Risk of Liver Toxicity with Nivolumab Immunotherapy in Cancer Patients.

PubMed

Zarrabi, Kevin; Wu, Shenhong

2018-01-01

Nivolumab is approved for the treatment of many cancers. This meta-analysis was conducted to determine the risk of hepatotoxicity with nivolumab therapy. An analysis from all phase I-III clinical trials up to December 2016 examining nivolumab was conducted. Data on elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were extracted from the safety profiles of each trial. Incidence and relative risk (RR) were calculated using random- or fixed-effects models with 95% confidence intervals (CIs). The incidences of all-grade and high-grade elevations in AST were 5.4% (95% CI 3.2-9.1) and 1.6% (95% CI 0.9-3.0), respectively. The incidences of all-grade and high-grade elevations in ALT were 4.9% (95% CI 2.9-8.2) and 1.7% (95% CI 0.9-3.1), respectively. Elevations of both laboratory markers were significantly increased when compared to control (p < 0.001). Nivolumab significantly increased the RR of AST/ALT elevations; RRs were 1.58 (95% CI 1.1-2.2) for all-grade AST elevation, and 1.62 (95% CI 1.2-2.3) for all-grade ALT elevation. Subgroup analysis of all-grade AST or ALT elevation revealed a signi-ficant variation among tumor types (p < 0.001) and with combination with ipilimumab (p < 0.001). Nivolumab is associated with significantly increased risk of liver toxicity. © 2018 S. Karger AG, Basel.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

PubMed

Li, Li; Chen, Jinglong; Xu, Weiran; Ding, Xiaosheng; Wang, Xiangyi; Liang, Jun

2017-10-26

Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P < 0.05. Using 8.78 ng/mL as the cut off value, serum AFP level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P < 0.05. There was significant difference between the time of diagnosis with HCC to serum AFP level elevation and the time of AFP elevation to death, P < 0.05. Prognosis of HCC patients with normal AFP level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS. © 2017 John Wiley & Sons Australia, Ltd.

Decreased C-reactive protein levels in Alzheimer disease.

PubMed

O'Bryant, Sid E; Waring, Stephen C; Hobson, Valerie; Hall, James R; Moore, Carol B; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2010-03-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histopathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 +/- 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 +/- 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 microg/mL) versus controls (4.9 microg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD.

Decreased C-Reactive Protein Levels in Alzheimer Disease

PubMed Central

O’Bryant, Sid E.; Waring, Stephen C.; Hobson, Valerie; Hall, James R.; Moore, Carol B.; Bottiglieri, Teodoro; Massman, Paul; Diaz-Arrastia, Ramon

2011-01-01

C-reactive protein (CRP) is an acute-phase reactant that has been found to be associated with Alzheimer disease (AD) in histo-pathological and longitudinal studies; however, little data exist regarding serum CRP levels in patients with established AD. The current study evaluated CRP levels in 192 patients diagnosed with probable AD (mean age = 75.8 ± 8.2 years; 50% female) as compared to 174 nondemented controls (mean age = 70.6 ± 8.2 years; 63% female). Mean CRP levels were found to be significantly decreased in AD (2.9 µg/mL) versus controls (4.9 µg/mL; P = .003). In adjusted models, elevated CRP significantly predicted poorer (elevated) Clinical Dementia Rating Scale sum of boxes (CDR SB) scores in patients with AD. In controls, CRP was negatively associated with Mini-Mental State Examination (MMSE) scores and positively associated with CDR SB scores. These findings, together with previously published results, are consistent with the hypothesis that midlife elevations in CRP are associated with increased risk of AD development though elevated CRP levels are not useful for prediction in the immediate prodrome years before AD becomes clinically manifest. However, for a subgroup of patients with AD, elevated CRP continues to predict increased dementia severity suggestive of a possible proinflammatory endophenotype in AD. PMID:19933496

[Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

PubMed

Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

2009-03-01

To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

Sensory processing issues in young children presenting to an outpatient feeding clinic.

PubMed

Davis, Ann M; Bruce, Amanda S; Khasawneh, Rima; Schulz, Trina; Fox, Catherine; Dunn, Winifred

2013-02-01

The aim of the study was to describe the relation between sensory issues and medical complexity in a series of patients presenting to an outpatient multidisciplinary feeding team for evaluation, by a standardized measure of sensory-processing abilities. A retrospective chart review of all of the patients seen from 2004 to 2009 on 2 key variables: medical diagnostic category and short sensory profile (SSP) score. On the SSP, 67.6% of children scored in the clinical ("definite difference") range. The most common diagnostic categories were developmental (n = 23), gastrointestinal (n = 16), and neurological (n = 13). Behavioral and cardiorespiratory medical diagnostic categories were significantly related to SSP total score and SSP definite difference score. Children who present for feeding evaluation do indeed tend to have clinically elevated scores regarding sensory processing, and these elevated scores are significantly related to certain medical diagnostic categories. Future research is needed to determine why these significant relations exist as well as their implications for treatment of feeding-related issues.

Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery.

PubMed

Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

2015-02-01

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.

Urinary heavy metals in Hispanics 40–85 years old in Doña Ana County, New Mexico

PubMed Central

Adams, Scott V.; Barrick, Brian; Freney, Emily P.; Shafer, Martin M.; Song, Xiaoling; Vilchis, Hugo; Newcomb, Polly A.; Ulery, April

2017-01-01

As, Cd, Pb, and U exposure among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults age 40–85y. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (P<0.05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population. PMID:26666397

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

PubMed

Nishiguchi, Tsuyoshi; Tanaka, Atsushi; Taruya, Akira; Emori, Hiroki; Ozaki, Yuichi; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Kubo, Takashi; Hozumi, Takeshi; Hayashi, Yasushi; Akasaka, Takashi

2016-12-01

Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention. © 2016 American Heart Association, Inc.

Dissociative phenomena in congenital monocular elevation deficiency.

PubMed

Olson, R J; Scott, W E

1998-04-01

Monocular elevation deficiency is characterized by unilateral limitation of elevation in both adduction and abduction and is usually present at birth. Dissociative phenomena such as dissociated vertical deviation are well recognized in association with conditions such as congenital esotropia but much less so in association with conditions such as congenital monocular elevation deficiency. All 129 patients given the diagnosis of monocular elevation deficiency or double elevator palsy in the Pediatric Ophthalmology and Strabismus Clinic at the University of Iowa Hospitals and Clinics between 1971 and 1995 were reviewed. After those with history of trauma, myasthenia gravis, thyroid eye disease, orbital lesions, Brown syndrome, or monocular elevation deficiency with acquired onset were excluded, 31 patients with congenital monocular elevation deficiency remained for retrospective study. First diagnosed at median age 2.6 years (although all were noted by parents at less than 6 months of age) with mean follow-up of 5.0 years (up to 15.5 years), 9 of 31 (29%) developed dissociated vertical deviation in the eye with monocular elevation deficiency, all of whom had undergone strabismus surgery 0 to 9.7 years previously (mean 3.5 years). Those who developed dissociated vertical deviation were generally younger, were followed up longer, and had more accompanying horizontal strabismus than did those who did not develop dissociated vertical deviation. The results did not reach significance. The current study demonstrates that dissociated vertical deviation occurs in association with monocular elevation deficiency.

Prevalence and clinical characteristics of isolated-office and true resistant hypertension determined by ambulatory blood pressure monitoring.

PubMed

Ríos, María T; Domínguez-Sardiña, Manuel; Ayala, Diana E; Gomara, Sonia; Sineiro, Elvira; Pousa, Lorenzo; Callejas, Pedro A; Fontao, María J; Fernández, José R; Hermida, Ramón C

