J.; Mierauskas, Pranas; Luoto, Severi; Krams, Indrikis A.

2017-12-01

Animals normally respond to stressful environmental stimuli by releasing glucocorticoid hormones. We investigated whether baseline corticosterone (CORT), handling-induced corticosterone concentration(s), and body condition indices of members of willow tit ( Poecile montanus) groups differed while wintering in old growth forests and managed young forests in mild weather conditions and during cold spells. Willow tits spend the winter season in non-kin groups in which dominant individuals typically claim their priority to access resources, while subordinate individuals may experience greater levels of stress and higher mortality, especially during cold spells. We captured birds to measure baseline CORT and levels of handling-induced CORT secretion after 20 min of capture. Willow tits in the young forests had higher baseline CORT and a smaller increase in CORT in response to capture than individuals in the old forests. Baseline CORT was higher in females and juvenile birds compared to adult males, whereas handling-induced CORT secretion did not differ between birds of different ages. During cold spells, baseline CORT of willow tits increased and handling-induced CORT secretion decreased, especially in birds in young forests. Willow tits' survival was higher in the old forests, with dominant individuals surviving better than subordinates. Our results show that changes in CORT secretion reflect responses to habitat quality and climate harshness, indicating young managed coniferous forests as a suboptimal habitat for the willow tit.

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

PubMed Central

Rossouw, Jacques E; Johnson, Karen C; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W; Manson, JoAnn E; Lakshminarayan, Kamakshi; Merino, Jose G; Lynch, John

2012-01-01

Background and Purpose To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT). Methods Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT. Results Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008. Conclusions Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT. PMID:22363056

The HBV DNA cutoff value for discriminating patients with HBeAgnegative chronic hepatitis B from inactive carriers.

PubMed

Kim, Eun Sun; Seo, Yeon Seok; Keum, Bora; Kim, Ji Hoon; A, Hyonggin; Yim, Hyung Joon; Kim, Yong Sik; Jeen, Yoon Tae; Lee, Hong Sik; Chun, Hoon Jai; Um, Soon Ho; Duck Kim, Chang; Ryu, Ho Sang

2011-05-01

Patients with HBeAg-negative chronic hepatitis B (CHB) has a significantly different prognosis than inactive carriers; there is however, no reliable strategy for accurately differentiating these two disease conditions. To determine a strategy for discriminating patients with HBeAg-negative CHB from inactive carriers. Consecutive inactive carriers (i.e. HBeAg-negativity, anti-HBe-positivity, normal ALT levels, and HBV DNA < 2000 IU/mL) were enrolled. HBV reactivation was defined as the elevation of the HBV DNA level to ≥ 2000 IU/mL. Patients were classified into true inactive carriers when their HBV DNA levels remained at < 2000 IU/mL or false inactive carriers when their HBV DNA levels increased to ≥ 2000 IU/mL during the first year. The Mean ± SD age of 208 inactive carriers (140 males) was 47.7 ± 12.6 years. The Mean ± SD serum ALT and HBV DNA levels were 22.8 ± 8.6 IU/L and 360 ± 482 IU/mL, respectively. HBV reactivation developed in 41 (19.7%) patients during the first year. Baseline HBV DNA and ALT levels differed significantly between true inactive and false inactive carriers. The AUROCs of the baseline ALT and HBV DNA levels for predicting a false inactive carrier were 0.609 and 0.831, respectively. HBV reactivation developed more often in patients with a baseline HBV DNA level of ≥ 200 IU/mL than in those with a baseline HBV DNA level of < 200 IU/mL during a Mean ± SD follow-up of 622 ± 199 days. The HBV DNA level was useful for discriminating patients with HBeAg-negative CHB from true inactive carriers. The follow-up strategies applied to inactive carriers need to vary with their HBV DNA levels.

Common Genetic Variants of the Human Steroid 21-Hydroxylase Gene (CYP21A2) Are Related to Differences in Circulating Hormone Levels

PubMed Central

Doleschall, Márton; Szabó, Julianna Anna; Pázmándi, Júlia; Szilágyi, Ágnes; Koncz, Klára; Farkas, Henriette; Tóth, Miklós; Igaz, Péter; Gláz, Edit; Prohászka, Zoltán; Korbonits, Márta; Rácz, Károly; Patócs, Attila

2014-01-01

Purpose Systematic evaluation of the potential relationship between the common genetic variants of CYP21A2 and hormone levels. Methods The relationships of CYP21A2 intron 2 polymorphisms and haplotypes with diverse baseline and stimulated blood hormone levels were studied in 106 subjects with non-functioning adrenal incidentaloma (NFAI). The rationale for using NFAI subjects is dual: i) their baseline hormone profiles do not differ from those of healthy subjects and ii) hormone levels after stimulation tests are available. Results The carriers (N = 27) of a well-defined CYP21A2 haplotype cluster (c5) had significantly elevated levels of cortisol (p = 0.0110), and 17-hydroxyprogesterone (p = 0.0001) after ACTH stimulation, and 11-deoxycortisol after metyrapone administration (p = 0.0017), but the hormone values were in normal ranges. In addition, the carriers (N = 33) of the C allele of the rs6462 polymorphism had a higher baseline aldosterone level (p = 0.0006). The prevalence of these genetic variants of CYP21A2 did not differ between NFAI and healthy subjects. Conclusions The common CYP21A2 variants presumably exert the same effect on hormone levels in the healthy and disease-affected populations. Therefore, they may contribute to complex diseases such as some cardiovascular diseases, and may influence the genotype-phenotype correlation in patients with congenital adrenal hyperplasia (CAH) including the individual need for hormone substitution. PMID:25210767

Effect of Exercise-Induced Lactate Elevation on Brain Lactate Levels During Hypoglycemia in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

PubMed

Wiegers, Evita C; Rooijackers, Hanne M; Tack, Cees J; Groenewoud, Hans J M M; Heerschap, Arend; de Galan, Bastiaan E; van der Graaf, Marinette

2017-12-01

Since altered brain lactate handling has been implicated in the development of impaired awareness of hypoglycemia (IAH) in type 1 diabetes, the capacity to transport lactate into the brain during hypoglycemia may be relevant in its pathogenesis. High-intensity interval training (HIIT) increases plasma lactate levels. We compared the effect of HIIT-induced hyperlacticacidemia on brain lactate during hypoglycemia between 1 ) patients with type 1 diabetes and IAH, 2 ) patients with type 1 diabetes and normal awareness of hypoglycemia, and 3 ) healthy participants without diabetes ( n = 6 per group). All participants underwent a hypoglycemic (2.8 mmol/L) clamp after performing a bout of HIIT on a cycle ergometer. Before HIIT (baseline) and during hypoglycemia, brain lactate levels were determined continuously with J-difference-editing 1 H-MRS, and time curves were analyzed using nonlinear mixed-effects modeling. At the beginning of hypoglycemia (after HIIT), brain lactate levels were elevated in all groups but most pronounced in patients with IAH. During hypoglycemia, brain lactate decreased ∼30% below baseline in patients with IAH but returned to baseline levels and remained there in the other two groups. Our results support the concept of enhanced lactate transport as well as increased lactate oxidation in patients with type 1 diabetes and IAH. © 2017 by the American Diabetes Association.

Vitamin A status of Filipino preschool children given a massive oral dose.

PubMed

Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

1996-12-01

The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

[Improvement in functional capacity after levothyroxine treatment in patients with chronic heart failure and subclinical hypothyroidism].

PubMed

Curotto Grasiosi, Jorge; Peressotti, Bruno; Machado, Rogelio A; Filipini, Eduardo C; Angel, Adriana; Delgado, Jorge; Cortez Quiroga, Gustavo A; Rus Mansilla, Carmen; Martínez Quesada, María del Mar; Degregorio, Alejandro; Cordero, Diego J; Dak, Marcelo; Izurieta, Carlos; Esper, Ricardo J

2013-10-01

To assess whether levothyroxine treatment improves functional capacity in patients with chronic heart failure (New York Heart Association class i-iii) and subclinical hypothyroidism. One hundred and sixty-three outpatients with stable chronic heart failure followed up for at least 6 months were enrolled. A physical examination was performed, and laboratory tests including thyroid hormone levels, Doppler echocardiogram, radionuclide ventriculography, and Holter monitoring were requested. Functional capacity was assessed by of the 6-min walk test. Patients with subclinical hypothyroidism were detected and, after undergoing the s6-min walk test, were given replacement therapy. When they reached normal thyrotropin (TSH) levels, the 6-min walk test was performed again. The distance walked in both tests was recorded, and the difference in meters covered by each patient was analyzed. Prevalence of subclinical hypothyroidism in patients with heart failure was 13%. These patients walked 292±63m while they were hypothyroid and 350±76m when TSH levels returned to normal, a difference of 58±11m (P<.011). Patients with normal baseline TSH levels showed no significant difference between the 2 6-min walk tests. Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Evaluation of the Chinese herbal medicine Jinlida in type 2 diabetes patients based on stratification: Results of subgroup analysis from a 12-week trial.

PubMed

Tian, Jiaxing; Lian, Fengmei; Yang, Libo; Tong, Xiaolin

2018-02-01

The Chinese herbal medicine Jinlida can significantly enhance the hypoglycemic action of metformin. However, the population showing the best responses to Jinlida has not been clarified. The aim of the present study was to compare the efficacy of Jinlida in type 2 diabetes mellitus (T2DM) after stratification. Data were analyzed from a 12-week randomized placebo-controlled double-blind multicenter study with 192 T2DM patients (186 completed the study). The efficacy evaluation included HbA1c, fasting plasma glucose (FPG), and 2-h postprandial glucose (2hPG) levels stratified by baseline HbA1c, sex, age, body mass index (BMI), and duration of T2DM diagnosis. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of β-cell function (HOMA-β) were also evaluated stratified by baseline insulin levels. In the Jinlida group, HbA1c was significantly reduced (P < 0.05). Greater reductions were observed in patients with baseline HbA1c >8.5%, in males and in those aged >60 years, with a BMI ≤24 kg/m 2 , or with a duration of T2DM diagnosis >5 years (P < 0.05). Compared with baseline, Jinlida significantly alleviated insulin resistance (P < 0.05) in patients with baseline insulin levels >20 mU/L. Jinlida also significantly improved β-cell function in patients with baseline insulin levels ≤20 mU/L (P < 0.05). Jinlida significantly improved glycemic control, with greater improvements in patients with poor glycemic control and male, elderly, of normal weight, or with a long disease course. Furthermore, Jinlida alleviated insulin resistance with hyperinsulinemia and promoted insulin secretion with hypoinsulinemia. These results need to be further confirmed in clinical trials. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Estimation of baseline dopamine D2 receptor occupancy in striatum and extrastriatal regions in humans with positron emission tomography with [18F] fallypride.

PubMed

Riccardi, Patrizia; Baldwin, Ron; Salomon, Ronald; Anderson, Sharlet; Ansari, Mohammad S; Li, Rui; Dawant, Benoit; Bauernfeind, Amy; Schmidt, Dennis; Kessler, Robert

2008-01-15

This study examined whether positron emission tomography (PET) studies with [18F] fallypride performed before and after alpha-methyl-para-tyrosine (AMPT) administration can be used to estimate baseline dopamine (DA) D2 receptor occupancy in striatal and extrastriatal regions. Six normal subjects underwent PET with [18 F] fallypride before and after administration of AMPT. The DA D2 receptor binding potentials (bp) were calculated with the reference region method. Percent changes in bp in striatal and extrastriatal regions were calculated with both region-of-interest analysis and on a voxel by voxel basis with parametric images of DA D2 receptor levels. The results of the current study indicate that AMPT treatment significantly increased the bp in the caudate, putamen, ventral striatum, and substantia nigra. A trend level increase was seen in the medial thalamus. This study demonstrates that PET with [18F] fallypride can be used to estimate baseline DA D2 receptor occupancy in striatal and extrastriatal regions.

Increased blood 8-hydroxy-2-deoxyguanosine levels in methamphetamine users during early abstinence.

PubMed

Huang, Ming-Chyi; Lai, Ying-Ching; Lin, Shih-Ku; Chen, Chun-Hsin

2018-01-01

Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p < 0.001). The 8-OHdG levels did not alter after 2 weeks of methamphetamine abstinence (0.32 ± 0.12 ng/mL, p = 0.051 compared to baseline measurement; p = 0.12 compared to healthy controls). No significant correlations were observed between baseline 8-OHdG levels in methamphetamine users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

Contribution of myofascial trigger points to migraine symptoms.

PubMed

Giamberardino, Maria Adele; Tafuri, Emmanuele; Savini, Antonella; Fabrizio, Alessandra; Affaitati, Giannapia; Lerza, Rosanna; Di Ianni, Livio; Lapenna, Domenico; Mezzetti, Andrea

2007-11-01

This study evaluated the contribution of myofascial trigger points (TrPs) to migraine pain. Seventy-eight migraine patients with cervical active TrPs whose referred areas (RAs) coincided with migraine sites (frontal/temporal) underwent electrical pain threshold measurement in skin, subcutis, and muscle in TrPs and RAs at baseline and after 3, 10, 30, and 60 days; migraine pain assessment (number and intensity of attacks) for 60 days before and 60 days after study start. Fifty-four patients (group 1) underwent TrP anesthetic infiltration on the 3rd, 10th, 30th, and 60th day (after threshold measurement); 24 (group 2) received no treatment. Twenty normal subjects underwent threshold measurements in the same sites and time points as patients. At baseline, all patients showed lower than normal thresholds in TrPs and RAs in all tissues (P < .001). During treatment in group 1, all thresholds increased progressively in TrPs and RAs (P < .0001), with sensory normalization of skin/subcutis in RAs at the end of treatment; migraine pain decreased (P < .001). Threshold increase in RAs and migraine reduction correlated linearly (.0001 < P < .006). In group 2 and normal subjects, no changes occurred. Cervical TrPs with referred areas in migraine sites thus contribute substantially to migraine symptoms, the peripheral nociceptive input from TrPs probably enhancing the sensitization level of central sensory neurons. This article shows the beneficial effects of local therapy of active myofascial trigger points (TrPs) on migraine symptoms in patients in whom migraine sites coincide with the referred areas of the TrPs. These results suggest that migraine pain is often contributed to by myofascial inputs that enhance the level of central neuronal excitability.

Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

PubMed

Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan

2017-10-01

Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

PubMed

Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

2008-07-01

States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

PubMed

Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

1984-03-01

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

A Tele-Behavioral Health Intervention to Reduce Depression, Anxiety, and Stress and Improve Diabetes Self-Management.

PubMed

Mochari-Greenberger, Heidi; Vue, Lee; Luka, Andi; Peters, Aimee; Pande, Reena L

2016-08-01

Depression is prevalent among individuals with diabetes and associated with suboptimal self-management. Little is known about the feasibility and potential impact of tele-behavioral therapy to improve depressive symptoms and self-management among diabetes patients. This was a retrospective observational study of consecutive graduates enrolled in a national 8-week diabetes behavioral telehealth program between August 1, 2014, and January 31, 2015 (N = 466; mean age 56.8 ± 5.0 years; 56% female). Participant characteristics (demographics, comorbidities) were obtained by standardized questionnaire. Depression, anxiety, and stress symptoms (DASS; validated Depression Anxiety and Stress Scale 21 survey), and glucose self-testing frequency and values (point-of-care monitor) were measured at program start and completion. Changes in DASS severity and glucose self-testing frequency were assessed by chi-square tests. Changes in DASS and blood glucose levels were evaluated by paired t-tests. At baseline, approximately one in three participants had elevated depression (32%), anxiety (33%), or stress (31%) scores. Significant reductions in average DASS, depression (-8.8), anxiety (-6.9), and stress (-9.9), scores were observed at graduation among those with elevated baseline scores (p < 0.0001); most (≥80%) improved to less severe depression, anxiety, or stress categories. Improved glucose self-testing frequency (69% vs. 60% tested ≥once per week; p = 0.0005) and significant reductions in mean morning glucose levels (-12.3 mg/dL; p = 0.0002) were observed from baseline to graduation. Participants with normal versus non-normal depression scores were more likely to have lower (

Influence of gestational age and time of day in baseline and heart rate variation of fetuses.

PubMed

Li, Guangfei; Zhang, Song; Yang, Lin; Li, Shufang; Wang, Yan; Hao, Dongmei; Yang, Yimin; Li, Xuwen; Zhang, Lei; Xu, Mingzhou

2016-04-29

Fetal electrocardiography (FECG) places electrodes on the maternal abdomen to convert the fetal electrocardiosignals into fetal heart rate (FHR), improving the accuracy and comfort of pregnant woman. At the same time, FECG simplifies the procedure of long term monitoring in the perinatal period. Investigating the influence of gestational age and time of day on FHR features to distinguish between non-stress test (NST) normal fetuses and NST suspicious fetuses. A novel method of FHR baseline estimation was presented; then baseline value and fetal heart rate variation (FHRV) were analyzed in the time domain using FHR signals recorded from 52 fetuses. Baseline values in 1:00, 2:00, 4:00, 5:00 and heart rate variation (HRV) distribution showed a significant difference (p< 0.05) between NST normal fetuses and NST suspicious fetuses. The results suggest that NST normal and suspicious fetuses had same outcome and different FHR features. Accurately distinguishing normal fetuses and suspicious fetuses is important for lowering the false positive rate and reducing unnecessary clinical intervention.

Autonomic Modulation in Older Women: Using Resistance Exercise as a Countermeasure

PubMed Central

GERHART, HAYDEN; TAI, YU LUN; FENNELL, CURTIS; MAYO, XIÁN; KINGSLEY, J. DEREK

2017-01-01

It is unclear if resistance training (RT) can be used to alter declines in autonomic modulation associated with aging. Young women (YW; range 18–25 yrs) and older women (OW; range 50–72 yrs) were compared at baseline. Only OW underwent supervised RT 2 days a week for 12-weeks. Baseline and post-training measurements included heart rate variability (HRV) and complexity (Sample Entropy) to assess autonomic modulation. The 12-weeks of RT consisted of 9 exercises performing 3 sets of 8–12 repetitions. At baseline, group differences in maximal strength, and autonomic modulation were evaluated with a one-way ANOVA with BMI as a covariate. In the OW, the effects of RT were evaluated with repeated-measures ANOVA in order to compare baseline to after RT. The YW had significantly (p≤0.05) lower diastolic, but not systolic blood pressure. The YW also had significantly (p≤0.05) greater absolute Ln (natural logarithm) high-frequency (HF) power and normalized HF power compared to the OW. In addition, there were significantly (p≤0.05) greater levels of normalized low-frequency power (LF) (and the LF/HF ratio) in the OW compared to the YW before RT. However, no difference was found for Sample Entropy. After RT, OW significantly (p≤0.05) increased the chest press (28%) and leg extension (33%). RT had no significant effect on any autonomic parameter suggesting that it may not be a sufficient stimulus to alter the effects of aging. PMID:28344732

Severity of Illness Scores May Misclassify Critically Ill Obese Patients.

PubMed

Deliberato, Rodrigo Octávio; Ko, Stephanie; Komorowski, Matthieu; Armengol de La Hoz, M A; Frushicheva, Maria P; Raffa, Jesse D; Johnson, Alistair E W; Celi, Leo Anthony; Stone, David J

2018-03-01

Severity of illness scores rest on the assumption that patients have normal physiologic values at baseline and that patients with similar severity of illness scores have the same degree of deviation from their usual state. Prior studies have reported differences in baseline physiology, including laboratory markers, between obese and normal weight individuals, but these differences have not been analyzed in the ICU. We compared deviation from baseline of pertinent ICU laboratory test results between obese and normal weight patients, adjusted for the severity of illness. Retrospective cohort study in a large ICU database. Tertiary teaching hospital. Obese and normal weight patients who had laboratory results documented between 3 days and 1 year prior to hospital admission. None. Seven hundred sixty-nine normal weight patients were compared with 1,258 obese patients. After adjusting for the severity of illness score, age, comorbidity index, baseline laboratory result, and ICU type, the following deviations were found to be statistically significant: WBC 0.80 (95% CI, 0.27-1.33) × 10/L; p = 0.003; log (blood urea nitrogen) 0.01 (95% CI, 0.00-0.02); p = 0.014; log (creatinine) 0.03 (95% CI, 0.02-0.05), p < 0.001; with all deviations higher in obese patients. A logistic regression analysis suggested that after adjusting for age and severity of illness at least one of these deviations had a statistically significant effect on hospital mortality (p = 0.009). Among patients with the same severity of illness score, we detected clinically small but significant deviations in WBC, creatinine, and blood urea nitrogen from baseline in obese compared with normal weight patients. These small deviations are likely to be increasingly important as bigger data are analyzed in increasingly precise ways. Recognition of the extent to which all critically ill patients may deviate from their own baseline may improve the objectivity, precision, and generalizability of ICU mortality prediction and severity adjustment models.

The effect of singing training on voice quality for people with quadriplegia.

PubMed

Tamplin, Jeanette; Baker, Felicity A; Buttifant, Mary; Berlowitz, David J

2014-01-01

Despite anecdotal reports of voice impairment in quadriplegia, the exact nature of these impairments is not well described in the literature. This article details objective and subjective voice assessments for people with quadriplegia at baseline and after a respiratory-targeted singing intervention. Randomized controlled trial. Twenty-four participants with quadriplegia were randomly assigned to a 12-week program of either a singing intervention or active music therapy control. Recordings of singing and speech were made at baseline, 6 weeks, 12 weeks, and 6 months postintervention. These deidentified recordings were used to measure sound pressure levels and assess voice quality using the Multidimensional Voice Profile and the Perceptual Voice Profile. Baseline voice quality data indicated deviation from normality in the areas of breathiness, strain, and roughness. A greater percentage of intervention participants moved toward more normal voice quality in terms of jitter, shimmer, and noise-to-harmonic ratio; however, the improvements failed to achieve statistical significance. Subjective and objective assessments of voice quality indicate that quadriplegia may have a detrimental effect on voice quality; in particular, causing a perception of roughness and breathiness in the voice. The results of this study suggest that singing training may have a role in ameliorating these voice impairments. Copyright © 2014 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.

PubMed

Derosa, Giuseppe; Mugellini, Amedeo; Ciccarelli, Leonardina; Crescenzi, Giuseppe; Fogari, Roberto

2003-02-01

Repaglinide and glimepiride are relatively new oral hypoglycemic agents. Few data are available concerning their effects on metabolic parameters other than measures of glycemic control. In addition to assessing the effects of repaglinide and glimepiride on glycemic control in patients with type 2 diabetes mellitus, this study also examined the effects of these agents on 3 metabolic parameters known to be cardiovascular risk factors--lipoprotein(a) (Lp[a]), plasminogen activator inhibitor-1 (PAI-1), and homocysteine (Hcy). This randomized, placebo-controlled, double-blind trial was conducted at a single center in Italy. Eligible patients were nonsmokers; had no hypertension or coronary heart disease; were taking no hypolipidemic drugs, diuretics, beta-blockers, or thyroxin; and had normal renal function. After an initial 4-week placebo washout period, patients were randomized to receive repaglinide 1 mg/d or glimepiride 1 mg/d. The dose of study drug was optimized over an 8-week titration period, which was followed by a 12-month treatment period. Measures of glycemic control (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPG], fasting plasma insulin [FPI], postprandial plasma insulin [PPI]) and the other metabolic parameters of interest were assessed after 6 and 12 months of treatment. One hundred twenty-four patients (63 women, 61 men) completed the study, 62 in each treatment group. There were no significant differences in demographic characteristics between groups. After 6 and 12 months of treatment, FPG levels and HbA1c values were significantly reduced from baseline in both groups (6 months, P < 0.05; 12 months, P < 0.01). After 6 months, PPG levels were significantly decreased only in the repaglinide group (P < 0.05 vs baseline); at 12 months, however, PPG levels were significantly reduced from baseline in both groups (P < 0.01 repaglinide, P < 0.05 glimepiride). No significant changes from baseline in FPI or PPI levels were seen in either group at 6 months, although FPI levels were significantly increased in the repaglinide group at 12 months (P < 0.05). Repaglinide significantly lowered levels of Lp(a), PAI-1, and Hcy after 12 months (all, P < 0.05 vs baseline). Glimepiride significantly lowered levels of Lp(a) and Hcy after 6 months (both, P < 0.05 vs baseline) and levels of Lp(a) (P < 0.01 vs baseline), Hcy (P < 0.01 vs baseline), and PAI-1 (P < 0.05 vs baseline) after 12 months. Repaglinide and glimepiride improved glycemic control and reduced levels of other metabolic parameters of interest in this population of patients with type 2 diabetes. It is possible that the reductions in Lp(a), PAI-1, and Hcy were the result of improved glucose metabolism; however, the possibility that repaglinide and glimepiride may have a direct effect on these parameters should not be excluded.

GLUTAMINE AND HYPERAMMONEMIC CRISES IN PATIENTS WITH UREA CYCLE DISORDERS

PubMed Central

Lee, B.; Diaz, G.A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S.A.; Le Mons, C.; Bartley, J.; Longo, N.; Nagamani, S.C.; Berquist, W.; Gallagher, R.C.; Harding, C.O.; McCandless, S.E.; Smith, W.; Schulze, A.; Marino, M.; Rowell, R.; Coakley, D.F.; Mokhtarani, M.; Scharschmidt, B.F.

2016-01-01

Blood ammonia and glutamine levels are used as biomarkers of control in patients with urea cycle disorders (UCDs). This study was undertaken to evaluate glutamine variability and utility as a predictor of hyperammonemic crises (HACs) in UCD patients. Methods The relationships between glutamine and ammonia levels and the incidence and timing of HACs were evaluated in over 100 adult and pediatric UCD patients who participated in clinical trials of glycerol phenylbutyrate. Results The median (range) intra-subject 24-hour coefficient of variation for glutamine was 15% (8–29%) as compared with 56% (28%–154%) for ammonia, and the correlation coefficient between glutamine and concurrent ammonia levels varied from 0.17 to 0.29. Patients with baseline (fasting) glutamine values >900 µmol/L had higher baseline ammonia levels (mean [SD]: 39.6 [26.2] µmol/L) than patients with baseline glutamine ≤900 µmol/L (26.6 [18.0] µmol/L). Glutamine values >900 µmol/L during the study were associated with an approximately 2-fold higher HAC risk (odds ratio [OR]=1.98; p=0.173). However, glutamine lost predictive significance (OR=1.47; p=0.439) when concomitant ammonia was taken into account, whereas the predictive value of baseline ammonia ≥ 1.0 upper limit of normal (ULN) was highly statistically significant (OR=4.96; p=0.013). There was no significant effect of glutamine >900 µmol/L on time to first HAC crisis (hazard ratio [HR]=1.14; p=0.813), but there was a significant effect of baseline ammonia ≥ 1.0 ULN (HR=4.62; p=0.0011). Conclusions The findings in this UCD population suggest that glutamine is a weaker predictor of HACs than ammonia and that the utility of the predictive value of glutamine will need to take into account concurrent ammonia levels. PMID:26586473

Interleukin-6 levels in the conjunctival epithelium of patients with dry eye disease treated with cyclosporine ophthalmic emulsion.

PubMed

Turner, K; Pflugfelder, S C; Ji, Z; Feuer, W J; Stern, M; Reis, B L

2000-07-01

To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium of patients with moderate to severe dry eye disease before and after treatment with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. Conjunctival cytology specimens were obtained from a subset of patients enrolled in a 6-month randomized, double-masked clinical trial of the efficacy and safety of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with 0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of IL-6 and G3PDH were measured and compared. There was no change from baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but showed a significant decrease from baseline in the group treated with 0.05% CsA (p = 0.048) at 6 months. No significant between-group differences were noted and no correlation was observed between the change in IL-6/G3PDH and corneal fluorescein staining. This preliminary, small-cohort study showed a decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye patients treated with 0.05% CsA for 6 months. The observed decrease suggests that dry eye disease involves immune-mediated inflammatory processes that may be decreased by treatment with topical ophthalmic cyclosporine.

Changes in hormone and lipid levels in male patients with focal seizures when switched from carbamazepine to lacosamide as adjunctive treatment to levetiracetam: A small phase IIIb, prospective, multicenter, open-label trial.

PubMed

Elger, Christian E; Rademacher, Michael; Brandt, Christian; Elmoufti, Sami; Dedeken, Peter; Eckhardt, Klaus; Tennigkeit, Frank; De Backer, Marc

2016-09-01

Treatment with enzyme-inducing antiepileptic drugs (AEDs) such as carbamazepine (CBZ) can lead to changes in reproductive, endocrine, and lipid parameters, resulting in clinical symptoms for some patients. Previous studies indicate that these changes can be reversed by switching to a nonenzyme-inducing AED. Lacosamide is a newer-generation AED, not known to induce or strongly inhibit cytochrome P450 (CYP450) enzymes. In this phase IIIb, prospective, multicenter, open-label, single-arm trial (NCT01375374), the serum concentrations of CYP-related reproductive hormones, thyroid hormones, and lipids were assessed in otherwise healthy male patients with focal seizures (N=11), before and after a switch from CBZ (600-1200mg/day at baseline) to lacosamide (target dose: 400mg/day by the end of titration) as adjunctive treatment to the nonenzyme-inducing AED levetiracetam (LEV, stable dosage of >1000mg/day throughout). Cross titration took place over 4weeks, followed by an 8-week maintenance period. Serum measurements were conducted at baseline and at the end of maintenance. The median serum sex-hormone-binding globulin (SHBG) concentration was towards the higher end of the normal range at baseline and decreased following the switch (61.7 to 47.5nmol/L, N=10, p=0.027 by Wilcoxon signed-rank test). Free androgen index (100×testosterone/SHBG) and free thyroxine serum concentration increased (25.4 to 36.4 and 13.0 to 14.9pmol/L, respectively, both N=10 and p=0.002). At baseline, the median progesterone serum concentration was below the normal range (0.7nmol/L), whereas median cholesterol and low-density lipoprotein concentrations were above the normal range (5.5 and 3.6mmol/L, respectively). By the end of maintenance, all measured parameters were within the normal range. The safety and tolerability profile of lacosamide was consistent with that observed in previous studies. Furthermore, antiseizure efficacy appeared to be maintained, suggesting that deinduction of CYP enzymes following a switch from CBZ to lacosamide as adjunctive therapy to LEV is feasible within 8weeks and is associated with normalization of serum parameters. Copyright © 2016. Published by Elsevier Inc.

Efficacy determinants of subcutaneous microdose glucagon during closed-loop control.

PubMed

Russell, Steven J; El-Khatib, Firas H; Nathan, David M; Damiano, Edward R

2010-11-01

During a previous clinical trial of a closed-loop blood glucose (BG) control system that administered insulin and microdose glucagon subcutaneously, glucagon was not uniformly effective in preventing hypoglycemia (BG<70 mg/dl). After a global adjustment of control algorithm parameters used to model insulin absorption and clearance to more closely match insulin pharmacokinetic (PK) parameters observed in the study cohort, administration of glucagon by the control system was more effective in preventing hypoglycemia. We evaluated the role of plasma insulin and plasma glucagon levels in determining whether glucagon was effective in preventing hypoglycemia. We identified and analyzed 36 episodes during which glucagon was given and categorized them as either successful or unsuccessful in preventing hypoglycemia. In 20 of the 36 episodes, glucagon administration prevented hypoglycemia. In the remaining 16, BG fell below 70 mg/dl (12 of the 16 occurred during experiments performed before PK parameters were adjusted). The (dimensionless) levels of plasma insulin (normalized relative to each subject's baseline insulin level) were significantly higher during episodes ending in hypoglycemia (5.2 versus 3.7 times the baseline insulin level, p=.01). The relative error in the control algorithm's online estimate of the instantaneous plasma insulin level was also higher during episodes ending in hypoglycemia (50 versus 30%, p=.003), as were the peak plasma glucagon levels (183 versus 116 pg/ml, p=.007, normal range 50-150 pg/ml) and mean plasma glucagon levels (142 versus 75 pg/ml, p=.02). Relative to mean plasma insulin levels, mean plasma glucagon levels tended to be 59% higher during episodes ending in hypoglycemia, although this result was not found to be statistically significant (p=.14). The rate of BG descent was also significantly greater during episodes ending in hypoglycemia (1.5 versus 1.0 mg/dl/min, p=.02). Microdose glucagon administration was relatively ineffective in preventing hypoglycemia when plasma insulin levels exceeded the controller's online estimate by >60%. After the algorithm PK parameters were globally adjusted, insulin dosing was more conservative and microdose glucagon administration was very effective in reducing hypoglycemia while maintaining normal plasma glucagon levels. Improvements in the accuracy of the controller's online estimate of plasma insulin levels could be achieved if ultrarapid-acting insulin formulations could be developed with faster absorption and less intra- and intersubject variability than the current insulin analogs available today. © 2010 Diabetes Technology Society.

Levels of fecal corticosterone in sandhill cranes during a human-led migration.

PubMed

Hartup, Barry K; Olsen, Glenn H; Czekala, Nancy M; Paul-Murphy, Joanne; Langenberg, Julia A

2004-04-01

Fourteen captive-reared greater sandhill cranes (Grus canadensis tabida) were conditioned to follow ultralight aircraft to promote migration between Wisconsin and Florida (USA) after release. Fecal samples were collected throughout the training period in Wisconsin and during a l977-km human-led migration to Florida to determine fecal corticosterone (FC) concentrations by radioimmunnoassay. The mean (+/-SE) FC concentration during the training period was 109.5 +/- 7.5 ng/g and was representative of baseline levels recorded previously from sandhill cranes. Fecal corticosterone concentrations increased in early migration compared to concentrations I mo prior to departure (P < 0.01) but were not different from baseline concentrations at tile end of the 6-wk migration period. The variability of FC concentrations in individual samples was greater throughout the migration than the training period. Increases in FC during migration were modest and generally consistent with normal corticosterone elevations observed in migrating birds.

Autotransfusion from experimental hemothorax: levels of coagulation factors.

PubMed

Napoli, V M; Symbas, P J; Vroon, D H; Symbas, P N

1987-03-01

The coagulation system was investigated in five dogs undergoing autotransfusion from experimental hemothorax. One fourth of the blood volume was bled into the pleural space, drained, and autotransfused. The hemothorax blood showed: very prolonged PT and PTT; very low platelets and fibrinogen; midly elevated FDP; very low coagulation factors VIII, and V; reduced XII, prothrombin, X, XI, and VII. Partial clotting, mild fibrinolysis, and fibrin deposition over the pulmonary pleura seemed to cause incoagulability of hemothorax blood. Post autotransfusion arterial blood showed: normal PT and PTT; 25% decrease in platelets, and 31% decrease in fibrinogen from baseline values. There was also an overall 20% reduction of fibrinogen from baseline values. There was also an overall 20% reduction of all clotting factors, but their levels remained above 50% activity. It was concluded that autotransfusion from a hemothorax of 25% the blood volume in dogs causes a mild loss of hemostatic components, but does not significantly compromise the clotting mechanism.

Analytical fuel property effects: Small combustors, phase 2

NASA Technical Reports Server (NTRS)

Hill, T. G.; Monty, J. D.; Morton, H. L.

1985-01-01

The effects of non-standard aviation fuels on a typical small gas turbine combustor were studied and the effectiveness of design changes intended to counter the effects of these fuels was evaluated. The T700/CT7 turboprop engine family was chosen as being representative of the class of aircraft power plants desired for this study. Fuel properties, as specified by NASA, are characterized by low hydrogen content and high aromatics levels. No. 2 diesel fuel was also evaluated in this program. Results demonstrated the anticipated higher than normal smoke output and flame radiation intensity with resulting increased metal temperatures on the baseline T700 combustor. Three new designs were evaluated using the non standard fuels. The three designs incorporated enhanced cooling features and smoke reduction features. All three designs, when burning the broad specification fuels, exhibited metal temperatures at or below the baseline combustor temperatures on JP-5. Smoke levels were acceptable but higher than predicted.

Association of body mass index with amnestic and non-amnestic mild cognitive impairment risk in elderly.

PubMed

Wang, Feng; Zhao, Minghui; Han, Zhaoli; Li, Dai; Zhang, Shishuang; Zhang, Yongqiang; Kong, Xiaodong; Sun, Ning; Zhang, Qiang; Lei, Ping

2017-09-15

Previous studies focused on the relationship between body mass index and cognitive disorder and obtained many conflicting results. This study explored the potential effects of body mass index on the risk of mild cognitive impairment (amnestic and non-amnestic) in the elderly. The study enrolled 240 amnestic mild cognitive impairment patients, 240 non-amnestic mild cognitive impairment patients and 480 normal cognitive function controls. Data on admission and retrospective data at baseline (6 years ago) were collected from their medical records. Cognitive function was evaluated using Mini-Mental State Examination and Montreal Cognitive Assessment. Being underweight, overweight or obese at baseline was associated with an increased risk of amnestic mild cognitive impairment (OR: 2.30, 95%CI: 1.50 ~ 3.52; OR: 1.74, 95%CI: 1.36 ~ 2.20; OR: 1.71, 95%CI: 1.32 ~ 2.22, respectively). Being overweight or obese at baseline was also associated with an increased risk of non-amnestic mild cognitive impairment (OR: 1.51, 95%CI: 1.20 ~ 1.92; OR: 1.52, 95%CI: 1.21 ~ 1.97, respectively). In subjects with normal weights at baseline, an increased or decreased body mass index at follow-up was associated with an elevated risk of amnestic mild cognitive impairment (OR: 1.80, 95%CI: 1.10 ~ 3.05; OR: 3.96, 95%CI: 2.88 ~ 5.49, respectively), but only an increased body mass index was associated with an elevated risk of non-amnestic mild cognitive impairment (OR: 1.71, 95%CI: 1.16 ~ 2.59). Unhealthy body mass index levels at baseline and follow-up might impact the risk of both types of mild cognitive impairment (amnestic and non-amnestic).

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

[Mild preeclampsia and serum insulin values in the third pregnancy trimester].

PubMed

Martínez-Abundis, E; González-Ortíz, M; Cardona-Muñoz, E G; Hernández-Chávez, A

1998-06-01

The purpose of this investigation was to determine the baseline insulin level in sera during fasting and after an oral glucose load in patients with mild preeclampsia and compare these values with those obtained from pregnant women with normal arterial pressure during the third trimester of their pregnancy. A cross-sectional study was realized in 38 patients with mild preeclamsia and 39 patients with normal arterial pressure values, both groups in their third trimester of pregnancy. We determined baseline arterial pressure, serum glucose and insulin, and the insulin/glucose ratio with at least 6 hours of fasting, and one hour after 50 g of glucose PO. The hypertensive group was under treatment with alfametildopa and/or hidralazine, patients with known coexistent conditions that would alter glucose or insulin levels were not included. The glucose was measured with the glucose oxidase method and the insulin levels by radioimmunoanalysis. The insulin/glucose ratio was obtained as the coefficient of insulin/glucose. Both patient groups had similar ages, number of pregnancies, gestational age and pre-pregnancy body mass index. We found no difference in glucose levels during fasting nor glucose post-load between groups. Insulin fasting levels were lower in the preeclampsia group compared with the normotensive one (7.1 +/- 3.8 vs 10.6 +/- 8.7 microU/mL, p = 0.02), however there was no difference in either group after the glucose load was administered (66.8 +/- 46.5 vs 71.0 +/- 51.9, p = N.S.). The insulin/glucose ratio had the same behavior than insulin. The hypertensive group showed a lower fasting insulin levels compared with the normotensive group. We suggest further research be done on this matter with strict selection criteria in order to emit final conclusions.

Effect of Chronic Blood Transfusion on Biomarkers of Coagulation Activation and Thrombin Generation in Sickle Cell Patients at Risk for Stroke

PubMed Central

Hyacinth, Hyacinth I.; Adams, Robert J.; Greenberg, Charles S.; Voeks, Jenifer H.; Hill, Allyson; Hibbert, Jacqueline M.; Gee, Beatrice E.

2015-01-01

Hypercoagulability in sickle cell disease (SCD) is associated with multiple SCD phenotypes, association with stroke risk has not been well described. We hypothesized that serum levels of biomarkers of coagulation activation correlate with high transcranial Doppler ultrasound velocity and decreases with blood transfusion therapy in SCD patients. Stored serum samples from subjects in the Stroke Prevention in Sickle Cell Anemia (STOP) trial were analyzed using ELISA and protein multiplexing techniques. 40 subjects from each treatment arm (Standard Care [SC] and Transfusion [Tx]) at three time points—baseline, study exit and one year post-trial and 10 each of age matched children with SCD but normal TCD (SNTCD) and with normal hemoglobin (HbAA) were analyzed. At baseline, median vWF, TAT and D-dimer levels were significantly higher among STOP subjects than either HbAA or SNTCD. At study exit, median hemoglobin level was significantly higher while median TCD velocity was significantly lower in Tx compared to SC subjects. Median vWF (409.6 vs. 542.9 μg/ml), TAT (24.8 vs. 40.0 ng/ml) and D-dimer (9.2 vs. 19.1 μg/ml) levels were also significantly lower in the Tx compared to the SC group at study exit. Blood levels of biomarkers coagulation activation/thrombin generation correlated positively with TCD velocity and negatively with number of blood transfusions. Biomarkers of coagulation activation/thrombin generation were significantly elevated in children with SCD, at high risk for stroke. Reduction in levels of these biomarkers correlated with reduction in stroke risk (lower TCD velocity), indicating a possible role for hypercoagulation in SCD associated stroke. PMID:26305570

40 CFR Appendix E to Part 75 - Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units

Code of Federal Regulations, 2010 CFR

2010-07-01

... the boiler at a normal or conservatively high excess oxygen level in conjunction with these tests....2Substitute 1.25 times the highest NOX emission rate from the baseline correlation tests for the fuel (or fuel... potential NOX emission rate (MER) (as defined in § 72.2 of this chapter) for each unit operating hour...

40 CFR Appendix E to Part 75 - Optional NOX Emissions Estimation Protocol for Gas-Fired Peaking Units and Oil-Fired Peaking Units

Code of Federal Regulations, 2012 CFR

2012-07-01

... the boiler at a normal or conservatively high excess oxygen level in conjunction with these tests....2Substitute 1.25 times the highest NOX emission rate from the baseline correlation tests for the fuel (or fuel... potential NOX emission rate (MER) (as defined in § 72.2 of this chapter) for each unit operating hour...

Flicker-induced retinal arteriole dilation is reduced by ambient lighting.

PubMed

Noonan, Jonathan E; Dusting, Gregory J; Nguyen, Thanh T; Man, Ryan E K; Best, William J; Lamoureux, Ecosse L

2014-08-07

To investigate the impact of ambient room lighting on the magnitude of flicker light-induced retinal vasodilations in healthy individuals. Twenty healthy nonsmokers participated in a balanced 2 × 2 crossover study. Retinal vascular imaging was performed with the dynamic vessel analyzer under reduced or normal ambient lighting, then again after 20 minutes under the alternate condition. Baseline calibers of selected arteriole and venule segments were recorded in measurement units. Maximum percentage dilations from baseline during 20 seconds of luminance flicker were calculated from the mean of three measurement cycles. Within-subject differences were assessed by repeated measures analysis of variance with the assumption of no carryover effects and pairwise comparisons from the fitted model. Mean (SD) maximum arteriole dilations during flicker stimulation under reduced and normal ambient lighting were 4.8% (2.3%) and 4.1% (1.9%), respectively (P = 0.019). Maximum arteriole dilations were (mean ± 95% confidence interval) 0.7% ± 0.6% lower under normal ambient lighting compared with reduced lighting. Ambient lighting had no significant effect on maximum venular dilations during flicker stimulation or on the baseline calibers of arterioles or venules. Retinal arteriole dilation in response to luminance flicker stimulation is reduced under higher ambient lighting conditions. Reduced responses with higher ambient lighting may reflect reduced contrast between the ON and OFF flicker phases. Although it may not always be feasible to conduct studies under reduced lighting conditions, ambient lighting levels should be consistent to ensure that comparisons are valid. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

A Systematic Review and Meta-Analysis of Baseline Ohip-Edent Scores.

PubMed

Duale, J M J; Patel, Y A; Wu, J; Hyde, T P

2018-03-01

OHIP-EDENT is widely used in the literature to assess Oral-Health-Related-Quality-of-Life (OHRQoL) for edentulous patients. However the normal variance and mean of the baseline OHIP scores has not been reported. It would facilitate critical appraisal of studies if we had knowledge of the normal variation and mean of baseline OHIP-EDENT scores. An established figure for baseline OHIP-EDENT, obtained from a meta-analysis, would simplify comparisons of studies and quantify variations in initial OHRQoL of the trial participants. The aim of this study is to quantify a normal baseline value for pre-operative OHIP-EDENT scores by a systematic review and meta-analysis of the available literature. A systematic literature review was carried. 83 papers were identified that included OHIP-EDENT values. After screening and eligibility assessment, 7 papers were selected and included in the meta-analysis. A meta-analysis for the 7 papers by a random-effect model yielded a mean baseline OHIP-EDENT score of 28.63 with a 95% Confidence intervals from 21.93 to 35.34. A pre-operative baseline OHIP-EDENT has been established by meta-analysis of published papers. This will facilitate the comparison of the initial OHRQoL of one study population to that found elsewhere in the published literature. Copyright© 2018 Dennis Barber Ltd.

Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males.

PubMed

Haustein, Knut-Olaf; Krause, Jörn; Haustein, Heidi; Rasmussen, Thomas; Cort, Nicholas

2003-04-01

This open study assessed the effects of nicotine replacement therapy (NRT) on the normalizing of exhaled carbon monoxide (CO), transcutaneous partial oxygen tension (tcpO(2)), plasma cotinine and thiocyanate levels, and cardiovascular risk markers in abstinent subjects compared with untreated smokers after 4, 8, 12, and 26 weeks. The trial enrolled 197 subjects in two parallel groups: 164 subjects who received NRT (patch plus gum) for 12 weeks and 33 untreated smokers (controls). At 26 weeks, 123/164 participants in the treatment group had completed the study; 51/123 (41.5%) sustained abstinence from smoking, whereas 72/123 (58.5%) had relapsed. Changes in cotinine (abstainers: 291.6 ng/ml at baseline vs. 27.3 ng/ml at week 26; p<.0001) and thiocyanate levels (abstainers: 10.4 ng/ml at baseline vs. 6.2 ng/ml at week 26; p<.0001) and expired CO (abstainers: 30.4 ppm at baseline vs. 4.2 ppm at week 26; p<.0001) accurately reflected the changes in smoking and/or NRT use in both abstainers and relapsers. After they stopping smoking, tcpO(2) significantly improved in abstainers (34.9 mmHg at baseline vs. 50.4 mmHg at week 26; p<0.0001). Inverse correlations between the number of daily cigarettes and plasma cotinine, thiocyanate, and exhaled CO levels were observed in both relapsers and smokers. A clinically significant increase in HDL cholesterol (39.0 vs. 44.7 mg/dl; p<.0001) occurred in the abstainers between baseline and study end. Use of combination NRT to achieve abstinence resulted in marked improvements in biochemical parameters in abstainers and partial improvements in relapsers. The safety of combination NRT was confirmed by the absence of overdose-related adverse events.

Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PubMed

Yalin, G Y; Tanrikulu, S; Gul, N; Uzum, A K; Aral, F; Tanakol, R

2017-08-01

High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

Intensive lifestyle intervention provides rapid reduction of serum fatty acid levels in women with severe obesity without lowering omega-3 to unhealthy levels.

PubMed

Lin, C; Andersen, J R; Våge, V; Rajalahti, T; Mjøs, S A; Kvalheim, O M

2016-08-01

Serum fatty acid (FA) levels were monitored in women with severe obesity during intensive lifestyle intervention. At baseline, total FA levels and most individual FAs were elevated compared to a matching cohort of normal and overweight women (healthy controls). After 3 weeks of intensive lifestyle intervention, total level was only 11-12% higher than in the healthy controls and with almost all FAs being significantly lower than at baseline, but with levels of omega-3 being similar to the healthy controls. This is contrary to observations for patients subjected to bariatric surgery where omega-3 levels dropped to levels significantly lower than in the lifestyle patients and healthy controls. During the next 3 weeks of treatment, the FA levels in lifestyle patients were unchanged, while the weight loss continued at almost the same rate as in the first 3 weeks. Multivariate analysis revealed that weight loss and change of serum FA patterns were unrelated outcomes of the intervention for lifestyle patients. For bariatric patients, these processes were associated probably due to reduced dietary input and increased input from the patients' own fat deposits, causing a higher rate of weight loss and simultaneous reduction of the ratio of serum eicosapentaenoic to arachidonic acid. © 2016 World Obesity.

Alteration of hypothalamus-pituitary-adrenal glands axis in colorectal cancer patients.

PubMed

Mussi, Chiara; Angelini, Carlo; Crippa, Stefano; Caprotti, Roberto; Fumagalli, Luca; Motta, Vittorio; Uggeri, Franco

2003-12-01

in advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period (surgical trauma response) is often found and is associated with poor prognosis. Furthermore it is well known that cortisol is strictly involved in the response to major surgical stress, has an important immunosuppression activity and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol and ACTH in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. 40 patients (22 female, 18 male with a median age of 66 yrs) with histologically proven colorectal cancer undergoing to surgery were enrolled in the study. Assessment of total lymphocyte, CD4+, cortisol level, circadian rhythm of cortisol (11 pm and 8 am) was performed at baseline and in 3rd and 7th postoperative days. ACTH levels (11 pm and 8 am) were studied in 18 patients. increase of cortisol serum level in the post-operative period vs baseline was statistically significant both in 3rd and 7th days. A significant decrease of total and CD4+ lymphocytes count was found on both 3rd and 7th postoperative days compared to baseline and to normal values. The rate of patients with an altered circadian rhythm was 68% and 53% at 3rd and 7th postoperative days respectively. At baseline 28% of patients had an altered cortisol circadian rhythm and it was significantly more frequent in patients with nodal involvement (P<0.005) and with metastatic spread (P<0.004). 44% of 18 patients evaluated for ACTH circadian rhythm displayed an alteration and it was significantly higher in patients with nodal involvement and metastatic disease (P<0.05). No relations between lymphocytopenia and alteration of night-cortisolemy, day-cortisolemy and cortisol and ACTH circadian rhythm were found, neither at baseline, 3rd and 7th postoperative days. it is known that lymphocytopenia, both at baseline and in the postoperative period, is associated with a poor prognosis in cancer patients and that cortisol plays an important role in the immune response. Our data show that lymphocytopenia often present in cancer patients, poor prognostic factor, seems not to be associated with ACTH and cortisol level and circadian rhythm alteration, both at baseline and after surgical stress. Otherwise even if paraneoplastic syndromes seems not to be related to colorectal cancer and no patient showed adrenocortical metastasis, an impairment of circadian rhythm of cortisol and ACTH was found at baseline in 28% and 44% respectively. It was significantly associated with the presence of metastatic disease. These preliminary results suggest further investigations on relation between cancer and endocrine system.

Improved epileptic seizure detection combining dynamic feature normalization with EEG novelty detection.

PubMed

Bogaarts, J G; Hilkman, D M W; Gommer, E D; van Kranen-Mastenbroek, V H J M; Reulen, J P H

2016-12-01

Continuous electroencephalographic monitoring of critically ill patients is an established procedure in intensive care units. Seizure detection algorithms, such as support vector machines (SVM), play a prominent role in this procedure. To correct for inter-human differences in EEG characteristics, as well as for intra-human EEG variability over time, dynamic EEG feature normalization is essential. Recently, the median decaying memory (MDM) approach was determined to be the best method of normalization. MDM uses a sliding baseline buffer of EEG epochs to calculate feature normalization constants. However, while this method does include non-seizure EEG epochs, it also includes EEG activity that can have a detrimental effect on the normalization and subsequent seizure detection performance. In this study, EEG data that is to be incorporated into the baseline buffer are automatically selected based on a novelty detection algorithm (Novelty-MDM). Performance of an SVM-based seizure detection framework is evaluated in 17 long-term ICU registrations using the area under the sensitivity-specificity ROC curve. This evaluation compares three different EEG normalization methods, namely a fixed baseline buffer (FB), the median decaying memory (MDM) approach, and our novelty median decaying memory (Novelty-MDM) method. It is demonstrated that MDM did not improve overall performance compared to FB (p < 0.27), partly because seizure like episodes were included in the baseline. More importantly, Novelty-MDM significantly outperforms both FB (p = 0.015) and MDM (p = 0.0065).

Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

PubMed

Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

2008-09-01

Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.

Early Choline Levels From 3-Tesla MR Spectroscopy After Exclusive Radiation Therapy in Patients With Clinically Localized Prostate Cancer are Predictive of Plasmatic Levels of PSA at 1 Year

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Maingon, Philippe; Gauthier, Melanie

2011-11-15

Purpose: To investigate the time course response of prostate metabolism to irradiation using magnetic resonance spectroscopy (MRS) at 3-month intervals and its impact on biochemical control. Methods and Materials: Between January 2008 and April 2010, 24 patients with localized prostate cancer were prospectively enrolled in the Evaluation of the Response to Irradiation with MR Spectroscopy (ERIS) trial. All the patients had been treated with intensity-modulated radiation therapy with or without long-term adjuvant hormonal therapy (LTHT) and underwent 3-T MRS and prostate-specific antigen (PSA) assays at baseline and every 3 months thereafter up to 12 months. Results: After radiation, the meanmore » normalized citrate level (citrate/water) decreased significantly over time, both in the peripheral zone (PZ) (p = 0.0034) and in the entire prostate (p = 0.0008), whereas no significant change was observed in mean normalized choline levels (choline/water) in the PZ (p = 0.84) and in the entire prostate (p = 0.95). At 6 months after radiation, the mean choline level was significantly lower in the PZ for patients with a PSA value of {<=}0.5 ng/mL at 12 months (4.9 {+-} 1.7 vs. 7.1 {+-} 1.5, p = 0.0378). Similar results were observed at 12 months in the PZ (6.2 {+-} 2.3 vs. 11.4 {+-} 4.1, p = 0.0117 for choline level and 3.4 {+-} 0.7 vs. 16.1 {+-} 6.1, p = 0.0054 for citrate level) and also in the entire prostate (6.2 {+-} 1.9 vs. 10.4 {+-} 3.2, p = 0.014 for choline level and 3.0 {+-} 0.8 vs. 13.3 {+-} 4.7, p = 0.0054 for citrate level). For patients receiving LTHT, there was no correlation between choline or citrate levels and PSA value, either at baseline or at follow-up. Conclusions: Low normalized choline in the PZ, 6 months after radiation, predicts which patients attained a PSA {<=}0.5 ng/mL at 1 year. Further analyses with longer follow-up times are warranted to determine whether or not these new biomarkers can conclusively predict the early radiation response and the clinical outcome for patients with or without LTHT.« less

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine.

PubMed

Stine, S M; Grillon, C G; Morgan, C A; Kosten, T R; Charney, D S; Krystal, J H

2001-03-01

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.

Uninstructed BIAT faking when ego depleted or in normal state: differential effect on brain and behavior.

PubMed

Wolff, Wanja; Schindler, Sebastian; Englert, Christoph; Brand, Ralf; Kissler, Johanna

2016-05-03

Deception can distort psychological tests on socially sensitive topics. Understanding the cerebral processes that are involved in such faking can be useful in detection and prevention of deception. Previous research shows that faking a brief implicit association test (BIAT) evokes a characteristic ERP response. It is not yet known whether temporarily available self-control resources moderate this response. We randomly assigned 22 participants (15 females, 24.23 ± 2.91 years old) to a counterbalanced repeated-measurements design. Participants first completed a Brief-IAT (BIAT) on doping attitudes as a baseline measure and were then instructed to fake a negative doping attitude both when self-control resources were depleted and non-depleted. Cerebral activity during BIAT performance was assessed using high-density EEG. Compared to the baseline BIAT, event-related potentials showed a first interaction at the parietal P1, while significant post hoc differences were found only at the later occurring late positive potential. Here, significantly decreased amplitudes were recorded for 'normal' faking, but not in the depletion condition. In source space, enhanced activity was found for 'normal' faking in the bilateral temporoparietal junction. Behaviorally, participants were successful in faking the BIAT successfully in both conditions. Results indicate that temporarily available self-control resources do not affect overt faking success on a BIAT. However, differences were found on an electrophysiological level. This indicates that while on a phenotypical level self-control resources play a negligible role in deliberate test faking the underlying cerebral processes are markedly different.

The value of P300 event related potentials in the assessment of cognitive function in subclinical hypothyroidism.

PubMed

Dejanović, Mirjana; Ivetić, Vesna; Nestorović, Vojkan; Milanović, Zvezdan; Erić, Mirela

2017-03-01

Mild hypothyroidism (thyroid stimulating hormone [TSH] less than 10 mIU/L) induces reversible cognitive dysfunction, which can be evaluated by event related potentials (ERP). So far, only little is known about the impact of subclinical hypothyroidism on ERP as electrophysiological markers of cognitive activity. The aim of this study was to follow-up P300 latencies and amplitudes in patients with subclinical hypothyroidism and to evaluate the influence of thyroxine treatment which led to the normalization of TSH level in serum. We recorded the P300 wave using an auditory oddball paradigm in 60 patients (mean age 51.1±6.2 years, range 40-62 years), with subclinical hypothyroidism (normal mean value of FT4, with elevated TSH levels) at baseline, after 3 months, after 6 months and in 30 healthy control subjects. 30 patients treated six months with L-thyroxine until the normalization of TSH and 30 patients received placebo. The P300 latencies in patients with subclinical hypothyroidism were significantly longer, and the P300 amplitudes were significantly smaller than those of the control group. In the thyroxine treated patients P300 latency continuously decreased over the observation period with a significant difference after 6 months compared to baseline (P<0.01). The amplitude P300 showed no significant changes over time. Our results show the importance of P300 event related potentials in the detection of cognitive changes in patients with hypothyroidism. The P300 latency stands out as a marker for cognitive function recovery during treatment with thyroxine.

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

PubMed

Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

2001-01-01

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

PubMed

Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

2018-02-01

Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427. Copyright © 2016 Shire Human Genetic Therapies, Inc. Published by Elsevier Inc. All rights reserved.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

PubMed

Liu, G; Liang, L; Bray, G A; Qi, L; Hu, F B; Rood, J; Sacks, F M; Sun, Q

2017-06-01

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05). In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Interval Colorectal Cancers following Guaiac Fecal Occult Blood Testing in the Ontario ColonCancerCheck Program.

PubMed

Paszat, Lawrence; Sutradhar, Rinku; Tinmouth, Jill; Baxter, Nancy; Rabeneck, Linda

2016-01-01

Background. This work examines the occurrence of interval colorectal cancers (CRCs) in the Ontario ColonCancerCheck (CCC) program. We define interval CRC as CRC diagnosed within 2 years following normal guaiac fecal occult blood testing (gFOBT). Methods. Persons aged 50-74 who completed a baseline CCC gFOBT kit in 2008 and 2009, without a prior history of CRC, or recent colonoscopy, flexible sigmoidoscopy, or gFOBT, were identified. Rates of CRC following positive and normal results at baseline and subsequent gFOBT screens were computed and overall survival was compared between those following positive and normal results. Results. Interval CRC was diagnosed within 24 months following the baseline screen among 0.16% of normals and following the subsequent screen among 0.18% of normals. Interval cancers comprised 38.70% of CRC following the baseline screen and 50.86% following the subsequent screen. Adjusting for age and sex, the hazard ratio (HR) for death following interval cancer compared to CRC following positive result was 1.65 (1.32, 2.05) following the first screen and 1.71 (1.00, 2.91) following the second screen. Conclusion. Interval CRCs following gFOBT screening comprise a significant proportion of CRC diagnosed within 2 years after gFOBT testing and are associated with a higher risk of death.

Blood Volume Response to Physical Activity and Inactivity

DTIC Science & Technology

2007-07-01

feedback to promote volume excretion and maintain blood volume at its normal baseline level. Physical activity does not alter either arterial pressure or...although this is less clear. The increase in total blood volume then increases the ability to maintain a high stroke volume and a lower heart rate for...compelling evidence that reduced blood vol- ume with age may be a result of a sedentary, high caloric lifestyle rather than the aging process. There

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

PubMed

McNearney, Terry A; Sallam, Hanaa S; Hunnicutt, Sonya E; Doshi, Dipti; Chen, Jiande D Z

2013-01-01

We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.

PubMed

Yu, Zhiping; Lowndes, Joshua; Rippe, James

2013-12-01

Intake of high-fructose corn syrup (HFCS) has been suggested to contribute to the increased prevalence of obesity, whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose. We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week, free-living period at these consumption levels. This was a randomized, prospective, double-blind, parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th, 50th, and 90th percentile population consumption of fructose (the equivalent of 40, 90, or 150 g of sugar per day in a 2000-kcal diet). Before and after the 10-week intervention, 24-hour blood samples were collected. The area under the curve (AUC) for glucose, insulin, leptin, active ghrelin, triglyceride, and uric acid was measured. There were no group differences at baseline or posttesting for all outcomes (interaction, P > .05). The AUC response of glucose, active ghrelin, and uric acid did not change between baseline and posttesting (P > .05), whereas the AUC response of insulin (P < .05), leptin (P < .001), and triglyceride (P < .01) increased over the course of the intervention when the 6 groups were averaged. We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low, medium, and high levels of consumption. © 2013 Elsevier Inc. All rights reserved.

Some case studies of skewed (and other ab-normal) data distributions arising in low-level environmental research.

PubMed

Currie, L A

2001-07-01

Three general classes of skewed data distributions have been encountered in research on background radiation, chemical and radiochemical blanks, and low levels of 85Kr and 14C in the atmosphere and the cryosphere. The first class of skewed data can be considered to be theoretically, or fundamentally skewed. It is typified by the exponential distribution of inter-arrival times for nuclear counting events for a Poisson process. As part of a study of the nature of low-level (anti-coincidence) Geiger-Muller counter background radiation, tests were performed on the Poisson distribution of counts, the uniform distribution of arrival times, and the exponential distribution of inter-arrival times. The real laboratory system, of course, failed the (inter-arrival time) test--for very interesting reasons, linked to the physics of the measurement process. The second, computationally skewed, class relates to skewness induced by non-linear transformations. It is illustrated by non-linear concentration estimates from inverse calibration, and bivariate blank corrections for low-level 14C-12C aerosol data that led to highly asymmetric uncertainty intervals for the biomass carbon contribution to urban "soot". The third, environmentally, skewed, data class relates to a universal problem for the detection of excursions above blank or baseline levels: namely, the widespread occurrence of ab-normal distributions of environmental and laboratory blanks. This is illustrated by the search for fundamental factors that lurk behind skewed frequency distributions of sulfur laboratory blanks and 85Kr environmental baselines, and the application of robust statistical procedures for reliable detection decisions in the face of skewed isotopic carbon procedural blanks with few degrees of freedom.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy.

PubMed

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J; Zetterberg, Henrik; Price, Richard W; Gisslén, Magnus; Spudich, Serena

2017-04-01

We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = -0.352 and P < .001 at baseline and r = -0.387 and P = .008 longitudinally) but not with neuropsychological performance. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Blood-Brain Barrier Disruption Is Initiated During Primary HIV Infection and Not Rapidly Altered by Antiretroviral Therapy

PubMed Central

Rahimy, Elham; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Robertson, Kevin; Meyerhoff, Dieter J.; Zetterberg, Henrik; Price, Richard W.; Gisslén, Magnus

2017-01-01

Abstract Background. We explored the establishment of abnormal blood-brain barrier (BBB) permeability and its relationship to neuropathogenesis during primary human immunodeficiency virus (HIV) infection by evaluating the cerebrospinal fluid (CSF) to serum albumin quotient (QAlb) in patients with primary HIV infection. We also analyzed effects of initiating combination antiretroviral therapy (cART). Methods. The QAlb was measured in longitudinal observational studies of primary HIV infection. We analyzed trajectories of the QAlb before and after cART initiation, using mixed-effects models, and associations between the QAlb and the CSF level of neurofilament light chain (NFL), the ratio of N-acetylaspartate to creatinine levels (a magnetic resonance spectroscopy neuronal integrity biomarker), and neuropsychological performance. Results. The baseline age-adjusted QAlb was elevated in 106 patients with primary HIV infection (median time of measurement, 91 days after infection), compared with that in 64 controls (P = .02). Before cART initiation, the QAlb increased over time in 84 participants with a normal baseline QAlb (P = .006) and decreased in 22 with a high baseline QAlb (P = .011). The QAlb did not change after a median cART duration of 398 days, initiated at a median interval of 225 days after infection (P = .174). The QAlb correlated with the NFL level at baseline (r = 0.497 and P < .001) and longitudinally (r = 0.555 and P < .001) and with the ratio of N-acetylaspartate to creatinine levels in parietal gray matter (r = −0.352 and P < .001 at baseline and r = −0.387 and P = .008 longitudinally) but not with neuropsychological performance. Conclusion. The QAlb rises during primary HIV infection, associates with neuronal injury, and does not significantly improve over a year of treatment. BBB-associated neuropathogenesis in HIV-infected patients may initiate during primary infection. PMID:28368497

NT-proBNP and Heart Failure Risk Among Individuals With and Without Obesity: The ARIC Study

PubMed Central

Ndumele, Chiadi E.; Matsushita, Kunihiro; Sang, Yingying; Lazo, Mariana; Agarwal, Sunil K.; Nambi, Vijay; Deswal, Anita; Blumenthal, Roger S.; Ballantyne, Christie M.; Coresh, Josef; Selvin, Elizabeth

2016-01-01

Background Obesity is a risk factor for heart failure (HF), but is associated with lower N-terminal of pro-Brain Natriuretic Peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. Methods and Results We followed 12,230 ARIC participants free of prior HF at baseline (visit 2, 1990–1992) with BMI ≥18.5 kg/m2. We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1,861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r = −0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall and even among those with severe obesity (BMI ≥35 kg/m2; improvement in c-statistic +0.032 [95% CI 0.011–0.053]). However, given higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP 100 to < 200 pg/ml, the average 10-year HF risk was <5% among normal weight individuals but >10% if severely obese. Conclusions Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information regarding the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population. PMID:26746175

Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.

PubMed

Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Gastaldelli, Amalia; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Musi, Nicolas; Reaven, Peter D; DeFronzo, Ralph A

2014-06-01

Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. © 2014 by the American Diabetes Association.

Baseline Adiponectin Levels Do Not Influence the Response to Pioglitazone in ACT NOW

PubMed Central

Tripathy, Devjit; Clement, Stephen C.; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Gastaldelli, Amalia; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Musi, Nicolas; Reaven, Peter D.

2014-01-01

OBJECTIVE Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status. RESEARCH DESIGN AND METHODS A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years. RESULTS Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group. CONCLUSIONS Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin. PMID:24705615

Effectiveness of a Type 2 Diabetes Screening Intervention in the Canadian Workplace.

PubMed

Tarride, Jean-Eric; Smofsky, Allan; Nykoliation, Priscilla; Allain, Stephen; Lewis-Daly, Linda; Satok, David; Schwartz, Jeremy; Pollack, Joshua Hart; Guertin, Jason Robert; McIntyre, Roger S

2017-12-18

There is a lack of Canadian data concerning the effectiveness of diabetes interventions in the workplace. The objective of this study was to evaluate the effectiveness of Motivaction, a diabetes screening and education pilot program, in the workplace. The Motivaction program involves a voluntary web-based diabetes health-risk assessment, the Canadian Diabetes Risk Questionnaire (CANRISK), combined with an opportunity for those eligible (i.e. having diabetes or having a CANRISK score ≥21) to attend 2 on-site biometric screening meetings with a registered nurse and 4 educational sessions by telephone with a certified diabetes educator. Biometric data, as well as information about self-efficacy, lifestyle changes, productivity, well-being, mental health and program satisfaction, were collected at baseline and at 6 months. Attendance at the initial and 6-month clinical visits included 293 people. At baseline, 21% were identified as having prediabetes (13%) or having diabetes (8%). Statistically significant reductions in glycated hemoglobin levels from baseline to the study's end were observed in those with prediabetes or diabetes. No statistically significant changes in glycated hemoglobin levels were observed in individuals with normal levels or in those at risk for diabetes at baseline. No statistical differences were observed in terms of productivity or mental health for the full population or across diabetes-risk categories. More than 90% of employees would recommend the Motivaction program to other employers. This study provides a framework for future diabetes interventions in the workplace and demonstrates that workplace interventions may reduce employees' diabetes risk levels and are valued by employees. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

PubMed Central

Weng, Ting-Chia; Chang, Chia-Hsuin; Dong, Yaa-Hui; Chang, Yi-Cheng; Chuang, Lee-Ming

2015-01-01

Objective To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B12 and folate levels. Data collection and analysis Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. Results Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. Conclusions RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range. PMID:26185175

Effect of walking on sand on gait kinematics in individuals with multiple sclerosis.

PubMed

van den Berg, Maayken E L; Barr, Christopher J; McLoughlin, James V; Crotty, Maria

2017-08-01

Walking in the real-world involves negotiating challenging or uneven surfaces, including sand. This can be challenging for people with Multiple Sclerosis (PWMS) due to motor deficits affecting the lower extremities. The study objective was to characterise kinematic gait adaptations made by PWMS when walking on sand and describe any immediate post-adaptation effects. 17 PWMS (mean age 51.4 ± 5.5, Disease Steps 2.4 ± 1.0), and 14 age-and gender matched healthy adults (HA) took part in a case-control study. 3D gait analysis was conducted using an eight-camera Vicon motion capture system. Each participant completed walking trials over level ground (baseline), sand (gait adaptation response), and again level ground (post-adaptation). Spatiotemporal data and kinematic data for the hip knee and ankle were recorded. At baseline PWMS showed significantly less total lower limb flexion (p<0.05) compared to HA. PWMS adapted to walking on sand by significantly increasing hip and knee flexion and ankle dorsiflexion (p<0.05) during swing, resulting in an overall 23° greater total lower limb flexion (p<0.05), reaching values within normal range. During the return to level ground walking values of temporal-spatial and kinematic parameters returned towards baseline values. PWMS adapted to walking on sand by increasing lower limb flexion during swing, and returned to their gait pattern to near baseline levels, in a manner similar to but with values not equalling HA. Further work is required to determine whether this mode of walking has potential to act as a gait retraining strategy to increase flexion of the lower limb. Copyright © 2017 Elsevier B.V. All rights reserved.

Responses to sulfur dioxide and exercise by medication-depend asthmatics: Effect of varying medication levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linn, W.S.; Shamoo, D.A.; Peng, R.C.

Twenty-one volunteers with moderate to severe asthma were exposed to sulfur dioxide (SO{sub 2}) at concentrations of O (control), 0.3, and 0.6 ppm in each of three medication states: (1) low (much of their usual asthma medication withheld), (2) normal (each subject on his own usual medication schedule), and (3) high (usual medication supplemented by inhaled metaproterenol before exposure). Theophylline, the medication usually taken by subjects, was often supplemented by beta-adrenergics. Exposures were for 10 min and were accompanied by continuous heavy exercise (ventilation {approximately} 50 1/min). Lung function and symptoms were measured before and after exposure. With normal medication,more » symptomatic bronchoconstriction occurred with exercise and was exacerbated by 0.6 ppm SO{sub 2}, as reported for mildly unmedicated asthmatics studied previously. Both baseline and post-exposure lung function were noticeably worse in the low-medication state. High medication improved baseline lung function and prevented most broncho-constrictive effect of SO{sup 2}/exercise. High medication also increased heart rate and apparently induced tremor or nervousness in some individuals.« less

Effects of Microwave Radiation on Humans. Monkeys Exposed to 1.25 GHZ pulsed Microwaves

DTIC Science & Technology

1992-03-13

matter. The entire retina was examined by indirect ophthalmoscopy. Photographic documentation included photomicrographs of the corneal endothelial cells...segment and retina appear normal. Photos of corneal endothelium pre and post irradiation demonstrated no change. The retinal photos also appeared normal...and photographic documentation. However, baseline fluorescein angiograms of the retina and iris were also included. It was determined that baseline

Quantification of normative ranges and baseline predictors of aortoventricular interface dimensions using multi-detector computed tomographic imaging in patients without aortic valve disease.

PubMed

Gooley, Robert P; Cameron, James D; Soon, Jennifer; Loi, Duncan; Chitale, Gauri; Syeda, Rifath; Meredith, Ian T

2015-09-01

Multidetector computed tomographic (MDCT) assessment of the aortoventricular interface has gained increased importance with the advent of minimally invasive treatment modalities for aortic and mitral valve disease. This has included a standardised technique of identifying a plane through the nadir of each coronary cusp, the basal plane, and taking further measurements in relation to this plane. Despite this there is no published data defining normal ranges for these aortoventricular metrics in a healthy cohort. This study seeks to quantify normative ranges for MDCT derived aortoventricular dimensions and evaluate baseline demographic and anthropomorphic associates of these measurements in a normal cohort. 250 consecutive patients undergoing MDCT coronary angiography were included. Aortoventricular dimensions at multiple levels of the aortoventricular interface were assessed and normative ranges quantified. Multivariate linear regression was performed to identify baseline predictors of each metric. The mean age was 59±12 years. The basal plane was eccentric (EI=0.22±0.06) while the left ventricular outflow tract was more eccentric (EI=0.32±0.06), with no correlation to gender, age or hypertension. Male gender, height and body mass index were consistent independent predictors of larger aortoventricular dimensions at all anatomical levels, while age was predictive of supra-annular measurements. Male gender, height and BMI are independent predictors of all aortoventricular dimensions while age predicts only supra-annular dimensions. Use of defined metrics such as the basal plane and formation of normative ranges for these metrics allows reference for clinical reporting and for future research studies by using a standardised measurement technique. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Biological stress systems, adverse life events and the onset of chronic multisite musculoskeletal pain: a 6-year cohort study.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Penninx, Brenda W J H; Dekker, Joost

2016-05-01

Dysregulated biological stress systems and adverse life events, independently and in interaction, have been hypothesised to initiate chronic pain. We examine whether (1) function of biological stress systems, (2) adverse life events, and (3) their combination predict the onset of chronic multisite musculoskeletal pain. Subjects (n=2039) of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were identified using the Chronic Pain Grade Questionnaire and followed up for the onset of chronic multisite musculoskeletal pain over 6 years. Baseline assessment of biological stress systems comprised function of the hypothalamic-pituitary-adrenal axis (1-h cortisol awakening response, evening levels, postdexamethasone levels), the immune system (basal and lipopolysaccharide-stimulated inflammation) and the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, respiratory sinus arrhythmia). The number of recent adverse life events was assessed at baseline using the List of Threatening Events Questionnaire. Hypothalamic-pituitary-adrenal axis, immune system and autonomic nervous system functioning was not associated with onset of chronic multisite musculoskeletal pain, either by itself or in interaction with adverse life events. Adverse life events did predict onset of chronic multisite musculoskeletal pain (HR per event=1.14, 95% CI 1.04 to 1.24, p=0.005). This longitudinal study could not confirm that dysregulated biological stress systems increase the risk of developing chronic multisite musculoskeletal pain. Adverse life events were a risk factor for the onset of chronic multisite musculoskeletal pain, suggesting that psychosocial factors play a role in triggering the development of this condition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

PubMed

Baillargeon, Jean-Patrice; Carpentier, André

2007-10-01

To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH. Clinical research center of an academic hospital. Nine lean women (body mass index

Long-Term Changes in Adiposity and Glycemic Control Are Associated With Past Adenovirus Infection

PubMed Central

Lin, Wan-Yu; Dubuisson, Olga; Rubicz, Rohina; Liu, Nianjun; Allison, David B.; Curran, Joanne E.; Comuzzie, Anthony G.; Blangero, John; Leach, Charles T.; Göring, Harald; Dhurandhar, Nikhil V.

2013-01-01

OBJECTIVE Ad36, a human adenovirus, increases adiposity but improves glycemic control in animal models. Similarly, natural Ad36 infection is cross-sectionally associated with greater adiposity and better glycemic control in humans. This study compared longitudinal observations in indices of adiposity (BMI and body fat percentage) and glycemic control (fasting glucose and insulin) in Ad36-infected versus uninfected adults. RESEARCH DESIGN AND METHODS Baseline sera from Hispanic men and women (n = 1,400) were screened post hoc for the presence of Ad36-specific antibodies. Indices of adiposity and glycemic control at baseline and at ∼10 years past the baseline were compared between seropositive and seronegative subjects, with adjustment for age and sex. In addition to age and sex, indices of glycemic control were adjusted for baseline BMI and were analyzed only for nondiabetic subjects. RESULTS Seropositive subjects (14.5%) had greater adiposity at baseline, compared with seronegative subjects. Longitudinally, seropositive subjects showed greater adiposity indices but lower fasting insulin levels. Subgroup analyses revealed that Ad36-seropositivity was associated with better baseline glycemic control and lower fasting insulin levels over time in the normal-weight group (BMI ≤25 kg/m2) and longitudinally, with greater adiposity in the overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2) men. Statistically, the differences between seropositive and seronegative individuals were modest in light of the multiple tests performed. CONCLUSIONS This study strengthens the plausibility that in humans, Ad36 increases adiposity and attenuates deterioration of glycemic control. Panoptically, the study raises the possibility that certain infections may modulate obesity or diabetes risk. A comprehensive understanding of these under-recognized factors is needed to effectively combat such metabolic disorders. PMID:23160725

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lopez, A.L.; Kohrs, M.B.; Horwitz, D.L.

To determine the effect of glucose loading on serum zinc concentrations, 34 elderly subjects aged 60-86 y were studied. Anthropometric data, medical and dietary histories were obtained. Serum zinc and glucose concentrations were obtained fasting and 1/2, 1, 1 1/2, 2 and 3 h after 75 g oral glucose load; glycohemoglobin and fasting serum lipids were also determined. For comparison, the subjects were categorized as: normal or low serum zinc concentrations; normal or high body mass index BMI; normal or high sum of skinfolds and normal or high serum cholesterol. Results showed that low serum zinc concentrations increased significantly overmore » baseline values after the glucose load and did not return to fasting levels. On the other hand, mean serum zinc concentrations significantly declined without recovery for those with normal zinc values. For the total group, no significant differences were noted between fasting values and subsequent time periods. No correlations were noted between fasting serum zinc and area under the curve for zinc except in the high BMI group (positive correlation observed). For the high BMI group, fasting serum zinc differed significantly from the succeeding measurements except for 30 min. For the group as a whole, mean serum zinc concentration was within normal limits (76.9 +/- 2.8 mcg/ml): mean zinc intake was less than 2/3rds the RDA. They conclude that glucose ingestion may alter serum zinc and should be considered in interpreting these levels.« less

Overall survival and self-reported fatigue in patients with esophageal cancer.

PubMed

Stauder, M C; Romero, Y; Kabat, B; Atherton, P J; Geno, D; Deschamps, C; Jatoi, A; Sloan, J A; Botros, M; Jung, K W; Arora, A S; Miller, R C

2013-02-01

A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Hepcidin plasma levels are not associated with changes in haemoglobin in early rheumatoid arthritis patients.

PubMed

Østgård, R D; Glerup, H; Jurik, A G; Kragstrup, T W; Stengaard-Pedersen, K; Hetland, M L; Hørslev-Petersen, K; Junker, P; Deleuran, B W

2017-11-01

A reduction in haemoglobin level is a frequent complication among rheumatoid arthritis (RA) patients. Hepcidin has been linked to disturbed erythropoiesis. The objective of this study was to investigate the longitudinal changes in hepcidin in patients with early RA. Hepcidin plasma concentrations were measured by enzyme-linked immunosorbent assay in patients with early RA (n = 80) and healthy volunteers (HV, n = 40). Haemoglobin and other iron-related proteins were also measured. At baseline, all patients had active disease and were treatment naïve. Patients were treated with disease-modifying anti-rheumatic drugs (DMARDs) and with additional adalimumab (ADA, n = 42) or placebo (PLA, n = 38) during 52 weeks, using a treat-to-target strategy, aiming for a 28-joint Disease Activity Score (DAS28) < 3.2. At baseline, hepcidin levels [median (interquartile range)] were 9.7 ng/mL (5.2-19.4 ng/mL) in DMARD + ADA and 11.3 ng/mL (5.9-19.1 ng/mL) in DMARD + PLA. Both were significantly higher than seen in HV (6.0 ng/mL (3.3-9.3 ng/mL) (p < 0.001). After 12 months, both treatment regimens resulted in normalization of hepcidin. DAS28 correlated with hepcidin at baseline (r = 0.48, p < 0.001). No correlation was observed between levels of haemoglobin and hepcidin at baseline or during the 52 week follow-up. No change in haemoglobin levels was seen as a function of hepcidin changes. In a mixed statistical model, no single factor was connected with the regulation of haemoglobin in early RA. The changes in hepcidin were not associated with changes in haemoglobin levels. Thus, hepcidin could not be used as a prognostic marker in patients with early RA.

Decreased N-Acetyl Aspartate/Myo-Inositol Ratio in the Posterior Cingulate Cortex Shown by Magnetic Resonance Spectroscopy May Be One of the Risk Markers of Preclinical Alzheimer’s Disease: A 7-Year Follow-Up Study

PubMed Central

Waragai, Masaaki; Moriya, Masaru; Nojo, Takeshi

2017-01-01

Although molecular positron emission tomography imaging of amyloid and tau proteins can facilitate the detection of preclinical Alzheimer’s disease (AD) pathology, it is not useful in clinical practice. More practical surrogate markers for preclinical AD would provide valuable tools. Thus, we sought to validate the utility of conventional magnetic resonance spectroscopy (MRS) as a screening method for preclinical AD. A total of 289 older participants who were cognitively normal at baseline were clinically followed up for analysis of MRS metabolites, including N-acetyl aspartate (NAA) and myo-inositol (MI) in the posterior cingulate cortex (PCC) for 7 years. The 289 participants were retrospectively divided into five groups 7 years after baseline: 200 (69%) remained cognitively normal; 53 (18%) developed mild cognitive impairment (MCI); 21 (7%) developed AD; eight (2%) developed Parkinson’s disease with normal cognition, and seven (2%) developed dementia with Lewy bodies (DLB). The NAA/MI ratios of the PCC in the AD, MCI, and DLB groups were significantly decreased compared with participants who maintained normal cognition from baseline to 7 years after baseline. MMSE scores 7 years after baseline were significantly correlated with MI/Cr and NAA/MI ratios in the PCC. These results suggest that cognitively normal elderly subjects with low NAA/MI ratios in the PCC might be at risk of progression to clinical AD. Thus, the NAA/MI ratio in the PCC measured with conventional 1H MRS should be reconsidered as a possible adjunctive screening marker of preclinical AD in clinical practice. PMID:28968236

Using Correlative Properties of Neighboring Pixels to Enhance Contrast-to-Noise Ratio of Abnormal Hippocampus in Patients With Intractable Epilepsy and Mesial Temporal Sclerosis.

PubMed

Parsons, Matthew S; Sharma, Aseem; Hildebolt, Charles

2018-06-12

To test whether an image-processing algorithm can aid in visualization of mesial temporal sclerosis on magnetic resonance imaging by selectively increasing contrast-to-noise ratio (CNR) between abnormal hippocampus and normal brain. In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, baseline coronal fluid-attenuated inversion recovery images of 18 adults (10 females, eight males; mean age 41.2 years) with proven mesial temporal sclerosis were processed using a custom algorithm to produce corresponding enhanced images. Average (Hmean) and maximum (Hmax) CNR for abnormal hippocampus were calculated relative to normal ipsilateral white matter. CNR values for normal gray matter (GM) were similarly calculated using ipsilateral cingulate gyrus as the internal control. To evaluate effect of image processing on visual conspicuity of hippocampal signal alteration, a neuroradiologist masked to the side of hippocampal abnormality rated signal intensity (SI) of hippocampi on baseline and enhanced images using a five-point scale (definitely abnormal to definitely normal). Differences in Hmean, Hmax, GM, and SI ratings for abnormal hippocampi on baseline and enhanced images were assessed for statistical significance. Both Hmean and Hmax were significantly higher in enhanced images as compared to baseline images (p < 0.0001 for both). There was no significant difference in the GM between baseline and enhanced images (p = 0.9375). SI ratings showed a more confident identification of abnormality on enhanced images (p = 0.0001). Image-processing resulted in increased CNR of abnormal hippocampus without affecting the CNR of normal gray matter. This selective increase in conspicuity of abnormal hippocampus was associated with more confident identification of hippocampal signal alteration. Copyright © 2018 Academic Radiology. Published by Elsevier Inc. All rights reserved.

Thyroid-stimulating hormone, 5-HTTLPR genotype, and antidepressant response in depressed women.

PubMed

Gressier, Florence; Trabado, Séverine; Verstuyft, Céline; Bouaziz, Elodie; Hardy, Patrick; Fève, Bruno; Becquemont, Laurent; Corruble, Emmanuelle

2011-10-01

Basal serum thyroid-stimulating hormone (TSH) levels may predict antidepressant efficacy in patients with major depressive episodes (MDE), but data are inconsistent. As the SS genotype of the 5-HTTLPR polymorphism has been associated with a lower antidepressant efficacy in women with MDE, we aimed at assessing the relationship between normal basal TSH, 5-HTTLPR, and antidepressant efficacy in women. A total of 71 women and 28 men, with normal baseline TSH serum levels, hospitalized for a MDE, were assessed for 5-HTTLPR genotypes and prospectively followed for short-term antidepressant efficacy. Women with SS genotype had higher TSH levels (P=0.002) and a worse antidepressant response (P=0.046) than the women with LL/LS genotype, whereas no significant difference was shown in men. In multivariate analyses, antidepressant response in women was explained by TSH and 5-HTTLPR, but not by other variables. Further research is needed to understand the underlying mechanism explaining interactions between sex, TSH, and serotonergic function.

Safety assessment of 4-week oral intake of proanthocyanidin-rich grape seed extract in healthy subjects.

PubMed

Sano, Atsushi

2017-10-01

A clinical study was conducted to assess the safety and tolerability of oral doses of proanthocyanidin-rich grape seed extract (GSE) in healthy Japanese adult volunteers. In an open-label, 4-week toxicity test, 29 subjects daily received 1000, 1500, or 2500 mg GSE orally. Serum Fe levels of two subjects in the 2500 mg GSE group decreased to 61 and 60 μg/100 mL from 205 and 182 μg/100 mL at baseline respectively, at second week of GSE consumption; these values are low but within the normal range for the Japanese population. Two weeks after completing the 4-week course of GSE ingestion, the serum Fe levels of both subjects returned to near baseline levels (210 and 189 μg/100 mL). No subject discontinued the study. Oral intake of GSE up to 2500 mg for 4 weeks was found to be generally safe and well tolerated in humans. Research with a larger number of subjects is required to confirm these findings. Copyright © 2016. Published by Elsevier Ltd.

Selenium, copper, zinc, iron levels and mortality in patients with sepsis and systemic inflammatory response syndrome in Western Black Sea Region, Turkey.

PubMed

Ayoglu, Hilal; Sezer, Ustun; Akin, Mehmet; Okyay, Dilek; Ayoglu, Ferruh; Can, Murat; Kucukosman, Gamze; Piskin, Ozcan; Aydin, Bengu; Cimencan, Murat; Gur, Abdullah; Turan, Isil

2016-04-01

To evaluate the changing levels of selenium, copper, zinc and iron in patients with sepsis and systemic inflammatory response syndrome and their influence on mortality. The prospective study was conducted at a tertiary care university hospital in Zonguldak city in the western Black Sea region of Turkey from January 2012 to December 2013, and comprised patients with sepsis and systemic inflammatory response syndrome. Blood samples were taken on 1st, 3rd, 5th and 7th days to measure serum selenium, copper, zinc and iron levels. Patients' demographic data, presence of additional diseases and mortality were recorded. Of the 57 patients, 28(49.1%) were female and 29(50.9%) were male, with an overall mean age of 60.3±19.4 years, mean height of 166.1±11.4cm, mean weight of 76.5±17.5kg. Copper and zinc levels were in the normal range, while selenium and iron levels were lower than the limit values at all measuring periods. There was no significant difference between first and other days in accordance with element levels (p>0.05). Baseline copper levels in patients with malignancy were lower than patients without malignancy (p< 0.05). In hypertensive patients, baseline copper levels were higher and 7th day levels were lower than non-hypertensive (p< 0.05). Baseline selenium levels of those who died were lower than the other patients (p< 0.05). Selenium and iron levels were decreased in patients with sepsis-systemic inflammatory response syndrome and copper levels were lower in patients with malignancy, hypertension and chronic obstructive pulmonary disease (p< 0.05). There was no change in zinc levels of the patients. Reduced basal selenium levels of patients with sepsis and systemic inflammatory response syndrome were associated with mortality.

Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

PubMed

Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

2014-11-01

Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms

PubMed Central

Owei, Ibiye; Umekwe, Nkiru; Wan, Jim

2016-01-01

Dyslipidemia and dysglycemia are etiologically associated, but the direction, chronology, and mechanisms of the association are not fully understood. We, therefore, analyzed data from 335 healthy adults (184 black, 151 white) enrolled in the Pathobiology of Prediabetes in A Biracial Cohort study. Subjects underwent oral glucose tolerance test (OGTT) and were enrolled if they had normal fasting and 2-h plasma glucose levels. Assessments during year 1 included anthropometry, fasting lipid profile, insulin sensitivity, and insulin secretion. Thereafter, OGTT was assessed annually for 5.5 years. The primary outcome was occurrence of prediabetes (impaired fasting glucose or impaired glucose tolerance) or diabetes. During a mean follow-up of 2.62 years, 110 participants (32.8%) developed prediabetes (N = 100) or diabetes (N = 10). In multivariate logistic regression models, higher baseline low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower HDL cholesterol levels significantly increased the risk of incident prediabetes. The combined relative risk (95% confidence interval [CI]) of prediabetes for participants with lower baseline HDL cholesterol (10th vs. 90th percentile), higher LDL cholesterol (90th vs. 10th percentile) and high triglycerides levels (90th vs. 10th percentile) was 4.12 (95% CI 1.61–10.56), P = 0.0032. At baseline, lipid values showed significant associations with measures of adiposity, glycemia, insulin sensitivity, and secretion. In both ethnic groups, waist circumference correlated positively with triglycerides and inversely with HDL cholesterol levels (P = 0.0004–<0.0001); fasting plasma glucose correlated positively with triglycerides and LDL cholesterol levels and inversely with HDL cholesterol levels (P = 0.006–<0.0001); insulin sensitivity correlated positively with HDL cholesterol and inversely with triglyceride levels (P < 0.0001), and insulin secretion correlated positively with triglycerides (P = 0.01) and inversely with HDL cholesterol (P < 0.0001). We conclude that a baseline lipidemic signature identifies normoglycemic individuals at high risk for future glycemic progression, via congruent associations with adiposity and glucoregulatory mechanisms. These findings suggest that early lifestyle intervention could ameliorate progressive dyslipidemia and dysglycemia. PMID:27430991

A neutral effect of testosterone therapy on macroprolactin content in men with macroprolactinemia and late-onset hypogonadism.

PubMed

Krysiak, Robert; Kowalska, Beata; Szkróbka, Witold; Okopień, Bogusław

2016-02-01

In the light of recent studies, macroprolactinemia seems to occur much more frequently than previously thought. In women, oral contraceptive pills exhibit a stimulatory effect on macroprolactin production. No previous study has investigated macroprolactin levels in androgen-treated hypogonadal men. We studied 10 men with isolated macroprolactinemia and 14 men with normal prolactin levels who because of late-onset hypogonadism were treated with intramuscular testosterone enanthate. Serum prolactin, macroprolactin content, serum testosterone and gonadotropin levels were assessed at baseline and after 4 months of therapy. Although baseline levels of testosterone and gonadotropins were similar in men with and without macroprolactinemia, clinical symptoms were more severe in patients with elevated big-big prolactin levels. As expected, testosterone treatment increased serum testosterone, slightly reduced serum gonadotropins, as well as improved clinical condition in both patients with and without macroprolactinemia, with no difference between the groups. However, testosterone therapy did not affect serum prolactin and macroprolactin content, even after replacing intramuscular testosterone enanthate with oral testosterone undecanoate. Our results suggest a negligible effect of testosterone replacement on macroprolactin levels in macroprolactinemic men with late-onset hypogonadism. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Early return to baseline range of motion and strength after anterior shoulder instability surgery: a Multicenter Orthopaedic Outcomes Network (MOON) shoulder group cohort study.

PubMed

Buckwalter V, Joseph A; Wolf, Brian R; Glass, Natalie; Bollier, Matt; Kuhn, John E; Hettrich, Carolyn M

2018-03-23

Patients often return to higher-level activities and sports at 4 to 8 months after anterior shoulder stabilization procedures. It is unknown what percentage of patients have regained normal function at this time frame and what factors predict residual deficits, range of motion (ROM), and strength after anterior shoulder instability surgery. Ten participating sites throughout the United States enrolled patients in a prospective cohort study including primary, revision, arthroscopic, and open anterior stabilization procedures. Baseline demographic data and patient outcomes questionnaires were collected with initial physical examination, treatment, surgical findings, and surgical repair details. At the 6-month follow-up visit, ROM and strength measurements were collected and compared with preoperative measurements. There were 348 patients identified who underwent surgical treatment for anterior shoulder instability. Of these, 259 patients (74.0%) returned to baseline, and 89 (26.0%) did not return to baseline shoulder ROM (≥20° loss of ROM) or strength. A higher Beighton score (P = .01) and number of dislocations (P < .01) were associated with failure to regain baseline ROM and strength at early follow-up. No surgical variables were found to influence return to baseline function, including open vs. arthroscopic surgery, primary vs. revision surgery, and number of suture anchors. By 4 to 8 months postoperatively, 76% of patients return to baseline ROM, 98% return to baseline strength, and 74% return to both baseline ROM and strength. An increased number of dislocations and generalized joint laxity were associated with failure to return to baseline ROM and strength at early follow-up after anterior shoulder instability surgery. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

PubMed Central

Ertl, Andrew C; Diedrich, André; Biaggioni, Italo; Levine, Benjamin D; Robertson, Rose Marie; Cox, James F; Zuckerman, Julie H; Pawelczyk, James A; Ray, Chester A; Buckey, Jay C; Lane, Lynda D; Shiavi, Richard; Gaffney, F Andrew; Costa, Fernando; Holt, Carol; Blomqvist, C Gunnar; Eckberg, Dwain L; Baisch, Friedhelm J; Robertson, David

2002-01-01

Astronauts returning from space have reduced red blood cell masses, hypovolaemia and orthostatic intolerance, marked by greater cardio–acceleration during standing than before spaceflight, and in some, orthostatic hypotension and presyncope. Adaptation of the sympathetic nervous system occurring during spaceflight may be responsible for these postflight alterations. We tested the hypotheses that exposure to microgravity reduces sympathetic neural outflow and impairs sympathetic neural responses to orthostatic stress. We measured heart rate, photoplethysmographic finger arterial pressure, peroneal nerve muscle sympathetic activity and plasma noradrenaline spillover and clearance, in male astronauts before, during (flight day 12 or 13) and after the 16 day Neurolab space shuttle mission. Measurements were made during supine rest and orthostatic stress, as simulated on Earth and in space by 7 min periods of 15 and 30 mmHg lower body suction. Mean (± s.e.m.) heart rates before lower body suction were similar pre–flight and in flight. Heart rate responses to −30 mmHg were greater in flight (from 56 ± 4 to 72 ± 4 beats min−1) than pre–flight (from 56 ± 4 at rest to 62 ± 4 beats min−1, P < 0.05). Noradrenaline spillover and clearance were increased from pre–flight levels during baseline periods and during lower body suction, both in flight (n = 3) and on post–flight days 1 or 2 (n = 5, P < 0.05). In–flight baseline sympathetic nerve activity was increased above pre–flight levels (by 10–33 %) in the same three subjects in whom noradrenaline spillover and clearance were increased. The sympathetic response to 30 mmHg lower body suction was at pre–flight levels or higher in each subject (35 pre–flight vs. 40 bursts min−1 in flight). No astronaut experienced presyncope during lower body suction in space (or during upright tilt following the Neurolab mission). We conclude that in space, baseline sympathetic neural outflow is increased moderately and sympathetic responses to lower body suction are exaggerated. Therefore, notwithstanding hypovolaemia, astronauts respond normally to simulated orthostatic stress and are able to maintain their arterial pressures at normal levels. PMID:11773339

Human muscle sympathetic nerve activity and plasma noradrenaline kinetics in space

NASA Technical Reports Server (NTRS)

Ertl, Andrew C.; Diedrich, Andre; Biaggioni, Italo; Levine, Benjamin D.; Robertson, Rose Marie; Cox, James F.; Zuckerman, Julie H.; Pawelczyk, James A.; Ray, Chester A.; Buckey, Jay C Jr;

Monosialotetrahexosylganglioside Inhibits the Expression of p-CREB and NR2B in the Auditory Cortex in Rats with Salicylate-Induced Tinnitus.