2013-03-01

Hypertension is defined as resistant to treatment when a therapeutic plan including ≥3 hypertension medications failed to sufficiently lower systolic (SBP) and diastolic (DBP) blood pressures (BPs). Most individuals, including those under hypertension therapy, show a "white-coat" effect that could cause an overestimation of their real BP. The prevalence and clinical characteristics of "white-coat" or isolated-office resistant hypertension (RH) has always been evaluated by comparing clinic BP values with either daytime home BP measurements or the awake BP mean obtained from ambulatory monitoring (ABPM), therefore including patients with either normal or elevated asleep BP mean. Here, we investigated the impact of including asleep BP mean as a requirement for the definition of hypertension on the prevalence, clinical characteristics, and estimated cardiovascular (CVD) risk of isolated-office RH. This cross-sectional study evaluated 3042 patients treated with ≥3 hypertension medications and evaluated by 48-h ABPM (1707 men/1335 women), 64.2 ± 11.6 (mean ± SD) yrs of age, enrolled in the Hygia Project. Among the participants, 522 (17.2%) had true isolated-office RH (elevated clinic BP and controlled awake and asleep ambulatory BPs while treated with 3 hypertension medications), 260 (8.6%) had false isolated-office RH (elevated clinic BP, controlled awake SBP/DBP means, but elevated asleep SBP or DBP mean while treated with 3 hypertension medications), and the remaining 2260 (74.3%) had true RH (elevated awake or asleep SBP/DBP means while treated with 3 medications, or any patient treated with ≥4 medications). Patients with false, relative to those with true, isolated-office RH had higher prevalence of microalbuminuria and chronic kidney disease (CKD), significantly higher albumin/creatinine ratio (p < .001), significantly higher 48-h SBP/DBP means by 9.6/5.3 mm Hg (p < .001), significantly lower sleep-time relative SBP and DBP decline (p < .001), and significantly greater prevalence of a non-dipper BP profile (96.9% vs. 38.9%; p < .001). Additionally, the prevalence of the riser BP pattern, which is associated with highest CVD risk, was much greater, 40.4% vs. 5.0% (p < .001), among patients with false isolated-office RH. The estimated hazard ratio of CVD events, using a fully adjusted model including the significant confounding variables of sex, age, diabetes, chronic kidney disease, asleep SBP mean, and sleep-time relative SBP decline, was significantly greater for patients with false compared with those with true isolated-office RH (2.13 [95% confidence interval: 1.95-2.32]; p < .001). Patients with false isolated-office hypertension and true RH, however, were equivalent for the prevalence of obstructive sleep apnea, metabolic syndrome, obesity, diabetes, microalbuminuria, and chronic kidney disease, and they had an equivalent estimated hazard ratio of CVD events (1.04 [95% confidence interval: .97-1.12]; p = .265). Our findings document a significantly elevated prevalence of a blunted nighttime BP decline in patients here categorized as either false isolated-office RH and true RH, jointly accounting for 82.8% of the studied sample. Previous reports of much lower prevalence of true RH plus a nonsignificant increased CVD risk of this condition compared with isolated-office RH are misleading by disregarding asleep BP mean for classification. Our results further indicate that classification of RH patients into categories of isolated-office RH, masked RH, and true RH cannot be based on the comparison of clinic BP with either daytime home BP measurements or awake BP mean from ABPM, as so far customary in the available literature, totally disregarding the highly significant prognostic value of nighttime BP. Accordingly, ABPM should be regarded as a clinical requirement for proper diagnosis of true RH.

The role of elevated serum procalcitonin in neuroendocrine neoplasms of digestive system.

PubMed

Chen, Luohai; Zhang, Yu; Lin, Yuan; Deng, Langhui; Feng, Shiting; Chen, Minhu; Chen, Jie

2017-12-01

Elevated serum procalcitonin (PCT) was reported in patients with certain type of neuroendocrine neoplasms (NENs). The aim of this study was to assess the role of elevated serum PCT in NENs from digestive system. Serum PCT and serum CgA level were measured in 155 patients with NENs from digestive system. Elevated serum PCT was found in 63 patients (40.6%). Grade 3 disease was a significant factor associated with elevated serum PCT (OR, 9.24; 95%CI, 3.04-28.08; P<0.001). Serum PCT level was significantly decreased after treatment both in patients with stable disease (P=0.003) and patients with partial remission (P=0.001). In these patients, serum PCT level significantly increased again at the time of progression disease (P=0.001). Elevated serum PCT was a significant factor of worse survival (HR, 2.86; 95%CI, 1.36-6.03; P=0.006). Compared with patients with normal serum PCT and CgA level, patients with either PCT or CgA elevated and patients with both PCT and CgA elevated had progressively worse survival. Additionally, PCT expression in tumor cells was found in 24.0% of patients but did not correlate with other clinicopathological factors, including serum PCT. Serum PCT is elevated in part of patients with NENs of digestive system, especially in patients with grade 3 disease. Serum PCT level can help evaluate treatment response and its elevation indicates poor prognosis. Combination of serum PCT and CgA can improve outcome prediction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Antimalarials as a risk factor for elevated muscle enzymes in systemic lupus erythematosus.

PubMed

Tselios, K; Gladman, D D; Su, Jiandong; Urowitz, M B

2016-04-01

To investigate the relationship between antimalarials (AM) and elevated muscle enzymes in systemic lupus erythematosus (SLE). 325 lupus patients with abnormal creatine phosphokinase (CPK) for at least two consecutive clinic visits were enrolled; 54 patients on statins/fibrates (n = 43) and/or active myositis (n = 14) were excluded. The control group consisted of 1453 lupus patients with no CPK elevation during follow-up. Descriptive statistics and Cox regression analyses were performed, p < 0.05 was considered significant. Cases and controls did not differ regarding age at SLE diagnosis, gender ratio, or disease duration. AM use was more frequent in cases, which had more prolonged AM use. Total frequency of elevated CPK in AM users was 216/1322 (16.3%). Chloroquine was associated with a 3.3-fold, and hydroxychloroquine with a 3.1-fold, increased risk for CPK elevation. Black race was associated with higher CPK (HR = 2.941), whereas female gender was protective (HR = 0.697). 203 patients were followed for 7.3 ± 5.6 years; 49.8% had persistent and 14.8% intermittent CPK elevation, while in 35.4% CPK was normalized. Clinical proximal muscle weakness developed in 5/203 patients. Chronic AM use is a potential risk factor for muscle enzyme elevation in SLE patients. CPK abnormalities persist in almost two thirds of the patients, but this remains mainly a biochemical finding, evolving to clinical myopathy in about 2.5%. © The Author(s) 2015.

Elevated blood pressure in the developing world: a role for clinical pharmacists.

PubMed

Smith, Michael T; Monahan, Megan P; Nelson, Paige; Moruzzi, Matthew; DeLucenay, Alexander J; Birnie, Christine R

2017-09-19

The objective of this study was to evaluate the prevalence and patient knowledge of elevated blood pressure amongst a cross-section of patients in underserved communities in three selected low-income countries worldwide: El Salvador, India and Kenya. Mobile medical clinics were established as part of medical mission trips in El Salvador, India and Kenya. Willing male and female patients, at least 25 years of age, who presented at each clinic were screened for elevated blood pressure, including 332 patients in El Salvador, 847 patients in India and 160 patients in Kenya. Patients were classified into Stage I or II elevated blood pressure based on modified JNCVII guidelines. A questionnaire was completed regarding their knowledge about the existence and management of their disease state. Of the 1339 patients screened, 368 presented with elevated blood pressure (27%). Of these patients, 147 had been previously informed of hypertension or an elevated blood pressure (39.9%), 28 reported receiving antihypertensive medication (7.6%) and 24 reported awareness of non-pharmaceutical treatment options (6.5%). In Kenya, 81 patients were screened in a rural setting and 79 in an urban setting. Patients demonstrating controlled blood pressure were 63 (78%) and 38 (48%), respectively, demonstrating a significant difference between the rural versus urban settings (P = 0.00359). All regions demonstrated similar trends in the prevalence of elevated blood pressure, highlighting the need for increased disease state education in these regions. © 2017 Royal Pharmaceutical Society.

MMPI-2-RF characteristics of individuals with interstitial cystitis.

PubMed

Fazio, Rachel L; Wunderlich, Ted; Wilson, Nicolas; Akeson, Steven

2014-11-01

This study aimed to describe the psychological functioning of interstitial cystitis/bladder pain syndrome patients utilizing MMPI-2-RF scoring. The MMPI-2 was administered to 60 individuals who reported a diagnosis of IC. Responses were scored in the MMPI-2-RF format. Fifty-one protocols were deemed valid. Elevations were discovered on scales FBS-r (symptom validity), RC1 (somatic complaints), and MLS (malaise). Participants were split into two groups based on extreme elevations on RC1; the high RC1 group produced higher scores on 39 scales including clinically significant elevations on 17 scales. Over 25% of this sample had an emotional component to their physical concerns. This knowledge about the psychological characteristics of IC patients may have clinical utility for physicians and other treatment providers. The results argue strongly for psychological evaluation as a component of IC diagnosis and treatment. Those with significant emotional overlay to their somatic complaints may be best managed through psychological interventions and minimally invasive treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

Elevated ambulatory blood pressure in a multi-ethnic population of obese children and adolescents.

PubMed

Aguilar, Alexandra; Ostrow, Vlady; De Luca, Francesco; Suarez, Elizabeth

2010-06-01

To evaluate the relationship among ambulatory blood pressure (ABP), body mass index (BMI), and homeostasis model assessment (HOMA) in a multi-ethnic population of obese children with clinic blood pressure in the reference range. A total of 43 obese normotensive children (7-17 years old) were recruited. ABP monitoring, oral glucose tolerance test, lipid levels, and urine microalbumin levels were obtained. Fourteen percent of the subjects had elevated 24-hour systolic blood pressure (SBP), 9.3% had elevated daytime SBP, and 32.6 % elevated nighttime SBP. For diastolic blood pressure, 4.7% of the sample had an elevated mean nighttime value. Children with more severe obesity (BMI SD score >2.5) had higher 24-hour and nighttime SBP than children with less severe obesity (BMI SD score < or =2.5). Children with HOMA values in the highest quartile had larger waist circumference and higher clinic blood pressure than children with HOMA values in the lowest quartile, and no difference in the mean ABP values was found in the 2 groups . Multiple linear regression analysis showed that 24-hour and nighttime SBP were significantly correlated with BMI SD score. Obese children with normal clinic blood pressure often exhibit elevated ABP. The risk for ambulatory hypertension appears to be correlated with the degree of obesity. Copyright 2010 Mosby, Inc. All rights reserved.