PubMed

Song, Rui-Biao; Lou, Wei-Hua

2015-01-01

This study investigated the effects of monosialotetrahexosylganglioside (GM1) on the expression of N-methyl-D-aspartate receptor subunit 2B (NR2B) and phosphorylated (p)-cyclic AMP response element-binding protein (CREB) in the auditory cortex of rats with tinnitus. Tinnitus-like behavior in rats was tested with the gap prepulse inhibition of acoustic startle paradigm. We then investigated the NR2B mRNA and protein and p-CREB protein levels in the auditory cortex of tinnitus rats compared with normal rats. Rats treated for 4 days with salicylate exhibited tinnitus. NR2B mRNA and protein and p-CREB protein levels were upregulated in these animals, with expression returning to normal levels 14 days after cessation of treatment; baseline levels of NR2B and p-CREB were also restored by GM1 administration. These data suggest that chronic salicylate administration induces tinnitus via upregulation of p-CREB and NR2B expression, and that GM1 can potentially be used to treat tinnitus.

Two-dimensional aerodynamic characteristics of several polygon-shaped cross-sectional models applicable to helicopter fuselages

NASA Technical Reports Server (NTRS)

Kelley, Henry L.; Crowell, Cynthia A.; Wilson, John C.

1992-01-01

A wind-tunnel investigation was conducted to determine 2-D aerodynamic characteristics of nine polygon-shaped models applicable to helicopter fuselages. The models varied from 1/2 to 1/5 scale and were nominally triangular, diamond, and rectangular in shape. Side force and normal force were obtained at increments of angle of flow incidence from -45 to 90 degrees. The data were compared with results from a baseline UH-60 tail-boom cross-section model. The results indicate that the overall shapes of the plots of normal force and side force were similar to the characteristic shape of the baseline data; however, there were important differences in magnitude. At a flow incidence of 0 degrees, larger values of normal force for the polygon models indicate an increase in fuselage down load of 1 to 2.5 percent of main-rotor thrust compared with the baseline value. Also, potential was indicated among some of the configurations to produce high fuselage side forces and yawing moments compared with the baseline model.

Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection.

PubMed

Suh, Joome; Sinclair, Elizabeth; Peterson, Julia; Lee, Evelyn; Kyriakides, Tassos C; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Price, Richard W; Gisslen, Magnus; Spudich, Serena

2014-12-03

Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Antiretroviral-naïve subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD)4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P <0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P <0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

Site, gender and age variation in normal skin colour on the back and the forearm: tristimulus colorimeter measurements.

PubMed

Fullerton, A; Serup, J

1997-02-01

To study whether anatomical location and age and gender of subjects had any influence on the objective skin colour measurements. Baseline colour in prone position was measured with the Minolta ChromaMeter® in the upper, middle and lower level of the upper back and on the forearm of 168 volunteers. These two sites are commonly used in skin testing. Higher basal a* and lower basal L* levels were found on the upper scapular region compared to the lower scapular region and the subscapular region. The basal b* level showed no variation relative to site. The basal a* and the basal b* levels were lower on the forearm compared to the upper back while the basal L* level was higher. Females above 65 years showed a less coloured skin with lower values as compared to those of younger age. Females were found to have a generally lower basal a* level than males both on the upper back and forearm skin. These relatively major differences and sources of variation have to be considered when planning irritancy studies where colour differences between erythema and normal skin is used.

Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex.

PubMed

Gerstner, Jason R; Koberstein, John N; Watson, Adam J; Zapero, Nikolai; Risso, Davide; Speed, Terence P; Frank, Marcos G; Peixoto, Lucia

2016-10-25

Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep). In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV). RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1-3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h) do so on average with a time constant that is similar to the time constant for the discharge of sleep need. We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally distinct classes of genes.

Is there any relationship between coronary artery disease and postprandial triglyceride levels?

PubMed

Atar, Inci Aslı; Atar, Ilyas; Aydınalp, Alp; Ertan, Cağatay; Bozbaş, Hüseyin; Ozin, Bülent; Yıldırır, Aylin; Müderrisoğlu, Haldun

2011-05-01

We aimed to evaluate the relationship between postprandial triglyceride (PPTG) levels and coronary artery disease (CAD). A total of 80 patients were included in this prospective cohort study. Oral lipid loading was used in order to measure PPTG levels. In the fasting state and after the high fat breakfast, triglyceride levels were measured by enzymatic methods at 2nd, 4th, 6th and 8th hours. We made subgroup analysis to show the effects of lipid loading on triglyceride levels in patients with and without fasting hypertriglyceridemia. We evaluated triglyceride levels and changes of triglyceride levels in percentages after lipid loading using a general linear model for repeated measures. Sample size analysis was performed. Baseline clinical, demographic and laboratory characteristics of both groups were similar. The peak triglyceride levels were seen at the 4th hour in both groups. Triglyceride levels were significantly increased after lipid-rich-breakfast loading compared to baseline levels in both groups (p<0.001) but these changes were not significant (p=0.279). In patients with elevated fasting triglyceride levels, the area under the plasma triglyceride concentration curve was significantly larger in CAD group than control group (334±103 vs. 233±58 mg/dl, p=0.02). Our data show that in patients who have a high fasting triglyceride level, high levels of PPTG may be related to CAD, however high PPTG levels are not related to CAD in patients with normal fasting levels of triglyceride.

Pulse oximetry in the evaluation of peripheral vascular disease.

PubMed

Jawahar, D; Rachamalla, H R; Rafalowski, A; Ilkhani, R; Bharathan, T; Anandarao, N

1997-08-01

The role of pulse oximetry in the evaluation of peripheral vascular disease (PVD) was investigated. In addition, the value of elevating the limb to improve the sensitivity of detection of PVD by the pulse oximeter was also determined. Pulse oximetry reading in the toes were obtained in 40 young, healthy volunteers and in 40 randomly selected patients referred to the vascular investigation laboratory over a period of two months. All 40 healthy volunteers had normal pulse oximetry readings. Normal pulse oximetry reading in the toes was defined as > 95% O2 Sat and +/-2 of finger pulse oximetry reading. In all 40 patients, pulse oximetry readings were either normal or not detected at all. Since there was no gradation in decrease in the pulse oximetry reading with severity of disease or with elevation of the patient's lower extremity, an absent or no reading was considered as an abnormal result from the test. The frequency of abnormal pulse oximetry readings increased significantly in groups with abnormal ankle-brachial pressure index (ABPI) and also varied significantly with elevation of the patients' lower limbs. In patients with no PVD detected by Doppler (ABPI > 0.9), pulse oximetry readings were normal in all. However, in patients with moderate PVD (ABPI, 0.5-0.9), 84% of the patients' lower limbs had normal pulse oximetry readings and 16% had an abnormal reading at baseline level (flat). An additional 12% of the lower limbs in this group had an abnormal reading on elevation of the limb to 12 inches. In patients with severe PVD (ABPI < 0.5), 54% of the patients' lower limbs had an abnormal reading at baseline and an additional 23% had an abnormal reading at elevation of the limb to 12 inches. In conclusion, pulse oximetry was not a sensitive test for detecting early PVD.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

PubMed

Schofield, P W; Marder, K; Dooneief, G; Jacobs, D M; Sano, M; Stern, Y

1997-05-01

The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Pre-treatment red blood cell distribution width provides prognostic information in multiple myeloma.

PubMed

Zhou, Di; Xu, Peipei; Peng, Miaoxin; Shao, Xiaoyan; Wang, Miao; Ouyang, Jian; Chen, Bing

2018-06-01

The red blood cell distribution width (RDW), a credible marker for abnormal erythropoiesis, has recently been studied as a prognostic factor in oncology, but its role in multiple myeloma (MM) hasn't been thoroughly investigated. We performed a retrospective study in 162 patients with multiple myeloma. Categorical parameters were analyzed using Pearson chi-squared test. The Mann-Whitney and Wilcoxon tests were used for group comparisons. Comparisons of repeated samples data were analyzed with the general linear model repeated-measures procedure. The Kaplan-Meier product-limit method was used to determine OS and PFS, and the differences were assessed by the log-rank test. High RDW baseline was significantly associated with indexes including haemoglobin, bone marrow plasma cell infiltration, and cytogenetics risk stratification. After chemotherapy, the overall response rate (ORR) decreased as RDW baseline increased. In 24 patients with high RDW baseline, it was revealed RDW value decreased when patients achieved complete remission (CR), but increased when the disease progressed. The normal-RDW baseline group showed both longer overall survival (OS) and progression-free survival (PFS) than the high-RDW baseline group. Our study suggests pre-treatment RDW level is a prognostic factor in MM and should be regarded as an important parameter for assessment of therapeutic efficiency. Copyright © 2018. Published by Elsevier B.V.

B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Syndrome.

PubMed

Verstappen, Gwenny M; Kroese, Frans G M; Meiners, Petra M; Corneth, Odilia B; Huitema, Minke G; Haacke, Erlin A; van der Vegt, Bert; Arends, Suzanne; Vissink, Arjan; Bootsma, Hendrika; Abdulahad, Wayel H

2017-01-01

To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS). Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed. In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21-producing and IL-17-producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index scores and serum IgG levels. B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.

Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

PubMed

Zick, Suzanna M; Turgeon, D Kim; Ren, Jianwei; Ruffin, Mack T; Wright, Benjamin D; Sen, Ananda; Djuric, Zora; Brenner, Dean E

2015-09-01

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk. © 2014 Wiley Periodicals, Inc.

Pilot Clinical Study of the Effects of Ginger Root Extract on Eicosanoids in Colonic Mucosa of Subjects at Increased Risk for Colorectal Cancer

PubMed Central

Zick, Suzanna M.; Turgeon, D. Kim; Ren, Jianwei; Ruffin, Mack T.; Wright, Benjamin D.; Sen, Ananda; Djuric, Zora; Brenner, Dean E.

2014-01-01

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxy-eicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk. PMID:24760534

Descriptive Statistics for Modern Test Score Distributions: Skewness, Kurtosis, Discreteness, and Ceiling Effects.

PubMed

Ho, Andrew D; Yu, Carol C

2015-06-01

Many statistical analyses benefit from the assumption that unconditional or conditional distributions are continuous and normal. More than 50 years ago in this journal, Lord and Cook chronicled departures from normality in educational tests, and Micerri similarly showed that the normality assumption is met rarely in educational and psychological practice. In this article, the authors extend these previous analyses to state-level educational test score distributions that are an increasingly common target of high-stakes analysis and interpretation. Among 504 scale-score and raw-score distributions from state testing programs from recent years, nonnormal distributions are common and are often associated with particular state programs. The authors explain how scaling procedures from item response theory lead to nonnormal distributions as well as unusual patterns of discreteness. The authors recommend that distributional descriptive statistics be calculated routinely to inform model selection for large-scale test score data, and they illustrate consequences of nonnormality using sensitivity studies that compare baseline results to those from normalized score scales.

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

PubMed

Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

2010-10-01

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.

Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication.

PubMed

Volkow, N D; Gillespie, H; Mullani, N; Tancredi, L; Grant, C; Valentine, A; Hollister, L

1996-05-31

Despite the widespread abuse of marijuana, knowledge about its effects in the human brain is limited. Brain glucose metabolism with and without delta 9 tetrahydrocannabinol (THC) (main psychoactive component of marijuana) was evaluated in eight normal subjects and eight chronic marijuana abusers with positron emission tomography. At baseline, marijuana abusers showed lower relative cerebellar metabolism than normal subjects. THC increased relative cerebellar metabolism in all subjects, but only abusers showed increases in orbitofrontal cortex, prefrontal cortex, and basal ganglia. Cerebellar metabolism during THC intoxication was significantly correlated with the subjective sense of intoxication. The decreased cerebellar metabolism in marijuana abusers at baseline could account for the motor deficits previously reported in these subjects. The activation of orbitofrontal cortex and basal ganglia by THC in the abusers but not in the normal subjects could underlie one of the mechanisms leading to the drive and the compulsion to self-administer the drug observed in addicted individuals.

Increased medial olivocochlear reflex strength in normal-hearing, noise-exposed humans

PubMed Central

2017-01-01

Research suggests that college-aged adults are vulnerable to tinnitus and hearing loss due to exposure to traumatic levels of noise on a regular basis. Recent human studies have associated exposure to high noise exposure background (NEB, i.e., routine noise exposure) with the reduced cochlear output and impaired speech processing ability in subjects with clinically normal hearing sensitivity. While the relationship between NEB and the functions of the auditory afferent neurons are studied in the literature, little is known about the effects of NEB on functioning of the auditory efferent system. The objective of the present study was to investigate the relationship between medial olivocochlear reflex (MOCR) strength and NEB in subjects with clinically normal hearing sensitivity. It was hypothesized that subjects with high NEB would exhibit reduced afferent input to the MOCR circuit which would subsequently lead to reduced strength of the MOCR. In normal-hearing listeners, the study examined (1) the association between NEB and baseline click-evoked otoacoustic emissions (CEOAEs) and (2) the association between NEB and MOCR strength. The MOCR was measured using CEOAEs evoked by 60 dB pSPL linear clicks in a contralateral acoustic stimulation (CAS)-off and CAS-on (a broadband noise at 60 dB SPL) condition. Participants with at least 6 dB signal-to-noise ratio (SNR) in the CAS-off and CAS-on conditions were included for analysis. A normalized CEOAE inhibition index was calculated to express MOCR strength in a percentage value. NEB was estimated using a validated questionnaire. The results showed that NEB was not associated with the baseline CEOAE amplitude (r = -0.112, p = 0.586). Contrary to the hypothesis, MOCR strength was positively correlated with NEB (r = 0.557, p = 0.003). NEB remained a significant predictor of MOCR strength (β = 2.98, t(19) = 3.474, p = 0.003) after the unstandardized coefficient was adjusted to control for effects of smoking, sound level tolerance (SLT) and tinnitus. These data provide evidence that MOCR strength is associated with NEB. The functional significance of increased MOCR strength is discussed. PMID:28886123

Effects of phosphate binders in moderate CKD.

PubMed

Block, Geoffrey A; Wheeler, David C; Persky, Martha S; Kestenbaum, Bryan; Ketteler, Markus; Spiegel, David M; Allison, Matthew A; Asplin, John; Smits, Gerard; Hoofnagle, Andrew N; Kooienga, Laura; Thadhani, Ravi; Mannstadt, Michael; Wolf, Myles; Chertow, Glenn M

2012-08-01

Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.

Bimatoprost sustained-release intracameral implant reduces episcleral venous pressure in dogs.

PubMed

Lee, Susan S; Burke, James; Shen, Jie; Almazan, Alexandra; Orilla, Werhner; Hughes, Patrick; Zhang, Jane; Li, Huajiang; Struble, Craig; Miller, Paul E; Robinson, Michael R

2018-02-19

To determine the effect of a bimatoprost sustained-release intracameral implant (Bimatoprost SR) on episcleral venous pressure (EVP) in normal dogs. Normotensive beagle dogs were randomized to receive Bimatoprost SR 30 μg (n = 7) or sham injection (needle insertion only, n = 7) in one eye on day 1. EVP was measured with an episcleral venomanometer through day 65. Episcleral aqueous outflow vessels were identified using fluorescence imaging following intracameral injection of indocyanine green in one additional animal. A separate cohort of dogs that had been trained for conscious intraocular pressure (IOP) measurements received Bimatoprost SR 30 μg (n = 8) in one eye; IOP was evaluated through day 66. Baseline mean EVP was 10.0 mmHg in the Bimatoprost SR group and 10.4 mmHg in the sham group. Eyes treated with Bimatoprost SR exhibited a transient increase in mean EVP that peaked at day 8, followed by a decrease to levels below baseline. From day 29 to day 65, the change in mean EVP from baseline ranged from -2.4 to -3.9 mmHg (P < 0.05 vs. sham). Baseline mean IOP in eyes treated with Bimatoprost SR was 14.9 mmHg, and a steady IOP reduction was maintained through day 66. Bimatoprost SR-treated eyes exhibited a selective, sustained dilation of aqueous outflow vessels that was not observed in sham-treated eyes. In normal dogs, Bimatoprost SR was associated with a transient increase in EVP followed by a sustained decrease. Changes in EVP were accompanied by a sustained dilation of aqueous outflow vessels. © 2018 Allergan. Veterinary Opthalmology published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Ophthalmologists.

Baseline neuropsychological profile and cognitive response to cerebrospinal fluid shunting for idiopathic normal pressure hydrocephalus.

PubMed

Thomas, George; McGirt, Matthew J; Woodworth, Graeme; Heidler, Jennifer; Rigamonti, Daniele; Hillis, Argye E; Williams, Michael A

2005-01-01

To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure monitoring and positive response in any of the NPH symptoms following large volume CSF drainage. Forty-two INPH patients underwent neurocognitive testing and Folstein Mini-Mental State Examination (MMSE) prior to shunting. Neurocognitive testing or MMSEwere performed at least 3 months after shunt insertion. Significant improvement in a neurocognitive subtest was defined as improvement by one standard deviation (1 SD) for the patient's age, sex and education level. Significant improvement in overall neurocognitive outcome was defined as a 4-point improvement in MMSE or improvement by 1 SD in 50% of the administered neurocognitive subtests. Nonparametric tests were used to assess changes. Predictors of outcome were assessed via logistic regression analysis. Twenty-two patients (52.3%) showed overall neurocognitive improvement, and significant improvement was seen in tests of verbal memory and psychomotor speed. Predictive analysis showed that patients scoring more than 1 SD below mean at baseline on verbal memory immediate recall were fourfold less likely to show overall cognitive improvement, and sixfold less likely if also associated with visuoconstructional deficit or executive dysfunction. Verbal memory scores at baseline were higher in patients who showed overall cognitive improvement. Shunting INPH patients on the basis of CSF pressure monitoring and drainage response shows a significant rate of cognitive improvement, and baseline neurocognitive test scores may distinguish patients likely to respond to shunt surgery from those who will not. Copyright (c) 2005 S. Karger AG, Basel.

The importance of archiving baseline wilderness data

Treesearch

David N. Cole

2007-01-01

Baseline wilderness data are of considerable importance for several reasons. One of the primary values of wilderness is as a reference that contrasts with those lands where humans dominate the landscape. Leopold (1941) called wilderness "a base-datum of normality, a picture of how healthy land maintains itself." To realize this value, baseline data on...

The effect of balneotherapy on antioxidant, inflammatory, and metabolic indices in patients with cardiovascular risk factors (hypertension and obesity)--a randomised, controlled, follow-up study.

PubMed

Oláh, Mihály; Koncz, Ágnes; Fehér, Judit; Kálmánczhey, Judit; Oláh, Csaba; Nagy, György; Bender, Tamás

2011-11-01

The primary objective of our study was to explore the changes of antioxidant, inflammatory, and metabolic parameters in obese and hypertension people patients during balneotherapy and to evaluate the safety of balneotherapy in these participants. Following randomisation, 22 obese and 20 hypertensive patients underwent balneotherapy with thermal water of 38°C temperature, in 15 sessions of 30 minutes. An additional 22 obese and 20 hypertensive patients served as controls. Antioxidant, inflammatory, and metabolic parameters were determined at baseline, as well as post-treatment and at the end of follow-up (at 15 weeks). As regards changes observed in hypertensive patients subjected to balneotherapy, differences could be detected between baseline and post-treatment albumin and haemoglobin A(1c) levels only; however, these were no longer significant after 3 months. Although the difference between transferrin levels determined at the end of balneotherapy and 3 months later was significant, it remained within the physiological range, as well as it was accompanied by normal serum iron level and therefore, it was considered irrelevant. C-reactive protein levels of balneotherapy patients decreased significantly after treatment. In obese patients, haemoglobin A(1c) level decreased after balneotherapy, but this difference was not observed either after 3 months. Similarly, both transferrin and C-reactive protein levels changed from baseline, but not between groups. This study contributes important information regarding the safety of balneotherapy in hypertensive and obese diabetics by showing no alterations of antioxidant, inflammatory, or metabolic indices. The findings of this study confirm that balneotherapy is not contraindicated for hypertensive or obese patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Functional status scale in children with traumatic brain injury: a prospective cohort study

PubMed Central

Bennett, Tellen D.; Dixon, Rebecca R.; Kartchner, Cory; DeWitt, Peter E.; Sierra, Yamila; Ladell, Diane; Kempe, Allison; Runyan, Desmond K.; Dean, J. Michael; Keenan, Heather T.

2016-01-01

Objective In children with traumatic brain injury (TBI), 1) to describe the hospital discharge functional outcome and change from baseline function using the Functional Status Scale (FSS) and 2) to determine any associations between discharge FSS and age, injury mechanism, neurologic exam, imaging, and other predictors of outcome. Design Prospective observational cohort study, May 2013 to November 2015. Setting Two U.S. children's hospitals designated as American College of Surgeons level 1 Pediatric Trauma Centers. Patients Children < 18 years old admitted to an intensive care unit (ICU) with acute TBI and either a surgical or critical care intervention within the first 24 hours or in-hospital mortality. Interventions None Measurements and Main Results The primary outcome was hospital discharge FSS. Most, 133/196 (68%), had severe TBI (admission GCS 3–8). Overall hospital mortality was 14%; 20% among those with severe TBI. Hospital discharge FSS had an inverse relationship with GCS: for each increase in admission GCS by 1, the discharge FSS decreased by 0.5 (95% CI: 0.7 to 0.3). Baseline FSS was collected at one site, N = 75. At that site, nearly all (61/62) of the survivors had normal or near-normal (≤ 7) pre-injury FSS. More than one-third, 23/62 (37%), of survivors had new morbidity at hospital discharge (increase in FSS ≥ 3). Among children with severe TBI who had baseline FSS collected, 21/41 (51%) of survivors had new morbidity at hospital discharge. The mean change in FSS from baseline to hospital discharge was 3.9 ± 4.9 overall and 5.2 ± 5.4 in children with severe TBI. Conclusions More than one-third of survivors, and approximately half of survivors with severe TBI, will have new morbidity. Hospital discharge FSS, change from baseline FSS, and new morbidity acquisition can be used as outcome measures for hospital-based care process improvement initiatives and interventional studies of children with TBI. PMID:27753754

Effects of oral amino acid supplementation on myocardial function in patients with type 2 diabetes mellitus.

PubMed

Scognamiglio, Roldano; Negut, Christian; Piccolotto, Roberto; Dioguardi, Francesco Saverio; Tiengo, Antonio; Avogaro, Angelo

2004-06-01

Diabetes mellitus is associated with an increased rate of cardiac amino acid catabolism that could interfere with cardiac function. We assessed the effects of an oral amino acids mixture (AAM) on myocardial function in patients with type 2 diabetes mellitus (DM2). We studied 65 consecutive patients with DM2 who had normal resting left ventricular ejection fraction (LVEF) and did not have obstructive coronary artery disease (CAD). After baseline evaluations, patients were randomized to receive, in a single-blinded fashion, AAM (12 grams/day) or placebo for 12 weeks, after which, treatment was crossed over for another similar period. At baseline and at the end of each treatment, 2-dimensional ecocardiography at rest and during isometric exercise (handgrip) was performed, as were biochemical assays. Twenty adults, matched for age, sex, and body mass index served as control subjects. At baseline and during AAM or placebo treatment, resting left ventricular dimensions and LVEF in patients with DM2 did not differ from those of control subjects. In patients with DM2, at baseline and during placebo treatment, peak handgrip LVEF decreased significantly in comparison with the resting value (63% +/- 9% vs 56% +/- 9%, P <.001; and 62% +/- 6% vs 55% +/- 8%, P <.001). During AAM treatment, peak handgrip LVEF did not differ from resting value (66% +/- 11% vs 64% +/- 9%, P = not significant). Thus, exercise LVEF was higher during AAM treatment than both baseline and placebo treatment (66% +/- 11% vs 56% +/- 9% and vs 55% +/- 8%, P <.001). In contrast to placebo treatment, after the AAM supply, a decreased glycated hemoglobin level was observed (7.0% +/- 1.3% vs 7.6% +/- 1.8%, P <.05). Myocardial dysfunction is easily inducible with isometric exercise in patients with DM2 who have normal resting LV function and do not have CAD. An increased amino acid supply prevents this phenomenon and improves metabolic control.

Stability of the Medial Olivocochlear Reflex as Measured by Distortion Product Otoacoustic Emissions

PubMed Central

Abdala, Carolina

2015-01-01

Purpose The purpose of this study was to assess the repeatability of a fine-resolution, distortion product otoacoustic emission (DPOAE)–based assay of the medial olivocochlear (MOC) reflex in normal-hearing adults. Method Data were collected during 36 test sessions from 4 normal-hearing adults to assess short-term stability and 5 normal-hearing adults to assess long-term stability. DPOAE level and phase measurements were recorded with and without contralateral acoustic stimulation. MOC reflex indices were computed by (a) noting contralateral acoustic stimulation-induced changes in DPOAE level (both absolute and normalized) at fine-structure peaks, (b) recording the effect as a vector difference, and (c) separating DPOAE components and considering a component-specific metric. Results Analyses indicated good repeatability of all indices of the MOC reflex in most frequency ranges. Short- and long-term repeatability were generally comparable. Indices normalized to a subject's own baseline fared best, showing strong short- and long-term stability across all frequency intervals. Conclusions These results suggest that fine-resolution DPOAE-based measures of the MOC reflex measured at strategic frequencies are stable, and natural variance from day-to-day or week-to-week durations is small enough to detect between-group differences and possibly to monitor intervention-related success. However, this is an empirical question that must be directly tested to confirm its utility. PMID:25320951

Fine Motor Skills of Children With Amblyopia Improve Following Binocular Treatment.

PubMed

Webber, Ann L; Wood, Joanne M; Thompson, Benjamin

2016-09-01

The purpose of this study was to determine whether reduced fine motor skills in children with amblyopia improve after binocular treatment and whether improvements are sustained once treatment has ceased. Fine motor skills (FMS [Bruininks-Oseretsky Test of Motor Proficiency]), visual acuity (VA [Early Treatment of Diabetic Retinopathy Study chart]) and level of binocular function (BF [Randot preschool stereoacuity and Worth 4 Dot]) were measured in children with amblyopia (n = 20; age: 8.5 ± 1.3 years; 11 anisometropic; 5 strabismic; 4 mixed) and in a group of visually normal children (n = 10; age: 9.63 ± 1.6 years). Eighteen children with amblyopia subsequently completed 5 weeks of binocular treatment provided by home-based dichoptic iPod game play. FMS, VA, and BF were retested at the end of treatment and 12 weeks after treatment cessation. All visually normal children also completed FMS measurements at baseline and 5 weeks later to assess test-retest variability of the FMS scores. Prior to treatment, FMS scores in children with amblyopia were poorer than those in children with normal vision (P < 0.05). In the children with amblyopia, binocular treatment significantly improved FMS scores (P < 0.05). Better baseline amblyopic eye VA and BF were associated with greater improvements in FMS score. Improvements were still evident at 12 weeks post treatment. In the visually normal children, FMS scores remained stable across the two test sessions. Binocular treatment provided by dichoptic iPod game play improved FMS performance in children with amblyopia, particularly in those with less severe amblyopia. Improvements were maintained at 3 months following cessation of treatment.

Factors Associated With Changes in Magnesium Levels in Asymptomatic Neonates: A Longitudinal Analysis.

PubMed

Mehta, Yogesh; Shitole, Charudatta; Setia, Maninder Singh

2016-02-01

Neonates and infants with hypomagnesemia present with seizures and psychomotor delay. The present study evaluated the changes in magnesium (Mg) levels and factors associated with these in the first three days of life. We monitored 50 clinically asymptomatic neonates; they were not given any magnesium supplements even if they had hypomagnesemia at baseline. The variables analysed were: serum Mg; gestational age; birth weight; length; and the ponderal index. We used random effects (RE) models for longitudinal analysis of these data. The mean standard deviation (SD) gestational age was 36.3 (3.6) weeks and the mean (SD) weight was 2604.2 (754.4) grams. About 31% of the neonates had hypomagnesemia (< 1.6 mg/dL) on day one; however, all had normal magnesium levels by day three of life (P < 0.001). At birth, after adjusting for intrauterine growth retardation status (IUGR), serum Mg levels were lower by 0.0097 mg/dL (95% CI: -0.019 to -0.0003) per 100 grams increase in weight of the neonate. After adjusting for IUGR status, the mean increase in the serum Mg levels was 0.14 mg/dL (95% confidence intervals [CI]: 0.10 to 0.18) per day. The per-day increase in magnesium levels was significantly higher in low birth weight babies (0.10, 95% CI: 0.01 to 0.18) compared with normal birth weight babies. Asymptomatic neonates may have a high prevalence of hypomagnesemia; however, the levels become normal without any magnesium supplementation. Even though regular monitoring of magnesium levels is useful, no supplements are required - particularly in clinically asymptomatic neonates.

Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial

PubMed Central

Liu, Gang; Liang, Liming; Bray, George A.; Qi, Lu; Hu, Frank B.; Rood, Jennifer; Sacks, Frank M.; Sun, Qi

2017-01-01

Background The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. Objectives To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Subjects/Methods Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year POUNDS LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine [T3], free thyroxine [T4], total T3, total T4, and thyroid stimulating hormone [TSH]), anthropometric measurements, and biochemical parameters were assessed at baseline, 6 months, and 24 months. Results Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6–24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index, and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss ± standard error was −3.87±0.9 vs −5.39±0.9 kg for free T3 (P trend=0.02) and −4.09±0.9 vs −5.88±0.9 kg for free T4 (P trend=0.004). The thyroid hormones did not predict weight regain in 6–24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides, and leptin at 6 months and 24 months (all P<0.05). Conclusions In this diet-induced weight-loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight-loss diets. PMID:28138133

Effect of the speed of a single-channel dynamic range compressor on intelligibility in a competing speech task

NASA Astrophysics Data System (ADS)

Stone, Michael A.; Moore, Brian C. J.

2003-08-01

Using a ``noise-vocoder'' cochlear implant simulator [Shannon et al., Science 270, 303-304 (1995)], the effect of the speed of dynamic range compression on speech intelligibility was assessed, using normal-hearing subjects. The target speech had a level 5 dB above that of the competing speech. Initially, baseline performance was measured with no compression active, using between 4 and 16 processing channels. Then, performance was measured using a fast-acting compressor and a slow-acting compressor, each operating prior to the vocoder simulation. The fast system produced significant gain variation over syllabic timescales. The slow system produced significant gain variation only over the timescale of sentences. With no compression active, about six channels were necessary to achieve 50% correct identification of words in sentences. Sixteen channels produced near-maximum performance. Slow-acting compression produced no significant degradation relative to the baseline. However, fast-acting compression consistently reduced performance relative to that for the baseline, over a wide range of performance levels. It is suggested that fast-acting compression degrades performance for two reasons: (1) because it introduces correlated fluctuations in amplitude in different frequency bands, which tends to produce perceptual fusion of the target and background sounds and (2) because it reduces amplitude modulation depth and intensity contrasts.

Post-exertion neurocognitive test failure among student-athletes following concussion.

PubMed

McGrath, Neal; Dinn, Wayne M; Collins, Michael W; Lovell, Mark R; Elbin, R J; Kontos, Anthony P

2013-01-01

The purpose of the present study was to examine post-exertion (PE) neurocognitive performance among student-athletes following concussion who were asymptomatic and returned to baseline normal neurocognitive test levels at rest. This study examined the neurocognitive performance of a sub-set of student-athletes who 'failed' to perform at baseline levels of neurocognitive function, i.e. exhibited downward reliable change index (RCI) alterations following a moderate exertional protocol during recovery from concussion. A retrospective records review was carried out of Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) and neuropsychological consultation data among athletes with sports-related concussion from a network of 22 schools and one junior hockey programme. Fifty-four student-athletes met inclusion criteria and participated in the study. A total of 27.7% of concussed student-athletes who were symptom-free and returned to baseline on ImPACT at rest (i.e. no longer demonstrated performance deficits on neurocognitive tests) exhibited cognitive decline following moderate physical exertion. The PE cognitive changes were not simply general performance effects, but significant changes in memory ability in the presence of intact processing speed functions. The PE-Pass and PE-Fail groups did not, however, differ on post-concussive symptoms or concussion history. Clinicians' return-to-play evaluation protocols should include post-exertional computerized neurocognitive testing.

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.

PubMed

Hendrie, Hugh C; Hake, Ann; Lane, Kathleen; Purnell, Christianna; Unverzagt, Frederick; Smith-Gamble, Valerie; Murrell, Jill; Ogunniyi, Adesola; Baiyewu, Olusegun; Callahan, Chris; Saykin, Andrew; Taylor, Stanley; Hall, Kathleen; Gao, Su

2015-08-07

To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. Indianapolis, Indiana. From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. Incident dementia and incident AD. After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.

Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges.

PubMed

Dua, Shelley; Dowey, James; Foley, Loraine; Islam, Sabita; King, Yvonne; Ewan, Pamela; Clark, Andrew T

2018-02-27

Serum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown. The objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction. Characterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff. Tryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78). Serum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Risk factors associated with the development of overt nephropathy in type 2 diabetes patients: A 12 years observational study

PubMed Central

Viswanathan, Vijay; Tilak, Priyanka; Kumpatla, Satyavani

2012-01-01

Background & objectives: Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal disease in developing countries. Early detection and risk reduction measures can prevent DN. The aim of the study was to determine the risk factors for the development of proteinuria over a period of 12 years of follow up in normoalbuminuric type 2 diabetes patients attending a specialized centre. Methods: Of the 2630 type 2 diabetes subjects newly registered in 1996, 152 (M:F;92:60) normoalbuminuric subjects had baseline and subsequent measurements of anthropometric, haemodynamic and biochemical details spanning 12 years. The subjects were divided into 2 groups based on the renal status during follow up visits. Group 1 (non-progressors) had persistent normoalbuminuria and group 2 (progressors) had persistent proteinuria. Presence of other diabetic complications during follow up and details on antidiabetic and antihypertensive agents were noted. Results: During median follow up of 11 years in subjects with normal renal function at baseline, 44.1 per cent developed proteinuria at follow up. Glucose levels, HbA1c, systolic blood pressure (SBP), triglycerides, and urea levels were significantly higher at baseline among progressors than non-progressors. Progressors had a longer duration of diabetes and significant fall in estimated glomerular filtration rate (eGFR) levels at follow up. In Cox's regression analysis, baseline age, duration of diabetes, baseline HbA1c and mean values of HbA1c, triglycerides, SBP and presence of retinopathy showed significant association with the development of macroalbuminuria. Interpretation & conclusions: Type 2 diabetes patients with uncontrolled diabetes and increase in blood pressure are at high risk of developing nephropathy. Age, long duration of diabetes, elevated BP, poor glycaemic control and presence of retinopathy were significantly associated with the progression of diabetic nephropathy. PMID:22885263

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC. Copyright © 2016 Pantarhei Bioscience. Published by Elsevier Inc. All rights reserved.

High-Dose Intramuscular Vitamin D Provides Long-Lasting Moderate Increases in Serum 25-Hydroxvitamin D Levels and Shorter-Term Changes in Plasma Calcium.

PubMed

Gorman, Shelley; Zafirau, Mark Zafir; Lim, Ee Mun; Clarke, Michael W; Dhamrait, Gursimran; Fleury, Naomi; Walsh, John P; Kaufmann, Martin; Jones, Glenville; Lucas, Robyn M

2017-09-01

The best management of vitamin D deficiency, defined as a 25-hydroxyvitamin D [(25(OH)D] level <50 nM, is unclear. Intramuscular (IM) injection of a large bolus of vitamin D (≥100 000 IU) is used, but its safety is uncertain. In 10 adults given an IM injection of 600 000IU vitamin D3, we measured at baseline and at 1, 2, 3, and 4 weeks postinjection the serum levels of vitamin D3, 25(OH)D3, 25(OH)D2, total 25(OH)D, 3-epi-25(OH)D3, and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] using a standardized LC with tandem MS (MS/MS) assay; serum levels of 25(OH)D using the Abbott ARCHITECT i2000 immunoassay; and markers of bone metabolism. Bone markers and 25(OH)D (immunoassay) were remeasured at 24 weeks. All participants had baseline total 25(OH)D levels >50 nM. Serum 25(OH)D levels increased at 3, 4, and 24 weeks postinjection, peaking at 4 weeks [mean ± SEM of 126 ± 7.9 nM (immunoassay) and 100 ± 5.5 nM (LC-MS/MS)] but generally remained <125 nM, the upper limit recommended by the U.S. Institute of Medicine. Serum 24,25(OH)2D3 levels increased at 3 and 4 weeks postinjection. Serum ionized calcium levels were higher than baseline at 1, 3, and 4 weeks postinjection but remained within the clinically normal range. Other biochemical parameters, including other vitamin D metabolites, plasma alkaline phosphatase, and parathyroid hormone levels, were unchanged. IM injection of a large bolus of vitamin D effectively increases serum 25(OH)D levels without evidence of metabolic abnormality.

Basal CD34+ Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony-Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study.

PubMed

Martino, Massimo; Gori, Mercedes; Pitino, Annalisa; Gentile, Massimo; Dattola, Antonia; Pontari, Antonella; Vigna, Ernesto; Moscato, Tiziana; Recchia, Anna Grazia; Barilla', Santina; Tripepi, Giovanni; Morabito, Fortunato

2017-07-01

A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/µL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/µL to 1 cells/µL predicts a median value of 50 cells/µL on day 5; a value of 2 cells/µL predicts a median value of 70.7 cells/µL; a value of 3 cells/µL to 4 cells/µL predicts a median value of 91.3 cells/µL, and a value ≥ 5 predicts a median value of 112 cells/µL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

PubMed

Cariani, E; Capucci, M; Micheletti, M; Spalenza, F; Zanella, I; Albertini, A; Rossi, G

2003-06-01

Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

Quantifying Normal Craniofacial Form and Baseline Craniofacial Asymmetry in the Pediatric Population.

PubMed

Cho, Min-Jeong; Hallac, Rami R; Ramesh, Jananie; Seaward, James R; Hermann, Nuno V; Darvann, Tron A; Lipira, Angelo; Kane, Alex A

2018-03-01

Restoring craniofacial symmetry is an important objective in the treatment of many craniofacial conditions. Normal form has been measured using anthropometry, cephalometry, and photography, yet all of these modalities have drawbacks. In this study, the authors define normal pediatric craniofacial form and craniofacial asymmetry using stereophotogrammetric images, which capture a densely sampled set of points on the form. After institutional review board approval, normal, healthy children (n = 533) with no known craniofacial abnormalities were recruited at well-child visits to undergo full head stereophotogrammetric imaging. The children's ages ranged from 0 to 18 years. A symmetric three-dimensional template was registered and scaled to each individual scan using 25 manually placed landmarks. The template was deformed to each subject's three-dimensional scan using a thin-plate spline algorithm and closest point matching. Age-based normal facial models were derived. Mean facial asymmetry and statistical characteristics of the population were calculated. The mean head asymmetry across all pediatric subjects was 1.5 ± 0.5 mm (range, 0.46 to 4.78 mm), and the mean facial asymmetry was 1.2 ± 0.6 mm (range, 0.4 to 5.4 mm). There were no significant differences in the mean head or facial asymmetry with age, sex, or race. Understanding the "normal" form and baseline distribution of asymmetry is an important anthropomorphic foundation. The authors present a method to quantify normal craniofacial form and baseline asymmetry in a large pediatric sample. The authors found that the normal pediatric craniofacial form is asymmetric, and does not change in magnitude with age, sex, or race.

Environmental enrichment of brown capuchins (Cebus apella): Behavioral and plasma and fecal cortisol measures of effectiveness

USGS Publications Warehouse

Boinski, S.; Swing, S.P.; Gross, T.S.; Davis, J.K.

1999-01-01

No consensus exists about the quantity and variety of environmental enrichment needed to achieve an acceptable level of psychological well-being among singly housed primates. Behavioral and plasma and fecal cortisol measures were used to evaluate the effectiveness of four levels of toy and foraging enrichment provided to eight wild-caught, singly housed adult male brown capuchins (Cebus apella). The 16-week-long study comprised six conditions and began with a 4-week-long preexperimental and ended with a 4-week-long postexperimental period during which the subjects were maintained at baseline enrichment levels. During the intervening 8 weeks, the subjects were randomly assigned to a sequence of four 2-week-long experimental conditions: control (baseline conditions), toy (the addition of two plastic toys to each cage), box (access to a foraging box with food treats hidden within crushed alfalfa), and box and toy (the addition of two plastic toys and access to a foraging box). Behavioral responses to changes in enrichment were rapid and extensive. Within-subject repeated-measure ANOVAs with planned post hoc contrasts identified highly significant reductions in abnormal and undesirable behaviors (and increases in normal behaviors) as the level of enrichment increased from control to toy to box to box and toy. No significant behavioral differences were found between the control and pre- and postexperimental conditions. Plasma and fecal cortisol measures revealed a different response to changing enrichment levels. Repeated-measure ANOVA models found significant changes in both these measures across the six conditions. The planned post hoc analyses, however, while finding dramatic increases in cortisol titers in both the pre- and postexperimental conditions relative to the control condition, did not distinguish cortisol responses among the four enrichment levels. Linear regressions among weekly group means in behavioral and cortisol measures (n = 16) found that plasma cortisol was significantly predicted by the proportions of both normal and abnormal behaviors; as the proportion of normal behaviors increased, the plasma cortisol measures decreased. Plasma cortisol weekly group means were also significantly and positively predicted by fecal cortisol weekly group means, but no behavioral measure significantly predicted fecal cortisol weekly group means. In sum, these findings argue strongly that access to a variety of toy and foraging enrichment positively affects behavioral and physiological responses to stress and enhances psychological well-being in singly housed brown capuchins.

Environmental enrichment of brown capuchins (Cebus apella): behavioral and plasma and fecal cortisol measures of effectiveness.

PubMed

Boinski, S; Swing, S P; Gross, T S; Davis, J K

1999-01-01

No consensus exists about the quantity and variety of environmental enrichment needed to achieve an acceptable level of psychological well-being among singly housed primates. Behavioral and plasma and fecal cortisol measures were used to evaluate the effectiveness of four levels of toy and foraging enrichment provided to eight wild-caught, singly housed adult male brown capuchins (Cebus apella). The 16-week-long study comprised six conditions and began with a 4-week-long preexperimental and ended with a 4-week-long postexperimental period during which the subjects were maintained at baseline enrichment levels. During the intervening 8 weeks, the subjects were randomly assigned to a sequence of four 2-week-long experimental conditions: control (baseline conditions), toy (the addition of two plastic toys to each cage), box (access to a foraging box with food treats hidden within crushed alfalfa), and box & toy (the addition of two plastic toys and access to a foraging box). Behavioral responses to changes in enrichment were rapid and extensive. Within-subject repeated-measure ANOVAs with planned post hoc contrasts identified highly significant reductions in abnormal and undesirable behaviors (and increases in normal behaviors) as the level of enrichment increased from control to toy to box to box & toy. No significant behavioral differences were found between the control and pre- and postexperimental conditions. Plasma and fecal cortisol measures revealed a different response to changing enrichment levels. Repeated-measure ANOVA models found significant changes in both these measures across the six conditions. The planned post hoc analyses, however, while finding dramatic increases in cortisol titers in both the pre- and postexperimental conditions relative to the control condition, did not distinguish cortisol responses among the four enrichment levels. Linear regressions among weekly group means in behavioral and cortisol measures (n=16) found that plasma cortisol was significantly predicted by the proportions of both normal and abnormal behaviors; as the proportion of normal behaviors increased, the plasma cortisol measures decreased. Plasma cortisol weekly group means were also significantly and positively predicted by fecal cortisol weekly group means, but no behavioral measure significantly predicted fecal cortisol weekly group means. In sum, these findings argue strongly that access to a variety of toy and foraging enrichment positively affects behavioral and physiological responses to stress and enhances psychological well-being in singly housed brown capuchins.

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

PubMed

Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

2018-02-12

Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

Antitissue Transglutaminase Normalization Postdiagnosis in Children With Celiac Disease.

PubMed

Isaac, Daniela Migliarese; Rajani, Seema; Yaskina, Maryna; Huynh, Hien Q; Turner, Justine M

2017-08-01

Limited pediatric data exist examining the trend and predictors of antitissue transglutaminase (atTG) normalization over time in children with celiac disease (CD). We aimed to evaluate time to normalization of atTG in children after CD diagnosis, and to assess for independent predictors affecting this duration. A retrospective chart review was completed in pediatric patients with CD diagnosed from 2007 to 2014 at the Stollery Children's Hospital Celiac Clinic (Edmonton, Alberta, Canada). The clinical predictors assessed for impact on time to atTG normalization were initial atTG, Marsh score at diagnosis, gluten-free diet compliance (GFDC), age at diagnosis, sex, ethnicity, medical comorbidities, and family history of CD. Kaplan-Meier survival analysis was completed to assess time to atTG normalization, and Cox regression to assess for independent predictors of this time. A total of 487 patients met inclusion criteria. Approximately 80.5% of patients normalized atTG levels. Median normalization time was 407 days for all patients (95% confidence interval [CI: 361-453]), and 364 days for gluten-free diet compliant patients (95% CI [335-393]). Type 1 diabetes mellitus (T1DM) patients took significantly longer to normalize at 1204 days (95% CI [199-2209], P < 0.001). Cox regression demonstrated T1DM (hazard ratio = 0.36 [0.24-0.55], P < 0.001) and higher baseline atTG (hazard ratio = 0.52 [0.43-0.63], P < 0.001) were significant predictors of longer atTG normalization time. GFDC was a significant predictor of earlier normalization (OR = 13.91 [7.86-24.62], P < 0.001). GFDC and lower atTG at diagnosis are predictors of earlier normalization. Patients with T1DM are less likely to normalize atTG levels, with longer normalization time. Additional research and education for higher-risk populations are needed.

Uncoupling oxidative phosphorylation with 2,4-dinitrophenol promotes development of the adhesion phenotype.

PubMed

Shavell, Valerie I; Fletcher, Nicole M; Jiang, Zhong L; Saed, Ghassan M; Diamond, Michael P

2012-03-01

To determine the effect of uncoupling oxidative phosphorylation with 2,4-dinitrophenol (DNP) on adhesion phenotype development. Prospective experimental study. Academic medical center. Women undergoing laparotomy for pelvic pain from whom normal peritoneum and adhesions were excised to create primary cultures of normal peritoneal and adhesion fibroblasts. Treatment of normal peritoneal and adhesion fibroblasts isolated from the same patient(s) with or without 0.2 mM DNP for 24 hours. Evaluation of adhesion phenotype markers type I collagen, vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF)-1α. In agreement with prior findings, adhesion fibroblasts exhibited significantly higher basal levels of type I collagen, VEGF, and HIF-1α compared with normal peritoneal fibroblasts. Treatment of normal peritoneal fibroblasts with DNP resulted in significant increases in type I collagen (10.2 ± 1.4 vs. 18.4 ± 1.9 fg/μg RNA) and VEGF (8.2 ± 1.1 vs. 13.7 ± 0.4 fg/μg RNA) over baseline. HIF-1α levels did not increase when normal peritoneal fibroblasts were treated with DNP. The adhesion phenotype, which is normally expressed in response to hypoxia, is reproduced in a normoxic environment by uncoupling oxidative phosphorylation with DNP, as evidenced by an increase in type I collagen and VEGF. Acquisition of the adhesion phenotype was via a mechanism distinct from up-regulation of HIF-1α. These observations are consistent with the hypothesis that the adhesion phenotype represents a state of intracellular metabolic depletion. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

PubMed Central

Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

2016-01-01

Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

The Whole-Brain "Global" Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism.

PubMed

Thompson, Garth J; Riedl, Valentin; Grimmer, Timo; Drzezga, Alexander; Herman, Peter; Hyder, Fahmeed

2016-07-01

The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI "nuisance signals" were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a "nuisance signal," also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states.

Comparison of demons deformable registration-based methods for texture analysis of serial thoracic CT scans

NASA Astrophysics Data System (ADS)

Cunliffe, Alexandra R.; Al-Hallaq, Hania A.; Fei, Xianhan M.; Tuohy, Rachel E.; Armato, Samuel G.

2013-02-01

To determine how 19 image texture features may be altered by three image registration methods, "normal" baseline and follow-up computed tomography (CT) scans from 27 patients were analyzed. Nineteen texture feature values were calculated in over 1,000 32x32-pixel regions of interest (ROIs) randomly placed in each baseline scan. All three methods used demons registration to map baseline scan ROIs to anatomically matched locations in the corresponding transformed follow-up scan. For the first method, the follow-up scan transformation was subsampled to achieve a voxel size identical to that of the baseline scan. For the second method, the follow-up scan was transformed through affine registration to achieve global alignment with the baseline scan. For the third method, the follow-up scan was directly deformed to the baseline scan using demons deformable registration. Feature values in matched ROIs were compared using Bland- Altman 95% limits of agreement. For each feature, the range spanned by the 95% limits was normalized to the mean feature value to obtain the normalized range of agreement, nRoA. Wilcoxon signed-rank tests were used to compare nRoA values across features for the three methods. Significance for individual tests was adjusted using the Bonferroni method. nRoA was significantly smaller for affine-registered scans than for the resampled scans (p=0.003), indicating lower feature value variability between baseline and follow-up scan ROIs using this method. For both of these methods, however, nRoA was significantly higher than when feature values were calculated directly on demons-deformed followup scans (p<0.001). Across features and methods, nRoA values remained below 26%.

Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Isaka, Y.; Kimura, K.; Etani, H.

The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mgmore » tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively.« less

Characterization of liver function parameter alterations after transjugular intrahepatic portosystemic shunt creation and association with early mortality.

PubMed

Casadaban, Leigh C; Parvinian, Ahmad; Couture, Patrick M; Minocha, Jeet; Knuttinen, M Grace; Bui, James T; Gaba, Ron C

2014-12-01

The purpose of this article is to characterize the temporal evolution and clinical impact of laboratory liver function parameters after transjugular intrahepatic portosystemic shunt (TIPS) creation. In this single-institution retrospective study, 157 patients (98 men and 59 women; median age, 55 years) underwent TIPS between 2000 and 2012 and had 1-month hepatobiliary laboratory follow-up. Medical record review was used to compare baseline, peak, and low bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, and international normalized ratio (INR) levels within 30 days after TIPS in surviving and dying patients to assess laboratory responses to shunt creation. TIPSs were created with a hemodynamic success rate of 98%, with median pressure gradient reduction of 13 mm Hg. Ninety-day mortality was 21%. Hepatobiliary laboratory values showed significant increases in the days after TIPS compared with baseline levels (bilirubin, 1.6 vs 3.5 mg/dL; AST, 49 vs 149 U/L; ALT, 26 vs 90 U/L; alkaline phosphatase, 97 vs 177 U/L; and INR, 1.5 vs 2.0; p<0.05 in all cases). Patients surviving to 90 days experienced statistically significant but transient laboratory value elevations-up to twofold over baseline-within days of TIPS, whereas patients dying within 90 days experienced three-to fourfold increases over a longer period that did not return to baseline. Differences in laboratory evolution were statistically significant in surviving versus dying patients. TIPS results in acute transient elevation of hepatobiliary enzymes, which may be more pronounced in patients with early mortality. An exaggerated laboratory elevation in excess of threefold greater than baseline or a prolonged increase exceeding 1 week may herald poorer clinical outcome.

Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism.

PubMed

Borrego Utiel, Francisco José; Bravo Soto, Juan Antonio; Merino Pérez, María José; González Carmelo, Isabel; López Jiménez, Verónica; García Álvarez, Teresa; Acosta Martínez, Yelenei; Mazuecos Blanca, María Auxiliadora

2015-01-01

Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

Brain-derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3-year follow-up.

PubMed

Francis, K; Dougali, A; Sideri, K; Kroupis, C; Vasdekis, V; Dima, K; Douzenis, A

2018-05-01

Several lines of evidence point to a probable relationship between brain-derived neurotrophic factor (BDNF) and autism spectrum disorder (ASD), but studies have yielded inconsistent findings on the BDNF serum level in ASD. The study aimed to assess those levels in children with ASD and their families. BDNF serum levels were measured in 45 ASD children without intellectual disability (ID) and allergies, age 30-42 months and age-matched normal controls. BDNF serum levels in the parents of the ASD subjects were compared to normal controls. BDNF serum levels in the ASD subjects were followed up for 3 years and correlated with adaptive functioning changes. BDNF serum levels were measured to be lower in children with ASD and independent of all the major baseline characteristics of the subjects. Having a child with ASD raises the BDNF levels in parents comparing to controls. Prospectively, no correlation between the change of BDNF variables in time and the change of the Vineland scores was found. Our results contradict those from recent published meta-analyses with the age, the presence of ID and allergies being possible contributing factors. The parents' data indeed point to a role of BDNF in the pathophysiology of ASD. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prognostic implications of left ventricular mass and geometry following myocardial infarction: the VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study.

PubMed

Verma, Anil; Meris, Alessandra; Skali, Hicham; Ghali, Jalal K; Arnold, J Malcolm O; Bourgoun, Mikhail; Velazquez, Eric J; McMurray, John J V; Kober, Lars; Pfeffer, Marc A; Califf, Robert M; Solomon, Scott D

2008-09-01

This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Mean LVMi and RWT were 98.8 +/- 28.4 g/m(2) and 0.38 +/- 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m(2) increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi. Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction.

Creation of dialysis vascular access with normal flow increases brain natriuretic peptide levels.

PubMed

Malík, Jan; Tuka, Vladimir; Krupickova, Zdislava; Chytilova, Eva; Holaj, Robert; Slavikova, Marcela

2009-12-01

Chronic heart failure is very common in hemodialyzed patients due to several factors such as intermittent volume overload, anemia, and hypertension. Dialysis access flow is usually considered to have a minor effect. We hypothesized that creation of dialysis access with "normal" flow would lead to elevation of B-type natriuretic peptide (BNP), which is a sensitive marker of heart failure. We included subjects with a newly created, well-functioning vascular access and normal left ventricular ejection fraction. They were examined before access creation (baseline), then again 6 weeks and 6 months after the surgery. Only subjects with access flow (Qa) < 1500 ml/min were included. Changes of BNP levels and their relation to access flow were studied. We examined 35 subjects aged 60.6 +/- 13.5 years. Qa was 789 +/- 361 and 823 +/- 313 ml/min at 6 weeks and 6 months after the surgery, respectively. Within 6 weeks after access creation, BNP rose from 217 (294) to 267 (550) ng/l (median (quartile range)) with P = 0.003. Qa was significantly related to BNP levels 6 weeks after access creation (r = 0.37, P = 0.036). Six months after access creation, there was only a trend of BNP decrease (235 (308) ng/l, P = 0.44). Creatinine, blood urea nitrogen and hemoglobin levels as well as patients' weight did not change significantly. Creation of dialysis access with "normal" flow volume leads to significant increase of BNP, which is related to the value of access flow. The increase of BNP probably mirrors worsening of clinically silent heart failure.

Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents.

PubMed

Tricò, Domenico; Prinsen, Hetty; Giannini, Cosimo; de Graaf, Robin; Juchem, Christoph; Li, Fangyong; Caprio, Sonia; Santoro, Nicola; Herzog, Raimund I

2017-07-01

Traditional risk factors for type 2 diabetes mellitus are weak predictors of changes in glucose tolerance and insulin sensitivity in youth. To identify early metabolic features of insulin resistance (IR) in youth and whether they predict deterioration of glycemic control. A cross-sectional and longitudinal study was conducted at the Yale Pediatric Obesity Clinic. Concentrations of α-hydroxybutyrate, β-hydroxybutyrate, lactate, and branched-chain amino acids (BCAAs) were measured by nuclear magnetic resonance spectroscopy in 78 nondiabetic adolescents during an oral glucose tolerance test (OGTT). Associations between baseline metabolic alterations and longitudinal changes in glucose control were tested in 16 subjects after a mean follow-up of 2.3 years. The relationship between metabolite levels, parameters of IR, and glycemic control, and their progression over time. Elevated fasting α-hydroxybutyrate levels were observed in adolescents with reduced insulin sensitivity after adjusting for age, sex, ethnicity, Tanner stage, and body mass index z-score (P = 0.014). Plasma α-hydroxybutyrate and BCAAs were increased throughout the course of the OGTT in this group (P < 0.03). Notably, borderline IR was associated with a progressive α-hydroxybutyrate decrease from elevated baseline concentrations to normal levels (P = 0.02). Increased baseline α-hydroxybutyrate concentrations were further associated with progressive worsening of glucose tolerance and disposition index. α-Hydroxybutyrate and BCAA concentrations during an OGTT characterize insulin-resistant youth and predict worsening of glycemic control. These findings provide potential biomarkers for risk assessment of type 2 diabetes and new insights into IR pathogenesis. Copyright © 2017 Endocrine Society

DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss Strategies: Energy-Restricted Diet or Bariatric Surgery.

PubMed

Nicoletti, Carolina Ferreira; Nonino, Carla Barbosa; de Oliveira, Bruno Affonso Parenti; Pinhel, Marcela Augusta de Souza; Mansego, Maria Luisa; Milagro, Fermin Ignacio; Zulet, Maria Angeles; Martinez, José Alfredo

2016-03-01

Weight loss can be influenced by genetic factors and epigenetic mechanisms that participate in the regulation of body weight. This study aimed to investigate whether the weight loss induced by two different obesity treatments (energy restriction or bariatric surgery) may affect global DNA methylation (LINE-1) and hydroxymethylation profile, as well as the methylation patterns in inflammatory genes. This study encompassed women from three differents groups: 1. control group (n = 9), normal weight individuals; 2. energy restriction group (n = 22), obese patients following an energy-restricted Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group (n = 14), obese patients underwent a hypocaloric diet followed by bariatric surgery. Anthropometric measurements and 12-h fasting blood samples were collected before the interventions and after 6 months. Lipid and glucose biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by MS-HRM) methylation levels were assessed in all participants. Baseline LINE-1 methylation was associated with serum glucose levels whereas baseline hydroxymethylation was associated with BMI, waist circumference, total cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not change after weight loss, whereas IL-6 methylation increased after energy restriction and decreased in the bariatric surgery group. An association between SERPINE-1 methylation and weight loss responses was found. Global DNA methylation and hydroxymethylation might be biomarkers for obesity and associated comorbidities. Depending on the obesity treatment (diet or surgery), the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation may be a predictor of weight loss values after bariatric surgery.

Unsupervised Ensemble Anomaly Detection Using Time-Periodic Packet Sampling

NASA Astrophysics Data System (ADS)

Uchida, Masato; Nawata, Shuichi; Gu, Yu; Tsuru, Masato; Oie, Yuji

We propose an anomaly detection method for finding patterns in network traffic that do not conform to legitimate (i.e., normal) behavior. The proposed method trains a baseline model describing the normal behavior of network traffic without using manually labeled traffic data. The trained baseline model is used as the basis for comparison with the audit network traffic. This anomaly detection works in an unsupervised manner through the use of time-periodic packet sampling, which is used in a manner that differs from its intended purpose — the lossy nature of packet sampling is used to extract normal packets from the unlabeled original traffic data. Evaluation using actual traffic traces showed that the proposed method has false positive and false negative rates in the detection of anomalies regarding TCP SYN packets comparable to those of a conventional method that uses manually labeled traffic data to train the baseline model. Performance variation due to the probabilistic nature of sampled traffic data is mitigated by using ensemble anomaly detection that collectively exploits multiple baseline models in parallel. Alarm sensitivity is adjusted for the intended use by using maximum- and minimum-based anomaly detection that effectively take advantage of the performance variations among the multiple baseline models. Testing using actual traffic traces showed that the proposed anomaly detection method performs as well as one using manually labeled traffic data and better than one using randomly sampled (unlabeled) traffic data.

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

The index ‘Treatment Duration Control’ for enabling randomized controlled trials with variation in duration of treatment of chronic pain patients

PubMed Central

2013-01-01

Background Treatment duration varies with the type of therapy and a patient’s recovery speed. Including such a variation in randomized controlled trials (RCTs) enables comparison of the actual therapeutic potential of different therapies in clinical care. An index, Treatment Duration Control (TDC) of outcome scores was developed to help decide when to end treatment and also to determine treatment outcome by a blinded assessor. In contrast to traditional Routine Outcome Monitoring which considers raw score changes, TDC uses relative change. Methods Our theory shows that if a patient with the largest baseline scores in a sample requires a relative decrease by treatment factor T to reach a zone of low score values (functional status), any patient with smaller baselines will attain functional status with T. Furthermore, the end score values are proportional to the baseline. These characteristics concur with findings from the literature that a patient’s assessment of ‘much improved’ following treatment (related to attaining functional status) is associated with a particular relative decrease in pain intensity yielding a final pain intensity that is proportional to the baseline. Regarding the TDC-procedure: those patient’s scores that were related to pronounced signs and symptoms, were selected for adaptive testing (reference scores). A Contrast-value was determined for each reference score between its reference level and a subsequent level, and averaging all Contrast-values yielded TDC. A cut-off point related to factor T for attaining functional status, was the TDC-criterion to end a patient’s treatment as being successful. The use of TDC has been illustrated in RCT data from 118 chronic pain patients with myogenous Temporomandibular Disorders, and the TDC-criterion was validated. Results The TDC-criterion of successful/unsuccessful treatment approximated the cut-off separating two patient subgroups in a bimodal post-treatment distribution of TDC-values. Pain intensity decreased to residual levels and Health-Related Quality of Life (HRQoL) increased to normal levels, following successful treatment according to TDC. The post-treatment TDC-values were independent from the baseline values of pain intensity or HRQoL, and thus independent from the patient’s baseline severity of myogenous Temporomandibular Disorders. Conclusions TDC enables RCTs that have a variable therapy- and patient-specific duration. PMID:24112821

Preoperative octreotide therapy and surgery in acromegaly: associations between glucose homeostasis and treatment response.

PubMed

Helseth, R; Carlsen, S M; Bollerslev, J; Svartberg, J; Øksnes, M; Skeie, S; Fougner, S L

2016-02-01

In acromegaly, high GH/IGF-1 levels associate with abnormal glucose metabolism. Somatostatin analogs (SSAs) reduce GH and IGF-1 but inhibit insulin secretion. We studied glucose homeostasis in de novo patients with acromegaly and changes in glucose metabolism after treatment with SSA and surgery. In this post hoc analysis from a randomized controlled trial, 55 de novo patients with acromegaly, not using antidiabetic medication, were included. Before surgery, 26 patients received SSAs for 6 months. HbA1c, fasting glucose, and oral glucose tolerance test were performed at baseline, after SSA pretreatment and at 3 months postoperative. Area under curve of glucose (AUC-G) was calculated. Glucose homeostasis was compared to baseline levels of GH and IGF-1, change after SSA pretreatment, and remission both after SSA pretreatment and 3 months postoperative. In de novo patients, IGF-1/GH levels did not associate with baseline glucose parameters. After SSA pretreatment, changes in GH/IGF-1 correlated positively to change in HbA1c levels (both p < 0.03). HbA1c, fasting glucose, and AUC-G increased significantly during SSA pretreatment in patients not achieving hormonal control (all p < 0.05) but did not change significantly in patients with normalized hormone levels. At 3 months postoperative, HbA1c, fasting glucose, and AUC-G were significantly reduced in both cured and not cured patients (all p < 0.05). To conclude, in de novo patients with acromegaly, disease activity did not correlate with glucose homeostasis. Surgical treatment of acromegaly improved glucose metabolism in both cured and not cured patients, while SSA pretreatment led to deterioration in glucose homeostasis in patients not achieving biochemical control.

B-type natriuretic peptide levels in patients with pericardial effusion undergoing pericardiocentesis.

PubMed

Lauri, Gianfranco; Rossi, Chiara; Rubino, Mara; Cosentino, Nicola; Milazzo, Valentina; Marana, Ivana; Cabiati, Angelo; Moltrasio, Marco; De Metrio, Monica; Grazi, Marco; Campodonico, Jeness; Assanelli, Emilio; Riggio, Daniela; Sandri, Maria Teresa; Bonomi, Alice; Veglia, Fabrizio; Marenzi, Giancarlo

2016-06-01

Pericardial effusion is characterized by progressive accumulation of fluid within the pericardial space, resulting in increased intra-pericardial pressure and compression of the heart. As B-type natriuretic peptide (BNP) is secreted by the ventricles in response to increased myocardial stretch, we hypothesized that pericardial effusion, as well as its resolution, might influence BNP plasma levels. We prospectively measured, in 146 consecutive patients with pericardial effusion, BNP plasma levels at baseline, soon after, and 24h after pericardiocentesis. A scoring system based on 7 clinical and echocardiographic parameters was developed, and patients were classified according to the number of variables as having low (0-2), intermediate (3-4), or high (5-7) severity score. Out of the 146 patients, 42 (29%) had normal values (<100pg/ml), whereas 104 (71%) had high BNP values at baseline. In the whole population, baseline BNP levels significantly decreased as the severity score increased (r=-0.21; P=0.01). 24h after pericardiocentesis, a significant increase in BNP was observed in patients with intermediate (P=0.004) score and with high (P<0.001) severity score; no increase occurred in low score patients (P=0.56). The higher was the severity score, the steeper was the increase in BNP through the three time-points considered (P=0.04). The results of the present study show that BNP plasma levels are suppressed in the presence of severe pericardial effusion, and that they rise after pericardiocentesis. Future studies should investigate the role of BNP in assisting clinicians in the decision-making process of pericardial fluid drainage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evidence for Ordering of Alzheimer’s Disease Biomarkers

PubMed Central

Jack, Clifford R.; Vemuri, Prashanthi; Wiste, Heather J.; Weigand, Stephen D.; Aisen, Paul S.; Trojanowski, John Q.; Shaw, Leslie M.; Bernstein, Matthew A.; Petersen, Ronald C.; Weiner, Michael W.

2012-01-01

Objective To empirically assess the concept that Alzheimer’s disease (AD) biomarkers significantly depart from normality in a temporally ordered manner. Design Validation sample Setting Multi-site, referral centers Patients We studied 401 elderly cognitively normal (CN), Mild Cognitive Impairment (MCI) and AD dementia subjects from the Alzheimer’s Disease Neuroimaging Initiative. We compared the proportions of three AD biomarkers – CSF Aβ42, CSF total tau (t-tau), and hippocampal volume adjusted by intra-cranial volume (HVa) - that were abnormal as cognitive impairment worsened. Cut-points demarcating normal vs. abnormal for each biomarker were established by maximizing diagnostic accuracy in independent autopsy samples. Interventions None Main Outcome measures AD biomarkers Results Within each clinical group in the entire sample (n=401) CSF Aβ42 was abnormal more often than t-tau or HVa. Among the 298 subjects with both baseline and 12 month data, the proportion of subjects with abnormal Aβ42 did not change from baseline to 12 months in any group. The proportion of subjects with abnormal t-tau increased from baseline to 12 months in CN (p=0.05) but not in MCI or dementia. In 209 subjects with abnormal CSF AB42 at baseline, the percent abnormal HVa, but not t-tau, increased from baseline to 12 months in MCI. Conclusions Reduction in CSF Aβ42 denotes a pathophysiological process that significantly departs from normality (i.e., becomes dynamic) early, while t-tau and HVa are biomarkers of downstream pathophysiological processes. T-tau becomes dynamic before HVa, but HVa is more dynamic in the clinically symptomatic MCI and dementia phases of the disease than t-tau. PMID:21825215

Effect of Taxane-Based Neoadjuvant Chemotherapy on Fibroglandular Tissue Volume and Percent Breast Density in the Contralateral Normal Breast: Evaluated at 3T MR

PubMed Central

Chen, Jeon-Hor; Pan, Wei-Fan; Kao, Julian; Lu, Jocelyn; Chen, Li-Kuang; Kuo, Chih-Chen; Chang, Chih-Kai; Chen, Wen-Pin; McLaren, Christine E.; Bahri, Shadfar; Mehta, Rita S.; Su, Min-Ying

2013-01-01

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty-four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer algorithm-based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV) and percent density (PD) (the ratio of FV over BV x100%). The reduction of FV and PD after treatment was compared to baseline using paired t-tests with a Bonferroni-Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared to the baseline. FV was 110.0ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3ml (66.6, 164.4) after 4 weeks (p< 0.0001), and 94.7ml (60.2, 144.4) after 12 weeks (comparison to baseline, p<0.0001; comparison to 4 weeks, p=0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p< 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison to baseline, p=0.0001; comparison to 4 weeks, p =0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r=0.28 for FV, p=0.07 and r=0.52 for PD, p=0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer-aided algorithm based on nonparametric nonuniformity normalization (N3) and an adaptive fuzzy C-means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane-based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age-related and duration-related. PMID:23940080

Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.

PubMed

Liang, Ling-Bo; Zhu, Xia; Yan, Li-Bo; Du, Ling-Yao; Liu, Cong; Liao, Juan; Tang, Hong

2016-11-01

The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored. A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation. A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

PubMed

Riales, R; Albrink, M J

1981-12-01

Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Biomarkers of Inflammation, Thrombogenesis, and Collagen Turnover in Patients With Atrial Fibrillation.

PubMed

Jabati, Sallu; Fareed, Jawed; Liles, Jeffrey; Otto, Abigail; Hoppensteadt, Debra; Bontekoe, Jack; Phan, Trung; Walborn, Amanda; Syed, Mushabbar

2018-07-01

The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF. Baseline plasma was collected from patients with AF prior to ablation surgery at Loyola University Medical Center. Individuals with AF had statistically significantly increased levels of PAI-1, CD40-L, and nucleosomes, when compared to the normal population ( P < .0001). Additionally, there was a statistically significant increase in the CRP ( P = .01), PIIINP ( P = .04), and PIIICP ( P = .0008) when compared to normal individuals. From this study, it is concluded that the prothrombotic, inflammatory, and collagen turnover biomarkers PAI-1, CD40-L, nucleosomes, CRP, PIIICP, and PIIINP are elevated in AF.

Placental baseline conditions modulate the hyperoxic BOLD-MRI response.

PubMed

Sinding, Marianne; Peters, David A; Poulsen, Sofie S; Frøkjær, Jens B; Christiansen, Ole B; Petersen, Astrid; Uldbjerg, Niels; Sørensen, Anne

2018-01-01

Human pregnancies complicated by placental dysfunction may be characterized by a high hyperoxic Blood oxygen level-dependent (BOLD) MRI response. The pathophysiology behind this phenomenon remains to be established. The aim of this study was to evaluate whether it is associated with altered placental baseline conditions, including a lower oxygenation and altered tissue morphology, as estimated by the placental transverse relaxation time (T2*). We included 49 normal pregnancies (controls) and 13 pregnancies complicated by placental dysfunction (cases), defined by a birth weight < 10th percentile in combination with placental pathological signs of vascular malperfusion. During maternal oxygen inhalation, we measured the relative ΔBOLD response ((hyperoxic BOLD - baseline BOLD)/baseline BOLD) from a dynamic single-echo gradient-recalled echo (GRE) MRI sequence and the absolute ΔT2* (hyperoxic T2*- baseline T2*) from breath-hold multi-echo GRE sequences. In the control group, the relative ΔBOLD response increased during gestation from 5% in gestational week 20 to 20% in week 40. In the case group, the relative ΔBOLD response was significantly higher (mean Z-score 4.94; 95% CI 2.41, 7.47). The absolute ΔT2*, however, did not differ between controls and cases (p = 0.37), whereas the baseline T2* was lower among cases (mean Z-score -3.13; 95% CI -3.94, -2.32). Furthermore, we demonstrated a strong negative linear correlation between the Log 10 ΔBOLD response and the baseline T2* (r = -0.88, p < 0.0001). The high hyperoxic ΔBOLD response demonstrated in pregnancies complicated by placental dysfunction may simply reflect altered baseline conditions, as the absolute increase in placental oxygenation (ΔT2*) does not differ between groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

PubMed

Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

2005-01-01

To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic information in patients with known or suspected residual tumor. BMD should be assessed at both appendicular and axial sites in patients with persistent tumor-induced osteomalacia.

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

PubMed

He, Zihong; Rankinen, Tuomo; Leon, Arthur S; Skinner, James S; Tchernof, André; Bouchard, Claude

2018-03-05

Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Ndumele, Chiadi E; Matsushita, Kunihiro; Sang, Yingying; Lazo, Mariana; Agarwal, Sunil K; Nambi, Vijay; Deswal, Anita; Blumenthal, Roger S; Ballantyne, Christie M; Coresh, Josef; Selvin, Elizabeth

2016-02-16

Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990-1992) with BMI ≥18.5 kg/m(2). We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=-0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m(2); improvement in C statistic, 0.032; 95% confidence interval, 0.011-0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese. Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population. © 2016 American Heart Association, Inc.

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

PubMed

Anuwatmatee, Sahapab; Allison, Matthew A; Shlipak, Michael G; McClelland, Robyn L; Kramer, Holly; Tang, Shudi; Hou, Liming; Rye, Kerry-Anne; Ong, Kwok Leung

2018-05-15

Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year). At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05). Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

Impact of a Traditional Dietary Supplement with Coconut Milk and Soya Milk on the Lipid Profile in Normal Free Living Subjects

PubMed Central

Ekanayaka, R. A. I.; Ekanayaka, N. K.; Perera, B.; De Silva, P. G. S. M.

2013-01-01

Background. The effects of coconut fat and soya fat on serum lipids are controversial. This study was designed to investigate the lipid effects of coconut milk and soya milk supplementation on the lipid profile of free living healthy subjects. Methods. Sixty (60) healthy volunteers aged 18–57 years were given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by a 2-week washout period, subsequent to which they received isoenergetic soya milk porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels decreased with CMP and reached statistical significance in the total study population and in the >130 baseline LDL group. The HDL (high density lipoprotein) levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We conclude that coconut fat in the form of CM does not cause a detrimental effect on the lipid profile in the general population and in fact is beneficial due to the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose baseline LDL levels are elevated. PMID:24282632

Data Normalization of (1)H NMR Metabolite Fingerprinting Data Sets in the Presence of Unbalanced Metabolite Regulation.

PubMed

Hochrein, Jochen; Zacharias, Helena U; Taruttis, Franziska; Samol, Claudia; Engelmann, Julia C; Spang, Rainer; Oefner, Peter J; Gronwald, Wolfram

2015-08-07

Data normalization is an essential step in NMR-based metabolomics. Conducted properly, it improves data quality and removes unwanted biases. The choice of the appropriate normalization method is critical and depends on the inherent properties of the data set in question. In particular, the presence of unbalanced metabolic regulation, where the different specimens and cohorts under investigation do not contain approximately equal shares of up- and down-regulated features, may strongly influence data normalization. Here, we demonstrate the suitability of the Shapiro-Wilk test to detect such unbalanced regulation. Next, employing a Latin-square design consisting of eight metabolites spiked into a urine specimen at eight different known concentrations, we show that commonly used normalization and scaling methods fail to retrieve true metabolite concentrations in the presence of increasing amounts of glucose added to simulate unbalanced regulation. However, by learning the normalization parameters on a subset of nonregulated features only, Linear Baseline Normalization, Probabilistic Quotient Normalization, and Variance Stabilization Normalization were found to account well for different dilutions of the samples without distorting the true spike-in levels even in the presence of marked unbalanced metabolic regulation. Finally, the methods described were applied successfully to a real world example of unbalanced regulation, namely, a set of plasma specimens collected from patients with and without acute kidney injury after cardiac surgery with cardiopulmonary bypass use.

Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia: Natural history, clinical correlates, and outcomes.

PubMed

Parikh, Sameer A; Leis, Jose F; Chaffee, Kari G; Call, Timothy G; Hanson, Curtis A; Ding, Wei; Chanan-Khan, Asher A; Bowen, Deborah; Conte, Michael; Schwager, Susan; Slager, Susan L; Van Dyke, Daniel L; Jelinek, Diane F; Kay, Neil E; Shanafelt, Tait D

2015-09-01

Although hypogammaglobulinemia is a well recognized complication in patients with chronic lymphocytic leukemia (CLL), its prevalence at the time of CLL diagnosis, and association with novel prognostic markers and clinical outcome is not well understood. All patients at the Mayo Clinic between January 1999 and July 2013 who had newly diagnosed CLL and had a baseline assessment of serum immunoglobulin G (IgG) were included. The relation between hypogammaglobulinemia at diagnosis and the novel prognostic parameters time to first treatment (TFT) and overall survival (OS) were evaluated. Of 1485 patients who met the eligibility criteria, 382 (26%) had hypogammaglobulinemia (median IgG, 624 mg/dL), whereas the remaining 1103 patients (74%) had normal serum IgG levels (median IgG, 1040 mg/dL). Patients who had hypogammaglobulinemia at diagnosis were more likely to have advanced Rai stage (III-IV; P = .001) and higher expression of CD49d (P < .001) compared with patients who had normal IgG levels. Although the median TFT for patients who had hypogammaglobulinemia was shorter compared with that for patients who had normal IgG levels (3.8 years vs 7.4 years; P < .001), on multivariable analysis, there was no difference in OS between these 2 groups (12.8 years vs 11.3 years, respectively; P = .73). Of 1103 patients who had CLL with normal IgG levels at diagnosis and who did not receive CLL therapy, the risk of acquired hypogammaglobulinemia was 11% at 5 years and 23% at 10 years. Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival. © 2015 American Cancer Society.

Autonomic correlates at rest and during evoked attention in children with attention-deficit/hyperactivity disorder and effects of methylphenidate.

PubMed

Negrao, Bianca Lee; Bipath, Priyesh; van der Westhuizen, Deborah; Viljoen, Margaretha

2011-01-01

The aim of this study was to assess autonomic nervous system functioning in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of methylphenidate and focussed attention. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulants. On both occasions, autonomic nervous system functioning was tested at baseline and during focussed attention. Autonomic nervous system functioning of control subjects was also tested at baseline and during focussed attention. Autonomic nervous system activity was determined by means of heart rate variability (HRV) and skin conductivity analyses. Attention was evoked by means of the BioGraph Infiniti biofeedback apparatus. HRV was determined by time domain, frequency domain and Poincaré analysis of RR interval data. Skin conductivity was determined by the BioGraph Infiniti biofeedback apparatus. The main findings of this study were (a) that stimulant-free children with ADHD showed a sympathetic underarousal and parasympathetic overarousal of the sympathovagal balance relative to control subjects; (b) methylphenidate shifted the autonomic balance of children with ADHD towards normal levels; however, a normal autonomic balance was not reached, and (c) stimulant-free children with ADHD exhibited a shift in the sympathovagal balance towards the sympathetic nervous system from baseline to focussed attention; however, methylphenidate appeared to abolish this shift. Stimulant-free children with ADHD have a parasympathetic dominance of the autonomic balance, relative to control subjects. Methylphenidate attempts to restore the normal autonomic balance in children with ADHD, but inhibits the normal autonomic nervous system response to a cognitive challenge. These results indicate that methylphenidate may have a suppressive effect on the normal stress response. Although this may be of benefit to those who interact with children who suffer from ADHD, the implications for the physiological and psychological well-being of the children themselves are debatable. Further research is needed. Only 19 children with ADHD and 18 control subjects were tested. Further studies should include prior testing in order to exclude children with possible co-existing learning disabilities. Cognitive function and emotional responses of children with ADHD were not tested. © 2010 S. Karger AG, Basel.

Variation of gene expression in Bacillus subtilis samples of fermentation replicates.

PubMed

Zhou, Ying; Yu, Wen-Bang; Ye, Bang-Ce

2011-06-01

The application of comprehensive gene expression profiling technologies to compare wild and mutated microorganism samples or to assess molecular differences between various treatments has been widely used. However, little is known about the normal variation of gene expression in microorganisms. In this study, an Agilent customized microarray representing 4,106 genes was used to quantify transcript levels of five-repeated flasks to assess normal variation in Bacillus subtilis gene expression. CV analysis and analysis of variance were employed to investigate the normal variance of genes and the components of variance, respectively. The results showed that above 80% of the total variation was caused by biological variance. For the 12 replicates, 451 of 4,106 genes exhibited variance with CV values over 10%. The functional category enrichment analysis demonstrated that these variable genes were mainly involved in cell type differentiation, cell type localization, cell cycle and DNA processing, and spore or cyst coat. Using power analysis, the minimal biological replicate number for a B. subtilis microarray experiment was determined to be six. The results contribute to the definition of the baseline level of variability in B. subtilis gene expression and emphasize the importance of replicate microarray experiments.

Sclerostin Levels and Bone Turnover Markers in Adolescents with Anorexia Nervosa and Healthy Adolescent Girls

PubMed Central

Faje, Alexander T.; Fazeli, Pouneh K.; Katzman, Debra K.; Miller, Karen K.; Breggia, Anne; Rosen, Clifford J.; Mendes, Nara; Klibanski, Anne; Misra, Madhusmita

2012-01-01

Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study objectives were to (i) assess associations of sclerostin with surrogate bone turnover markers in girls with AN and controls and (ii) examine effects of transdermal estradiol on sclerostin in AN. 69 girls (44 with AN and 25 normal-weight controls) 13–18 years old were studied at baseline. 22 AN girls were randomized to transdermal estradiol (plus cyclic medroxyprogesterone) or placebo in a double-blind study for 12 months. Sclerostin correlated positively with P1NP and CTX in controls (r = 0. 67 and 0. 53, p = 0. 0002 and 0. 005, respectively) but not in AN despite comparable levels at baseline. Changes in sclerostin over twelve months did not differ in girls randomized to estradiol or placebo. The relationship between sclerostin and bone turnover markers is disrupted in adolescent girls with AN. Despite an increase in BMD with estradiol administration in AN, estrogen does not impact sclerostin levels in this group. PMID:22728230

HPA axis response to social stress is attenuated in schizophrenia but normal in depression: evidence from a meta-analysis of existing studies.

PubMed

Ciufolini, Simone; Dazzan, Paola; Kempton, Matthew J; Pariante, Carmine; Mondelli, Valeria

2014-11-01

We conducted a meta-analysis to investigate the HPA axis response to social stress in studies that used the Trier Social Stress Test (TSST), or comparable distressing paradigms, in individuals with either depression or schizophrenia. Sample size-adjusted effect sizes (Hedge's g statistic) were calculated to estimate the HPA axis stress response to social stress. We used a meta-regression model to take into account the moderating effect of the baseline cortisol level. Participants with depression show an activation pattern to social stress similar to that of healthy controls. Despite a normal cortisol production rate, individuals with schizophrenia have lower cortisol levels than controls both in anticipation and after exposure to social stress. Participants with depression and higher cortisol levels before the task have an increased cortisol production and reached higher cortisol levels during the task. This may be explained by the presence of an impaired negative feedback. The activation pattern present in schizophrenia may explain the reduced ability to appropriately contextualize past experiences shown by individuals with psychosis in social stressful situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Colour vision impairment is associated with disease severity in multiple sclerosis.

PubMed

Martínez-Lapiscina, Elena H; Ortiz-Pérez, Santiago; Fraga-Pumar, Elena; Martínez-Heras, Eloy; Gabilondo, Iñigo; Llufriu, Sara; Bullich, Santiago; Figueras, Marc; Saiz, Albert; Sánchez-Dalmau, Bernardo; Villoslada, Pablo

2014-08-01

Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). The objective of this paper is to investigate the association between impaired colour vision and disease severity. We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. Colour vision impairment is associated with greater MS severity. © The Author(s) 2013.

[Relationship between hypothyroidism and cholesterol out of the records of 1756 patients].

PubMed

Sampaolo, Guido; Campanella, Nando; Catozzo, Vania; Ferretti, Maurizio; Vichi, Giovanna; Morosini, Pierpaolo

2014-02-01

Subclinical hypothyroidism (SH) is settled whenever high levels of serum thyroid-stimulating hormone (TSH) are detected, whereas free thyroid hormone levels are within the normal range. Benefits and risks of therapy for SH have been debated for 2 decades. However, consensus has not yet been achieved. Besides preventing the progression to overt hypothyroidism, the decision of undertaking replacement therapy in SH is made mainly by basing on the risk of metabolic (dyslypidemia) and subsequent cardiovascular complications. A series, made up of 1756 patients (mean age 42,8±16,8, range 0,5-94) and filed from 1984 to 2013, was studied retrospectively. 169 patients were affected by clinical (overt) hypothyroidism (IC: TSH >40). 1587 patients were affected by SH, out of whom 1121 were mild (TSH <10) and 466 medium (TSH ≥ 10 ≤40). The series of patients was properly followed-up. The mean follow-up time was 6 years. In all patients TSH, Ft4, and total cholesterol were evaluated basally and after appropriate (TSH normalized) medical therapy. By medical replacement treatment, clinical hypothyroidism (CI) related hypercholesterolemia decreased significantly in 28%. In SH, the baseline serum cholesterol levels were wide. However, replacement treatment did not reduce such levels. No major cardiovascular accident occurred to any patient over the follow-up period. Hypercholesterolemia is certainly due to CI, therapy reduces cholesterol levels that not always fall below 200 mg/dl and this condition persists over time. SH is not characterized by hypercholesterolemia. Cholesterol levels in these patients are variable equal to the normal people and can not be reduced with thyroxine.

Network meta-analysis of disconnected networks: How dangerous are random baseline treatment effects?

PubMed

Béliveau, Audrey; Goring, Sarah; Platt, Robert W; Gustafson, Paul

2017-12-01

In network meta-analysis, the use of fixed baseline treatment effects (a priori independent) in a contrast-based approach is regularly preferred to the use of random baseline treatment effects (a priori dependent). That is because, often, there is not a need to model baseline treatment effects, which carry the risk of model misspecification. However, in disconnected networks, fixed baseline treatment effects do not work (unless extra assumptions are made), as there is not enough information in the data to update the prior distribution on the contrasts between disconnected treatments. In this paper, we investigate to what extent the use of random baseline treatment effects is dangerous in disconnected networks. We take 2 publicly available datasets of connected networks and disconnect them in multiple ways. We then compare the results of treatment comparisons obtained from a Bayesian contrast-based analysis of each disconnected network using random normally distributed and exchangeable baseline treatment effects to those obtained from a Bayesian contrast-based analysis of their initial connected network using fixed baseline treatment effects. For the 2 datasets considered, we found that the use of random baseline treatment effects in disconnected networks was appropriate. Because those datasets were not cherry-picked, there should be other disconnected networks that would benefit from being analyzed using random baseline treatment effects. However, there is also a risk for the normality and exchangeability assumption to be inappropriate in other datasets even though we have not observed this situation in our case study. We provide code, so other datasets can be investigated. Copyright © 2017 John Wiley & Sons, Ltd.

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation.

PubMed

Hartmann, E K; Duenges, B; Boehme, S; Szczyrba, M; Liu, T; Klein, K U; Baumgardner, J E; Markstaller, K; David, M

2014-09-01

During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA /Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA /Q under CPR conditions in a pig model. Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/ Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Intergroup differences were analysed by non-parametric testing. MIGET measurements were feasible in all animals with an excellent correlation of measured and predicted arterial oxygen partial pressure (R(2)  = 0.96, n = 21 for baseline; R(2)  = 0.82, n = 21 for CPR). CPR induces a significant shift from normal VA /Q ratios to the high VA /Q range. Electrical impedance tomography indicates a dorsal to ventral shift of the ventilation distribution. Diverging pulmonary shunt fractions induced by the three inspired oxygen levels considerably increased during CPR and were traceable by MIGET, while 100% oxygen most negatively influenced the VA /Q. Return of spontaneous circulation were achieved in 52% of the animals. VA /Q assessment by MIGET is feasible during CPR and provides a novel tool for experimental purposes. Changes in VA /Q caused by different oxygen fractions are traceable during CPR. Beyond pulmonary perfusion deficits, these data imply an influence of the inspired oxygen level on VA /Q. Higher oxygen levels significantly increase shunt fractions and impair the normal VA /Q ratio. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Functional and Structural Findings of Neurodegeneration in Early Stages of Diabetic Retinopathy: Cross-sectional Analyses of Baseline Data of the EUROCONDOR Project.

PubMed

Santos, Ana Rita; Ribeiro, Luísa; Bandello, Francesco; Lattanzio, Rosangela; Egan, Catherine; Frydkjaer-Olsen, Ulrik; García-Arumí, José; Gibson, Jonathan; Grauslund, Jakob; Harding, Simon P; Lang, Gabriele E; Massin, Pascale; Midena, Edoardo; Scanlon, Peter; Aldington, Stephen J; Simão, Sílvia; Schwartz, Christian; Ponsati, Berta; Porta, Massimo; Costa, Miguel Ângelo; Hernández, Cristina; Cunha-Vaz, José; Simó, Rafael

2017-09-01

This cross-sectional study evaluated the relationship between 1 ) functional and structural measurements of neurodegeneration in the initial stages of diabetic retinopathy (DR) and 2 ) the presence of neurodegeneration and early microvascular impairment. We analyzed baseline data of 449 patients with type 2 diabetes enrolled in the European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR) study (NCT01726075). Functional studies by multifocal electroretinography (mfERG) evaluated neurodysfunction, and structural measurements using spectral domain optical coherence tomography (SD-OCT) evaluated neurodegeneration. The mfERG P1 amplitude was more sensitive than the P1 implicit time and was lower in patients with Early Treatment of Diabetic Retinopathy Study (ETDRS) level 20-35 than in patients with ETDRS level <20 ( P = 0.005). In 58% of patients, mfERG abnormalities were present in the absence of visible retinopathy. Correspondence between SD-OCT thinning and mfERG abnormalities was shown in 67% of the eyes with ETDRS <20 and in 83% of the eyes with ETDRS level 20-35. Notably, 32% of patients with ETDRS 20-35 presented no abnormalities in mfERG or SD-OCT. We conclude that there is a link between mfERG and SD-OCT measurements that increases with the presence of microvascular impairment. However, a significant proportion of patients in our particular study population (ETDRS ≤35) had normal ganglion cell-inner plexiform layer thickness and normal mfERG findings. We raise the hypothesis that neurodegeneration may play a role in the pathogenesis of DR in many but not in all patients with type 2 diabetes. © 2017 by the American Diabetes Association.

Baseline sediment trace metals investigation: Steinhatchee River estuary, Florida, Northeast Gulf of Mexico

USGS Publications Warehouse

Trimble, C.A.; Hoenstine, R.W.; Highley, A.B.; Donoghue, J.F.; Ragland, P.C.

1999-01-01

This Florida Geological Survey/U.S. Department of the Interior, Minerals Management Service Cooperative Study provides baseline data for major and trace metal concentrations in the sediments of the Steinhatchee River estuary. These data are intended to provide a benchmark for comparison with future metal concentration data measurements. The Steinhatchee River estuary is a relatively pristine bay located within the Big Bend Wildlife Management Area on the North Central Florida Gulf of Mexico coastline. The river flows 55 km through woodlands and planted pines before emptying into the Gulf at Deadman Harbor. Water quality in the estuary is excellent at present. There is minimal development within the watershed. The estuary is part of an extensive system of marshes that formed along the Florida Gulf coast during the Holocene marine transgression. Sediment accretion rate measurements range from 1.4 to 4.1 mm/yr on the basis of lead-210 measurements. Seventy-nine short cores were collected from 66 sample locations, representing four lithofacies: clay- and organic-rich sands, organic-rich sands, clean quartz sands, and oyster bioherms. Samples were analyzed for texture, total organic matter, total carbon, total nitrogen, clay mineralogy, and major and trace-metal content. Following these analyses, metal concentrations were normalized against geochemical reference elements (aluminum and iron) and against total weight percent organic matter. Metals were also normalized granulometrically against total weight percent fines (<0.062 mm). Concentrations were determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES) for all metals except mercury. Mercury concentrations were determined by cold-flameless atomic absorption spectrometry (AAS). Granulometric measurements were made by sieve and pipette analyses. Organic matter was determined by two methods: weight loss upon ignition and elemental analysis (by Carlo-Erba Furnace) of carbon and nitrogen. X-ray diffraction was used to determine clay mineralogy. Trace-metal concentrations were best correlated when normalized with respect to sediment aluminum concentrations. Normalizations indicate that most major and trace-metal concentrations fall within 95% prediction limits of the expected value. This finding suggests that little significant metal contamination occurred within this system prior to 1994 sediment sampling. Exceptions include lead, mercury, copper, zinc, potassium, and phosphorous. Lead and mercury are elements that generally enter this watershed through atmospheric deposition; thus, anomalous levels of these metals are not necessarily associated with activities within the watershed of the Steinhatchee River estuary. Anomalous concentrations of other metals such as zinc, copper, and phosphorous probably do originate within the Steinhatchee watershed. Copper failed to correlate well with any geochemical or granulometric normalizer, and this condition was not limited to a single facies or area within the estuary. This finding may indicate copper contamination in the system. Increased zinc and copper levels may be attributed to marine paints. Phosphorous levels also appeared to be elevated in a few locations in the two marsh facies sampled. This may be due to nutrient loading from two small communities, Jena and Steinhatchee, or from the application of this element in fertilizer to reduce moisture stress to young planted pines on tree farms within the watershed.The Florida Geological Survey/US Department of the Interior, Minerals Management Service Cooperative Study provides baseline data for major and trace metal concentrations in the sediments of the Steinhatchee River estuary. The data are intended to provide a benchmark for comparison with metal concentration data measurements. Seventy nine short cores were collected from 66 sample locations and analyzed. Metal concentrations were normalized against geochemical reference elements and against total weight percen

Cyclical secretion of prorenin during the menstrual cycle: synchronization with luteinizing hormone and progesterone.