Successful treatment of refractory TAFRO syndrome with elevated vascular endothelial growth factor using thyroxine supplements.

PubMed

Oka, Satoko; Ono, Kazuo; Nohgawa, Masaharu

2018-04-01

Although the clinical significance of hypothyroidism in TAFRO syndrome is unknown, vascular endothelial growth factor (VEGF) levels decreased with improvements in the condition of our refractory TAFRO cases after thyroxine supplement therapy. Our results indicate that elevated VEGF levels are a potential factor in the pathogenesis and anasarca of TAFRO syndrome with hypothyroidism.

An Assessment of Oral and Maxillofacial Vietnam War Casualties 10-15 Years Post-Injury.

DTIC Science & Technology

1986-12-20

the Depression (D) and Schizophrenia (Sc) scales. Furthermore, there are borderline elevations on the Hypochondriasis , Psychopathic Deviate and...Hysteria, Psychopathic Deviate, and Schizophrenia are the scales with frequent clinical elevations, with Hypochondriasis , Depression, Psychasthenia, and...hypomanic patients, exces- sive somatic complaints and depression. Twenty-three subjects reported very significant patterns of psychopathology. They had

Temporal seizure focus and status epilepticus are associated with high-sensitive troponin I elevation after epileptic seizures.

PubMed

Chatzikonstantinou, Anastasios; Ebert, Anne D; Hennerici, Michael G

2015-09-01

Postictal elevation of high-sensitive troponin I (TNI), a highly specific biomarker for myocardial ischemia, has been reported. We aimed at evaluating its association of high-sensitive troponin I (TNI) with seizure type and focus, as well as vascular risk factors. TNI was measured in 247 patients admitted to our clinic via the emergency room with an acute epileptic seizure. TNI control measurements were performed in 61.5% of cases. All patients underwent electroencephalography and cerebral imaging. Seizure focus - when possible - was determined using results from these examinations as well as clinical data. Of 247 patients, 133 (53.8%) were men, the mean age was 59 ± 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05 ± 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus and temporal seizure focus were significantly associated with TNI elevation in multivariate analysis. In 21 (13.8%) of the patients with TNI control measurement, TNI was continuously elevated. Higher age and temporal seizure focus were significantly associated with continuously high TNI. Coronary heart disease and vascular risk factors were significantly associated with high TNI only in univariate analysis. No patient had a symptomatic myocardial ischemia. Postictal TNI elevation is relatively common in older patients with status epilepticus or temporal seizure focus. These data support the concept of relevant and possibly dangerous ictal effects on cardiac function especially in temporal lobe seizures. Although the risk of manifest postictal myocardial infarction seems to be very low, selected patients could profit from closer monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

A prospective echocardiographic evaluation of pulmonary hypertension in chronic hemodialysis patients in the United States: prevalence and clinical significance.

PubMed

Ramasubbu, Kumudha; Deswal, Anita; Herdejurgen, Cheryl; Aguilar, David; Frost, Adaani E

2010-10-05

Pulmonary hypertension (PH), a disease which carries substantial morbidity and mortality, has been reported to occur in 25%-45% of dialysis patients. No prospective evaluation of the prevalence or clinical significance of PH in chronic dialysis patients in the United States (US) has been undertaken. Echocardiograms were performed prospectively in chronic hemodialysis patients prior to dialysis at a single dialysis center. PH was defined as a tricuspid regurgitant jet ≥2.5 m/s and "more severe PH" as ≥3.0 m/s. Clinical outcomes recovered were all-cause hospitalizations and death at 12 months. In a cohort of 90 patients, 42 patients (47%) met the definition of PH. Of those, 18 patients (20%) met the definition of more severe PH. At 12 months, mortality was significantly higher in patients with PH (26%) compared with patients without PH (6%). All-cause hospitalizations were similar in patients with PH and without PH. Echocardiographic findings suggesting impaired left ventricular function and elevated pulmonary capillary wedge pressure were significantly associated with PH. This prospective cross-sectional study of a single dialysis unit suggests that PH may be present in nearly half of US dialysis patients and when present is associated with increased mortality. Echocardiographic findings demonstrate an association between elevated filling pressures, elevated pulmonary artery pressures, and higher mortality, suggesting that the PH may be secondary to diastolic dysfunction and compounded by volume overload.

A prospective echocardiographic evaluation of pulmonary hypertension in chronic hemodialysis patients in the United States: prevalence and clinical significance

PubMed Central

Ramasubbu, Kumudha; Deswal, Anita; Herdejurgen, Cheryl; Aguilar, David; Frost, Adaani E

2010-01-01

Background Pulmonary hypertension (PH), a disease which carries substantial morbidity and mortality, has been reported to occur in 25%–45% of dialysis patients. No prospective evaluation of the prevalence or clinical significance of PH in chronic dialysis patients in the United States (US) has been undertaken. Methods Echocardiograms were performed prospectively in chronic hemodialysis patients prior to dialysis at a single dialysis center. PH was defined as a tricuspid regurgitant jet ≥2.5 m/s and “more severe PH” as ≥3.0 m/s. Clinical outcomes recovered were all-cause hospitalizations and death at 12 months. Results In a cohort of 90 patients, 42 patients (47%) met the definition of PH. Of those, 18 patients (20%) met the definition of more severe PH. At 12 months, mortality was significantly higher in patients with PH (26%) compared with patients without PH (6%). All-cause hospitalizations were similar in patients with PH and without PH. Echocardiographic findings suggesting impaired left ventricular function and elevated pulmonary capillary wedge pressure were significantly associated with PH. Conclusion This prospective cross-sectional study of a single dialysis unit suggests that PH may be present in nearly half of US dialysis patients and when present is associated with increased mortality. Echocardiographic findings demonstrate an association between elevated filling pressures, elevated pulmonary artery pressures, and higher mortality, suggesting that the PH may be secondary to diastolic dysfunction and compounded by volume overload. PMID:21042428

Patterns of clinical response to PSA elevation in American Indian/Alaska Native men: a multi-center pilot study.

PubMed

Tilburt, Jon C; Koller, Kathryn; Tiesinga, James J; Wilson, Robin T; Trinh, Anne C; Hill, Kristin; Hall, Ingrid J; Smith, Judith Lee; Ekwueme, Donatus U; Petersen, Wesley O

2013-11-01

To assess clinical treatment patterns and response times among American Indian/Alaska Native men with a newly elevated PSA. We retrospectively identified men ages 50-80 receiving care in one of three tribally-operated clinics in Northern Minnesota, one medical center in Alaska, and who had an incident PSA elevation (> 4 ng/ml) in a specified time period. A clinical response was considered timely if it was documented as occurring within 90 days of the incident PSA elevation. Among 82 AI/AN men identified from medical records with an incident PSA elevation, 49 (60%) received a timely clinical response, while 18 (22%) had no documented clinical response. One in five AI/AN men in our study had no documented clinical action following an incident PSA elevation. Although a pilot study, these findings suggest the need to improve the documentation, notification, and care following an elevated PSA at clinics serving AI/AN men.

More inclusive bipolar mixed depression definitions by requiring fewer non-overlapping mood elevation symptoms.

PubMed

Kim, W; Kim, H; Citrome, L; Akiskal, H S; Goffin, K C; Miller, S; Holtzman, J N; Hooshmand, F; Wang, P W; Hill, S J; Ketter, T A

2016-09-01

Assess strengths and limitations of mixed bipolar depression definitions made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by requiring fewer than three 'non-overlapping' mood elevation symptoms (NOMES). Among bipolar disorder (BD) out-patients assessed with Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using less inclusive (≥3 NOMES, DSM-5), more inclusive (≥2 NOMES), and most inclusive (≥1 NOMES) definitions. Among 153 depressed BD, compared to less inclusive DSM-5 threshold, our more and most inclusive thresholds, yielded approximately two- and five-fold higher mixed depression rates (7.2%, 15.0%, and 34.6% respectively), and important statistically significant clinical correlates for mixed compared to pure depression (e.g. more lifetime anxiety disorder comorbidity, more current irritability), which were not significant using the DSM-5 threshold. Further studies assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including assessing the extent to which enhanced statistical power vs. other factors contributes to more vs. less inclusive mixed bipolar depression thresholds having more statistically significant clinical correlates, and whether 'overlapping' mood elevation symptoms should be counted. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of clinical and histopathologic prognostic factors for survival in canine osteosarcoma of the extracranial flat and irregular bones.