PubMed Central

Sealey, J E; Atlas, S A; Glorioso, N; Manapat, H; Laragh, J H

1985-01-01

Plasma prorenin, a high molecular weight precursor form of renin, (renin, EC 3.4.23.15; old number, EC 3.4.99.19), was measured three times weekly in normal young women during the menstrual cycle and was related to changes in luteinizing hormone, estradiol, and progesterone. In all subjects a stable baseline level of prorenin occurred during the follicular phase. Then, simultaneously or soon after the luteinizing hormone peak, plasma prorenin consistently increased about 2-fold. Baseline prorenin ranged from 18 to 40 ng per ml per hr, and peak prorenin ranged from 35 to 65 ng per ml per hr. The maximum increase in prorenin averaged 80%. Prorenin remained elevated during the mid-luteal phase of the menstrual cycle and returned to baseline during the late-luteal phase in coordination with the decrease in progesterone. The changes in prorenin were not synchronized with changes in active renin which was significantly increased only during the mid-luteal phase. These findings suggest that prorenin may be involved in reproductive physiology. PMID:3909151

Nutritional status, cachexia, and anorexia in women with peritoneal metastasis and intraperitoneal chemotherapy: a longitudinal analysis.

PubMed

Hilal, Ziad; Rezniczek, Günther A; Klenke, Robert; Dogan, Askin; Tempfer, Clemens B

2017-11-01

To describe the nutritional status of women with peritoneal metastasis (PM) from recurrent ovarian, fallopian, or peritoneal cancer and to assess longitudinal variations of the cachexia-anorexia syndrome (CAS) during palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC). Nutritional assessment included body mass index (BMI), bioelectrical impedance analysis (BIA), and blood chemistry. CAS presence/absence was recorded before and during repeated cycles (1-11) of PIPAC. Eighty-four patients with peritoneal cancer (n=5) or PM from recurrent ovarian (n=77) or fallopian tube (n=2) cancer were included. At baseline, resting metabolism (RM) (1,432±172 kcal/day), visceral fat level (7.5±3.2), skeletal muscle mass (27.2%±4.6%), upper arm circumference (27.9±4.6 cm), lower leg circumference (35.1±3.9 cm), serum parameters (albumin [3.5±0.7 g/dL], total protein [6.3±0.9 g/dL], and transferrin [202±60 mg/dL]) were below normal limits. C-reactive protein (CRP) (4.3±6.8 mg/dL), caliper body fat (35.7%±6.3%), and total body fat mass (35.6%±8.5%) were above normal limits. Nineteen/84 (23%) patients had CAS at baseline. Deterioration or stabilization/improvement of CAS was observed in 9/55 (16.4%) and 46/55 (83.6%) patients with follow-up data, respectively. Baseline body fat mass, visceral fat level, skeletal muscle mass, caliper body fat, BMI, ascites, Karnofsky index, RM, and CRP, as well as tumor response were not predictive of CAS deterioration. Nutritional decline and onset or deterioration of CAS are difficult to predict. Careful measuring and monitoring of nutritional parameters and CAS in all patients seems to be necessary in order to identify those patients in need of enteral/parenteral nutrition support. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Severe hyperkalemia requiring hospitalization: predictors of mortality

PubMed Central

2012-01-01

Introduction Severe hyperkalemia, with potassium (K+) levels ≥ 6.5 mEq/L, is a potentially life-threatening electrolyte imbalance. For prompt and effective treatment, it is important to know its risk factors, clinical manifestations, and predictors of mortality. Methods An observational cohort study was performed at 2 medical centers. A total of 923 consecutive Korean patients were analyzed. All were 19 years of age or older and were hospitalized with severe hyperkalemia between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made either at the time of admission to the hospital or during the period of hospitalization. Demographic and baseline clinical characteristics at the time of hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital mortality were reviewed, using the institutions' electronic medical record systems. Results Chronic kidney disease (CKD) was the most common underlying medical condition, and the most common precipitating factor of hyperkalemia was metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7% had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality rate was 30.7%; the rate was strongly correlated with the difference between serum K+ levels at admission and at their highest point, and with severe medical conditions such as malignancy, infection, and bleeding. Furthermore, a higher in-hospital mortality rate was significantly associated with the presence of cardiac arrest and/or MOF at the time of diagnosis, emergent admission, and intensive care unit treatment during hospitalization. More importantly, acute kidney injury (AKI) in patients with normal baseline renal function was a strong predictor of mortality, compared with AKI superimposed on CKD. Conclusions Severe hyperkalemia occurs in various medical conditions; the precipitating factors are similarly diverse. The mortality rate is especially high in patients with severe underlying disease, coexisting medical conditions, and those with normal baseline renal function. PMID:23171442

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

2015-12-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733. Copyright© Ferrata Storti Foundation.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID:26430171

Relationship between general intelligence, emotional intelligence, stress levels and stress reactivity.

PubMed

Singh, Yogesh; Sharma, Ratna

2012-07-01

Stressful life events and daily life stresses have both deleterious and cumulative effects on human body. In several studies, stress has been shown to affect various parameter of higher mental function like attention, concentration, learning and memory. Present study was designed to explore the relationship among GI level, EI level, psychological stress levels and acute stress reactivity in young normal healthy subjects. The study was conducted on thirty four healthy male student volunteers to study a) acute stress reactivity in subjects with varying levels of General Intelligence (GI) and Emotional Intelligence (EI) and b) correlation between GI, EI, acute stress and perceived stress. Baseline GI and EI and acute stress and perceived stress scores were measured by standard assessment scales. Using median value of GI and EI scores as cutoff values, subjects were categorized into four groups. Among different GI-EI groups, acute stress reactivity was similar but salivary Cortisol (especially post stressor level) and perceived stress level was a differentiating factor. High level of EI was associated inversely with acute and chronic perceived stress level. Significant correlation was found between acute and chronic perceived stress levels. Level of general intelligence showed no relation to acute or chronic stress levels as well as acute stress reactivity. The differences in various groups of GI and EI had no effect on the baseline and post stress performance on Sternberg memory test and all the three conditions of Stroop test. In conclusion emotional intelligence as an attribute is better suited to handle day to day acute stress and chronic perceived stress.

Long-Term Coarse Particulate Matter Exposure and Heart Rate Variability in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Adhikari, Richa; D’Souza, Jennifer; Solimon, Elsayed Z.; Burke, Gregory L.; Daviglus, Martha; Jacobs, David R.; Park, Sung Kyun; Sheppard, Lianne; Thorne, Peter S.; Kaufman, Joel D.; Larson, Timothy V.; Adar, Sara D.

2017-01-01

Background Reduced heart rate variability, a marker of impaired cardiac autonomic function, has been linked to short-term exposure to airborne particles. This research adds to the literature by examining associations with long-term exposures to coarse particles (PM10-2.5). Methods Using electrocardiogram recordings from 2,780 participants (45-84 years) from three Multi-Ethnic Study of Atherosclerosis sites, we assessed the standard deviation of normal-to-normal intervals (SDNN) and root-mean square differences of successive normal-to-normal intervals (rMSSD) at a baseline (2000-2002) and follow-up (2010-2012) examination (mean visits/person=1.5). Annual average concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin were estimated using site-specific spatial prediction models. We assessed associations for baseline heart rate variability and rate of change in heart rate variability over time using multivariable mixed models adjusted for time, sociodemographic, lifestyle, health, and neighborhood confounders, including co-pollutants. Results In our primary models adjusted for demographic and lifestyle factors and site, PM10-2.5 mass was associated with 1.0% (95% CI: -4.1, 2.1%) lower SDNN levels per interquartile range of 2 μg/m3. Stronger associations, however, were observed prior to site adjustment and with increasing residential stablity. Similar patterns were found for rMSSD. We found little evidence for associations with other chemical species and with with the rate of change in heart rate variability, though endotoxin was associated with increasing heart rate variability over time. Conclusion We found only weak evidence that long-term PM10-2.5 exposures are associated with lowered heart rate variability. Stronger associations among residentially stable individuals suggest that confirmatory studies are needed. PMID:27035690

Your brain on bikes: P3, MMN/N2b, and baseline noise while pedaling a stationary bike.

PubMed

Scanlon, Joanna E M; Sieben, Alex J; Holyk, Kevin R; Mathewson, Kyle E

2017-06-01

Increasingly, there is a trend to measure brain activity in more ecologically realistic scenarios. Normally, the confines of the laboratory and sedentary tasks mitigate sources of electrical noise on EEG measurement. Moving EEG outside of the lab requires understanding of the impact of complex movements and activities on traditional EEG and ERP measures. Here, we recorded EEG with active electrodes while participants were either riding or sitting on a stationary bike in an electrical and sound-attenuated chamber in the lab. Participants performed an auditory oddball task, pressing a button when they detected rare target tones in a series of standard frequent tones. We quantified both the levels of spectral, single-trial baseline, and ERP baseline noise, as well as classic MMN/N2b and P3 ERP components measured during both biking and sitting still. We observed slight increases in posterior high frequency noise in the spectra, and increased noise in the baseline period during biking. However, morphologically and topographically similar MMN/N2b and P3 components were measured reliably while both biking and sitting. A quantification of the power to reliably measure ERPs as a function of the number of trials revealed slight increases in the number of trials needed during biking to achieve the same level of power. Taken in sum, our results confirm that classic ERPs can be measured reliably during biking activities in the lab. Future directions will employ these techniques outside the lab in ecologically valid situations. © 2017 Society for Psychophysiological Research.

Effect of anthelminthic treatment on helminth infection and related anaemia among school-age children in northwestern Ethiopia.

PubMed

Yimam, Yonas; Degarege, Abraham; Erko, Berhanu

2016-10-28

Information about improvements in the health status of population at-risk of helminth infection after anthelminthic treatment helps to evaluate the effectiveness of the large scale deworming program. The objectives of this study were to assess the impact of anthelminthic treatment on the prevalence and intensity of intestinal helminth infection, haemoglobin level and prevalence of anaemia among school-age children. A total of 403 children attending Tikur Wuha Elementary School in Jiga, northwestern Ethiopia were enrolled in this study between February and March 2011. Formol-ether concentration and Kato-Katz methods were used to examine stool for intestinal helminth infections at baseline and one month after anthelminthic treatment. Haemoglobin level was measured using Hemocue machine at baseline and one month after anthelminthic treatment. Out of 403 school children examined, 15.4 % were anaemic and 58.3 % were infected with intestinal helminths at baseline. Hookworms (46.9 %), Schistosoma mansoni (24.6 %), Ascaris lumbricoides (4.2 %) and Trichuris trichiura (1.7 %) infections were common. The odds of anaemia was higher among children infected with helminths (adjusted odds ratio (aOR) = 3.83, 95 % CI = 1.92, 7.62) especially in those infected with hookworm (aOR = 2.42, 95 % CI = 1.34, 4.39) or S. mansoni (aOR = 2.67, 95 % CI = 1.46, 4.88) and two or more helminth species (aOR = 7.31, 95 % CI = 3.27, 16.35) than those uninfected with intestinal helminths at baseline. Significant reduction in prevalence of helminth infection (77.0 %) and increment in mean haemoglobin level (+3.65 g/l) of children infected with helminths was observed one month after anthelminthic treatment. The increase in haemoglobin level after anthelminthic treatment was significantly positively associated with the age, but negatively associated with the haemoglobin level at baseline. The change in mean haemoglobin level was significantly higher among undernourished than normal children. Percent reduction in the prevalence of anaemia among children infected with helminths was 25.4 % after anthelminthic treatment. The present study provides evidence that anthelminthic treatment of school-age children infected with intestinal helminth can improve haemoglobin level in addition to reducing the prevalence and intensity of helminth infections one month after treatment. This suggests that deworming of children may benefit the health of children in sub-Sharan Africa where hookworm and S. mansoni infections are prevalent.

Tall stature without growth hormone: four male patients with aromatase deficiency.

PubMed

Rochira, Vincenzo; Zirilli, Lucia; Maffei, Laura; Premrou, Valeria; Aranda, Claudio; Baldi, Matteo; Ghigo, Ezio; Aimaretti, Gianluca; Carani, Cesare; Lanfranco, Fabio

2010-04-01

From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. A case-control study was conducted. Four adult men with aromatase deficiency were compared with 12 normal subjects. We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

Safety of disclosing amyloid status in cognitively normal older adults.

PubMed

Burns, Jeffrey M; Johnson, David K; Liebmann, Edward P; Bothwell, Rebecca J; Morris, Jill K; Vidoni, Eric D

2017-09-01

Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test-related distress were present after disclosure and were related to greater baseline levels of anxiety and depression. Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre- and postdisclosure counseling has a low risk of psychological harm. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Categorical improvements in disease severity in patients with major depressive disorder treated with vilazodone: post hoc analysis of four randomized, placebo-controlled trials.

PubMed

Durgam, Suresh; Chen, Changzheng; Gommoll, Carl P; Edwards, John; Citrome, Leslie

2016-01-01

In three 8-week studies of vilazodone 40 mg/d (NCT00285376, NCT00683592, and NCT01473394) and a 10-week study of vilazodone 20 or 40 mg/d (NCT01473381), adults with major depressive disorder (MDD) showed significantly greater improvement with vilazodone versus placebo in global disease severity as measured by mean change from baseline in Clinical Global Impression of Severity (CGI-S) score. To assess the proportion of patients achieving clinically meaningful improvement, a post hoc pooled analysis was conducted using categorical shifts in disease severity based on CGI-S scores at baseline and end of treatment (EOT). Analyses were conducted in the pooled intent-to-treat population (N=2,218). Definitions of categorical shifts included CGI-S ≥4 (moderately ill or worse) at baseline to CGI-S ≤2 (normal or borderline ill) at EOT; CGI-S ≥5 (markedly ill or worse) at baseline to CGI-S ≤2 at EOT; and CGI-S ≥6 (severely ill or worse) at baseline to CGI-S ≤3 (mildly ill or better) at EOT. At baseline, 2,217 patients were moderately ill or worse. The percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (40.0% versus 27.8%; odds ratio [OR] =1.7, P <0.001; number needed to treat [NNT] =9). In the 979 patients who were markedly ill or worse at baseline, the percentage who improved to normal or borderline ill was significantly higher with vilazodone than with placebo (36.8% versus 25.5%; OR =1.7, P <0.001; NNT =9). The small number of severely ill patients at baseline (n =43) provided inadequate power to detect statistically significant between-group differences, but an NNT =5 was found for improvement to mildly ill or better. Categorical shift analyses, defined using baseline and EOT CGI-S scores, showed that significantly higher proportions of patients had clinically meaningful improvements in global disease severity with vilazodone 20-40 mg/d versus placebo. This type of analysis may be useful for evaluating the effects of antidepressant treatment in adults with MDD.

Dose Adjustment for Normal Eating (DAFNE) in routine clinical practice: who benefits?

PubMed

Keen, A J A; Duncan, E; McKillop-Smith, A; Evans, N D; Gold, A E

2012-05-01

To explore the effectiveness of Dose Adjustment for Normal Eating in routine clinical practice in the UK. Participants were 124 adults with Type 1 diabetes who had completed a Dose Adjustment for Normal Eating course. Data were collected before the course and again 1 year later on a variety of biological, psychological and social measures. There were a range of significant benefits consistent with Dose Adjustment for Normal Eating aims, including: better control among those with baseline HbA(1c) ≥ 81 mmol/mol (9.6%) (z = -2.8, P = 0.004); reduced number of participants reporting severe hypoglycaemia (χ² = 4.27, P = 0.039); total eradication of diabetic ketoacidosis (χ² = 4.17, P = 0.041) and lower diabetes-related distress (z = -4.5, P < 0.001). The most deprived of the clinic population were significantly under-represented (χ² = 17.8, P = 0.001) and the levels of clinical depression were unusually low. These results indicate that Dose Adjustment for Normal Eating delivered in routine clinical practice is associated with a range of benefits and that certain clinical and psychosocial characteristics are associated with better outcomes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

PubMed

Barceló, Antonia; Morell-Garcia, Daniel; Salord, Neus; Esquinas, Cristina; Pérez, Gerardo; Pérez, Antonio; Monasterio, Carmen; Gasa, Merce; Fortuna, Ana Maria; Montserrat, Josep Maria; Mayos, Mercedes

2017-12-01

There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P < 0.005). With respect to patients with normal glucose tolerance (NGT), patients with impaired glucose tolerance (IGT) had higher baseline levels of isoleucine (78 ± 16 versus 70 ± 13 μmol L -1 , P = 0.014) and valine (286 ± 36 versus 268 ± 41 μmol L -1 , P = 0.049), respectively. Changes in levels of leucine and isoleucine after treatment were related negatively to changes in fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea. © 2017 European Sleep Research Society.

Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon β-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.

PubMed

Lanzillo, R; Di Somma, C; Quarantelli, M; Carotenuto, A; Pivonello, C; Moccia, M; Cianflone, A; Marsili, A; Puorro, G; Saccà, F; Russo, C V; De Luca Picione, C; Ausiello, F; Colao, A; Brescia Morra, V

2017-02-01

Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon β (IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients. Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years. Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P < 0.001) and GH levels (P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence. Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression. © 2016 EAN.

Weather analysis and interpretation procedures developed for the US/Canada wheat and barley exploratory experiment

NASA Technical Reports Server (NTRS)

Trenchard, M. H. (Principal Investigator)

1980-01-01

Procedures and techniques for providing analyses of meteorological conditions at segments during the growing season were developed for the U.S./Canada Wheat and Barley Exploratory Experiment. The main product and analysis tool is the segment-level climagraph which depicts temporally meteorological variables for the current year compared with climatological normals. The variable values for the segment are estimates derived through objective analysis of values obtained at first-order station in the region. The procedures and products documented represent a baseline for future Foreign Commodity Production Forecasting experiments.

Serial C-reactive protein measurements in patients treated for suspected abdominal tuberculosis.

PubMed

Sharma, Vishal; Mandavdhare, Harshal S; Lamoria, Sandeep; Singh, Harjeet; Kumar, Amit

2018-06-01

Response to treatment is often used as a criterion for the diagnosis of abdominal tuberculosis. To determine utility of serum C reactive protein (CRP) in assessment of response to anti-tubercular therapy (ATT) in abdominal tuberculosis (ATB). We retrospectively analysed the database of patients with suspected ATB (intestinal and/or peritoneal). Response to ATT was assessed using subjective and objective (ulcer healing or ascites resolution) parameters. Serum CRP levels were estimated at baseline and then at 2 months and 6 months of ATT. One hundred and twelve patients were included in the analysis. The mean age was 36.57 ± 15.04 years and 54.46% (61/112) were males. Sixty-six patients (58.92%) had intestinal, 28 (25%) had peritoneal and 18 (16.07%) had both. Eleven patients had a normal CRP at baseline while 101 had elevated levels. The CRP levels declined in 94 patients at 6 months. One patient with increased levels at 2 months had multi-drug resistant TB. Seven patients showed elevated or plateaued CRP levels on follow-up. These patients had underlying Crohn's disease (3 patients), peritoneal carcinomatosis (1), inter-current infection (1), lymphoma (1) and non-healing ulcers (1). Lack of decline in CRP may suggest alternative diagnosis or drug-resistant tuberculosis. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Molt-associated changes in hematologic and plasma biochemical values and stress hormone levels in African penguins (Spheniscus demersus).

PubMed

Mazzaro, Lisa M; Meegan, Jenny; Sarran, Delphine; Romano, Tracy A; Bonato, Vinicius; Deng, Shibing; Dunn, J Lawrence

2013-12-01

Handling, including blood collection, has often been discouraged in molting penguins because it is considered an additional stress imposed on birds already experiencing major physiologic stress associated with molting. To evaluate the degree of physiologic stress posed by molting, we compared the hematologic and plasma biochemical values and hormone levels of molting and nonmolting African penguins, Spheniscus demersus. Five male and 5 female penguins randomly chosen were given complete physical examinations, were weighed, and blood samples were taken at 7 time points before, during, and after the molt. Data were analyzed by linear mixed-model analysis of variance. Throughout the study, behavior and appetite remained normal. Catecholamine levels were highly variable within and among subjects, whereas mean corticosterone levels were significantly different between baseline, molt, and postmolt values. Significant differences from baseline values were observed in many of the hematologic analytes; however, only decreases in hematocrit and red blood cell count values were considered clinically significant. Anemia due to experimentally induced blood loss as a possible cause of the significant hematologic changes was ruled out based on results of a follow-up control study during the nonmolt season, which showed no significant changes in hematocrit level or total red blood cell counts when using similar sampling protocols, which indicates that these changes were associated with molt.

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

PubMed

Javaid, J I; Notorangelo, M P; Pandey, S C; Reddy, P L; Pandey, G N; Davis, J M

1994-07-01

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs.

PubMed

Broussard, Josiane L; Kolka, Cathryn M; Castro, Ana V B; Asare Bediako, Isaac; Paszkiewicz, Rebecca L; Szczepaniak, Edward W; Szczepaniak, Lidia S; Knutson, Kristen L; Kim, Stella P; Bergman, Richard N

2015-11-01

A normal consequence of increased energy intake and insulin resistance is compensatory hyperinsulinaemia through increased insulin secretion and/or reduced insulin clearance. Failure of compensatory mechanisms plays a central role in the pathogenesis of type 2 diabetes mellitus; consequently, it is critical to identify in vivo signal(s) involved in hyperinsulinaemic compensation. We have previously reported that high-fat feeding leads to an increase in nocturnal NEFA concentration. We therefore designed this study to test the hypothesis that elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation for insulin resistance. Blood sampling was conducted in male dogs to determine 24 h profiles of NEFA at baseline and during high-fat feeding with and without acute nocturnal NEFA suppression using a partial A1 adenosine receptor agonist. High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIR(g)). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIR(g) with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIR(g). This relationship indicates that the hyperinsulinaemic compensation induced in response to high-fat feeding was prevented when the nocturnal NEFA pattern was returned to baseline. Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.

Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes.

PubMed

Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Hollmann, Charleen; Crystal, Ronald G

2018-05-14

Little is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes. Ten never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of "Blu" brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals. Two hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine. This study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking. ClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats.

PubMed

Yanagida, M; Ide, Y; Imai, A; Toriyama, M; Aoki, T; Harada, K; Izumi, H; Uzumaki, H; Kusaka, M; Tokiwa, T

1997-12-01

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

Thyroid hormones and mortality risk in euthyroid individuals: the Kangbuk Samsung health study.

PubMed

Zhang, Yiyi; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Pastor-Barriuso, Roberto; Rampal, Sanjay; Han, Won Kon; Shin, Hocheol; Guallar, Eliseo

2014-07-01

Hyperthyroidism and hypothyroidism, both overt and subclinical, are associated with all-cause and cardiovascular mortality. The association between thyroid hormones and mortality in euthyroid individuals, however, is unclear. To examine the prospective association between thyroid hormones levels within normal ranges and mortality endpoints. A prospective cohort study of 212 456 middle-aged South Korean men and women who had normal thyroid hormone levels and no history of thyroid disease at baseline from January 1, 2002 to December 31, 2009. Free T4 (FT4), free T3 (FT3), and TSH levels were measured by RIA. Vital status and cause of death ascertainment were based on linkage to the National Death Index death certificate records. After a median follow-up of 4.3 years, 730 participants died (335 deaths from cancer and 112 cardiovascular-related deaths). FT4 was inversely associated with all-cause mortality (HR = 0.77, 95% confidence interval 0.63-0.95, comparing the highest vs lowest quartile of FT4; P for linear trend = .01), and FT3 was inversely associated cancer mortality (HR = 0.62, 95% confidence interval 0.45-0.85; P for linear trend = .001). TSH was not associated with mortality endpoints. In a large cohort of euthyroid men and women, FT4 and FT3 levels within the normal range were inversely associated with the risk of all-cause mortality and cancer mortality, particularly liver cancer mortality.

Long-term outcome of macroprolactinomas.

PubMed

Képénékian, Lori; Cebula, Hélène; Castinetti, Frédéric; Graillon, Thomas; Brue, Thierry; Goichot, Bernard

2016-12-01

Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But few data exist on the long-term outcome of these patients. Retrospective descriptive multicenter study of patients with macroprolactinoma followed for at least 5 years between 1973 and 2008 at the University Hospitals of Strasbourg and Marseille. Forty-eight patients were included with 27 men, hypopituitarism in 33.3% of all patients and mean serum prolactin (PRL) level at diagnosis 2218.2±4154.7μg/L. Among the patients, 58.3% received medical treatment, 25% had additional surgery and 12.5% surgery and radiotherapy. The mean follow-up duration was 196±100 months. At the end of follow-up, 10 patients (20.8%) were cured (i.e. normal PRL level and normal imaging, no symptoms and withdrawal of DA≥1 year), 33 (68.8%) were controlled (i.e. normal PRL level, normal or abnormal imaging, no symptoms, DA in progress) and 5 (10.4%) were uncontrolled. Uncontrolled patients had significant higher baseline PRL level (P=0.0412) and cabergoline cumulative dose (P=0.0065) compared to the controlled group. There was no increase in frequency of hypopituitarism. Clinically significant valvular heart disease was found in 2 patients but screening was not systematic. Macroprolactinoma is currently most often a chronic disease controlled with DA. However, uncertainty about the adverse effects associated with high cumulative doses and the lack of data on the prognosis at very long-term should incite to revisit current strategies, including the role of surgery combined to medical treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Behavioral Impulsivity Does Not Predict Naturalistic Alcohol Consumption or Treatment Outcomes

PubMed Central

Mullen, Jillian; Mathias, Charles W.; Karns, Tara E.; Liang, Yuanyuan; Hill-Kapturczak, Nathalie; Roache, John D.; Lamb, Richard J.; Dougherty, Donald M.

2016-01-01

Objective The purpose of this study was to determine if behavioral impulsivity under multiple conditions (baseline, after alcohol consumption or after serotonin depletion) predicted naturalistic alcohol use or treatment outcomes from a moderation-based contingency management intervention. Method The current data analysis pulls information from three phases of a large study: 1) Phase 1 examined baseline and the effects of alcohol use and serotonin depletion on three types of behavioral impulsivity: response initiation (IMT task), response inhibition (GoStop task), and delay discounting (SKIP task); 2) Phase 2 involved 28 days of naturalistic drinking; and 3) Phase 3 involved 3 months of contingency management. During phases 2 and 3 alcohol use was measured objectively using transdermal alcohol monitors. The results of each individual phase has been previously published showing that at a group level the effects of alcohol consumption on impulsivity were dependent on the component of impulsivity being measured and the dose of alcohol consumed but serotonin depletion had no effect on impulsivity, and that a moderation-based contingency management intervention reduced heavy drinking. Results The current analysis combining data from those who completed all three phases (n = 67) showed that impulsivity measured at baseline, after alcohol consumption, or after serotonin depletion did not predict naturalistic drinking or treatment outcomes from a moderation-based CM treatment. Conclusions Contingency management interventions may prove to be an effective intervention for impulsive individuals, however, normal variations in measured impulsivity do not seem to relate to normal variations in drinking pattern or response to moderation-based contingency management. PMID:27746702

Changes in physical fitness and nutritional status of schoolchildren in a period of 30 years (1980-2010)

PubMed Central

Ferrari, Gerson Luis de Moraes; Matsudo, Victor Keihan Rodrigues; Fisberg, Mauro

2015-01-01

Objective: To analyze and compare the changes in physical fitness according to the nutritional status and gender of schoolchildren during a period of 30 years (1980-2010). Methods: Four cross-sectional evaluations were performed every 10 years in a period of 30 years from 1978 to 1980 (baseline), 1988-1990 (10 years), 1998-2000 (20 years) and 2008-2010 (30 years). The sample consisted of 1291 schoolchildren (188 in baseline, 307 in 10 years; 375 in 20 years; 421 in 30 years) of 10 and 11 years old. The variables assessed were: body weight (kg), height (cm), upper limb strength (ULS; kg), lower limb strength (LLS; cm), agility (seconds) and velocity (seconds). Schoolchildren were classified as normal weight and overweight according to World Health Organization reference of body mass index for age and gender. Comparisons among periods applied ANOVA followed by Bonferroni test, with a significance level set at of p<0.01. Variation between baseline and 30 years was assessed by the percentage delta. Seven different percentile values were presented for each variable. Results: In eutrophic boys and girls, mean values of ULS (−16.7%; −3.2%), agility (−1.5%; −1.6%) decreased significantly after 30 years (p<0.001). In the overweight boys and girls, only the average ULS (−15.5%; −12.5%) decreased significantly over time (p<0.001). After 30 years, the ULS percentile changed in boys. Conclusions: The decline in physical fitness was greater in schoolchildren with normal weight than in those with overweight. PMID:26298653

Verbal short-term memory development and spoken language outcomes in deaf children with cochlear implants.

PubMed

Harris, Michael S; Kronenberger, William G; Gao, Sujuan; Hoen, Helena M; Miyamoto, Richard T; Pisoni, David B

2013-01-01

Cochlear implants (CIs) help many deaf children achieve near-normal speech and language (S/L) milestones. Nevertheless, high levels of unexplained variability in S/L outcomes are limiting factors in improving the effectiveness of CIs in deaf children. The objective of this study was to longitudinally assess the role of verbal short-term memory (STM) and working memory (WM) capacity as a progress-limiting source of variability in S/L outcomes after CI in children. Longitudinal study of 66 children with CIs for prelingual severe-to-profound hearing loss. Outcome measures included performance on digit span forward (DSF), digit span backward (DSB), and four conventional S/L measures that examined spoken-word recognition (Phonetically Balanced Kindergarten word test), receptive vocabulary (Peabody Picture Vocabulary Test ), sentence-recognition skills (Hearing in Noise Test), and receptive and expressive language functioning (Clinical Evaluation of Language Fundamentals Fourth Edition Core Language Score; CELF). Growth curves for DSF and DSB in the CI sample over time were comparable in slope, but consistently lagged in magnitude relative to norms for normal-hearing peers of the same age. For DSF and DSB, 50.5% and 44.0%, respectively, of the CI sample scored more than 1 SD below the normative mean for raw scores across all ages. The first (baseline) DSF score significantly predicted all endpoint scores for the four S/L measures, and DSF slope (growth) over time predicted CELF scores. DSF baseline and slope accounted for an additional 13 to 31% of variance in S/L scores after controlling for conventional predictor variables such as: chronological age at time of testing, age at time of implantation, communication mode (auditory-oral communication versus total communication), and maternal education. Only DSB baseline scores predicted endpoint language scores on Peabody Picture Vocabulary Test and CELF. DSB slopes were not significantly related to any endpoint S/L measures. DSB baseline scores and slopes taken together accounted for an additional 4 to 19% of variance in S/L endpoint measures after controlling for the conventional predictor variables. Verbal STM/WM scores, process measures of information capacity, develop at an average rate in the years after cochlear implantation, but were found to consistently lag in absolute magnitude behind those reported for normal-hearing peers. Baseline verbal STM/WM predicted long-term endpoint S/L outcomes, but verbal STM slopes predicted only endpoint language outcomes. Verbal STM/WM processing skills reflect important underlying core elementary neurocognitive functions and represent potential intervention targets for improving endpoint S/L outcomes in pediatric CI users.

RADON BASELINE MONITORING AROUND A POTENTIAL SHALE GAS DEVELOPMENT SITE IN YORKSHIRE, ENGLAND.

PubMed

Daraktchieva, Z; Wasikiewicz, J M; Howarth, C B; Bradley, E J

2017-11-01

The Vale of Pickering in Yorkshire, England has been identified as a potential area for shale gas extraction. Public Health England joined a collaboration led by the British Geological Survey for environmental baseline monitoring near the potential shale gas extraction site following a grant award from UK Government Department for Business, Energy and Industrial Strategy. The analysis of results for the first 6 months of indoor monitoring indicated that the results followed a log-normal distribution. The numbers of homes found to be at or above the Action Level followed the numbers predicted by the radon potential maps. The results from the measurements of outdoor air in this study indicated that the radon concentrations are slightly higher than previously measured but close to the detection limit of the technique. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10.

PubMed

Zhang, Ren-Wen; Shao, Cui-Ping; Huo, Na; Li, Min-Ran; Xi, Hong-Li; Yu, Min; Xu, Xiao-Yuan

2015-09-07

To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients. One hundred and thirty-nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNα-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline. The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNα-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 ± 244.2 pg/mL vs 310.0 ± 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non-TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014). Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.

Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults.

PubMed

Moon, Jae Hoon; Lim, Soo; Han, Ji Won; Kim, Kyoung Min; Choi, Sung Hee; Park, Kyong Soo; Kim, Ki Woong; Jang, Hak Chul

2015-04-01

We investigated the association between cardiovascular risk factors, including carotid intima-media thickness (CIMT), and future risk of mild cognitive impairment (MCI) and dementia in elderly subjects. We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Our study included 348 participants who were nondemented at the baseline (mean age, 71.7±6.3 years) and underwent cognitive evaluation at the 5-year follow-up. Baseline cardiovascular risk factors were compared according to the development of MCI or dementia during the study period. At the baseline evaluation, 278 subjects were cognitively normal and 70 subjects had MCI. Diagnoses of cognitive function either remained unchanged or improved during the study period in 292 subjects (nonprogression group), whereas 56 subjects showed progression of cognitive impairment to MCI or dementia (progression group). The progression group exhibited a higher prevalence of hypertension and greater CIMT compared with the nonprogression group. Other baseline cardiovascular risk factors, including sex, body mass index, diabetes mellitus, insulin resistance, total cholesterol, waist-to-hip ratio, visceral fat, pulse wave velocity, and ankle-brachial index, were not significantly different between 2 groups. The association between greater baseline CIMT and the progression of cognitive impairment was maintained after adjustment for conventional baseline risk factors of cognitive impairment. Greater baseline CIMT was also independently associated with the development of MCI in the subjects whose baseline cognitive function was normal. Greater baseline CIMT was independently associated with the risk of cognitive impairment, such as MCI and dementia in elderly subjects. © 2015 American Heart Association, Inc.

The association of short-term memory and cognitive impairment with ghrelin, leptin, and cortisol levels in non-diabetic and diabetic elderly individuals.

PubMed

Sang, Yu Ming; Wang, Li Jun; Mao, Hong Xian; Lou, Xue Yong; Zhu, Yi Jun

2018-06-01

This study assessed short-term memory and biochemical indicators with the levels of ghrelin, leptin, and cortisol between cognitive impairment and normal older adults with or without diabetes. We enrolled 286 older adults (aged 65-85 years) with or without diabetes from the local community. Short-term memory was assessed using pictures of common objects; cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The physiological indexes assessed were plasma levels of fasting ghrelin and leptin, ghrelin level at 2_h after breakfast, 24-h urinary cortisol value, body mass index, and plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. In both non-diabetic and diabetic subjects, short-term memory was significantly lower in the impaired cognition group (5.99 ± 2.90 in non-diabetic subjects and 4.71 ± 2.14 in diabetic subjects) than in the normal cognition group (8.14 ± 2.23 in non-diabetic subjects and 7.82 ± 3.37 in diabetic subjects). Baseline ghrelin level was significantly lower in the impaired cognition group (9.07 ± 1.13 ng/mL in non-diabetic subjects and 7.76 ± 1.34 ng/mL in diabetic subjects) than in the normal cognition group (10.94 ± 1.53 ng/mL in non-diabetic subjects and 9.93 ± 1.76 ng/mL in diabetic subjects); plasma cortisol levels at 8:00 a.m., 4:00 p.m., and 12:00 p.m. were significantly higher in the impaired cognition group than in the normal cognition group, while no significant difference was observed in plasma levels of fasting leptin between different groups. Fasting plasma ghrelin and cortisol levels may be markers of cognitive decline and memory loss. It is possible that adjusting their levels may have a therapeutic effect, and this should be investigated in future studies.

High-dose oral colecalciferol loading in obesity: impact of body mass index and its utility prior to bariatric surgery to treat vitamin D deficiency.

PubMed

King, R J; Chandrajay, D; Abbas, A; Orme, S M; Barth, J H

2017-04-01

Obesity is associated with lower vitamin D levels compared with normal weight subjects, and if levels are not replaced prior to bariatric surgery, this can increase fracture risk as bone density typically falls post-operatively. We analysed the effect of body mass index (BMI) on vitamin D levels in response to 300 000 IU of colecalciferol in patients with vitamin D deficiency (<30 nmol L -1 ). Patients were grouped according to their BMI as normal weight (20-24.9 kg m -2 ), overweight (25-29.9 kg m -2 ), obese class I (30-34.9 kg m -2 ) and obese class II and above (>35 kg m -2 ). The records were retrospectively analysed to investigate the effects of BMI on vitamin D (total 25-hydroxy vitamin D [25(OH)D]), serum Ca 2+ and parathyroid hormone (PTH) levels at 6, 12, 26 and 52 weeks compared with baseline. Compared with normal weight subjects, overweight and obese patients achieved lower mean peak total 25(OH)D levels (6 weeks post-loading), which was most significant in the class II and above group (mean total 25(OH)D levels 96.5 ± 24.2 nmol L -1 and 72.42 ± 24.9 nmol L -1 , respectively; P = 0.003). By 26 weeks, total 25(OH)D levels fell in all groups; however, there was now a significant difference between the normal weight subjects and all other groups (mean total 25(OH)D levels 84.1 ± 23.7 nmol L -1 ; 58 ± 20 nmol L -1 , P = 0.0002; 62.65 ± 19.2 nmol L -1 , P = 0.005; 59.2 ± 21 nmol L -1 , P = 0.005, respectively). Far fewer patients in the overweight and obese groups maintained levels above the recommended level of 75 nmol L -1 52 weeks post-loading (93%; 20%, P = 0.0003; 23%, P = 0.01; and 14%, P = 0.001, respectively). Alternative regimes for the treatment of vitamin D deficiency are needed in overweight and obese patients, especially those in whom bariatric surgery is planned. © 2017 World Obesity Federation.

Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

PubMed

Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

2015-05-01

Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels <50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p < 0.001). At T 26, 25OHD levels >75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p < 0.05). Side effects or hypercalcemia were not observed. No improvement of performance tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

Iowa Gambling Task with non-clinical participants: effects of using real + virtual cards and additional trials

PubMed Central

Overman, William H.; Pierce, Allison

2013-01-01

Performance on the Iowa Gambling Task (IGT) in clinical populations can be interpreted only in relation to established baseline performance in normal populations. As in all comparisons of assessment tools, the normal baseline must reflect performance under conditions in which subjects can function at their best levels. In this review, we show that a number of variables enhance IGT performance in non-clinical participants. First, optimal performance is produced by having participants turn over real cards while viewing virtual cards on a computer screen. The use of only virtual cards results in significantly lower performance than the combination of real + virtual cards. Secondly, administration of more than 100 trials also enhances performance. When using the real/virtual card procedure, performance is shown to significantly increase from early adolescence through young adulthood. Under these conditions young (mean age 19 years) and older (mean age 59 years) adults perform equally. Females, as a group, score lower than males because females tend to choose cards from high-frequency-of-gain Deck B. Groups of females with high or low gonadal hormones perform equally. Concurrent tasks, e.g., presentation of aromas, decrease performance in males. Age and gender effects are discussed in terms of a dynamic between testosterone and orbital prefrontal cortex. PMID:24376431

MULTIFUNCTION ENERGY PLATFORM (MFP) PILOT

EPA Science Inventory

• Multi-sector Baseline Survey:  A five-sector survey (agriculture, energy, water, health, and general - demogr...

• Anterior Cingulate Glutamate Is Reduced by Acamprosate Treatment in Patients With Alcohol Dependence.

  PubMed

  Frye, Mark A; Hinton, David J; Karpyak, Victor M; Biernacka, Joanna M; Gunderson, Lee J; Feeder, Scott E; Choi, Doo-Sup; Port, John D

  2016-12-01

  Although the precise drug mechanism of action of acamprosate remains unclear, its antidipsotropic effect is mediated in part through glutamatergic neurotransmission. We evaluated the effect of 4 weeks of acamprosate treatment in a cohort of 13 subjects with alcohol dependence (confirmed by a structured interview, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) on proton magnetic resonance spectroscopy glutamate levels in the midline anterior cingulate cortex (MACC). We compared levels of metabolites with a group of 16 healthy controls. The Pennsylvania Alcohol Craving Scale was used to assess craving intensity. At baseline, before treatment, the mean cerebrospinal fluid-corrected MACC glutamate (Glu) level was significantly elevated in subjects with alcohol dependence compared with controls (P = 0.004). Four weeks of acamprosate treatment reduced glutamate levels (P = 0.025), an effect that was not observed in subjects who did not take acamprosate. At baseline, there was a significant positive correlation between cravings, measured by the Pennsylvania Alcohol Craving Scale, and MACC (Glu) levels (P = 0.019). Overall, these data would suggest a normalizing effect of acamprosate on a hyperglutamatergic state observed in recently withdrawn patients with alcohol dependence and a positive association between MACC glutamate levels and craving intensity in early abstinence. Further research is needed to evaluate the use of these findings for clinical practice, including monitoring of craving intensity and individualized selection of treatment with antidipsotropic medications in subjects with alcohol dependence.

• Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency or leptin administration in humans.

  PubMed

  Kang, Eun Seok; Magkos, Faidon; Sienkiewicz, Elizabeth; Mantzoros, Christos S

  2011-06-01

  Animal and in vitro studies indicate that leptin alleviates starvation-induced reduction in circulating vaspin and stimulates the production of visfatin. We thus examined whether vaspin and visfatin are affected by short- and long-term energy deprivation and leptin administration in human subjects in vivo. We measured circulating levels of vaspin and visfatin i) before and after 72 h of starvation (leading to severe hypoleptinemia) with or without leptin administration in replacement doses in 13 normal-weight subjects, ii) before and after 72 h of starvation with leptin administration in pharmacological doses in 13 lean and obese subjects, iii) during chronic energy deficiency in eight women with hypothalamic amenorrhea on leptin replacement for 3 months, and iv) during chronic energy deficiency in 18 women with hypothalamic amenorrhea on leptin replacement or placebo for 3 months. Acute starvation decreased serum leptin to 21% of baseline values, (P=0.002) but had no significant effect on vaspin and visfatin concentrations (P>0.05). Nor did normalization of leptin levels affect the concentrations of these two adipokines (P>0.9). Leptin replacement in women with hypothalamic amenorrhea did not significantly alter vaspin and visfatin concentrations, whether relative to baseline or placebo administration (P>0.25). Pharmacological doses of leptin did not affect circulating vaspin and visfatin concentrations (P>0.9). Circulating vaspin and visfatin are not affected by acute or chronic energy deficiency leading to hypoleptinemia and are not regulated by leptin in human subjects, indicating that these adipocyte-secreted hormonal regulators of metabolism are independently regulated in humans.

• The acute phase response of C3, C5, ceruloplasmin, and C-reactive protein induced by turpentine pleurisy in the rabbit.

  PubMed Central

  Giclas, P. C.; Manthei, U.; Strunk, R. C.

  1985-01-01

  Concentrations of five serum proteins, C3, C5, ceruloplasmin, C-reactive protein, and albumin, have been measured during the acute phase response in rabbits with turpentine-induced pleurisy. C-reactive protein concentrations in the circulation rose abruptly between 12 and 36 hours to a level greater than 50 times the pretreatment concentration, then returned to undetectable amounts by 96 hours. C3 and ceruloplasmin both showed some increase in concentration by 12 hours and reached their maximum concentrations of two to three times the baseline levels 48-72 hours after the turpentine treatment. Concentrations were still elevated at 120 hours, after which time they gradually returned to normal. C5 and albumin concentrations in the turpentine-treated rabbits did not differ from the baseline concentrations. The same five proteins were measured in the inflammatory exudate. C-reactive protein was not detectable at any of the time points. C3, C5, ceruloplasmin, and albumin were present in normal pleural fluid at roughly half their serum concentrations. The activities of C3, C5, and ceruloplasmin were low in the early exudate, but C3 and C5 activity rose relative to their concentrations in the later samples of pleural fluid. The specific activities of C3 and C5 were higher in the pleural fluid at 72 hours than in plasma, while that of ceruloplasmin remained less in the pleural fluid than in plasma throughout the experiment. The involvement of these proteins and their relation to the inflammatory response are discussed. Images Figure 6 PMID:2409807

• Nutritional effect of nandrolone decanoate in predialysis patients with chronic kidney disease.

  PubMed

  Eiam-Ong, Somchai; Buranaosot, Somphon; Eiam-Ong, Somchit; Wathanavaha, Arpar; Pansin, Pongsuk

  2007-05-01

  The study objective was to examine the nutritional effect of nandrolone decanoate, an androgen derivative, in predialysis patients with chronic kidney disease (CKD). This was a prospective and experimental study. The study was performed at the institutional level of clinical care. Twenty-nine predialysis patients with CKD, with a glomerular filtration rate between 5 and 30 mL/min and moderate to severe malnutrition, were included and randomly divided into control (n = 13) and nandrolone decanoate (NAN, n = 16) groups. Patients in the control group received optimally conventional treatment of CKD. Patients in the NAN group, in addition to the conventional treatment, were intramuscularly injected with nandrolone decanoate at the dose of 100 mg per for 3 months. Nutritional markers, including lean body mass (LBM), normalized protein catabolic rate, serum albumin, and lipids, were determined at baseline and 3-month periods. Baseline parameters in both groups were not different. After 3 months, the patients in the NAN group had increased LBM (P < .01) and decreased serum albumin levels (P < .05), but no changes in the values of normalized protein catabolic rate, serum lipids, hematocrit, and glomerular filtration rate. No alterations in all parameters were identified in the control group. Changes in LBM in the NAN group were significantly higher than in the control group (P < .05). Minor adverse effects were observed in a few patients in the NAN group. Nandrolone decanoate expresses an anabolic effect on LBM without altering the renal function and thus would provide nutritional benefit in predialysis patients with CKD.

• Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight.

  PubMed

  Chao, Ariana M; Jastreboff, Ania M; White, Marney A; Grilo, Carlos M; Sinha, Rajita

  2017-04-01

  To examine whether baseline chronic stress, morning cortisol, and other appetite-related hormones (leptin, ghrelin, and insulin) predict future weight gain and food cravings in a naturalistic, longitudinal, 6-month follow-up study. A prospective community cohort of 339 adults (age 29.1 ± 9.0 years; BMI = 26.7 ± 5.4 kg/m 2 ; 56.9% female; 70.2% white) completed assessments at baseline and 6-month follow-up. Fasting blood draws were used to assess cortisol and other appetite-related hormone levels at baseline. At baseline and follow-up, body weight was measured, and the Cumulative Adversity Interview and Food Craving Inventory were administered. Data were analyzed using linear mixed models adjusting for demographic and clinical covariates. Over the 6-month period, 49.9% of the sample gained weight. Food cravings and chronic stress decreased over 6 months (Ps < 0.05). However, after adjusting for covariates, individuals with higher baseline total ghrelin had significantly higher food cravings at 6 months (P = 0.04). Furthermore, higher cortisol, insulin, and chronic stress were each predictive of greater future weight gain (Ps < 0.05). These results suggest that ghrelin plays a role in increased food cravings and reward-driven eating behaviors. Studies are needed that examine the utility of stress reduction methods for normalizing disrupted cortisol responses and preventing future weight gain. © 2017 The Obesity Society.