PubMed

Kruse, M A; Holmes, E S; Balko, J A; Fernandez, S; Brown, D C; Goldschmidt, M H

2013-07-01

Osteosarcoma is the most common bone tumor in dogs. However, current literature focuses primarily on appendicular osteosarcoma. This study examined the prognostic value of histological and clinical factors in flat and irregular bone osteosarcomas and hypothesized that clinical factors would have a significant association with survival time while histological factors would not. All osteosarcoma biopsy samples of the vertebra, rib, sternum, scapula, or pelvis were reviewed while survival information and clinical data were obtained from medical records, veterinarians, and owners. Forty-six dogs were included in the analysis of histopathological variables and 27 dogs with complete clinical data were included in the analysis of clinical variables. In the histopathologic cox regression model, there was no significant association between any histologic feature of osteosarcoma, including grade, and survival time. In the clinical cox regression model, there was a significant association between the location of the tumor and survival time as well as between the percent elevation of alkaline phosphatase (ALP) above normal and survival time. Controlling for ALP elevation, dogs with osteosarcoma located in the scapula had a significantly greater hazard for death (2.8) compared to dogs with tumors in other locations. Controlling for tumor location, every 100% increase in ALP from normal increased the hazard for death by 1.7. For canine osteosarcomas of the flat and irregular bones, histopathological features, including grade do not appear to be rigorous predictors of survival. Clinical variables such as increased ALP levels and tumor location in the scapula were associated with decreased survival times.

The accuracy of serum interleukin-6 and tumour necrosis factor as markers for ovarian torsion.

PubMed

Cohen, S B; Wattiez, A; Stockheim, D; Seidman, D S; Lidor, A L; Mashiach, S; Goldenberg, M

2001-10-01

The aim of this study was to investigate a possible role for interleukin-6 (IL-6) and tumour necrosis factor (TNF-alpha) as pre-operative markers for the diagnosis of ovarian torsion. Twenty consecutive patients admitted to the gynaecological emergency room with suspected clinical diagnosis of ovarian torsion were prospectively assigned to the study. Blood samples were drawn pre-operatively and examined for serum concentrations of IL-6 and TNF-alpha. Surgeons were blinded to laboratory results prior to laparoscopy. The pre-operative diagnosis of ovarian torsion was confirmed during an urgent diagnostic laparoscopy in 8 (40%) patients. The surgical diagnosis among the remaining 12 patients was a large ovarian cyst not in torsion. In six out of eight (75.0%) patients with ovarian torsion serum IL-6 concentrations were elevated. None of the 12 patients without torsion had elevated serum IL-6 concentrations. This difference was statistically significant (P < 0.001). There was no significant difference in the proportion of women with elevated serum TNF-alpha concentrations, two of eight (25.0%) patients with torsion and four of 12 (33.3%) control cases. Elevated serum IL-6 concentrations, but not serum TNF-alpha concentrations, were significantly associated with the occurrence of ovarian torsion. In patients with vague clinical signs of ovarian torsion, serum IL-6 might help to distinguish which patients should undergo diagnostic laparoscopy.

Complementary Roles for Biomarkers of Biomechanical Strain ST2 and N-Terminal Prohormone B-Type Natriuretic Peptide in Patients With ST-Elevation Myocardial Infarction

PubMed Central

Sabatine, Marc S.; Morrow, David A.; Higgins, Luke J.; MacGillivray, Catherine; Guo, Wei; Bode, Christophe; Rifai, Nader; Cannon, Christopher P.; Gerszten, Robert E.; Lee, Richard T.

2014-01-01

Background ST2 is a member of the interleukin-1 receptor family with a soluble form that is markedly upregulated on application of biomechanical strain to cardiac myocytes. Circulating ST2 levels are elevated in the setting of acute myocardial infarction, but the predictive value of ST2 independent of traditional clinical factors and of an established biomarker of biomechanical strain, N-terminal prohormone B-type natriuretic peptide (NT-proBNP), has not been established. Methods and Results We measured ST2 at baseline in 1239 patients with ST-elevation myocardial infarction from the CLopidogrel as Adjunctive ReperfusIon TherapY–Thrombolysis in Myocardial Infarction 28 (CLARITY-TIMI 28) trial. Per trial protocol, patients were to undergo coronary angiography after 2 to 8 days and were followed up for 30 days for clinical events. In contrast to NT-proBNP, ST2 levels were independent of clinical factors potentially related to chronic increased left ventricular wall stress, including age, hypertension, prior myocardial infarction, and prior heart failure; levels also were only modestly correlated with NT-proBNP (r=0.14). After adjustment for baseline characteristics and NT-proBNP levels, an ST2 level above the median was associated with a significantly greater risk of cardiovascular death or heart failure (third quartile: adjusted odds ratio, 1.42; 95% confidence interval, 0.68 to 3.57; fourth quartile: adjusted odds ratio, 3.57; 95% confidence interval, 1.87 to 6.81; P<0.0001 for trend). When both ST2 and NT-proBNP were added to a model containing traditional clinical predictors, the c statistic significantly improved from 0.82 (95% confidence interval, 0.77 to 0.87) to 0.86 (95% confidence interval, 0.81 to 0.90) (P=0.017). Conclusions In ST-elevation myocardial infarction, high baseline ST2 levels are a significant predictor of cardiovascular death and heart failure independently of baseline characteristics and NT-proBNP, and the combination of ST2 and NT-proBNP significantly improves risk stratification. These data highlight the prognostic value of multiple, complementary biomarkers of biomechanical strain in ST-elevation myocardial infarction. PMID:18378613