• Stress, cortisol, and other appetite-related hormones: Prospective prediction of 6-month changes in food cravings and weight

  PubMed Central

  Chao, Ariana M.; Jastreboff, Ania M.; White, Marney A.; Grilo, Carlos M.; Sinha, Rajita

  2017-01-01

  Objective To examine whether baseline chronic stress, morning cortisol, and other appetite-related hormones (leptin, ghrelin, and insulin) predict future weight gain and food cravings in a naturalistic longitudinal 6-month follow-up study. Methods A prospective community cohort of three hundred and thirty-nine adults (age=29.1± 9.0 years; BMI=26.7±5.4 kg/m2; 56.9% female; 70.2% White) completed assessments at baseline and 6-month follow-up. Fasting blood draws were used to assess cortisol and other appetite-related hormones levels at baseline. At baseline and follow-up, body weight was measured and the Cumulative Adversity Interview and Food Craving Inventory were administered. Data were analyzed using linear mixed models adjusting for demographic and clinical covariates. Results Over the 6-month period, 49.9% of the sample gained weight. Food cravings and chronic stress decreased over 6 months (ps<0.05). However, after adjusting for covariates, individuals with higher baseline total ghrelin had significantly higher food cravings at 6 months (p=0.04). Furthermore, higher cortisol, insulin, and chronic stress were each predictive of greater future weight gain (ps<0.05). Conclusions These results suggest that ghrelin plays a role in increased food cravings and reward-driven eating behaviors. Studies are needed that examine the utility of stress reduction methods for normalizing disrupted cortisol responses and preventing future weight gain. PMID:28349668

• Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly.

  PubMed

  Dogansen, Sema Ciftci; Yalin, Gulsah Yenidunya; Tanrikulu, Seher; Yarman, Sema

  2018-05-01

  In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly. © Georg Thieme Verlag KG Stuttgart · New York.

• Effect of soy protein supplementation in patients with chronic hepatitis C: A randomized clinical trial

  PubMed Central

  Oliveira, Lucivalda PM; de Jesus, Rosangela P; Boulhosa, Ramona SSB; Mendes, Carlos Mauricio C; Gnoatto, Maria Cecilia; Lemaire, Denise C; Toralles, Maria Betania P; Cavalcante, Lourianne N; Lyra, Andre C; Lyra, Luiz GC

  2012-01-01

  AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients’ baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients. PMID:22611313

• Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

  PubMed Central

  Hämäläinen, Anssi; Sipponen, Taina; Kolho, Kaija-Leena

  2011-01-01

  AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the patient was doing well. RESULTS: At introduction of infliximab, median fecal calprotectin level was 1150 μg/g (range 54-6032 μg/g). By week 2, the fecal calprotectin level had declined to a median 261 μg/g (P < 0.001). In 37% of the patients, fecal calprotectin was normal (< 100 μg/g) at 2 wk. By week 6, there was no additional improvement in the fecal calprotectin level (median 345 μg/g). In 22% of the patients, fecal calprotectin levels increased by week 6 to pretreatment levels or above, suggesting no response (or a loss of early response). Thus, in CD, the proportion of non-responsive patients by week 6 seemed lower, because only 9% showed no improvement in their fecal calprotectin level when compared to the respective figure of 46% of the UC patients (P < 0.05). CONCLUSION: When treated with infliximab, fecal calprotectin levels reflecting intestinal inflammation normalized rapidly in one third of pediatric patients suggesting complete mucosal healing. PMID:22215940

• Ovarian cancer-related hypophosphatemic osteomalacia--a case report.

  PubMed

  Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao; Tsai, Keh-Sung

  2014-12-01

  Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. We investigated a 57-year-old woman with progressive low back pain. Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

• Glucose-lowering effect of whey protein depends upon clinical characteristics of patients with type 2 diabetes.

  PubMed

  Almario, Rogelio U; Buchan, Wendy M; Rocke, David M; Karakas, Sidika E

  2017-01-01

  Whey protein (WP) intake has been shown to reduce postprandial glycemia. Majority of WP research in type 2 diabetes (T2DM) involved acute challenge or weight loss studies. It is not known if WP supplementation can provide sustained glucose lowering. Our goal was to investigate the effects of WP on glycemia comprehensively by using continuous glucose monitoring (CGM) while avoiding the confounding effects of variable food intake through controlled feeding. This double-blinded and placebo (PL)-controlled study included 22 patients with T2DM patients (11 male, 11 female; age 57.1±12.6 years) on diet or metformin monotherapy. First, one serving (21 g) of WP was compared with PL in parallel-armed acute challenge studies. Next, in a crossover design, each patient underwent CGM twice, over 2 consecutive weeks, 3.5 days each week. Identical diets were provided by the study during both CGM periods. During the first CGM, one serving of either WP or PL was consumed before breakfast and another before dinner. During the second CGM, participants switched to the alternate supplement. Order of the supplements was randomized. During acute challenge studies, WP stimulated insulin and glucagon-like peptide (GLP)-1 secretion; suppressed ghrelin (all p<0.05), while PL had no effect. During CGM, glucose response to WP varied depending on the baseline characteristics of the patients. When evaluated using linear regression, the most predictive baseline variables were body mass index (BMI) (p=0.0006), triglycerides (p=8.3×10 -5 ) and GLP-1 (p=0.006). Lower BMI, triglyceride and GLP-1 predicted decreased glucose levels on WP. Obesity, hypertriglyceridemia and high fasting GLP-1 concentrations predicted increased glucose levels. Effects of WP supplementation on glycemia in T2DM depend on the baseline characteristics. Lower body weight, normal triglyceride and lower GLP-1 levels predict glucose lowering. In contrast, obesity, hypertriglyceridemia and high baseline GLP-1 predict increased glucose response.

• Biomarkers for the early detection of relapses in metastatic colorectal cancers.

  PubMed

  Chereches, Gabriela; Barbos, Otilia; Buiga, Rares; Balacescu, Ovidiu; Iancu, Dana; Todor, Nicolae; Balacescu, Loredana; Miron, Nicu; Bejinariu, Nona; Ciuleanu, Tudor-Eliade

  2017-01-01

  To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.

• Renal function, cardiovascular disease risk factors' prevalence and 5-year disease incidence; the role of diet, exercise, lipids and inflammation markers: the ATTICA study.

  PubMed

  Chrysohoou, C; Panagiotakos, D B; Pitsavos, C; Skoumas, J; Toutouza, M; Papaioannou, I; Stefanadis, C

  2010-06-01

  We aimed to evaluate the association between renal function and various cardiovascular disease (CVD) risk factors, as well as 5-year incidence of CVD, in a sample of CVD free adults. (i) Cross-sectional information from n = 1975. Greek men and women (>18 years) without CVD and hypertension at baseline examination and (ii) 5-year (2001-06) survival data from n = 2101 individuals without CVD at baseline, all participants in the ATTICA study, were analysed in this work. Kidney function was quantified by the baseline estimated creatinine clearance rate (C(cr)), using the Cockcroft-Gault formula and the National Kidney Foundation recommendations. Outcome of interest was the development of CVD that was defined according to WHO-ICD-10 criteria. At baseline, the prevalence of moderate-to-severe renal dysfunction (i.e. C(cr) < 60) was 2.8% in males and 7.7% in females. Physical activity status, cigarette smoking, hypercholesterolemia and homocysteine levels and greater adherence to the Mediterranean diet were inversely associated with C(cr) rate (P < 0.05), while no association was found with history of diabetes. During the 5-year follow-up, people with moderate-to-severe renal dysfunction as compared with normal, had 3.21 times higher CVD risk [95% confidence interval (CI) 1.98-5.19], after adjusting for history of hypertension (hazard ratio = 2.15, 95% CI 1.48-3.11), hypercholesterolemia (1.37, 0.98-1.98), diabetes (3.28, 2.15-5.00), smoking habits (0.89, 0.60-1.32) and physical activity status (0.86, 0.56-1.21). Renal function seems to be associated with the levels of lifestyle and bio-clinical CVD risk factors and contribute to the long-term incidence of cardiac events. Public health care practitioners should take into account renal function in better preventing the burden of CVD at individual, and population level, as well.

Treatment of pain in fibromyalgia patients with testosterone gel: Pharmacokinetics and clinical response.

PubMed

White, Hillary D; Brown, Lin A J; Gyurik, Robert J; Manganiello, Paul D; Robinson, Thomas D; Hallock, Linda S; Lewis, Lionel D; Yeo, Kiang-Teck J

2015-08-01

To test our hypothesis that testosterone deficiency plays an important role in chronic pain, a Phase I/II pilot study was initiated with 12 fibromyalgia patients to verify that a daily dose for 28days with transdermal testosterone gel would 1) significantly and safely increase mean serum testosterone concentrations from low baseline levels to mid/high-normal levels, and 2) effectively treat the pain and fatigue symptoms of fibromyalgia. Pharmacokinetic data confirmed that serum free testosterone concentrations were raised significantly above baseline levels, by assessment of maximum hormone concentration (Cmax) and area under the curve (AUC) parameters: free testosterone Cmax was significantly raised from a mean of 2.64pg/mL to 3.91pg/mL (p<0.05), and 24hour free testosterone AUC was significantly raised from a mean of 35.0pg-hr/mL to 53.89pg-hr/mL. Assessment of the typical symptoms of fibromyalgia by patient questionnaire and tender point exam demonstrated significant change in: decreased muscle pain, stiffness, and fatigue, and increased libido during study treatment. These results are consistent with the hypothesized ability of testosterone to relieve the symptoms of fibromyalgia. Symptoms not tightly related to fibromyalgia were not improved. Copyright © 2015. Published by Elsevier B.V.

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects.

PubMed

McGinnigle, Samantha; Eperjesi, Frank; Naroo, Shehzad A

2014-04-01

To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60 min. The aberration data were analyzed over a 5mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Hypromellose drops caused an increase in total higher order aberrations (p=<0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p=<0.01, dry eyes p=0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60 min. Differences in comfort levels failed to reach statistical significance. Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Cumulative lactate and hospital mortality in ICU patients

PubMed Central

2013-01-01

Background Both hyperlactatemia and persistence of hyperlactatemia have been associated with bad outcome. We compared lactate and lactate-derived variables in outcome prediction. Methods Retrospective observational study. Case records from 2,251 consecutive intensive care unit (ICU) patients admitted between 2001 and 2007 were analyzed. Baseline characteristics, all lactate measurements, and in-hospital mortality were recorded. The time integral of arterial blood lactate levels above the upper normal threshold of 2.2 mmol/L (lactate-time-integral), maximum lactate (max-lactate), and time-to-first-normalization were calculated. Survivors and nonsurvivors were compared and receiver operating characteristic (ROC) analysis were applied. Results A total of 20,755 lactate measurements were analyzed. Data are srpehown as median [interquartile range]. In nonsurvivors (n = 405) lactate-time-integral (192 [0–1881] min·mmol/L) and time-to-first normalization (44.0 [0–427] min) were higher than in hospital survivors (n = 1846; 0 [0–134] min·mmol/L and 0 [0–75] min, respectively; all p < 0.001). Normalization of lactate <6 hours after ICU admission revealed better survival compared with normalization of lactate >6 hours (mortality 16.6% vs. 24.4%; p < 0.001). AUC of ROC curves to predict in-hospital mortality was the largest for max-lactate, whereas it was not different among all other lactate derived variables (all p > 0.05). The area under the ROC curves for admission lactate and lactate-time-integral was not different (p = 0.36). Conclusions Hyperlactatemia is associated with in-hospital mortality in a heterogeneous ICU population. In our patients, lactate peak values predicted in-hospital mortality equally well as lactate-time-integral of arterial blood lactate levels above the upper normal threshold. PMID:23446002

Intoxicated Speech Detection: A Fusion Framework with Speaker-Normalized Hierarchical Functionals and GMM Supervectors

PubMed Central

Bone, Daniel; Li, Ming; Black, Matthew P.; Narayanan, Shrikanth S.

2013-01-01

Segmental and suprasegmental speech signal modulations offer information about paralinguistic content such as affect, age and gender, pathology, and speaker state. Speaker state encompasses medium-term, temporary physiological phenomena influenced by internal or external biochemical actions (e.g., sleepiness, alcohol intoxication). Perceptual and computational research indicates that detecting speaker state from speech is a challenging task. In this paper, we present a system constructed with multiple representations of prosodic and spectral features that provided the best result at the Intoxication Subchallenge of Interspeech 2011 on the Alcohol Language Corpus. We discuss the details of each classifier and show that fusion improves performance. We additionally address the question of how best to construct a speaker state detection system in terms of robust and practical marginalization of associated variability such as through modeling speakers, utterance type, gender, and utterance length. As is the case in human perception, speaker normalization provides significant improvements to our system. We show that a held-out set of baseline (sober) data can be used to achieve comparable gains to other speaker normalization techniques. Our fused frame-level statistic-functional systems, fused GMM systems, and final combined system achieve unweighted average recalls (UARs) of 69.7%, 65.1%, and 68.8%, respectively, on the test set. More consistent numbers compared to development set results occur with matched-prompt training, where the UARs are 70.4%, 66.2%, and 71.4%, respectively. The combined system improves over the Challenge baseline by 5.5% absolute (8.4% relative), also improving upon our previously best result. PMID:24376305

Peripapillary nerve fiber layer thickness measurement reproducibility using optical coherence tomography.

PubMed

Villain, Max A; Greenfield, David S

2003-01-01

To assess reproducibility of quadrantic and clock hour sectors of retinal nerve fiber layer thickness in normal eyes using optical coherence tomography. Normal eyes of healthy volunteers meeting eligibility criteria were imaged by two inexperienced operators. Six 360 degrees circular scans with a diameter of 3.4 mm centered on the optic disc were obtained during each scanning session, and a baseline image was formed using 3 high-quality images defined by the software. Images were obtained on three different days within a 4-week period. Variance and coefficient of variation (CV) were calculated for quadrantic and retinal nerve fiber layer clock hour sectors obtained from the baseline image. Five normal eyes were scanned. Intraoperator reproducibility was high. The mean (+/- SD) CV for total retinal nerve fiber layer thickness was 5.3 +/- 3.82% and 4.33 +/- 3.7% for operators 1 and 2, respectively. Interoperator reproducibility was good with statistically similar variance for all quadrantic and clock hour retinal nerve fiber layer parameters (P = .42 to .99). The nasal retinal nerve fiber layer was the most variable sector for both operators (mean CV: 10.42% and 7.83% for operators 1 and 2, respectively). Differences in mean total, nasal, temporal, and superior retinal nerve fiber layer thickness were not statistically significant between operators for all eyes; however, for inferior retinal nerve fiber layer thickness, there was a significant (P = .0007) difference between operators in one eye. Peripapillary retinal nerve fiber layer thickness assessments using optical coherence tomography have good intraoperator and interoperator reproducibility. Inexperienced operators can generate useful measurement data with acceptable levels of variance.

Interrelationships Among Flow-Mediated Vasodilation, Nitroglycerine-Induced Vasodilation, Baseline Brachial Artery Diameter, Hyperemic Shear Stress, and Cardiovascular Risk Factors.

PubMed

Maruhashi, Tatsuya; Iwamoto, Yumiko; Kajikawa, Masato; Oda, Nozomu; Kishimoto, Shinji; Matsui, Shogo; Hashimoto, Haruki; Aibara, Yoshiki; Yusoff, Farina Mohamad; Hidaka, Takayuki; Kihara, Yasuki; Chayama, Kazuaki; Noma, Kensuke; Nakashima, Ayumu; Goto, Chikara; Hida, Eisuke; Higashi, Yukihito

2017-12-29

Flow-mediated vasodilation (FMD) of the brachial artery has been used for the assessment of endothelial function. Considering the mechanism underlying the vasodilatory response of the brachial artery to reactive hyperemia, hyperemic shear stress (HSS), a stimulus for FMD; nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation; and baseline brachial artery diameter (BAD) are also involved in vasodilatory response. The purpose of this study was to investigate the interrelationships among FMD, HSS, NID, baseline BAD, and cardiovascular risk factors. We measured FMD, HSS, NID, and baseline BAD simultaneously in 1033 participants (633 men and 400 women; mean age: 58.6±17.0 years). Framingham risk score was negatively correlated with FMD, HSS, and NID and was positively correlated with baseline BAD. HSS and NID were positively correlated with FMD, and baseline BAD was negatively correlated with FMD. In participants with normal NID, FMD was correlated with HSS, NID, and baseline BAD, all of which were independent variables of FMD in multivariate analysis. In participants with impaired NID, FMD was correlated with NID and baseline BAD, both of which were independent variables of FMD in multivariate analysis, but there was no association between FMD and HSS. NID and baseline BAD were independent variables of FMD regardless of the status of endothelium-independent vasodilation, whereas there was a significant association between FMD and HSS in participants with normal NID but not in those with impaired NID. The influence of HSS on FMD seems to be dependent on the status of endothelium-independent vasodilation. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Bone health in long-term gastric cancer survivors: A prospective study of high-dose vitamin D supplementation using an easy administration scheme.

PubMed

Climent, Marta; Pera, Manuel; Aymar, Isabel; Ramón, José M; Grande, Luis; Nogués, Xavier

2018-07-01

Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24 months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12 months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30 ng/mL at baseline received 16,000 IU of vitamin D3 every 10 days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109) months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3 months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30 ng/mL. After 12 months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.

One year B-vitamins increases serum and whole blood folate forms and lowers plasma homocysteine in older Germans.

PubMed

Kirsch, Susanne H; Herrmann, Wolfgang; Kruse, Vera; Eckert, Rudolf; Gräber, Stefan; Geisel, Jürgen; Obeid, Rima

2015-02-01

We aimed to study the effect of long-term supplementation of B-vitamins on folate forms in serum and whole blood (WB) in elderly German subjects. 59 participants (mean age 67 years) were randomized to daily receive either vitamin D3 (1200 IU), folic acid (500 μg), vitamin B12 (500 μg), vitamin B6 (50 mg), and calcium carbonate (456 mg) or vitamin D3 plus calcium carbonate. Serum and WB folate forms were measured before and after 6 and 12 months. B-vitamins supplementation for 6 months led to higher concentrations of 5-methyltetrahydrofolate (5-methylTHF) in serum (mean 49.1 vs. 19.6 nmol/L) and WB (1332 vs. 616 nmol/L). Also non-methyl-folate concentrations in serum and WB were higher after 6 months with B-vitamins supplementation. Unmetabolized folic acid (UFA) increased after supplementation. tHcy concentration was lowered after 1 year of B-vitamin supplementation (mean 13.1 vs. 9.6 μmol/L). A stronger reduction of tHcy after 1 year was found in participants who had baseline level >12.5 μmol/L (mean 17.0 vs. 11.9 μmol/L) compared to those with baseline tHcy lower than this limit (mean 9.1 vs. 7.4 μmol/L). In contrast, the increases in serum and WB 5-methylTHF were comparable between the two groups. One year B-vitamins supplementation increased the levels of 5-methylTHF and non-methyl-folate in serum and WB, normalized tHcy, but caused an increase in the number of cases with detectable UFA in serum. Lowering of tHcy was predicted by baseline tHcy, but not by baseline serum or WB 5-methylTHF.

Affect-based profiles of bulimia nervosa: The utility and validity of indicators assessed in the natural environment.

PubMed

Leraas, Bethany C; Smith, Kathryn E; Utzinger, Linsey M; Cao, Li; Engel, Scott G; Crosby, Ross D; Mitchell, James E; Wonderlich, Stephen A

2018-01-01

Theoretical conceptualizations of bulimia nervosa (BN) emphasize the role of emotion dysregulation in the development and maintenance of symptoms, which has been supported by ecological momentary assessment studies. Given the importance of affective disturbances in BN, this study aimed to classify a sample of adult women with BN (N = 130) based on primarily momentary affective indicators, including negative and positive affect, negative and positive affective lability, and depression. Participants completed baseline assessments followed by a two-week ecological momentary assessment protocol. Latent profile analysis revealed four groups: (1) a "stable normal" group characterized by low affective lability and intensity; (2) a "stable depressed" group characterized by low affective lability and higher affect intensity; (3) an "unstable normal" group characterized by higher affective lability but lower affect intensity; and (4) an "unstable depressed" group characterized by higher affective lability and intensity. The stable depressed group evidenced the highest levels of eating psychopathology, borderline personality traits, and childhood trauma history, while the stable normal group generally evidenced the lowest levels of psychopathology. The findings demonstrate significant heterogeneity in the topography of affect experienced by individuals with BN, and suggest that chronic, intense negative affect may be particularly important to address in treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of Isotretinoin Therapy for Cushing's Disease: Results of a Prospective Study

PubMed Central

Vilar, Lucio; Albuquerque, José Luciano; Lyra, Ruy; Trovão Diniz, Erik; Rangel Filho, Frederico; Gadelha, Patrícia; Thé, Ana Carolina; Ibiapina, George Robson; Gomes, Barbara Sales; Santos, Vera; Melo da Fonseca, Maíra; Frasão Viana, Karoline; Lopes, Isis Gabriella; Araújo, Douglas; Naves, Luciana

2016-01-01

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6–12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6–12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism. PMID:27034666

Time course of Paclitaxel-induced apoptosis in an experimental model of virus-induced breast cancer.

PubMed

Erba, Paola A; Manfredi, Chiara; Lazzeri, Elena; Minichilli, Fabrizio; Pauwels, Ernest K J; Sbrana, Alberto; Strauss, H William; Mariani, Giuliano

2010-05-01

Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. (99m)Tc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer. The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of (99m)Tc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein. Baseline uptake of (99m)Tc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline levels at 6 h. These results define the time course of various biologic events taking place in this model of murine breast cancer after a proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo uptake of (99m)Tc-annexin V reflects the degree of apoptosis, the study also suggests that the apoptotic response to antitumor therapy may differ from tumor type to tumor type. Therefore, contradicting results previously reported may depend on an inadequate time window chosen for imaging with (99m)Tc-annexin V.

Blood Glucose Levels in Diabetic Patients Following Corticosteroid Injections into the Subacromial Space of the Shoulder.

PubMed

Aleem, Alexander W; Syed, Usman Ali M; Nicholson, Thema; Getz, Charles L; Namdari, Surena; Beredjiklian, Pedro K; Abboud, Joseph A

2017-09-01

Corticosteroid injections are used to treat a variety of orthopedic conditions with the goal of decreasing pain and inflammation. Administration of systemic or local corticosteroids risks temporarily increasing blood glucose levels, especially diabetic patients. The purpose of this study is to quantify the effects of corticosteroid injections on blood glucose levels in diabetic patients with shoulder pathology. Diabetic patients who regularly monitored their blood glucose levels and were indicated for a subacromial corticosteroid injection were included in this prospective investigation. The typical normal morning fasting glucose and most recent hemoglobin A1c level was recorded for each patient. After injection, patients were contacted daily to confirm their fasting morning glucose level for 10 days post-injection. Seventeen consecutive patients were enrolled. Patients with hemoglobin A1c of <7% had an average rise in blood glucose of 38 mg/dL compared to 98 mg/dL in the poorly controlled group after injection ( P <0.001). Well-controlled patients' glucose levels returned to near baseline levels around post-injection day 8, while poorly controlled patients levels remained elevated. Similarly, insulin-dependent diabetic patients had an average increase in fasting glucose level of 99 mg/dL versus 50 mg/dL in non-insulin-dependent diabetic patients ( P <0.001). After corticosteroid injection, patients with well-controlled diabetes experience smaller elevations and faster return to baseline glucose levels than patients with poor control. Insulin dependent diabetics experienced similar findings as patients with poor control. Future studies are needed to evaluate dosing to optimize the risks of blood glucose elevation while maintaining therapeutic benefit.

Consonant identification in noise using Hilbert-transform temporal fine-structure speech and recovered-envelope speech for listeners with normal and impaired hearinga)

PubMed Central

Léger, Agnès C.; Reed, Charlotte M.; Desloge, Joseph G.; Swaminathan, Jayaganesh; Braida, Louis D.

2015-01-01

Consonant-identification ability was examined in normal-hearing (NH) and hearing-impaired (HI) listeners in the presence of steady-state and 10-Hz square-wave interrupted speech-shaped noise. The Hilbert transform was used to process speech stimuli (16 consonants in a-C-a syllables) to present envelope cues, temporal fine-structure (TFS) cues, or envelope cues recovered from TFS speech. The performance of the HI listeners was inferior to that of the NH listeners both in terms of lower levels of performance in the baseline condition and in the need for higher signal-to-noise ratio to yield a given level of performance. For NH listeners, scores were higher in interrupted noise than in steady-state noise for all speech types (indicating substantial masking release). For HI listeners, masking release was typically observed for TFS and recovered-envelope speech but not for unprocessed and envelope speech. For both groups of listeners, TFS and recovered-envelope speech yielded similar levels of performance and consonant confusion patterns. The masking release observed for TFS and recovered-envelope speech may be related to level effects associated with the manner in which the TFS processing interacts with the interrupted noise signal, rather than to the contributions of TFS cues per se. PMID:26233038

Environmental lead exposure accelerates progressive diabetic nephropathy in type II diabetic patients.

PubMed

Huang, Wen-Hung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Hsu, Ching-Wei; Chen, Kuan-Hsing; Yen, Tzung-Hai

2013-01-01

Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600  μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80  μ g) and low-normal BLB (<80  μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100  μ g increment in BLB and each 10  μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.

Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

PubMed

de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

2015-06-01

Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for identification of patients who respond to PPIs but would be classified as having FH based on conventional impedance-pH measurements. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes.

PubMed

Wu, M-F; Nienhuis, R; Maidment, N; Lam, H A; Siegel, J M

2011-11-07

Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study we have compared the effects of treadmill running, to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level beyond baseline, whereas yard play produces a substantial increase in Hcrt, even though both activities produce comparable increases in heart rate, respiration and body temperature. We conclude that motor and cardiovascular changes are not sufficient to elevate CSF levels of Hcrt and we hypothesize that the emotional aspects of yard play account for the observed increase in Hcrt.

Improved search for muon-neutrino to electron-neutrino oscillations in MINOS

DOE PAGES

Adamson, P.

2011-10-27

The authors report the results of a search for ν e appearance in ν μ beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 x 10 20 protons on the NuMI target at Fermilab, they find that 2 sin 2 (θ 23 sin 2 (θ 13) < 0.12 (0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best fit of 2 sin 2θ 23) sin 2 (2θ 13) = 0.041 -0.031 +0.047 (0.079 -0.053 +0.071). The θ 13= 0 hypothesis is disfavored bymore » the MINOS data at the 89% confidence level.« less

Trajectories of BMI change impact glucose and insulin metabolism.

PubMed

Walsh, E I; Shaw, J; Cherbuin, N

2018-03-01

The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

PubMed

Witek, Przemysław; Zieliński, Grzegorz; Szamotulska, Katarzyna; Witek, Joanna; Kamiński, Grzegorz

2016-01-01

Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

Interleukin-20 circulating levels in obese women: effect of weight loss.

PubMed

Maiorino, M I; Schisano, B; Di Palo, C; Vietri, M T; Cioffi, M; Giugliano, G; Giugliano, D; Esposito, K

2010-03-01

Obesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight. Fifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P=0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r=0.35; P=0.02) and visceral fat (waist-hip ratio; r=0.32; P=0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153)pg/ml (median and 25%/75%; P=0.03), and it was positively associated with changes in body mass index and waist-hip ratio. In premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist-hip ratio, and are reduced by weight loss. (c) 2009 Elsevier B.V. All rights reserved.

A New Statistics-Based Online Baseline Restorer for a High Count-Rate Fully Digital System.

PubMed

Li, Hongdi; Wang, Chao; Baghaei, Hossain; Zhang, Yuxuan; Ramirez, Rocio; Liu, Shitao; An, Shaohui; Wong, Wai-Hoi

2010-04-01

The goal of this work is to develop a novel, accurate, real-time digital baseline restorer using online statistical processing for a high count-rate digital system such as positron emission tomography (PET). In high count-rate nuclear instrumentation applications, analog signals are DC-coupled for better performance. However, the detectors, pre-amplifiers and other front-end electronics would cause a signal baseline drift in a DC-coupling system, which will degrade the performance of energy resolution and positioning accuracy. Event pileups normally exist in a high-count rate system and the baseline drift will create errors in the event pileup-correction. Hence, a baseline restorer (BLR) is required in a high count-rate system to remove the DC drift ahead of the pileup correction. Many methods have been reported for BLR from classic analog methods to digital filter solutions. However a single channel BLR with analog method can only work under 500 kcps count-rate, and normally an analog front-end application-specific integrated circuits (ASIC) is required for the application involved hundreds BLR such as a PET camera. We have developed a simple statistics-based online baseline restorer (SOBLR) for a high count-rate fully digital system. In this method, we acquire additional samples, excluding the real gamma pulses, from the existing free-running ADC in the digital system, and perform online statistical processing to generate a baseline value. This baseline value will be subtracted from the digitized waveform to retrieve its original pulse with zero-baseline drift. This method can self-track the baseline without a micro-controller involved. The circuit consists of two digital counter/timers, one comparator, one register and one subtraction unit. Simulation shows a single channel works at 30 Mcps count-rate with pileup condition. 336 baseline restorer circuits have been implemented into 12 field-programmable-gate-arrays (FPGA) for our new fully digital PET system.

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

PubMed

Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

2016-01-01

To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.

High serum selenium levels are associated with impaired fasting glucose and elevated fasting serum glucose in Linyi, China.

PubMed

Li, Zhe; Li, Xia; Ju, Wen; Wu, Guanrui; Yang, Xiaomei; Fu, Xiaofeng; Gao, Xibao

2018-01-01

The relationship between selenium level and impaired fasting glucose or elevated fasting serum glucose remains controversial. This study aimed to evaluate these associations in China. This observational population study adopted a cluster sampling approach to enroll participants. Baseline information on selenium categories was tested using one-way analysis of variance and Kruskal-Wallis equality-of-populations rank tests. Multivariable logistic regression was used to investigate the association between serum selenium level and impaired fasting glucose or elevated fasting serum glucose. The mean serum selenium concentration was 121.5μg/L which in a relatively high baseline Se status. Differences were observed among individuals with normal, impaired fasting glucose and elevated fasting serum glucose levels in their basic information, physical examination results and laboratory findings. After adjusting for their basic information, physical examination results and laboratory findings, compared with the low-selenium group, the high-selenium groups (124.9-143.9 and above 143.9μg/L) had ORs for elevated fasting serum glucose of 2.31 (1.37-3.90) and 2.67 (1.59-4.48), respectively (both P<0.05). A sex-difference was observed, and a significant association between selenium levels and impaired fasting glucose was observed for males but not for females. The findings of this observational study suggest that relatively high selenium levels might be positively associated with elevated fasting serum glucose and relatively high selenium levels might be positively associated with impaired fasting glucose in men. Copyright © 2017 Elsevier GmbH. All rights reserved.

Levels of chemical contaminants in nonoccupationally exposed U. S. residents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holleman, J.W.; Hammons, A.S.

1978-08-01

Data are presented on the levels of all chemical contaminants resulting from environmental pollution which have been found in human tissues including blood, urine, breast milk, and tissue samples obtained at autopsy. Most data results from specific surveys to determine health hazards. The roles of trace elements and recognition of the need to determine baseline levels of chemicals introduced into the environment are factors which have motivated surveys by individual investigators. Thus, most data on chemicals in human tissues record levels of pesticides (e.g., DDT and metabolites), levels of trace metals such as lead, cadmium, and mercury, or levels ofmore » nutritionally essential elements such as zinc, copper, manganese, and fluoride. Data available on iron and calcium are not presented as their presence in the environment is generally not considered hazardous. Data on several uncommon chemicals, such as indium and ytterbium, are included basically as items of interest and to further document their presence in healthy individuals. Baseline data were presented where available to provide perspective as to chemical levels which might be expected under conditions where exposure could be considered normal or not directly related to a pollutant source. Nearly 600 cited surveys or investigations, most of which were reported within the past decade, are listed. Ninety-four different chemical contaminants, primarily trace metals and organochlorine pesticides, are reported. It is estimated that over 75% of the data published during the past 30 years on chemical contaminants derived from environmental pollution and found in human tissue in the United States are represented in this report.« less

Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

PubMed

Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

2015-01-01

Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

Efficacy of a chairside diagnostic test kit for estimation of C-reactive protein levels in periodontal disease.

PubMed

Nagarale, Girish; Ravindra, S; Thakur, Srinath; Setty, Swati

2010-10-01

C-reactive protein [CRP] levels increase to hundreds of mg/mL within hours following infection. Studies have shown that serum CRP levels were elevated in periodontal disease. However, in all the previous studies, CRP levels were measured by using high-sensitivity CRP assay kits with minimal detection limits of 0.1 to 3 mg/L, which was much below the normal value of 10 mg/L. These high-sensitivity CRP assays need a proper laboratory setup, and these methods cannot be used as a routine chair-side test in the dental office. The purpose of this study was to investigate the serum CRP levels in subjects with periodontal disease by using a rapid chair-side diagnostic test kit with a lower detection limit of 6 mg/L and to compare the CRP levels before and after periodontal therapy. A total of 45 systemically healthy subjects were selected for the study. Subjects were divided into three groups: group A: healthy controls, group B: gingivitis, group C: periodontitis. Serum levels of CRP were determined by using a latex slide agglutination method with commercially available kit with lower detection limit of 6 mg/L. CRP was negative in all the 15 subjects in groups A and B at baseline, 7th and 30th day. CRP was positive only in 2 subjects in Group C at baseline and 7th day. Estimation of serum CRP by using a rapid chair-side diagnostic test kit is not of any significance in subjects with periodontitis.

Efficacy of a chairside diagnostic test kit for estimation of C-reactive protein levels in periodontal disease

PubMed Central

Nagarale, Girish; Ravindra, S.; Thakur, Srinath; Setty, Swati

2010-01-01

Background: C-reactive protein [CRP] levels increase to hundreds of mg/mL within hours following infection. Studies have shown that serum CRP levels were elevated in periodontal disease. However, in all the previous studies, CRP levels were measured by using high-sensitivity CRP assay kits with minimal detection limits of 0.1 to 3 mg/L, which was much below the normal value of 10 mg/L. These high-sensitivity CRP assays need a proper laboratory setup, and these methods cannot be used as a routine chair-side test in the dental office. Aim: The purpose of this study was to investigate the serum CRP levels in subjects with periodontal disease by using a rapid chair-side diagnostic test kit with a lower detection limit of 6 mg/L and to compare the CRP levels before and after periodontal therapy. Materials and Methods: A total of 45 systemically healthy subjects were selected for the study. Subjects were divided into three groups: group A: healthy controls, group B: gingivitis, group C: periodontitis. Serum levels of CRP were determined by using a latex slide agglutination method with commercially available kit with lower detection limit of 6 mg/L. Results: CRP was negative in all the 15 subjects in groups A and B at baseline, 7th and 30th day. CRP was positive only in 2 subjects in Group C at baseline and 7th day. Conclusion: Estimation of serum CRP by using a rapid chair-side diagnostic test kit is not of any significance in subjects with periodontitis. PMID:21731244

Neuroendocrine abnormalities in hypothalamic amenorrhea: spectrum, stability, and response to neurotransmitter modulation.

PubMed

Perkins, R B; Hall, J E; Martin, K A

1999-06-01

To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12-24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns. The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. 1) HA represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA.

High normal urine albumin-to-creatinine ratio predicts development of hypertension in Korean men.

PubMed

Park, Sung Keun; Moon, Soo Young; Oh, Chang-Mo; Ryoo, Jae-Hong; Park, Min Suk

2014-01-01

Microalbuminuria is known as a risk factor for hypertension. Recently it was suggested that urine albumin-to-creatinine ratio (UACR), even within the normal range, can be associated with hypertension, but the temporal relationship between normal range UACR and hypertension was not confirmed. Therefore the aim of this study was to verify an association between normal range UACR and the development of hypertension in Korean men. This prospective cohort study was performed on 1,284 initially non-hypertensive Korean men. The total follow-up period was 4,109.5 person-years and the mean follow-up period was 3.2±1.51 years. Cox proportional hazards model was used to estimate the hazard ratios (HR) for the risk of hypertension development. After adjusting for multiple covariates, the HR (95% confidence interval [CI]) for incident hypertension, comparing the second to the fourth quartiles of UACR level to the first quartile, were 1.35 (95% CI: 0.93-1.97), 1.55 (95% CI: 1.07-2.25) and 1.89 (95% CI: 1.31-2.71), respectively (P for trend=0.001). High UACR within the normal range was significantly associated with hypertension development. Furthermore, this association remained significant after adjusting for multiple baseline covariates. 

Plasma adiponectin levels and incident glucose intolerance in Japanese-Brazilians: a seven-year follow-up study.

PubMed

Vendramini, Marcio F; Ferreira, Sandra R G; Gimeno, Suely G A; Kasamatsu, Teresa S; Miranda, Walkiria L; Moisés, Regina S

2006-09-01

The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.

Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial

PubMed Central

2014-01-01

Introduction Osteopontin (OPN) is a malignancy-associated glycoprotein that contributes functionally to tumor aggressiveness. In metastatic breast cancer, we previously demonstrated that elevated OPN in primary tumor and blood was associated with poor prognosis. Methods We measured OPN in plasma by ELISA, and in tumors by immunohistochemistry, in 624 (94%) and 462 (69%), respectively, of 667 postmenopausal women with hormone responsive early breast cancer treated by surgery followed by adjuvant treatment with tamoxifen +/− octreotide in a randomized trial (NCIC CTG MA.14; National Cancer Institute of Canada Clinical Trials Group Mammary.14). Results Plasma OPN was measured in 2,540 samples; 688 at baseline and 1,852 collected during follow-up. Mean baseline plasma OPN was 46 ng/ml (range 22.6 to 290) which did not differ from normal levels. Mean percentage OPN tumor cell positivity was 33.9 (95% CI: 30.2 to 37.9). There was no correlation between plasma and tumor OPN values. In multivariate analysis, neither was associated with event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), bone RFS or non-bone RFS. An exploratory analysis in patients with recurrence showed higher mean OPN plasma levels 60.7 ng/ml (23.9 to 543) in the recurrence period compared with baseline levels. Conclusions The hypothesis that OPN tumor expression would have independent prognostic value in early breast cancer was not supported by multivariate analysis of this study population. Plasma OPN levels in women with hormone responsive early breast cancer in the MA.14 trial were not elevated and there was no evidence for prognostic value of plasma OPN in this defined group of patients. However, our finding of elevated mean OPN plasma level around the time of recurrence warrants further study. Trial registration NCT00002864, http://clinicaltrials.gov/show/NCT00002864 PMID:24451146

Differential effect of quetiapine and lithium on functional connectivity of the striatum in first episode mania.

PubMed

Dandash, Orwa; Yücel, Murat; Daglas, Rothanthi; Pantelis, Christos; McGorry, Patrick; Berk, Michael; Fornito, Alex

2018-03-06

Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au.

Longitudinal association of delta activity at sleep onset with cognitive and affective function in community-dwelling older adults.

PubMed

Kawai, Makoto; Beaudreau, Sherry A; Gould, Christine E; Hantke, Nathan C; Cotto, Isabelle; Jordan, Josh T; Hirst, Rayna B; O'Hara, Ruth

2016-10-01

This investigation sought to determine whether delta activity at sleep onset (DASO) in the sleep electroencephalography of older adults represents normal variation or is associated with clinical pathology. To this end, we examined its longitudinal associations with cognitive and affective function in older adults without dementia. Participants were 153 community-dwelling older adults without dementia. We evaluated polysomnography (PSG), cognitive performance, and affective function at four time points: baseline, 12, 24, and 36 months. All participants completed PSG and measures of global cognition, delayed verbal memory, information processing speed, attention, inhibition, verbal naming, visuospatial ability, and measures of anxiety and depression. DASO was defined as sequences of rhythmic anterior delta activity on PSG in the transition from awake to sleep during the baseline assessment (Figure ). At the baseline, 83 women and 70 men, mean age 71.3 ± 0.6 years participated and 19.6% of participants exhibited DASO. Age, years of education, gender, and body mass index did not differ according to DASO status. Linear mixed modeling showed that the presence of DASO was actually associated with lower levels of anxiety and depression. Further, participants with DASO, versus those without DASO, exhibited a trend towards better cognitive performance over time, although none of these associations reached statistical significance. Whereas DASO was associated with better affective function, no significant association was found between DASO and cognitive change over time. These longitudinal findings support the view that the presence of DASO in healthy older adults represents normal variation rather than pathological aging. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women.

PubMed

Stomby, A; Simonyte, K; Mellberg, C; Ryberg, M; Stimson, R H; Larsson, C; Lindahl, B; Andrew, R; Walker, B R; Olsson, T

2015-05-01

Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women. Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied. Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months. Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation.

PubMed

de Oliveira, G L V; Ferreira, A F; Gasparotto, E P L; Kashima, S; Covas, D T; Guerreiro, C T; Brum, D G; Barreira, A A; Voltarelli, J C; Simões, B P; Oliveira, M C; de Castro, F A; Malmegrim, K C R

2017-03-01

Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts. In the BEAM group, BAK, BIK, BIM EL , FAS, FASL, A1, BCL2, BCLX L , CFLIP L and CIAP2 genes were up-regulated after AHSCT. With the exception of BIK, BIM EL and A1, all genes reached levels similar to controls at day + 720 post-transplantation. Furthermore, in these patients, we observed increased CD8 + Fas + T cell frequencies after AHSCT when compared to baseline. In the CY group, we observed increased BAX, BCLW, CFLIP L and CIAP1 and decreased BIK and BID gene expressions after transplantation. At day + 720 post-AHSCT, the expression of BAX, FAS, FASL, BCL2, BCLX L and CIAP1 was similar to that of controls. Protein analyses showed increased Bcl-2 expression before transplantation. At 1 year post-AHSCT, expression of Bak, Bim, Bcl-2, Bcl-xL and cFlip-L was decreased when compared to baseline values. In summary, our findings suggest that normalization of apoptosis-related molecules is associated with the early therapeutic effects of AHSCT in MS patients. These mechanisms may be involved in the re-establishment of immune tolerance during the first 2 years post-transplantation. © 2016 British Society for Immunology.

[Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status].

PubMed

López-Alarcón, Mardia; Chávez-Negrete, Adolfo; Montalvo-Velarde, Irene; Maldonado-Hernández, Jorge; Vital-Reyes, Víctor Saúl

2011-01-01

Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.

[Changes in physical fitness and nutritional status of schoolchildren in a period of 30 years (1980-2010)].

PubMed

de Moraes Ferrari, Gerson Luis; Matsudo, Victor Keihan Rodrigues; Fisberg, Mauro

2015-12-01

To analyze and compare the changes in physical fitness according to the nutritional status and gender of schoolchildren during a period of 30 years (1980-2010). Four cross-sectional evaluations were performed every 10 years in a period of 30 years from 1978 to 1980 (baseline), 1988-1990 (10 years), 1998-2000 (20 years) and 2008-2010 (30 years). The sample consisted of 1,291 schoolchildren (188 in baseline, 307 in 10 years; 375 in 20 years; 421 in 30 years) of 10 and 11 years old. The variables assessed were: body weight (kg), height (cm), upper limb strength (ULS; kg), lower limb strength (LLS; cm), agility (seconds) and velocity (seconds). Schoolchildren were classified as normal weight and overweight according to World Health Organization reference of body mass index for age and gender. Comparisons among periods applied ANOVA folled by Bonferroni test, with a significance level set at of p<0.01. Variation between baseline and 30 years was assessed by the percentage delta. Seven different percentile values were presented for each variable. In eutrophic boys and girls, mean values of ULS (-16.7%; -3.2%), agility (-1.5%; -1.6%) decreased significantly after 30 years (p<0,001). In the overweight boys and girls, only the average ULS (-15.5%; -12.5%) decreased significantly over time (p<0,001). After 30 years, the ULS percentile changed in boys. the decline in physical fitness was greater in schoolchildren with normal weight than in those with overweight. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Humoral immunity to AAV-6, 8, and 9 in normal and dystrophic dogs.

PubMed

Shin, Jin-Hong; Yue, Yongping; Smith, Bruce; Duan, Dongsheng

2012-03-01

Adeno-associated virus (AAV)-6, 8, and 9 are promising gene-delivery vectors for testing novel Duchenne muscular dystrophy gene therapy in the canine model. Humoral immunity greatly influences in vivo AAV transduction. However, neutralizing antibodies to AAV-6, 8, and 9 have not been systemically examined in normal and dystrophic dogs. To gain information on the seroprevalence of antibodies to AAV-6, 8, and 9, we measured neutralizing antibody titers using an in vitro transduction inhibition assay. We examined 72 naive serum samples and 26 serum samples obtained from dogs that had received AAV gene transfer. Our data demonstrated that AAV-6 neutralizing antibody was the most prevalent antibody in dogs irrespective of age, gender, disease status (dystrophic or not), and prior parvovirus vaccination history. Surprisingly, high-level anti-AAV-6 antibody was detected at birth in newborn puppies. Further, a robust antibody response was induced in affected, but not normal newborn dogs following systemic AAV gene transfer. Taken together, our data have provided an important baseline on the seroprevalence of AAV-6, 8, and 9 neutralizing antibodies in normal and Duchenne muscular dystrophy dogs. These results will help guide translational AAV gene-therapy studies in dog models of muscular dystrophy.

Turbulent Flow Field Measurements of Separate Flow Round and Chevron Nozzles with Pylon Interaction Using Particle Image Velocimetry

NASA Technical Reports Server (NTRS)

Doty, Michael J.; Henerson, Brenda S.; Kinzie, Kevin W.

2004-01-01

Particle Image Velocimetry (PIV) measurements for six separate flow bypass ratio five nozzle configurations have recently been obtained in the NASA Langley Jet Noise Laboratory. The six configurations include a baseline configuration with round core and fan nozzles, an eight-chevron core nozzle at two different clocking positions, and repeats of these configurations with a pylon included. One run condition representative of takeoff was investigated for all cases with the core nozzle pressure ratio set to 1.56 and the total temperature to 828 K. The fan nozzle pressure ratio was set to 1.75 with a total temperature of 350 K, and the freestream Mach number was M = 0.28. The unsteady flow field measurements provided by PIV complement recent computational, acoustic, and mean flow field studies performed at NASA Langley for the same nozzle configurations and run condition. The PIV baseline configuration measurements show good agreement with mean flow field data as well as existing PIV data acquired at NASA Glenn. Nonetheless, the baseline configuration turbulence profile indicates an asymmetric flow field, despite careful attention to concentricity. The presence of the pylon increases the upper shear layer turbulence levels while simultaneously decreasing the turbulence levels in the lower shear layer. In addition, a slightly shorter potential core length is observed with the addition of the pylon. Finally, comparisons of computational results with PIV measurements are favorable for mean flow, slightly over-predicted for Reynolds shear stress, and underpredicted for Reynolds normal stress components.

Effect of a marathon run on serum lipoproteins, creatine kinase, and lactate dehydrogenase in recreational runners.

PubMed

Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A

2005-12-01

The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride level was significantly elevated postrace, then fell 30% below baseline 1 day after the run, and returned to baseline after 1 week. Total cholesterol responded less dramatically but with a similar pattern. High-density lipoprotein cholesterol remained significantly elevated and low-density lipoprotein cholesterol was transiently reduced for 3 days after the run. The total cholesterol/high-density cholesterol ratio was significantly lowered for 3 days. Serum lactate dehydrogenase activity significantly doubled postrace and then declined but remained elevated for 2 weeks. Serum creatine kinase activity peaked 24 hr after the run, with a 15-fold rise, and returned to baseline after 1 week. The rise of these enzymes reflects mechanically damaged muscle cells leaking contents into the interstitial fluid. It is concluded that a prolonged strenuous exercise bout in recreational runners, such as a marathon, produces beneficial changes in lipid blood profiles that are significant for only 3 days. However, muscle damage is also evident for 1 week or more from the dramatic and long-lasting effect on enzyme levels. Laboratory values for these runners were outside normal ranges for some days after the race.

Cholecalciferol 20 000 IU Once Weekly in HIV-Positive Patients with Low Vitamin D Levels: Result from a Cohort Study.

PubMed

Noe, Sebastian; Heldwein, Silke; Pascucchi, Rita; Oldenbüttel, Celia; Wiese, C; von Krosigk, Ariane; Jägel-Guedes, Eva; Jäger, Hans; Mayer, Wolfgang; Spinner, Christoph D; Wolf, Eva

To evaluate efficacy and safety of 20 000 IU cholecalciferol weekly in HIV-infected patients. Longitudinal data for 243 HIV-infected patients with paired 25-OH-vitamin D3 values for the same month in 2 consecutive years were stratified by the initiation of supplementation in this retrospective study. After 1 year of administration of cholecalciferol 20 000 IU weekly, about 78% of patients with initial vitamin D level <20 µg/L achieved vitamin D levels >20 µg/L and 42% achieved levels >30 µg/L. Supplemented patients with baseline vitamin D levels <20 µg/L showed a significant risk reduction for hypocalcemia ( P = .006; risk difference: 20.8%) and a significantly lower increase in alkaline phosphatase (AP) compared to those in the nonsubstituted group. The dose of 20 000 IU of cholecalciferol once weekly was found to be safe and effective. Normalization of vitamin D levels within 1 year was observed in 42% to 75% of the patients.

Central and peripheral effects of chronic food restriction and weight restoration in the rat.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Tao, Erin E

2009-02-01

Previous studies have demonstrated that some endocrine consequences of long-term caloric restriction persist after weight restoration in human subjects. Here we evaluate effects of chronic food restriction in rats that were restricted to 70% of control kcal for 4 wk and subsequently weight restored. Measures were taken from rats at 80% (chronically restricted; CR), 90% (partially weight restored; PR), 100% (fully weight restored; FR), and after 4 wk at 100% body weight of controls (extended weight restored; ER). Plasma insulin and leptin were decreased, and ghrelin was increased in CR compared with controls. Leptin and ghrelin normalized with weight restoration at PR, FR, and ER; however, baseline insulin was not normalized until the ER state. Hypothalamic mRNA expression levels for proopiomelanocortin (POMC), agouti-related protein (AgRP), and neuropeptide Y (NPY) revealed significantly less POMC mRNA expression in CR and PR rats, and significantly less arcuate NPY mRNA in PR and FR. In the dorsomedial hypothalamus, CR, PR, and FR rats had significantly increased NPY expression that was not normalized until the ER state. In response to a test meal, insulin and ghrelin release patterns were altered through the FR stage, and ghrelin remained affected at ER. Collectively, these data demonstrate that mere weight restoration is not sufficient to normalize hypothalamic gene expression levels and endocrine responses to a meal, and that meal-related ghrelin responses persist despite weight restoration for up to 4 wk.

NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

EPA Science Inventory

Abstract

The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

Anti-Mullerian hormone levels do not predict response to pulsatile GnRH in women with hypothalamic amenorrhea.

PubMed

Billington, Emma O; Corenblum, Bernard

2016-09-01

Pulsatile GnRH is used to induce ovulation in women with hypothalamic amenorrhea (HA), but tools to predict response are lacking. We assessed whether baseline AMH levels are associated with response to pulsatile GnRH in 16 women with HA. AMH levels were compared between non-responders and women who achieved follicular development or pregnancy. Median AMH for the cohort was 2.2 ng/mL. AMH levels were undetectable or low in four women, normal in nine and high in three. Follicular development was observed in 13 (81%) women (82% of cycles) and pregnancy achieved in 10 (63%) women (29% of cycles). All four women with low or undetectable AMH had follicular response and three achieved pregnancy. Of the 12 women with normal or high AMH, 10 had a follicular response and seven achieved pregnancy. Median AMH levels were comparable in those who achieved follicular development and those who did not (2.2 ng/mL versus 1.3 ng/mL, p = 0.78) and in those who became pregnant and those who did not (2.2 ng/mL versus 1.9 ng/mL, p = 0.52). In summary, low AMH does not preclude response to ovulation induction in women with HA, suggesting that ovarian potential may not be the primary determinant of AMH concentrations in this population.

Changes in Maxillary Canine Pulpal Blood Flow During Dentoalveolar Distraction Osteogenesis.

PubMed

Ersahan, Seyda; Sabuncuoglu, Fidan Alakus

2016-05-01

The aim of this study was to assess the effects of dentoalveolar distraction osteogenesis (DD) on the pulpal blood flow (PBF) of maxillary canines. A laser Doppler flowmeter (LDF) was used to measure PBF in maxillary canines of 10 patients undergoing DD (study group) and 10 nonsurgical subjects who received no orthodontic treatment (control group). PBF was measured at baseline, at 4 and 7 days postoperatively, at the end of distraction and at the end of consolidation in the study group and at similar time-points in nonsurgical control subjects. Data were analyzed using paired and Student t tests, with the significance level set at 0.05. Study findings showed that baseline PBF values did not differ significantly between groups. PBF in the control group did not vary over time; however, in the study group, an initial decrease in PBF was observed at 4 days postoperatively and was followed by a gradual increase to preoperative levels at the end of distraction. During the DD latency period, there appears to be a short-lived ischemic phase when perfusion of pulp tissue declines; however, blood-flow returns to normal by the end of distraction.

Treatment of hyperfunctioning thyroid nodules by percutaneous ethanol injection.

PubMed

Larijani, Bagher; Pajouhi, Mohammad; Ghanaati, Hossein; Bastanhagh, Mohammad-Hassan; Abbasvandi, Fereshteh; Firooznia, Kazem; Shirzad, Mahmood; Amini, Mohammad-Reza; Sarai, Maryam; Abbasvandi, Nasreen; Baradar-Jalili, Reza

2002-12-06

BACKGROUND: Autonomous thyroid nodules can be treated by a variety of methods. We assessed the efficacy of percutaneous ethanol injection in treating autonomous thyroid nodules. METHODS: 35 patients diagnosed by technetium-99 scanning with hyperfunctioning nodules and suppressed sensitive TSH (sTSH) were given sterile ethanol injections under ultrasound guidance. 29 patients had clinical and biochemical hyperthyroidism. The other 6 had sub-clinical hyperthyroidism with suppressed sTSH levels (<0.24 &mgr;IU/ml) and normal thyroid hormone levels. Ethanol injections were performed once every 1-4 weeks. Ethanol injections were stopped when serum T3, T4 and sTSH levels had returned to normal, or else injections could no longer be performed because significant side effects. Patients were followed up at 3, 6 and, in 15 patients, 24 months after the last injection. RESULTS: Average pre-treatment nodule volume [18.2 PlusMinus; 12.7 ml] decreased to 5.7 PlusMinus; 4.6 ml at 6 months follow-up [P < 0.001]. All patients had normal thyroid hormone levels at 3 and 6 months follow-up [P < 0.001 relative to baseline]. sTSH levels increased from 0.09 PlusMinus; 0.02 &mgr;IU/ml to 0.65 PlusMinus; 0.8 &mgr;IU/ml at the end of therapy [P < 0.05]. Only 3 patients had persistent sTSH suppression at 6 months post-therapy. T4 and sTSH did not change significantly between 6 months and 2 years [P > 0.05]. Ethanol injections were well tolerated by the patients, with only 2 cases of transient dysphonia. CONCLUSION: Our findings indicate that ethanol injection is an alternative to surgery or radioactive iodine in the treatment of autonomous thyroid nodules.

Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38).

PubMed

Deetman, Petronella E; Alkhalaf, Alaa; Landman, Gijs W D; Groenier, Klaas H; Kootstra-Ros, Jenny E; Navis, Gerjan; Bilo, Henk J G; Kleefstra, Nanne; Bakker, Stephan J L

2015-08-01

Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine the associations of log2 -transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to noncardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P = 0.003). In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV

PubMed Central

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-01

Background As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8+ T cell death in responses to ART and IL-2 therapy. Methods Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Results Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4+ T cells, leading to an increase in CD4 cell counts. CD8+ T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% ± 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8+ T cell apoptosis at baseline (mean 2.2% ± 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8+ T cell apoptosis (mean CD4 cell counts 1,209 ± 164 vs 754 ± 320 cells/mm3; CD4:CD8 ratios 1.55 vs. 0.70, respectively). Conclusion We postulate that CD8+ T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4+ T cells to rebound. Levels of CD8+ T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study. PMID:17263884

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV.

PubMed

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-30

As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8(+) T cell death in responses to ART and IL-2 therapy. Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4(+) T cells, leading to an increase in CD4 cell counts. CD8(+) T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% +/- 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8(+) T cell apoptosis at baseline (mean 2.2% +/- 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8(+) T cell apoptosis (mean CD4 cell counts 1,209 +/- 164 vs 754 +/- 320 cells/mm(3); CD4:CD8 ratios 1.55 vs. 0.70, respectively). We postulate that CD8(+) T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4(+) T cells to rebound. Levels of CD8(+) T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study.

Performance of Thermal Mass Flow Meters in a Variable Gravitational Environment

NASA Technical Reports Server (NTRS)

Brooker, John E.; Ruff, Gary A.

2004-01-01

The performance of five thermal mass flow meters, MKS Instruments 179A and 258C, Unit Instruments UFM-8100, Sierra Instruments 830L, and Hastings Instruments HFM-200, were tested on the KC-135 Reduced Gravity Aircraft in orthogonal, coparallel, and counterparallel orientations relative to gravity. Data was taken throughout the parabolic trajectory where the g-level varied from 0.01 to 1.8 times normal gravity. Each meter was calibrated in normal gravity in the orthogonal position prior to flight followed by ground testing at seven different flow conditions to establish a baseline operation. During the tests, the actual flow rate was measured independently using choked-flow orifices. Gravitational acceleration and attitude had a unique effect on the performance of each meter. All meters operated within acceptable limits at all gravity levels in the calibrated orthogonal position. However, when operated in other orientations, the deviations from the reference flow became substantial for several of the flow meters. Data analysis indicated that the greatest source of error was the effect of orientation, followed by the gravity level. This work emphasized that when operating thermal flow meters in a variable gravity environment, it is critical to orient the meter in the same direction relative to gravity in which it was calibrated. Unfortunately, there was no test in normal gravity that could predict the performance of a meter in reduced gravity. When operating in reduced gravity, all meters indicated within 5 percent of the full scale reading at all flow conditions and orientations.

The impact of obesity on pentraxin 3 and inflammatory milieu to acute aerobic exercise.

PubMed

Slusher, Aaron L; Mock, J Thomas; Whitehurst, Michael; Maharaj, Arun; Huang, Chun-Jung

2015-02-01

Pentraxin 3 (PTX3) has recently been linked to obesity-associated inflammation, serving as a cardioprotective modulator against cardiovascular disease (CVD). Aerobic exercise has been shown to enhance plasma PTX3 levels; however, the impact of obesity on PTX3 response to exercise remains unknown. Therefore, this study sought to examine whether obese subjects would have an attenuated plasma PTX3 response compared to normal-weight subjects following acute aerobic exercise. The relationship of plasma PTX3 with pro-inflammatory cytokines (IL-6 and TNF-α) was also examined. Twenty healthy subjects (10 obese [4 males and 6 females] and 10 normal-weight [4 males, 6 females]) performed 30min of continuous submaximal aerobic exercise. At baseline, obese subjects exhibited approximately 40% lower plasma PTX3 and a 7-fold greater IL-6 concentration compared to normal-weight subjects. In response to exercise, no difference was observed in PTX3 or IL-6 as indicated by area-under-the-curve "with respect to increase" (AUCi) analyses. Furthermore, PTX3 AUCi was positively correlated with cardiorespiratory fitness levels (VO(2max)) (r=0.594, p=0.006), even after controlling for body mass index. These findings suggest that in addition to obesity-associated complications, low cardiorespiratory fitness levels could impact exercise-induced PTX3 elevations, thereby potentially diminishing PTX3's effects of anti-inflammation and/or cardioprotection. Copyright © 2015 Elsevier Inc. All rights reserved.

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

PubMed

Truong, Dinh Quang; Darwish, Ahmed A; Gras, Jérémie; Wieërs, Grégoire; Cornet, Anne; Robert, Annie; Mourad, Michel; Malaise, Jacques; de Ville de Goyet, Jean; Reding, Raymond; Latinne, Dominique

2007-06-01

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs.

PubMed

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average -4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = -19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

Effect of a Modest Weight Loss in Normalizing Blood Pressure in Obese Subjects on Antihypertensive Drugs

PubMed Central

Gilardini, Luisa; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

2016-01-01

Objective To assess the effect of a lifestyle intervention in lowering/normalizing blood pressure (BP) levels in hypertensive (controlled or not) obese patients. Methods In this prospective observational study, 490 obese hypertensive patients, 389 controlled (BP < 140/90 mm Hg; CH) and 101 uncontrolled (BP ≥ 140/90 mm Hg; UH) attended a 3-month lifestyle intervention. Before and after the intervention we assessed weight, waist circumference, fat mass, BP, metabolic and renal variables, and physical activity. A multivariate regression model was used to determine the predictors of BP changes. Results 18.9% of CH and 20.0% of UH were on ≥ 3 antihypertensive drugs. Weight change (average −4.9 ± 2.7%) was independent of the antihypertensive drugs employed. Systolic BP (SBP) decreased by 23 mm Hg and diastolic BP (DBP) by 9 mm Hg, in patients with UH most of whom (89%) normalized BP levels (in 49% after a weight loss < 5%). Age, gender, whole and central obesity, concomitance of type 2 diabetes, chronic renal disease, physical activity intensification, and pharmacological therapy did not affect BP lowering. In the regression analysis with SBP change as dependent variable, weight reduction (β = 0.523, p = 0.005) and group (UH vs. CH, β = −19.40, p = 0.0005) remained associated with SBP reduction. When DBP change was entered as dependent variable, baseline uric acid remained associated with DBP reduction (β = 0.824, p < 0.05). Conclusion Lifestyle interventions are useful for all obese hypertensive patients in most of whom a modest weight loss is sufficient to normalize BP levels avoiding the aggressive use of multiple antihypertensive drugs. PMID:27454447

Thyrotropin and free thyroxine levels and coronary artery disease: cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

de Miranda, E J F Peixoto; Bittencourt, M S; Staniak, H L; Sharovsky, R; Pereira, A C; Foppa, M; Santos, I S; Lotufo, P A; Benseñor, I M

2018-03-15

Data on the association between subclinical thyroid dysfunction and coronary artery disease (CAD) is scarce. We aimed to analyze the association between thyroid function and CAD using baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We included subjects with normal thyroid function (0.4-4.0 mIU/L, and normal free thyroxine, FT4, or 0.8 to 1.9 ng/dL), subclinical hypothyroidism (SCHypo; TSH>4.0 mIU/L and normal FT4), and subclinical hyperthyroidism (SCHyper; TSH<0.4 mIU/L and normal FT4) evaluated by coronary computed tomography angiography. We excluded individuals using medications that interfere in thyroid function or with past medical history of cardiovascular disease. Logistic regression models evaluated the presence of CAD, segment involvement score (SIS) >4, and segment severity score (SSS) >4 of coronary arteries as the dependent variables, and quintiles of TSH and FT4 as the independent variables, adjusted for demographical data and cardiovascular risk factors. We included 767 subjects, median age 58 years (IQR=55-63), 378 (49.3%) women, 697 euthyroid (90.9%), 57 (7.4%) with SCHypo, and 13 (1.7%) with SCHyper. No association between TSH and FT4 quintiles and CAD prevalence was noted. Similarly, no association between TSH levels and the extent or severity of CAD, represented by SIS>4 and SSS>4 were seen. Restricting analysis to euthyroid subjects did not alter the results. TSH levels were not significantly associated with the presence, extent, or severity of CAD in a middle-aged healthy population.

Clinical efficacy and metabolic impact of two different dosages of ethinyl-estradiol in association with drospirenone in normal-weight women with polycystic ovary syndrome: a randomized study.

PubMed

Romualdi, D; De Cicco, S; Busacca, M; Gagliano, D; Lanzone, A; Guido, M

2013-09-01

The estrogenic component of estro- progestin (EP) is responsible for a negative impact on the metabolic and lipid assessment in women with polycystic ovary syndrome (PCOS). To evaluate the risk/benefit ratio of two EP combinations, containing the same progestin (3 mg drospirenone) and a different dose of ethinyl-estradiol (EE) (20 vs 30 μg) and to compare their effects on the clinical and endocrine-metabolic parameters in normal-weight PCOS women. In this randomized pilot study, we enrolled 30 young normal-weight PCOS women. Fifteen subjects were allocated to group A (20 μg EE) and 15 PCOS subjects to group B (30 μg EE). Hirsutism score, hormonal assays, oral glucose tolerance test, euglycemic hyperinsulinemic clamp and lipid profile were performed at baseline, and after 6 and 12 months of therapy. Main outcome measures were signs of hyperandrogenism, glucose and insulin metabolism, lipid profile. Both treatment regimens induced a significant improvement in hirsutism score, testosterone, DHEAS, and SHBG levels. Androstenedione significantly dropped only in patients of Group A, while 17(OH)P only in those from Group B. Both the formulations did not significantly modify gluco-insulinemic metabolism. Total cholesterol, LDL cholesterol, and HDL cholesterol levels significantly increased in both groups. Triglycerides levels, which increased as well, resulted more markedly influenced by the formulation with 30 μg EE. In association with drospirenone, 20 μg EE results as effective as 30 μg in improving clinical and hormonal features of normal-weight PCOS women, while exhibiting a milder influence on lipidic parameters.

Effect of angiotensin converting enzyme inhibitor on glomerular hyperfiltration in patients with type 1 diabetes

PubMed Central

Naqvi, S. A. Jaffar; Ahsan, Shahid; Fawwad, Asher; Basit, Abdul; Shera, A Samad

2016-01-01

Objective: To assess the effect of angiotensin converting enzyme inhibition on glomerular filtration rate (GFR) in normotensive patient with type 1 diabetes. Methods: A two year non-placebo control prospective study was conducted after ethical approval at Diabetes Centre of Diabetic Association of Pakistan, a WHO collaborating centre in Karachi, Pakistan. All patients with type 1 diabetes visited the out-patients department from August 2009 till July 2011 and those who fulfilled the inclusion criteria were invited to participate. A total of 121 people aged ≥18 years and ≥ 5 years of diabetes were included. Pregnant and lactating woman and those aged <18 years were excluded. GFR was calculated by using CKD-EPI formula (eGFR) at baseline and after two year. On the basis of estimated GFR, patients at baseline were divided according to KDIGO classification of chronic kidney diseases into, hyperfiltration (eGFR ≥ 100 ml/min) and normal filtration group (eGFR < 100 ml/min). All subjects in hyperfiltration group received ACE inhibitor (treatment group) while patients with normal filtration did not receive ACE inhibitor (control group). Results: Fifty two patients (43%) were in the treatment and sixty nine (57%) were in the control group. At baseline eGFR, systolic and diastolic blood pressures between groups were non-significantly different. After two years, compared to baseline, eGFR of the treatment group declined and the control group increased significantly. No significant difference in systolic while diastolic blood pressure of the treatment group increased significantly after two years compared to baseline. In contrast both systolic and diastolic blood pressure of control group increased significantly after two years compared to their baseline values. Conclusion: Present study demonstrated that initiation of ACEI in hyperfiltration stage declined GFR and keep blood pressure within normal range. PMID:27375689

The effects of baseline heart rate recovery normality and exercise training protocol on heart rate recovery in patients with heart failure.

PubMed

Yaylalı, Yalın Tolga; Fındıkoğlu, Gülin; Yurtdaş, Mustafa; Konukçu, Sibel; Şenol, Hande

2015-09-01

It is unclear which exercise training protocol yields superior heart rate recovery (HRR) improvement in heart failure (HF) patients. Whether baseline HRR normality plays a role in the improvement is unknown. We hypothesized that an exercise training protocol and baseline HRR normality would be factors in altering HRR in HF patients. In this prospective, randomized, controlled and 3 group parallel study, 41 stable HF patients were randomly assigned to 3-times-weekly training sessions for 12 weeks, consisting of i) 30 minutes of interval training (IT) (n=17, 63.7±8.8 years old) versus ii) 30 minutes of continuous training (CT) (n=13, 59.6±6.8 years old) versus iii) no training (CON) (n=11, 60.6±9.9 years old). Each patient had cardiopulmonary exercise testing before and after the training program. Maximum heart rates attained during the test and heart rates at 1 and 2 min (HRR1 and HRR2) during the recovery phase were recorded. Paired samples t-test or Wilcoxon signed-rank test was used for comparisons before and after training. One-way ANOVA or Kruskal-Wallis variance analysis was used for comparisons among groups. HRR1 was unchanged after training. HRR2 improved in the IT group after training, and post-training HRR2 values were significantly faster in the IT group than in controls. Both HRR1 and HRR2 was significantly faster, irrespective of exercise protocol in patients with abnormal baseline values after training. HRR1 did not improve after training. HRR2 improved only in the IT group. Both HRRs in patients with abnormal baseline values improved after both exercise protocols. IT might be superior to CT in improving HRR2. Baseline HRR might play a role in its response to exercise.

Effect of sedation with detomidine on intraocular pressure with and without topical anesthesia in clinically normal horses.

PubMed

Holve, Dana L

2012-02-01

To determine the effect of sedation with detomidine on intraocular pressure (IOP) in standing horses and whether topical ocular application of anesthetic alters this effect. Clinical trial. 15 clinically normal horses. Horses were assigned to group 1 (n = 7) or 2 (8). Intraocular pressure measurements were obtained at baseline (before sedation) and 10 minutes after IV administration of detomidine (0.02 mg/kg [0.009 mg/lb]). Group 1 horses had an additional IOP measurement at 20 minutes after sedation. For group 2 horses, topical ocular anesthetic was administered 10 minutes prior to baseline IOP measurements. Mean ± SD baseline IOP for horses without topical anesthesia (group 1 horses; IOP, 24.30 ± 3.09 mm Hg) was significantly lower, compared with that of horses with topical anesthesia (group 2 horses; IOP, 30.40 ± 3.25 mm Hg). Compared with baseline values, IOP at 10 minutes after sedation decreased significantly in all horses (by 3.61 ± 1.48 mm Hg and 5.78 ± 4.32 mm Hg in groups 1 and 2, respectively). In group 1 horses, IOP at 10 (20.69 ± 3.45 mm Hg) and 20 (19.96 ± 2.13 mm Hg) minutes after sedation was significantly decreased, compared with baseline values; however, the difference between IOP at 10 versus 20 minutes was not significant. The difference in IOP between group 1 and 2 horses at 10 minutes after sedation was not significant. IV administration of detomidine caused a decrease in IOP in clinically normal horses and may be a safe sedative when performing ocular procedures.

The Importance of Mid-to-Late-Life Body Mass Index Trajectories on Late-Life Gait Speed.

PubMed

Windham, B Gwen; Griswold, Michael E; Wang, Wanmei; Kucharska-Newton, Anna; Demerath, Ellen W; Gabriel, Kelley Pettee; Pompeii, Lisa A; Butler, Kenneth; Wagenknecht, Lynne; Kritchevsky, Stephen; Mosley, Thomas H

2017-08-01

Prior studies suggest being overweight may be protective against poor functional outcomes in older adults. Body mass index (BMI, kg/m2) was measured over 25 years across five visits (1987-2011) among Atherosclerosis Risk in Communities Study participants (baseline Visit 1 n = 15,720, aged 45-64 years). Gait speed was measured at Visit 5 ("late-life", aged ≥65 years, n = 6,229). BMI trajectories were examined using clinical cutpoints and continuous mixed models to estimate effects of patterns of BMI change on gait speed, adjusting for demographics and comorbidities. Mid-life BMI (baseline visit; 55% women; 27% black) was associated with late-life gait speed 25 years later; gait speeds were 94.3, 89.6, and 82.1 cm/s for participants with baseline normal BMI (<25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30) (p < .001). In longitudinal analyses, late-life gait speeds were 96.9, 88.8, and 81.3 cm/s for participants who maintained normal, overweight, and obese weight status, respectively, across 25 years (p < .01). Increasing BMI over 25 years was associated with poorer late-life gait speeds; a 1%/year BMI increase for a participant with a baseline BMI of 22.5 (final BMI 28.5) was associated with a 4.6-cm/s (95% confidence interval: -7.0, -1.8) slower late-life gait speed than a participant who maintained a baseline BMI of 22.5. Being overweight in older age was not protective of mobility function. Maintaining a normal BMI in mid- and late-life may help preserve late-life mobility. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Locally Sustainable School Lunch Intervention Improves Hemoglobin and Hematocrit Levels and Body Mass Index among Elementary Schoolchildren in Rural West Java, Indonesia

PubMed Central

Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

2017-01-01

School lunch is not provided in public elementary schools in Indonesia, and students frequently buy and eat snacks at school. We hypothesized that providing a traditional Sundanese meal as school lunch would be beneficial for children in rural West Java. To test this hypothesis, we evaluated the effect of a 1-month school lunch intervention aiming at sustainability and based on children’s nutritional intake, hemoglobin and hematocrit levels, and body mass index (BMI). A lunch (including rice, vegetable dish, animal protein dish, plant protein dish, and fruit) containing one-third of the recommended daily allowance of energy was offered every school day for 1 month, targeting 68 fourth-grade elementary schoolchildren. At baseline, the prevalence of anemia was 33.3%. The prevalence of stunting and underweight were 32.4% and 2.9%, respectively, whereas that of overweight and obesity combined was 17.6%, indicating a double burden of malnutrition among the subjects. During the intervention, intakes of protein (p < 0.05), calcium (p < 0.05), and vitamin C (p < 0.001) significantly increased, while that of fat significantly decreased (p < 0.001). After the intervention, hemoglobin (p < 0.05) and hematocrit (p < 0.05) levels were significantly improved, thereby almost halving the rate of anemia. These changes were significantly larger in the baseline anemic group than the non-anemic group (p < 0.01). BMI significantly increased in the baseline underweight/normal group (p < 0.001) but not in the overweight/obese group. The school lunch intervention significantly improved nutritional intakes and health statuses, implying its potential for reducing anemia and resolving the double burden of malnutrition among rural Indonesian schoolchildren. PMID:28805668

Locally Sustainable School Lunch Intervention Improves Hemoglobin and Hematocrit Levels and Body Mass Index among Elementary Schoolchildren in Rural West Java, Indonesia.

PubMed

Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

2017-08-12

School lunch is not provided in public elementary schools in Indonesia, and students frequently buy and eat snacks at school. We hypothesized that providing a traditional Sundanese meal as school lunch would be beneficial for children in rural West Java. To test this hypothesis, we evaluated the effect of a 1-month school lunch intervention aiming at sustainability and based on children's nutritional intake, hemoglobin and hematocrit levels, and body mass index (BMI). A lunch (including rice, vegetable dish, animal protein dish, plant protein dish, and fruit) containing one-third of the recommended daily allowance of energy was offered every school day for 1 month, targeting 68 fourth-grade elementary schoolchildren. At baseline, the prevalence of anemia was 33.3%. The prevalence of stunting and underweight were 32.4% and 2.9%, respectively, whereas that of overweight and obesity combined was 17.6%, indicating a double burden of malnutrition among the subjects. During the intervention, intakes of protein ( p < 0.05), calcium ( p < 0.05), and vitamin C ( p < 0.001) significantly increased, while that of fat significantly decreased ( p < 0.001). After the intervention, hemoglobin ( p < 0.05) and hematocrit ( p < 0.05) levels were significantly improved, thereby almost halving the rate of anemia. These changes were significantly larger in the baseline anemic group than the non-anemic group ( p < 0.01). BMI significantly increased in the baseline underweight/normal group ( p < 0.001) but not in the overweight/obese group. The school lunch intervention significantly improved nutritional intakes and health statuses, implying its potential for reducing anemia and resolving the double burden of malnutrition among rural Indonesian schoolchildren.

Single-Trial Normalization for Event-Related Spectral Decomposition Reduces Sensitivity to Noisy Trials

PubMed Central

Grandchamp, Romain; Delorme, Arnaud

2011-01-01

In electroencephalography, the classical event-related potential model often proves to be a limited method to study complex brain dynamics. For this reason, spectral techniques adapted from signal processing such as event-related spectral perturbation (ERSP) – and its variant event-related synchronization and event-related desynchronization – have been used over the past 20 years. They represent average spectral changes in response to a stimulus. These spectral methods do not have strong consensus for comparing pre- and post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial-based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time–frequency responses and behavior compared to classical ERSP methods. PMID:21994498

Hypoxic Challenge Testing (Fitness to Fly) in children with complex congenital heart disease.

PubMed

Naqvi, Nitha; Doughty, Victoria L; Starling, Luke; Franklin, Rodney C; Ward, Simon; Daubeney, Piers E F; Balfour-Lynn, Ian M

2018-02-14

Commercial airplanes fly with an equivalent cabin fraction of inspired oxygen of 0.15, leading to reduced oxygen saturation (SpO 2 ) in passengers. How this affects children with complex congenital heart disease (CHD) is unknown. We conducted Hypoxic Challenge Testing (HCT) to assess need for inflight supplemental oxygen. Children aged <16 years had a standard HCT. They were grouped as (A) normal versus abnormal baseline SpO 2 (≥95% vs <95%) and (B) absence versus presence of an actual/potential right-to-left (R-L) shunt. We measured SpO 2 , heart rate, QT interval corrected for heart rate and partial pressure of carbon dioxide measured transcutaneously (PtcCO 2 ). A test failed when children with (1) normal baseline SpO 2 desaturated to 85%, (2) baseline SpO 2 85%-94% desaturated by 15% of baseline; and (3) baseline SpO 2 75%-84% desaturated to 70%. There were 68 children, mean age 3.3 years (range 10 weeks-14.5 years). Children with normal (n=36) baseline SpO 2 desaturated from median 99% to 91%, P<0.0001, and 3/36 (8%) failed the test. Those with abnormal baseline SpO 2 (n=32) desaturated from median 84% to 76%, P<0.0001, and 5/32 (16%) failed (no significant difference between groups). Children with no R-L shunt (n=25) desaturated from median 99% to 93%, P<0.0001, but 0/25 failed. Those with an actual/potential R-L shunt (n=43) desaturated from median 87% to 78%, P<0.0001, and 8/43 (19%) failed (difference between groups P<0.02). PtcCO 2 , heart rate and QT interval corrected for heart rate were unaffected by the hypoxic state. This is the first evidence to help guide which children with CHD need a preflight HCT. We suggest all children with an actual or potential R-L shunt should be tested. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of 6-min Walk Test on pro-BNP Levels in Patients with Pulmonary Arterial Hypertension.

PubMed

Pathak, Vikas; Aris, Robert; Jensen, Brian C; Huang, Wei; Ford, Hubert James

2018-06-01

Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions. Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30 days or more were enrolled. After resting the patient for 30 min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2 h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student's paired t tests. There were 17 females and 3 male subjects. The mean age was 53 ± 11 years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50 ± 15 mmHg with a mean pulmonary vascular resistance of 10 ± 4 Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377 ± 140 m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1 h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2 h post 6MWT. There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1 h. Pro-BNP levels then return to baseline at 2 h post 6MWT.

Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV.

PubMed

Liu, Chun-Jen; Chuang, Wan-Long; Sheen, I-Shyan; Wang, Horng-Yuan; Chen, Chi-Yi; Tseng, Kuo-Chih; Chang, Ting-Tsung; Massetto, Benedetta; Yang, Jenny C; Yun, Chohee; Knox, Steven J; Osinusi, Anu; Camus, Gregory; Jiang, Deyuan; Brainard, Diana M; McHutchison, John G; Hu, Tsung-Hui; Hsu, You-Chun; Lo, Gin-Ho; Chu, Chi-Jen; Chen, Jyh-Jou; Peng, Cheng-Yuan; Chien, Ron-Nan; Chen, Pei-Jer

2018-03-01

There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log 10 IU/mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase >2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation >2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV reactivation. The most common adverse events were headache, upper respiratory infection, and fatigue. In a prospective study, the combination of ledipasvir and sofosbuvir for 12 weeks produced a sustained virologic response in 100% of patients with HCV infection who were coinfected with HBV. Most patients had an increase in level of HBV DNA not associated with signs or symptoms. ClinicalTrials.gov no: NCT02613871. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Proteinuria is associated with neurocognitive impairment in antiretroviral therapy treated HIV-infected individuals.

PubMed

Kalayjian, Robert C; Wu, Kunling; Evans, Scott; Clifford, David B; Pallaki, Muraldihar; Currier, Judith S; Smryzynski, Marlene

2014-09-01

Proteinuria is a marker of vascular dysfunction that predicted increased cardiovascular mortality and is associated with neurocognitive impairment (NCI) in population-based studies. We examined associations between proteinuria and HIV-associated NCI. Multivariable logistic regression was used to examine associations between NCI at the first neurocognitive assessment (baseline) and simultaneous, clinically significant proteinuria [as random spot urine protein-to-creatinine ratios (UP/Cr) ≥200 mg/g] in a prospective multicenter observational cohort study. Generalized estimating equations were used to examine associations between baseline proteinuria and subsequent NCI among subjects without NCI at baseline. NCI was defined as a Z-score, derived from the combination of normalized scores from the Trailmaking A and B and the Wechsler Adult Intelligence Scale-Revised Digit Symbol tests. A total of 1972 subjects were included in this analysis. Baseline proteinuria was associated with increased odds of NCI [odds ratio (OR): 1.41, 95% confidence interval (CI): 1.08 to 1.85; P = 0.01] and with subsequent NCI among subjects without NCI at baseline (OR: 1.39, 95% CI: 1.01 to 1.93; P = 0.046) in multivariable models adjusted for risk factors and potential confounders. Similar associations were evident when these analyses were limited to visits at which time study subjects maintained plasma HIV RNA levels <200 copies per milliliter. The association between proteinuria and NCI observed in this study adds to a growing body of evidence implicating contributions by vascular disease to NCI in antiretroviral treated individuals. Studies examining interventions that improve vascular function are warranted.

Factors that influence the efficacy of acarbose and metformin as initial therapy in Chinese patients with newly diagnosed type 2 diabetes: a subanalysis of the MARCH trial.

PubMed

Zhang, Jinping; Wang, Na; Xing, Xiaoyan; Yang, Zhaojun; Wang, Xin; Yang, Wenying

2016-01-01

To conduct a subanalysis of the randomized MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment) trial to investigate whether specific characteristics are associated with the efficacy of either acarbose or metformin as initial therapy. A total of 657 type 2 diabetes patients who were randomly assigned to 48 weeks of therapy with either acarbose or metformin in the MARCH trial were divided into two groups based upon their hemoglobin A1c (HbA1c) levels at the end of follow-up: HbA1c <7% (<53 mmol/mol) and ≥7% (≥53 mmol/mol). Univariate, multivariate, and stepwise linear regression analyses were applied to identify the factors associated with treatment efficacy. Because this was a subanalysis, no measurement was performed. Univariate analysis showed that the efficacy of acarbose and metformin was influenced by HbA1c, fasting blood glucose (FBG), and 2 hour postprandial venous blood glucose (2hPPG) levels, as well as by changes in body mass index (BMI) (p ≤ 0.006). Multivariate analysis and stepwise linear regression analyses indicated that lower baseline 2hPPG values and greater changes in BMI were factors that positively influenced efficacy in both treatment groups (p ≤ 0.05). Stepwise regression model analysis also revealed that a lower baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR) and higher serum insulin area under the curve (AUC) were factors positively influencing HbA1c normalization in all patients (p ≤ 0.032). Newly diagnosed type 2 diabetes patients with lower baseline 2hPPG and HOMA-IR values are more likely to achieve glucose control with acarbose or metformin treatment. Furthermore, the change in BMI after acarbose or metformin treatment is also a factor influencing HbA1c normalization. A prospective study with a larger sample size is necessary to confirm our results as well as measure β cell function and examine the influence of the patients' dietary habits.

[Effects of long-term antihypertensive therapy with losartan on blood pressure and cognitive function in patients with essential hypertension and other cerebrovascular risk factors (AWARE observational study)].

PubMed

Schrader, Jürgen; Lüders, Stephan; Diener, Hans-Christoph; Haller, Hermann; Schmieder, Roland E; Wahle, Klaus; Smolka, Wenefrieda; Jung, Claudia; Bestehorn, Kurt

2008-07-15

As arterial hypertension is the most important risk factor for ischemic stroke, the relevant guidelines recommend rigorous treatment to normalize blood pressure. Hypertension can also be associated with cognitive decline and dementia. Therefore, the effect of a long-term therapy with the AT(1) antagonist losartan (+/- hydro chloro thiazide [HCTZ]) on cognitive function in patients with essential hypertension and additional cerebrovascular risk factors was investigated. Prospective, open observational study in 6,206 adult patients with known essential hypertension and cerebrovascular risk factors (most with a 10-year stroke risk of >or= 20% based on the Framingham Score). Demographic data, blood pressure, selected laboratory parameters, and cognitive function (c.I. test) were determined at baseline and after 3, 6, and 12 months. The patients' mean age was 65.8+/-10.7 years and 46.1% of the patients were male. In addition to treatment with losartan +/- HCTZ, 54.1% of the patients received one or more additional antihypertensive agents. After 1 year of treatment, systolic/diastolic blood pressure fell from its baseline level of 158.1/90.3 mmHg to 137.3/80.6 mmHg (-20.8/-9.7 mmHg). The proportion of patients with no/mild/severe cognitive impairment was 30.0%/30.3%/39.7% at baseline and 34.8%/28.1%/37.1% at the end of the study. In patients with cognitive impairment, fibrinogen and hsCRP (high-sensitive C-reactive protein) levels were significantly elevated. Adverse events (AEs) were reported in 231 patients (3.7%), while serious/nonserious AEs possibly related to the study medication were reported in only six (0.1%) and 38 patients (0.6%), respectively. A high proportion of patients with hypertension shows cognitive impairment; therefore, use of appropriate tests to detect this should be considered. The losartan-based antihypertensive treatment increased the proportion of patients with normal cognitive function, reduced blood pressure, and was well tolerated in the primary-care setting.

[Relationship between cognitive function and physical activities: a longitudinal study among community-dwelling elderly].

PubMed

Konagaya, Yoko; Watanabe, Tomoyuki; Ohta, Toshiki

2012-01-01

The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.

Baseline Response Levels Are a Nuisance in Infant Contingency Learning

ERIC Educational Resources Information Center

Millar, W. S.; Weir, Catherine

2015-01-01

The impact of differences in level of baseline responding on contingency learning in the first year was examined by considering the response acquisition of infants classified into baseline response quartiles. Whereas the three lower baseline groups showed the predicted increment in responding to a contingency, the highest baseline responders did…

Percutaneous ethanol injection treatment in benign thyroid lesions: role and efficacy.

PubMed

Guglielmi, Rinaldo; Pacella, Claudio Maurizio; Bianchini, Antonio; Bizzarri, Giancarlo; Rinaldi, Roberta; Graziano, Filomena Maria; Petrucci, Lucilla; Toscano, Vincenzo; Palma, Enzo; Poggi, Maurizio; Papini, Enrico

2004-02-01

To establish the role of percutaneous ethanol injection (PEI) treatment in benign thyroid lesions by evaluating: (1) the long-term efficacy and side effects of the treatment, (2) the factors predictive of efficacy of PEI, and (3) the cost effectiveness of the procedure. Fifty-eight recurrent cystic nodules, 95 autonomously functioning nodules (AFTN), and 17 hyperfunctioning nodules causing thyrotoxicosis (toxic nodules) were treated by PEI from 1990 to 1996 in our center. Ultrasound (US) and color flow doppler (CFD) examinations were carried out before and after each treatment. In patients with AFTN, serum thyrotropin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb) levels were tested before and after PEI. All patients were independently reexamined by two external reviewers after a minimum follow-up of 5 years (median, 6.9 years). The median number of treatments was 2.0 (range, 1.0-4.0) for cystic nodules, 4 (range, 2.0-6.0) for AFTN, and 5 (range, 3.0-7.0) for toxic nodules. At the 5-year evaluation cystic nodules showed a volume reduction greater than 75% versus baseline in 86.2% of cases and an improvement of local symptoms in 91.4% of cases. AFTN presented serum TSH within normal limits in 60.0% of patients. Toxic nodules showed a detectable serum TSH and normal FT3 and FT4 values in 35.3% of cases. Two cases of transient dysphonia were observed. In cystic lesions no significant correlation was found between the baseline and the final volume (r2 = 0.17) and no significant predictor of treatment efficacy was found. However, unilocularity was associated with a lower number of treatments than multilocularity (median, 2.0 vs. 3.0). Independent predictors of clinical efficacy in both AFTN and toxic nodules were a baseline volume less than 5.0 mL and a fluid component greater than 30% (odds ratio [OR] = 6.1 and 3.3, respectively). Most recurrent cystic lesions of the thyroid can be cured by PEI, which should become the first line of treatment. The majority of AFTN and toxic nodules with volume less than 5.0 mL presented a marked volume decrease and normal serum TSH levels when treated by PEI, which seems a valid alternative to clinical follow-up alone in patients refusing 131I. PEI is not indicated in large or toxic nodules, for which 131I is the treatment of choice.

Contractile reserve and calcium regulation are depressed in myocytes from chronically unloaded hearts

NASA Technical Reports Server (NTRS)

Ito, Kenta; Nakayama, Masaharu; Hasan, Faisal; Yan, Xinhua; Schneider, Michael D.; Lorell, Beverly H.

2003-01-01

BACKGROUND: Chronic cardiac unloading of the normal heart results in the reduction of left ventricular (LV) mass, but effects on myocyte contractile function are not known. METHODS AND RESULTS: Cardiac unloading and reduction in LV mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. Contractility and [Ca(2+)](i) regulation in LV myocytes were studied at both 2 and 5 weeks after transplantation. Native in situ hearts from recipient animals were used as the controls for all experiments. Contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 Hz, 1.2 mmol/L [Ca(2+)](o), and 36 degrees C) and in response to stimulation with high [Ca(2+)](o) (range 2.5 to 4.0 mmol/L). In myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic [Ca(2+)](i) at baseline; however, time to 50% relengthening and time to 50% decline in [Ca(2+)](i) were prolonged compared with controls. Severe defects in fractional cell shortening and peak-systolic [Ca(2+)](i) were elicited in myocytes from 5-week unloaded hearts in response to high [Ca(2+)](o). However, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. In 5-week unloaded hearts, but not in 2-week unloaded hearts, LV protein levels of phospholamban were increased (345% of native heart values). Protein levels of sarcoplasmic reticulum Ca(2+) ATPase and the Na(+)/Ca(2+) exchanger were not changed. CONCLUSIONS: Chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.

Using Family-Focused Garden, Nutrition, and Physical Activity Programs To Reduce Childhood Obesity: The Texas! Go! Eat! Grow! Pilot Study.

PubMed

Spears-Lanoix, Erica C; McKyer, E Lisako J; Evans, Alexandra; McIntosh, William Alex; Ory, Marcia; Whittlesey, Lisa; Kirk, Alice; Hoelscher, Deanna M; Warren, Judith L

2015-12-01

The TEXAS! GROW! EAT! GO! (TGEG) randomized, control trial is a 5-year study to measure the impact of a nutrition and gardening intervention and/or physical activity (PA) intervention on the weight status of third-grade students. This article describes the results of the pilot study to test the feasibility of two interventions and test the measures to be used in the main trial. The pilot study was conducted in one school with third-grade students and their parents or guardians. The Junior Master Gardner (JMG) and Walk Across Texas (WAT) interventions were implemented over a 5-month period in three third-grade classrooms during spring 2012. The respective interventions focused on improving healthy eating and PA behaviors of children and their families. Baseline and immediate post-test data were collected from students and parents/guardians to measure four child, four parent, and four parent-child interaction behaviors. Process data regarding implementation were also collected from teachers and school administration. Forty-four students and 34 parents or guardians provided both pre- and post-test data. Paired-sample t-tests showed statistically significant changes in student knowledge, vegetable preferences, vegetable consumption, and home food availability (all p < 0.05). At baseline, participants' weight status categories included 57% obese, 10% overweight, and 31% normal weight. Postintervention, weight status categories included 39% obese, 16% overweight, and normal 45%. Data collected from teachers indicated high levels of implementation fidelity. Implementation of both interventions occurred at a very high fidelity level, which led to positive changes in BMI status, and several dietary and PA behaviors. Although the pilot study indicated feasibility of the two interventions for school implementation, results guided revisions to the TGEG program and its survey instruments.

A Yoga Strengthening Program Designed to Minimize the Knee Adduction Moment for Women with Knee Osteoarthritis: A Proof-Of-Principle Cohort Study

PubMed Central

2015-01-01

People with knee osteoarthritis may benefit from exercise prescriptions that minimize knee loads in the frontal plane. The primary objective of this study was to determine whether a novel 12-week strengthening program designed to minimize exposure to the knee adduction moment (KAM) could improve symptoms and knee strength in women with symptomatic knee osteoarthritis. A secondary objective was to determine whether the program could improve mobility and fitness, and decrease peak KAM during gait. The tertiary objective was to evaluate the biomechanical characteristics of this yoga program. In particular, we compared the peak KAM during gait with that during yoga postures at baseline. We also compared lower limb normalized mean electromyography (EMG) amplitudes during yoga postures between baseline and follow-up. Primary measures included self-reported pain and physical function (Knee injury and Osteoarthritis Outcome Score) and knee strength (extensor and flexor torques). Secondary measures included mobility (six-minute walk, 30-second chair stand, stair climbing), fitness (submaximal cycle ergometer test), and clinical gait analysis using motion capture synchronized with electromyography and force measurement. Also, KAM and normalized mean EMG amplitudes were collected during yoga postures. Forty-five women over age 50 with symptomatic knee osteoarthritis, consistent with the American College of Rheumatology criteria, enrolled in our 12-week (3 sessions per week) program. Data from 38 were analyzed (six drop-outs; one lost to co-intervention). Participants experienced reduced pain (mean improvement 10.1–20.1 normalized to 100; p<0.001), increased knee extensor strength (mean improvement 0.01 Nm/kg; p = 0.004), and increased flexor strength (mean improvement 0.01 Nm/kg; p = 0.001) at follow-up compared to baseline. Participants improved mobility on the six-minute walk (mean improvement 37.7 m; p<0.001) and 30-second chair stand (mean improvement 1.3; p = 0.006) at follow-up compared to baseline. Fitness and peak KAM during gait were unchanged between baseline and follow-up. Average KAM during the yoga postures were lower than that of normal gait. Normalized mean EMG amplitudes during yoga postures were up to 31.0% of maximum but did not change between baseline and follow-up. In this cohort study, the yoga-based strengthening postures that elicit low KAMs improved knee symptoms and strength in women with knee OA following a 12 week program (3 sessions per week). The program also improved mobility, but did not improve fitness or reduce peak KAM during gait. The KAM during the yoga postures were lower than that of normal gait. Overall, the proposed program may be useful in improving pain, strength, and mobility in women with knee osteoarthritis. Clinical efficacy needs to be assessed using a randomized controlled trial design. Trial Registration ClinicalTrials.gov NCT02146105 PMID:26367862

Comparative evaluation of therapy with L-thyroxine versus no treatment in children with idiopathic and mild subclinical hypothyroidism.

PubMed

Wasniewska, Malgorzata; Corrias, Andrea; Aversa, Tommaso; Valenzise, Mariella; Mussa, Alessandro; De Martino, Lucia; Lombardo, Fortunato; De Luca, Filippo; Salerno, Mariacarolina

2012-01-01

The question of whether children with subclinical hypothyroidism (SH) should be treated or not is controversial due to the lack of studies on outcomes of SH children treated with L-thyroxine (L-T(4)) versus those receiving no therapy. (a) To evaluate thyroid tests under L-T(4) and after therapy withdrawal in 69 SH children (group A) and (b) to compare our results with those recorded in 92 untreated children (group B). Group A children were treated for 24 months and TSH and FT(4) levels 3 months after therapy withdrawal were compared with those measured in group B at the end of follow-up in order to investigate treatment effects. The prevalence of children who had normalized TSH at the end of follow-up was higher in group A, but the prevalence of those who had normalized or maintained unchanged TSH was similar in the two groups, as was the prevalence of children who exhibited a TSH increase >10 mU/l. In group A, TSH values at 27 months were associated with baseline values. (a) Two-year treatment in SH children is unable to modify posttherapy outcome of hyperthyrotropinemia; (b) therapy is unable to prevent the risk of further TSH increase after treatment withdrawal, and (c) posttherapy TSH outcome is conditioned by baseline TSH. Copyright © 2012 S. Karger AG, Basel.

NREL Solar Radiation Research Laboratory (SRRL): Baseline Measurement System (BMS); Golden, Colorado (Data)

DOE Data Explorer

Stoffel, T.; Andreas, A.

1981-07-15

The SRRL was established at the Solar Energy Research Institute (now NREL) in 1981 to provide continuous measurements of the solar resources, outdoor calibrations of pyranometers and pyrheliometers, and to characterize commercially available instrumentation. The SRRL is an outdoor laboratory located on South Table Mountain, a mesa providing excellent solar access throughout the year, overlooking Denver. Beginning with the basic measurements of global horizontal irradiance, direct normal irradiance and diffuse horizontal irradiance at 5-minute intervals, the SRRL Baseline Measurement System now produces more than 130 data elements at 1-min intervals that are available from the Measurement & Instrumentation Data Center Web site. Data sources include global horizontal, direct normal, diffuse horizontal (from shadowband and tracking disk), global on tilted surfaces, reflected solar irradiance, ultraviolet, infrared (upwelling and downwelling), photometric and spectral radiometers, sky imagery, and surface meteorological conditions (temperature, relative humidity, barometric pressure, precipitation, snow cover, wind speed and direction at multiple levels). Data quality control and assessment include daily instrument maintenance (M-F) with automated data quality control based on real-time examinations of redundant instrumentation and internal consistency checks using NREL's SERI-QC methodology. Operators are notified of equipment problems by automatic e-mail messages generated by the data acquisition and processing system. Radiometers are recalibrated at least annually with reference instruments traceable to the World Radiometric Reference (WRR).

Preoperative Statin Therapy in Cardiac Surgery Is More Effective in Patients Who Display Preoperative Activation of the Inflammatory System

PubMed Central

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass. PMID:23466655

Preoperative statin therapy in cardiac surgery is more effective in patients who display preoperative activation of the inflammatory system.

PubMed

Martínez-Comendador, José; Alvarez, José Rubio; Sierra, Juan; Teijeira, Elvis; Adrio, Belén

2013-01-01

We sought to determine whether preoperative statin treatment is more effective in reducing, after cardiac surgery with cardiopulmonary bypass, systemic inflammatory response and myocardial damage markers in patients who have elevated preoperative interleukin-6 levels than in patients who have normal preoperative interleukin-6 levels. The study involved a prospective cohort of 164 patients who underwent coronary and valvular surgery with cardiopulmonary bypass. There were 2 study groups: group A (n = 60), patients with elevated preoperative interleukin-6 levels; and group B (n = 104), patients with normal preoperative interleukin-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Accordingly, the subdivided study groups were A1 (n = 40), A2 (n = 20), B1 (n = 56), and B2 (n = 48). The plasma levels of proinflammatory interleukin-6 were measured 1, 6, 24, and >72 hours after surgery. The baseline, operative, and postoperative morbidity and mortality characteristics were similar in all groups. Group A1 had significantly lower levels of interleukin-6 and troponin I than did group A2 at all postoperative time points. Group B1 had significantly lower levels of interleukin-6 than did group B2 postoperatively. There were no significant differences in troponin I levels between groups B1 and B2. We conclude that, in patients with preoperative activation of the inflammatory system, preoperative treatment with statins is associated with lower postoperative interleukin-6 and troponin I levels after cardiac surgery with cardiopulmonary bypass.

Baseline Correction of Diffuse Reflection Near-Infrared Spectra Using Searching Region Standard Normal Variate (SRSNV).

PubMed

Genkawa, Takuma; Shinzawa, Hideyuki; Kato, Hideaki; Ishikawa, Daitaro; Murayama, Kodai; Komiyama, Makoto; Ozaki, Yukihiro

2015-12-01

An alternative baseline correction method for diffuse reflection near-infrared (NIR) spectra, searching region standard normal variate (SRSNV), was proposed. Standard normal variate (SNV) is an effective pretreatment method for baseline correction of diffuse reflection NIR spectra of powder and granular samples; however, its baseline correction performance depends on the NIR region used for SNV calculation. To search for an optimal NIR region for baseline correction using SNV, SRSNV employs moving window partial least squares regression (MWPLSR), and an optimal NIR region is identified based on the root mean square error (RMSE) of cross-validation of the partial least squares regression (PLSR) models with the first latent variable (LV). The performance of SRSNV was evaluated using diffuse reflection NIR spectra of mixture samples consisting of wheat flour and granular glucose (0-100% glucose at 5% intervals). From the obtained NIR spectra of the mixture in the 10 000-4000 cm(-1) region at 4 cm intervals (1501 spectral channels), a series of spectral windows consisting of 80 spectral channels was constructed, and then SNV spectra were calculated for each spectral window. Using these SNV spectra, a series of PLSR models with the first LV for glucose concentration was built. A plot of RMSE versus the spectral window position obtained using the PLSR models revealed that the 8680–8364 cm(-1) region was optimal for baseline correction using SNV. In the SNV spectra calculated using the 8680–8364 cm(-1) region (SRSNV spectra), a remarkable relative intensity change between a band due to wheat flour at 8500 cm(-1) and that due to glucose at 8364 cm(-1) was observed owing to successful baseline correction using SNV. A PLSR model with the first LV based on the SRSNV spectra yielded a determination coefficient (R2) of 0.999 and an RMSE of 0.70%, while a PLSR model with three LVs based on SNV spectra calculated in the full spectral region gave an R2 of 0.995 and an RMSE of 2.29%. Additional evaluation of SRSNV was carried out using diffuse reflection NIR spectra of marzipan and corn samples, and PLSR models based on SRSNV spectra showed good prediction results. These evaluation results indicate that SRSNV is effective in baseline correction of diffuse reflection NIR spectra and provides regression models with good prediction accuracy.

Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC).

PubMed

Ji, Jun Ho; Song, Haa-Na; Kim, Rock Bum; Oh, Sung Yong; Lim, Ho Yeong; Park, Joon Oh; Park, Se Hoon; Kim, Moon Jin; Lee, Soon Il; Ryou, Sung Hyeok; Hwang, In Gyu; Jang, Joung-Soon; Kim, Hong Jun; Choi, Jun Young; Kang, Jung-Hun

2015-03-01

Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An altered peripheral IL6 response in major depressive disorder.

PubMed

Money, Kelli M; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A; Shelton, Richard C; Mirnics, Karoly

2016-05-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of anti-depressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated pro-inflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

An altered peripheral IL6 response in major depressive disorder

PubMed Central

Money, Kelli M.; Olah, Zita; Korade, Zeljka; Garbett, Krassimira A.; Shelton, Richard C.; Mirnics, Karoly

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent major psychiatric disorders with a lifetime prevalence of 17%. Recent evidence suggests MDD is not only a brain dysfunction, but a systemic disease affecting the whole body. Central and peripheral inflammatory changes seem to be a centerpiece of MDD pathology: a subset of patients show elevated blood cytokine and chemokine levels that partially normalize with symptom improvement over the course of antidepressant treatment. As this inflammatory process in MDD is poorly understood, we hypothesized that the peripheral tissues of MDD patients will respond differently to inflammatory stimuli, resulting in an aberrant transcriptional response to elevated proinflammatory cytokines. To test this, we used MDD patient- and control-derived dermal fibroblast cultures to investigate their response to an acute treatment with IL6, IL1β, TNFα, or vehicle. Following RNA isolation and subsequent cDNA synthesis, quantitative PCR was used to determine the relative expression level of several families of inflammation-responsive genes. Our results showed comparable expression of the tested genes between MDD patients and controls at baseline. In contrast, MDD patient fibroblasts had a diminished transcriptional response to IL6 in all the gene sets tested (oxidative stress response, mitochondrial function, and lipid metabolism). We also found a significant increase in baseline and IL6 stimulated transcript levels of the IL6 receptor gene. This IL6 receptor transcript increase in MDD fibroblasts was accompanied by an IL6 stimulated increase in induction of SOCS3, which dampens IL6 receptor signaling. Altogether our results demonstrate that there is an altered transcriptional response to IL6 in MDD, which may represent one of the molecular mechanisms contributing to disease pathophysiology. Ultimately we hope that these studies will lead to validation of novel MDD drug targets focused on normalizing the altered IL6 response in patients. PMID:26804030

Relationship Between Vitamin D Deficiency and the Components of Metabolic Syndrome in Patients with Morbid Obesity, Before and 1 Year After Laparoscopic Roux-en-Y Gastric Bypass or Sleeve Gastrectomy.

PubMed

Obispo Entrenas, Ana; Legupin Tubio, David; Lucena Navarro, Fabiola; Martin Carvajal, Francisco; Gandara Adan, Norberto; Redondo Bautista, Maximino; Abiles Osinaga, Jimena

2017-05-01

Vitamin D deficiency (VDD) is associated with obesity and metabolic syndrome (MS). After bariatric surgery (BS), high rates of VDD often persist and some patients are refractory to the resolution of comorbidities. The aim of the present study is to analyse the relationship between the levels of vitamin D and the persistence of MS components at 12 months after BS, according to the surgical technique used. We performed a retrospective study of 46 patients undergoing BS: 23 underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) and 23 laparoscopic sleeve gastrectomy (LSG). These patients had an average BMI of 45 kg/m 2 (34-63). Levels of vitamin D were classified as deficient (<20 ng/dl), insufficient (20-30 ng/dl) or normal (>30 ng/dl) and analysed in relation to the components of MS (high blood pressure (HBP), dyslipidaemia (DL) and type 2 diabetes mellitus (T2DM) preoperatively and 12 months after surgery. VDD was observed in 77% of the patients prior to surgery. There were no significant associations between predisposing factors and baseline vitamin D. After surgery, plasma levels of vitamin D increased in both groups, but only 18% of the patients achieved normal values. Both groups had achieved significant improvements in MS components. Thus, 63% of all the patients achieved complete resolution of HBP, 54% that of DL and 77% that of T2DM. Moreover, MS was present in 11% of the patients, compared to 63% at baseline, and the MS resolution rate was 83%, with no significant differences between LRYGBP and LSG. There is a relationship between VDD and persistence of MS, and particularly so with T2DM. VDD could represent a predictor of MS persistence at 12 months after surgery.

Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity.

PubMed

Händel, Mina Nicole; Larsen, Sofus Christian; Rohde, Jeanett Friis; Stougaard, Maria; Olsen, Nanna Julie; Heitmann, Berit Lilienthal

2017-01-01

There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling. From a baseline study population of 635 normal weight 2-6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children's Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. ClinicalTrials.gov NCT01583335.

Effects of the Healthy Start randomized intervention trial on physical activity among normal weight preschool children predisposed to overweight and obesity

PubMed Central

Larsen, Sofus Christian; Rohde, Jeanett Friis; Stougaard, Maria; Olsen, Nanna Julie; Heitmann, Berit Lilienthal

2017-01-01

Background There is limited evidence to support the effectiveness of primary interventions aiming to prevent excess weight gain among young children. Evaluating behavioral changes, such as physical activity (PA), may add to future development of efficient interventions. The objective was to evaluate the effect on PA outcomes of the 15 month Healthy Start intervention that focused on changing diet, PA, sleep and stress management among normal weight but obesity-prone preschool children. Children were defined as obesity-prone if they had a birth weight > 4,000 g, mothers with a pre-pregnancy body mass index of > 28 kg/m2, or mothers with ≤ 10 years of schooling. Method From a baseline study population of 635 normal weight 2–6 year old preschool children from the greater Copenhagen area, parents of 307 children had given information on PA at both the baseline and follow-up examinations. PA was obtained from a 7 days recording in the Children’s Physical Activity Questionnaire. Time used for sport activities were combined with outdoor playing time to achieve a proxy of total PA level of moderate to vigorous intensity. Results Linear regression analyses revealed that at follow-up the intervention group spent more time on sports and outdoor activities combined per week than the control group (ITT analyses: intervention: 400 min/week; 95% confidence interval (CI): 341, 459 versus control: 321 min/week; 95% CI: 277, 366; p = 0.02), although no significant intervention effects were seen for each of the subcategories, e.g. sports participation, outdoor activities, screen time, or commuting frequency. Conclusion Our results suggest that the overall time spent on sports and outdoor activities combined was increased at follow-up among normal weight obesity-prone children, as a result of the Healthy Start intervention. Trial registration ClinicalTrials.gov NCT01583335 PMID:28991907

Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial).

PubMed

Schutte, Elise; Lambers Heerspink, Hiddo J; Lutgers, Helen L; Bakker, Stephan J L; Vart, Priya; Wolffenbuttel, Bruce H R; Umanath, Kausik; Lewis, Julia B; de Zeeuw, Dick; Gansevoort, Ron T

2015-09-01

Low serum bicarbonate level has been reported to be an independent predictor of kidney function decline and mortality in patients with chronic kidney disease. Mechanisms underlying low serum bicarbonate levels may differ in patients with and without diabetes. We aimed to specifically investigate the association of serum bicarbonate level with kidney disease progression and cardiovascular outcome in a cohort of patients with type 2 diabetes and nephropathy. Post hoc analysis of 2 multicenter randomized controlled trials. 2,628 adults with type 2 diabetes and nephropathy. Serum bicarbonate level. Incidence of: (1) end-stage renal disease (ESRD), (2) ESRD or doubling of serum creatinine level, (3) all-cause mortality, (4) cardiovascular events (fatal/nonfatal stroke/myocardial infarction), and (5) heart failure. Serum bicarbonate was measured at baseline as total carbon dioxide. Associations of baseline serum bicarbonate level with end points were investigated using Cox regression models. Serum bicarbonate levels were studied as a continuous variable and stratified in quartiles. Follow-up was 2.8±1.0 (SD) years. Cox regression analyses showed that serum bicarbonate level had inverse associations with incident ESRD (HR, 0.91; 95% CI, 0.89-0.93; P<0.001) and incidence of the combined end point of ESRD or serum creatinine doubling (HR, 0.94; 95% CI, 0.92-0.96; P<0.001). These associations were independent of age, sex, and cardiovascular risk factors, but disappeared after adjustment for baseline estimated glomerular filtration rate (all P>0.05). Analysis of bicarbonate quartiles showed similar results for the quartile with the lowest bicarbonate (≤21 mEq/L) versus the quartile with normal bicarbonate levels (24-26 mEq/L). There was no association of bicarbonate level with cardiovascular events and heart failure. Post hoc analysis and single measurement of serum bicarbonate. In this cohort of patients with type 2 diabetes with nephropathy, serum bicarbonate level associations with kidney disease end points were not retained after adjustment for estimated glomerular filtration rate, which is in contrast to results of earlier studies in nondiabetic populations. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.

PubMed

Gao, Ya; Wang, Changjiang; Pan, Tianrong; Luo, Li

2014-02-01

Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

PubMed Central

Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

2014-01-01

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

Two Seating Systems' Effects on an Adolescent With Cerebral Palsy and Severe Scoliosis.

PubMed

Lephart, Kim; Kaplan, Sandra L

2015-01-01

To compare physiological functioning, communication switch activation, and response accuracy in a 19-year-old young man with quadriplegic cerebral palsy and neurological scoliosis using 2 seating systems within the school setting. Prospective single-subject alternating treatment design with 2 conditions: baseline phase with standard planar inserts (A1), custom-molded back with original seat (B), and return to baseline (A2). Measures included oxygen saturation (SaO2), heart rate (HR), respiration rate (RR), body temperature (BT), processing time to activate switches, and response accuracy. SaO2 levels increased from "distressed" to "normal"; variability decreased. HR, RR, and BT fluctuations decreased with the custom-molded back. Processing time decreased with increased variability, affected by subject's motivation; accuracy improved slightly. Reported social approachability and student-initiated communication increased. SaO2 increased and HR, RR, and BT fluctuations decreased with a custom-molded back. Graphing data may help determine seating effect with complex clients.

Arterial blood pressure oscillation after active standing up in kidney transplant recipients.

PubMed

Gerhardt, U; Schäfer, M; Hohage, H

2000-04-12

Dynamic arterial blood pressure (FINAPRES) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state arterial blood pressure level to measure sympathetic vasomotor function in healthy subjects [group 1: n=50, 10 female subjects, age 51+/-2.5 years; weight 78+/-2.3 kg; height 174+/-1.4 cm (mean+/-standard error of the mean)] and in kidney transplant recipients under basal (group 2a: n=50, age 51.7+/-1.7 years; weight 77+/-2.1 kg; height 174+/-1.5 cm) and under high (group 2b: same subjects as in group 2a) cyclosporine A whole blood levels. Furthermore, baroreflex sensitivity and the activity of the generating compounds of the sympathetic nervous systems (Mayer waves) were measured. Systolic and diastolic overshoot values did not differ statistically significant in the present study. In the control subjects, a systolic overshoot of 15.4+/-2.7 mmHg and a diastolic overshoot of 15.2+/-2 mmHg was detected. The systolic overshoot disappeared in 57% of group 2a (-7.1+/-2.7 mmHg; P<0.001) and in 50% of group 2b recipients (-8.0+/-2.7 mmHg; P<0.001). Systolic early steady-state level was not lower in kidney transplant recipients before cyclosporine (baseline+2 mmHg) intake, but after cyclosporine administration (baseline-3 mmHg; controls: baseline+3 mmHg; P<0.05). There was a strong association between the overshoot and steady-state levels (P for chi(2)<0.001, n=150). Overshoot of group 1 levels (r=0.428; P<0.01) and group 2 levels (r=0.714; P<0. 001) correlated to their respective steady-state blood pressure. Furthermore, recipients had reduced baroreceptor sensitivities estimated by sequence analysis as compared to controls (10+/-1 ms/mmHg vs. 7.5+/-1.4 ms/mmHg; P<0.05). Mayer waves amplitudes of the heart rate spectrum were elevated statistically significant in renal transplant recipients (44.4+/-0.2 vs. 43.8+/-2.2 A.U.). In conclusion, baroreceptor reflex-dependent overshoot of the arterial blood pressure after active standing up is diminished in kidney transplant recipients, whereas no association to the cyclosporine A whole blood level has been detected. The reduced overshoot may be due to the diminished baroreceptor sensitivity which could be shown in renal transplant recipients.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana – A Cohort Study

PubMed Central

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Background Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Methods and Findings Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. Conclusions There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings. PMID:26327623

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

PubMed

Owusu, Ruth; Asante, Kwaku Poku; Mahama, Emmanuel; Awini, Elizabeth; Anyorigiya, Thomas; Dosoo, David; Amu, Alberta; Jakpa, Gabriel; Ofei, Emmanuel; Segbaya, Sylvester; Oduro, Abraham Rexford; Gyapong, Margaret; Hodgson, Abraham; Bart-Plange, Constance; Owusu-Agyei, Seth

2015-01-01

Sulphadoxine-Pyrimethamine (SP) is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp) in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb) drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp. Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb) levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women).The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia. There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger study is required to confirm consistency of findings.

Acute high-intensity interval exercise induces comparable levels of circulating cell-free DNA and Interleukin-6 in obese and normal-weight individuals.

PubMed

Ferrandi, Peter J; Fico, Brandon G; Whitehurst, Michael; Zourdos, Michael C; Bao, Fanchen; Dodge, Katelyn M; Rodriguez, Alexandra L; Pena, Gabriel; Huang, Chun-Jung

2018-06-01

Obesity is associated with lipid aggregation in adipocytes and macrophage infiltration, leading to increased oxidative stress and inflammation. Increased cell-free DNA (cfDNA) concentrations have been observed in clinical conditions of systemic inflammation. While the beneficial effects of regular physical activity on the release of circulating cfDNA still remain unknown, acute intense exercise has been shown to increase inflammatory cytokines and cfDNA concentrations in normal-weight individuals. Therefore, the primary purpose of this study was to examine the effect of acute high-intensity interval Exercise (HIIE) on plasma cfDNA and interleukin-6 (IL-6) responses in obese and normal-weight subjects. Fourteen male subjects (7 obese and 7 normal-weight) participated in an acute HIIE protocol (30 min, 4x4min @ 80% - 90% of VO 2max ) on a treadmill. Between HIIE intervals, subjects performed 3 min of active recovery at 50-60% VO 2max . Blood samples were collected prior to, immediately following exercise, and one hour into recovery for measurements of plasma cfDNA and IL-6. Our results demonstrated a significant elevation in plasma cfDNA immediately following acute HIIE in both obese and normal-weight subjects. A comparable elevation in the concentration of plasma IL-6 was also found between two groups in response to acute HIIE. Furthermore, the level of plasma cfDNA was not correlated with IL-6 either at baseline or in response to acute HIIE. These findings may support the utilization of HIIE as a time-efficient exercise protocol to understand the obesity-associated cfDNA and inflammatory responses. Published by Elsevier Inc.

Parkinson's disease: increased motor network activity in the absence of movement.

PubMed

Ko, Ji Hyun; Mure, Hideo; Tang, Chris C; Ma, Yilong; Dhawan, Vijay; Spetsieris, Phoebe; Eidelberg, David

2013-03-06

We used a network approach to assess systems-level abnormalities in motor activation in humans with Parkinson's disease (PD). This was done by measuring the expression of the normal movement-related activation pattern (NMRP), a previously validated activation network deployed by healthy subjects during motor performance. In this study, NMRP expression was prospectively quantified in (15)O-water PET scans from a PD patient cohort comprised of a longitudinal early-stage group (n = 12) scanned at baseline and at two or three follow-up visits two years apart, and a moderately advanced group scanned on and off treatment with either subthalamic nucleus deep brain stimulation (n = 14) or intravenous levodopa infusion (n = 14). For each subject and condition, we measured NMRP expression during both movement and rest. Resting expression of the abnormal PD-related metabolic covariance pattern was likewise determined in the same subjects. NMRP expression was abnormally elevated (p < 0.001) in PD patients scanned in the nonmovement rest state. By contrast, network activity measured during movement did not differ from normal (p = 0.34). In the longitudinal cohort, abnormal increases in resting NMRP expression were evident at the earliest clinical stages (p < 0.05), which progressed significantly over time (p = 0.003). Analogous network changes were present at baseline in the treatment cohort (p = 0.001). These abnormalities improved with subthalamic nucleus stimulation (p < 0.005) but not levodopa (p = 0.25). In both cohorts, the changes in NMRP expression that were observed did not correlate with concurrent PD-related metabolic covariance pattern measurements (p > 0.22). Thus, the resting state in PD is characterized by changes in the activity of normal as well as pathological brain networks.

Leuprolide acetate-stimulated androgen response during female puberty.

PubMed

Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

2015-08-01

A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty. © 2014 John Wiley & Sons Ltd.

The effect of continuous positive airway pressure on middle ear pressure.

PubMed

Lin, Fred Y; Gurgel, Richard K; Popelka, Gerald R; Capasso, Robson

2012-03-01

While continuous positive airway pressure (CPAP) is commonly used for obstructive sleep apnea treatment, its effect on middle ear pressure is unknown. The purpose of this study was to measure the effect of CPAP on middle ear pressure and describe the correlation between CPAP levels and middle ear pressures. Retrospective review of normal tympanometry values and a prospective cohort evaluation of subjects' tympanometric values while using CPAP at distinct pressure levels. A total of 3,066 tympanograms were evaluated to determine the normal range of middle ear pressures. Ten subjects with no known history of eustachian tube dysfunction or obstructive sleep apnea had standard tympanometry measurements while wearing a CPAP device. Measurements were taken at baseline and with CPAP air pressures of 0, 5, 10, and 15 cm H(2)O. The percentage of normal control patients with middle ear pressures above 40 daPa was 0.03%. In the study population, prior to a swallowing maneuver to open the eustachian tube, average middle ear pressures were 21.67 daPa, 22.63 daPa, 20.42, daPa, and 21.58 daPa with CPAP pressures of 0, 5, 10, and 15 cm H(2) 0, respectively. After swallowing, average middle ear air pressures were 18.83 daPa, 46.75 daPa, 82.17 daPa, and 129.17 daPa with CPAP pressures of 0, 5, 10, and 15 cm H(2)0, respectively. The postswallow Pearson correlation coefficient correlating CPAP and middle ear pressures was 0.783 (P < 0.001). Middle ear air pressure is directly proportional to CPAP air pressure in subjects with normal eustachian tube function. Middle ear pressure reaches supraphysiologic levels at even minimal CPAP levels. Although further investigation is necessary, there may be otologic implications for patients who are chronically CPAP dependent. These findings may also influence the perioperative practice of otologic and skull base surgeons. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Dependence of future mortality changes on global CO2 concentrations: A review.

PubMed

Lee, Jae Young; Choi, Hayoung; Kim, Ho

2018-05-01

The heterogeneity among previous studies of future mortality projections due to climate change has often hindered comparisons and syntheses of resulting impacts. To address this challenge, the present study introduced a novel method to normalize the results from projection studies according to different baseline and projection periods and climate scenarios, thereby facilitating comparison and synthesis. This study reviewed the 15 previous studies involving projected climate change-related mortality under Representative Concentration Pathways. To synthesize their results, we first reviewed the important study design elements that affected the reported results in previous studies. Then, we normalized the reported results by CO 2 concentration in order to eliminate the effects of the baseline period, projection period, and climate scenario choices. For twenty-five locations worldwide, the normalized percentage changes in temperature-attributable mortality per 100 ppm increase in global CO 2 concentrations ranged between 41.9% and 330%, whereas those of total mortality ranged between 0.3% and 4.8%. The normalization methods presented in this work will guide future studies to provide their results in a normalized format and facilitate research synthesis to reinforce our understanding on the risk of climate change. Copyright © 2018 Elsevier Ltd. All rights reserved.

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

PubMed Central

Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI. PMID:26474181

Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

PubMed

Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

2015-01-01

During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Machine Learning-based Individual Assessment of Cortical Atrophy Pattern in Alzheimer's Disease Spectrum: Development of the Classifier and Longitudinal Evaluation.

PubMed

Lee, Jin San; Kim, Changsoo; Shin, Jeong-Hyeon; Cho, Hanna; Shin, Dae-Seock; Kim, Nakyoung; Kim, Hee Jin; Kim, Yeshin; Lockhart, Samuel N; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

2018-03-07

To develop a new method for measuring Alzheimer's disease (AD)-specific similarity of cortical atrophy patterns at the individual-level, we employed an individual-level machine learning algorithm. A total of 869 cognitively normal (CN) individuals and 473 patients with probable AD dementia who underwent high-resolution 3T brain MRI were included. We propose a machine learning-based method for measuring the similarity of an individual subject's cortical atrophy pattern with that of a representative AD patient cohort. In addition, we validated this similarity measure in two longitudinal cohorts consisting of 79 patients with amnestic-mild cognitive impairment (aMCI) and 27 patients with probable AD dementia. Surface-based morphometry classifier for discriminating AD from CN showed sensitivity and specificity values of 87.1% and 93.3%, respectively. In the longitudinal validation study, aMCI-converts had higher atrophy similarity at both baseline (p < 0.001) and first year visits (p < 0.001) relative to non-converters. Similarly, AD patients with faster decline had higher atrophy similarity than slower decliners at baseline (p = 0.042), first year (p = 0.028), and third year visits (p = 0.027). The AD-specific atrophy similarity measure is a novel approach for the prediction of dementia risk and for the evaluation of AD trajectories on an individual subject level.

Improved Topographic Mapping Through Multi-Baseline SAR Interferometry with MAP Estimation

NASA Astrophysics Data System (ADS)

Dong, Yuting; Jiang, Houjun; Zhang, Lu; Liao, Mingsheng; Shi, Xuguo

2015-05-01

There is an inherent contradiction between the sensitivity of height measurement and the accuracy of phase unwrapping for SAR interferometry (InSAR) over rough terrain. This contradiction can be resolved by multi-baseline InSAR analysis, which exploits multiple phase observations with different normal baselines to improve phase unwrapping accuracy, or even avoid phase unwrapping. In this paper we propose a maximum a posteriori (MAP) estimation method assisted by SRTM DEM data for multi-baseline InSAR topographic mapping. Based on our method, a data processing flow is established and applied in processing multi-baseline ALOS/PALSAR dataset. The accuracy of resultant DEMs is evaluated by using a standard Chinese national DEM of scale 1:10,000 as reference. The results show that multi-baseline InSAR can improve DEM accuracy compared with single-baseline case. It is noteworthy that phase unwrapping is avoided and the quality of multi-baseline InSAR DEM can meet the DTED-2 standard.

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B.

PubMed

Wong, Grace Lai-Hung; Chan, Henry Lik-Yuen; Tse, Yee-Kit; Yip, Terry Cheuk-Fung; Lam, Kelvin Long-Yan; Lui, Grace Chung-Yan; Wong, Vincent Wai-Sun

2018-06-18

Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB). A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded. A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ± 1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001). Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients. We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

PubMed Central

Irwin, Michael R.; Olmstead, Richard; Valladares, Edwin M.; Breen, Elizabeth Crabb; Ehlers, Cindy L.

2009-01-01

Background In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults. Methods In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order. Polysomnographic sleep was measured at baseline and for 3 nights after the acute dose of etanercept or placebo. Results Compared with placebo, administration of etanercept produced significant decreases in the amount and percentage of REM sleep. Decreases in REM sleep were robust and approached low levels typically found in age-comparable control subjects. Individual differences in biologically active drug as indexed by circulating levels of soluble tumor necrosis factor receptor II negatively correlated with the percentage of REM sleep. Conclusions Pharmacologic neutralization of TNF-α activity is associated with significant reductions in REM sleep in abstinent alcohol-dependent patients. These data suggest that circulating levels of TNF-α may have a physiologic role in the regulation of REM sleep in humans. PMID:19185287

Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout.

PubMed

Meng, Juan; Li, Yanchun; Yuan, Xiaoxu; Lu, Yuewu

2017-02-01

We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P < 0.05). After 4-, 12-, and 24-week febuxostat treatments, UA and hs-CRP concentrations were significantly lower than baseline (P < 0.05). INS and HOM-IR decreased slightly after a 4-week treatment with febuxostat but declined significantly after 12 and 24 weeks of treatment. Importantly, hs-CRP values positively correlated with those of HOMA-IR (r = 0.353, P = 0.018) and INS (r = 0.426, P = 0.034). Our findings confirm that IR exists in gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.

Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients.

PubMed

Berruti, A; Dogliotti, L; Mosca, A; Tarabuzzi, R; Torta, M; Mari, M; Gorzegno, G; Fontana, D; Angeli, A

2001-05-15

The concept that neuroendocrine cells detected within prostate adenocarcinoma produce paracrine factors, that may exert a proliferative effect on exocrine prostate tumor cells, provides a rationale for the use of somatostatin analogs with the aim to counteract or delay the tumor progression. This study was designed to provide preliminary information on the effect of the administration of a long-acting somatostatin analog, lanreotide, on plasma levels of chromogranin A (CgA). Secondary aims were the evaluation of changes in circulating prostate-specific antigen (PSA) and insulin-like growth factor-1 (IGF-1). Lanreotide (Ipstyl 30 mg; Ipsen, Milan, Italy) was administered intramuscularly every 14 days for 2 months to nine heavily pretreated prostate cancer patients with hormone refractory disease. All patients had, at baseline conditions, CgA values above the normal range. Androgen deprivation was maintained during the study period, while other concomitant antineoplastic treatments were not allowed. Serum PSA levels and plasma CgA and IGF-1 values were measured every week. Lanreotide treatment was very well tolerated and no patient experienced major toxicity. Plasma CgA values at baseline: mean 109 U/liter, standard deviation +/- 85 decreased significantly after treatment as follows: 42 U/liter, +/- 17.8; 27.2 U/liter +/- 13.6; 31.4 U/liter, +/- 17.8 and 27.6 U/liter, +/- 17.0; after 7, 14, 21, and 28 days, respectively (P < 0.01, Friedman ANOVA). Serum PSA did not change. Baseline IGF-1 was found to be above the detection limit in four cases, all of them showing a decrease after lanreotide. Lanreotide administration to prostate cancer patients induces a decrease in plasma CgA and IGF-1 levels, without any influence on serum PSA values. Prostate 47:205-211, 2001. Copyright 2001 Wiley-Liss, Inc.

Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children.

PubMed

Bellone, J; Aimaretti, G; Bellone, S; Baffoni, C; Corneli, G; Origlia, C; Cappa, M; Ghigo, E

2000-02-01

The hormonal diagnosis of GH deficiency in childhood is conventionally based on the GH response to at least two provocative stimuli. Among these, arginine (ARG) has long been considered a classical, centrally mediated stimulus of GH secretion. ARG is also able to potentiate the GH response to GHRH, likely inhibiting hypothalamic somatostatin; this combined test is one of the most potent to explore the maximal secretory capacity of somatotroph cells. Based on these premises, we verified whether the sequential administration of ARG and ARG+GHRH could be feasible as single step provocative test to evaluate the GH releasable pool in short children. To this goal, 48 normal short children (35 M and 13 F, 12.0+/-0.4 yr, PS 1: 255 II-IV: 23) underwent a test with ARG (0.5 g/kg i.v. from 0 to +30 min) followed by a coadministration of ARG (from +120 to 150 min) plus GHRH (1 microg/kg i.v. at +120 min). ARG alone elicited a clear GH response (mean peak vs baseline: 12.1+/-1.7 vs 2.0+/-0.4 microg/l, p<0.001, Cmax range 12-51.0 microg/l). Following this GH rise, the hormonal levels at +120 min approached to baseline levels (4.2+/-0.8 microg/l) but then showed marked response to the coadministration of ARG+GHRH. The GH peak following ARG+GHRH (mean peak: 47.8+/-3.3 microg/l, p<0.001; Cmax 22.4-150.0 microg/l) was clearly higher (p<0.001) than that recorded after ARG alone. The GH responses to both ARG and ARG+GHRH were independent of gender, puberty, height velocity, body mass index (BMI) and IGF-I levels. Nine normal short children (16%) had GH peaks lower than 7 microg/l after ARG alone, while none showed GH peak below 20 microg/l after ARG+GHRH. Thus, ARG alone is a good stimulus of GH secretion but false positive responses frequently occur in normal short children. ARG+GHRH is a more potent stimulus giving no false positive responses even after previous challenge with ARG alone. Testing with sequential administration of ARG and ARG+GHRH may allow the single step evaluation of the somatotroph response to central and pituitary stimuli in short children.

Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma.

PubMed

Shakir, Mohamed K M; Krook, Linda S; Schraml, Frank V; Hays, James H; Clyde, Patrick W

2008-07-01

Strategies to improve I131 uptake in thyroid carcinoma include levothyroxine (LT4) withdrawal or thyrotropin (TSH) administration along with a low-iodine diet. We report five patients with papillary or follicular thyroid carcinoma who developed symptomatic hyponatremia during LT4 withdrawal and low-iodine diet. Four patients had pulmonary and/or brain metastases. All had restricted iodine intakes during LT4 withdrawal. Presenting complaints included weakness, dizziness, fainting spells, lethargy, and/or nausea. Baseline serum sodium levels while on LT4 suppression were normal. During presentation all were hypothyroid and serum sodium ranged from 110 to 121 mmol/L (normal 135-148). Despite hyponatremia, the plasma renin activity and serum aldosterone levels were suppressed, indicating volume expansion. The hyponatremia responded to fluid restriction and normalized after LT4 replacement. Low sodium intake, inappropriate antidiuretic hormone secretion syndrome (SIADH)-like disorder secondary to hypothyroidism and/or lung or cerebral metastases may have contributed to hyponatremia. The development of hyponatremia during LT4 withdrawal and low-iodine diet in otherwise healthy patients with thyroid carcinoma is extremely rare. However, elderly patients with metastatic thyroid carcinoma need observation during LT4 withdrawal combined with a low-iodine diet and should receive instruction to take iodine-free sodium chloride. Free water restriction may be necessary in some patients.

Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program.

PubMed

Urata, Satoko; Kitagawa, Yasuhide; Matsuyama, Satoko; Naito, Renato; Yasuda, Kenji; Mizokami, Atsushi; Namiki, Mikio

2017-04-01

To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

Obesity, lipid profiles and oxidative stress in children after liver transplantation.

PubMed

Czubkowski, Piotr; Wierzbicka, Aldona; Pawłowska, Joanna; Jankowska, Irena; Socha, Piotr

2017-01-01

In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx). We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85 th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95 th and >85 Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a). Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.

Influence of Renal Function on the 52-Week Efficacy and Safety of the Sodium Glucose Cotransporter 2 Inhibitor Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus.

PubMed

Haneda, Masakazu; Seino, Yutaka; Inagaki, Nobuya; Kaku, Kohei; Sasaki, Takashi; Fukatsu, Atsushi; Kakiuchi, Haruka; Sato, Yuri; Sakai, Soichi; Samukawa, Yoshishige

2016-01-01

To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin (TS-071) in Japanese patients with type 2 diabetes mellitus (T2DM). Study 1 was a 52-week, Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin (or increased to 5 mg/d) in patients with T2DM with moderate renal impairment. During the initial 24 weeks, efficacy and safety of luseogliflozin were compared with placebo. Study 2 was a pooled analysis of four 52-week, Phase III studies of luseogliflozin, including Study 1, to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function. Patients were stratified into 3 groups by baseline estimated glomerular filtration rate (eGFR): normal renal function (≥90 mL/min/1.73 m(2)), mild impairment (≥60 to <90 mL/min/1.73 m(2)), and moderate impairment (≥30 to <60 mL/min/1.73 m(2)). Patients with moderate impairment were further divided into those with mild-moderate (≥45 to <60 mL/min/1.73 m(2)) and moderate-severe (≥30 to <45 mL/min/1.73 m(2)). In both studies, efficacy end points included changes in glycated hemoglobin (HbA1c) level, fasting plasma glucose (FPG) level, and body weight. The safety end points included adverse events (AEs) and laboratory parameters. In Study 1, HbA1c, FPG, and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo, with the decrease in these parameters also observed with luseogliflozin at Week 52. The incidence of AEs was similar between groups. In Study 2, 1030 patients were included (normal, 275; mildly impaired, 598; and moderately impaired, 157). At Week 52, HbA1c, FPG, and body weight were significantly decreased from baseline in all groups. In between-group comparisons, the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function; however, the HbA1c-lowering efficacy was reduced by nearly half, whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group. Furthermore, a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR. The incidence of AEs during 52 weeks was similar among all groups, with the majority being mild. Luseogliflozin improved glycemic control and reduced body weight in all eGFR groups, and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment. Luseogliflozin was well tolerated and safe, with no significant safety issues identified, regardless of baseline eGFR. The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center, and the study registry identification numbers are JapicCTI-111507, JapicCTI-111508, JapicCTI-111509, and JapicCTI-111543. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Higher Ratio of Serum Alpha-Fetoprotein Could Predict Outcomes in Patients with Hepatitis B Virus-Associated Hepatocellular Carcinoma and Normal Alanine Aminotransferase

PubMed Central

Park, Joong-Won

2016-01-01

Background The role of serum alpha-fetoprotein (AFP) levels in the surveillance and diagnosis of hepatocellular carcinoma (HCC) is controversial. The aim of this study was to investigate the value of serially measured serum AFP levels in HCC progression or recurrence after initial treatment. Methods A total of 722 consecutive patients newly diagnosed with HCC and treated at the National Cancer Center, Korea, between January 2004 and December 2009 were enrolled. The AFP ratios between 4–8 weeks post-treatment and those at the time of HCC progression or recurrence were obtained. Multivariate logistic regression analysis was performed to correlate the post-treatment AFP ratios with the presence of HCC progression or recurrence. Results The etiology of HCC was related to chronic hepatitis B virus (HBV) infection in 562 patients (77.8%), chronic hepatitis C virus (HCV) infection in 74 (10.2%), and non-viral cause in 86 (11.9%). There was a significant decrease in serum AFP levels from the baseline to 4 to 8 weeks after treatment (median AFP, 319.6 ng/mL vs. 49.6 ng/mL; p< 0.001). Multivariate analysis showed that an AFP ratio > 1.0 was an independently associated with HCC progression or recurrence. Among the different causes of HCC analyzed, this association was significant only for HCC related to chronic hepatitis B (p< 0.001) and non-viral causes (p<0.05), and limited only to patients who had normal alanine aminotransferase (ALT) levels. Conclusion Serial measurements of serum AFP ratios could be helpful in detecting progression or recurrence in treated patients with HBV-HCC and normal ALT. PMID:27304617

Cytokine and chemokine levels in tears from healthy subjects.

PubMed

Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

2010-11-01

There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

PubMed

Rich, Alisa L; Patel, Jay T; Al-Angari, Samiah S

2016-01-01

Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.

Links between early baseline cortisol, attachment classification, and problem behaviors: A test of differential susceptibility versus diathesis-stress.

PubMed

Fong, Michelle C; Measelle, Jeffrey; Conradt, Elisabeth; Ablow, Jennifer C

2017-02-01

The purpose of the current study was to predict concurrent levels of problem behaviors from young children's baseline cortisol and attachment classification, a proxy for the quality of caregiving experienced. In a sample of 58 children living at or below the federal poverty threshold, children's baseline cortisol levels, attachment classification, and problem behaviors were assessed at 17 months of age. We hypothesized that an interaction between baseline cortisol and attachment classification would predict problem behaviors above and beyond any main effects of baseline cortisol and attachment. However, based on limited prior research, we did not predict whether or not this interaction would be more consistent with diathesis-stress or differential susceptibility models. Consistent with diathesis-stress theory, the results indicated no significant differences in problem behavior levels among children with high baseline cortisol. In contrast, children with low baseline cortisol had the highest level of problem behaviors in the context of a disorganized attachment relationship. However, in the context of a secure attachment relationship, children with low baseline cortisol looked no different, with respect to problem behavior levels, then children with high cortisol levels. These findings have substantive implications for the socioemotional development of children reared in poverty. Copyright © 2017 Elsevier Inc. All rights reserved.

Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Streja, Elani; Tortorici, Amanda R; Rhee, Connie M; Soohoo, Melissa; Kim, Taehee; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-07-07

There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model ( P trend <0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality ( P trend <0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality. Copyright © 2017 by the American Society of Nephrology.

Physical activity, obesity, weight change, and risk of atrial fibrillation: the Atherosclerosis Risk in Communities study.

PubMed

Huxley, Rachel R; Misialek, Jeffrey R; Agarwal, Sunil K; Loehr, Laura R; Soliman, Elsayed Z; Chen, Lin Y; Alonso, Alvaro

2014-08-01

Physical activity (PA) has previously been suggested to attenuate the risk of atrial fibrillation (AF) conferred by excess body weight and weight gain. We prospectively examined the relationship between body size, weight change, and level of PA in a biracial cohort of middle-aged men and women. Baseline characteristics on risk factor levels were obtained on 14 219 participants from the Atherosclerosis Risk in Communities Study. AF incidence was ascertained from 1987 to 2009. Adjusted Cox proportional hazards models were used to estimate the associations between body mass index, waist circumference, relative weight change, and PA level with incident AF. During follow-up, there were 1775 cases of incident AF. Body mass index and waist circumference were positively associated with AF as was weight loss/gain of >5% initial body weight. An ideal level of PA had a small protective effect on AF risk and partially attenuated the risk of AF associated with excess weight in men but not women: compared with men with a normal body mass index, the risk of AF in obese men with an ideal, intermediate, and poor level of PA at baseline was increased by 37%, 129%, and 156% (Pinteraction=0.04). During follow-up, PA did not modify the association between weight gain and risk of AF. Obesity and extreme weight change are risk factors for incident AF, whereas being physically active is associated with a small reduction in risk. In men only, being physically active offset some, but not all, of the risk incurred with excess body weight. © 2014 American Heart Association, Inc.

Prediction of risk for hepatocellular carcinoma by response of serum α-fetoprotein to entecavir therapy.

PubMed

Yang, Sung Wook; Kim, Gi Hyun; Chung, Jung Wha; Sohn, Hyung Rae; Lee, Sang Soo; Hong, Sukho; Chung, Seong Min; Jang, Eun Sun; Jeong, Sook-Hyang; Kim, Jin-Wook

2015-07-01

Serum α-fetoprotein (AFP) is frequently elevated in patients with chronic hepatitis B (CHB) who do not have hepatocellular carcinoma (HCC). Entecavir (ETV) treatment reduces AFP levels in these patients, but the clinical significance of AFP response to ETV has not been fully studied. The aims of this study were to elucidate the temporal response of AFP to ETV therapy and to determine the relationship between AFP response and the subsequent development of HCC. All consecutive nucleos(t)ide-naïve CHB patients who started ETV therapy between March 2007 and February 2009 were selected from an electronic medical record database at a tertiary referral center (BESTCare). Clinical, biochemical, and virologic parameters were evaluated in relation to the serial AFP levels tested during ETV treatment. Among the 244 enrolled patients, 66 had elevated AFP levels before ETV therapy. Low serum albumin was a significant predictor for elevated AFP. During 12 months of ETV therapy, AFP levels normalized in approximately three fourths of these patients. The decrease in AFP was delayed in patients with high baseline hepatitis B virus titers and in patients who subsequently developed HCC during ETV therapy. Incidence of HCC was similar regardless of baseline AFP levels. Among patients with elevated AFP, however, HCC developed exclusively in the subgroup where elevated AFP persisted for more than 6 months of ETV therapy. Delayed AFP response to ETV may serve as an indicator of high HCC risk. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Summary of long-baseline systematics session at CETUP*2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cherdack, Daniel; Worcester, Elizabeth

2015-10-15

A session studying systematics in long-baseline neutrino oscillation physics was held July 14-18, 2014 as part of CETUP* 2014. Systematic effects from flux normalization and modeling, modeling of cross sections and nuclear interactions, and far detector effects were addressed. Experts presented the capabilities of existing and planned tools. A program of study to determine estimates of and requirements for the size of these effects was designed. This document summarizes the results of the CETUP* systematics workshop and the current status of systematic uncertainty studies in long-baseline neutrino oscillation measurements.