Amyloid-β--associated clinical decline occurs only in the presence of elevated P-tau.

PubMed

Desikan, Rahul S; McEvoy, Linda K; Thompson, Wesley K; Holland, Dominic; Brewer, James B; Aisen, Paul S; Sperling, Reisa A; Dale, Anders M

2012-06-01

To elucidate the relationship between the 2 hallmark proteins of Alzheimer disease (AD), amyloid-(Aβ) and tau, and clinical decline over time among cognitively normal older individuals. A longitudinal cohort of clinically and cognitively normal older individuals assessed with baseline lumbar puncture and longitudinal clinical assessments. Research centers across the United States and Canada. We examined 107 participants with a Clinical Dementia Rating (CDR) of 0 at baseline examination. Using linear mixed effects models, we investigated the relationship between cerebrospinal fluid (CSF) phospho-tau 181 (p-tau(181p)),CSF Aβ(1-42), and clinical decline as assessed using longitudinal change in global CDR, CDR-Sum of Boxes, and the Alzheimer Disease Assessment Scale-cognitive subscale. We found a significant relationship between decreased CSF Aβ(1-42) and longitudinal change in global CDR,CDR-Sum of Boxes, and Alzheimer Disease Assessment Scale-cognitive subscale in individuals with elevated CSFp-tau(181p). In the absence of CSF p-tau(181p), the effect of CSF Aβ(1-42) on longitudinal clinical decline was not significantly different from 0. In cognitively normal older individuals,A-associated clinical decline during a mean of 3 years may occur only in the presence of ongoing downstream neurodegeneration.

Examining Trauma and Readiness to Change among Women in a Community Re-Entry Program.

PubMed

Killian, Michael; Cimino, Andrea N; Mendoza, Natasha S; Shively, Randy; Kunz, Kami

2018-03-21

Posttraumatic stress disorder (PTSD) and co-occurring substance use disorders (SUDs) are common among women who are incarcerated. The purpose of this study was to examine the relationship between trauma and readiness to change substance use behaviors. This study used data from 103 participants enrolled in a residential re-entry program for women with SUDs and trauma history. Women reporting clinically elevated Trauma Symptom Inventory (TSI) subscale scores were compared to those without elevated scores on the University of Rhode Island Change Assessment (URICA) readiness to change instrument. Primary analyses included t-tests and ANCOVA to control for age and ethnicity. In general, women with clinically elevated trauma scores also reported greater readiness to change. The analyses revealed significant differences on the URICA Readiness to Change scores between women who had elevated Defensive Avoidance and Impaired Self-Reference according to the TSI. Results approached significance for women who had elevated TSI subscale scores for Sexual Concerns and Dissociation. These results point to a need to further understand links between trauma and readiness to change, particularly, the role of posttraumatic growth and psychological distress. This study has implications for social workers and clinicians delivering evidence-based treatment. Women who had high trauma symptoms were more willing to address change. Findings also suggest a need to tailor interventions to include motivational components that are also trauma-informed.

Muscular exercise can cause highly pathological liver function tests in healthy men

PubMed Central

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-01-01

Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice. What is already known about this subject The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals.Physical exercise can result in transient elevations of liver function tests.There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting.Liver function tests are significantly increased for at least 7 days after weightlifting.It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. PMID:17764474

Muscular exercise can cause highly pathological liver function tests in healthy men.

PubMed

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-02-01

The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Efficacy of Punch Elevation Combined with Fractional Carbon Dioxide Laser Resurfacing in Facial Atrophic Acne Scarring: A Randomized Split-face Clinical Study

PubMed Central

Faghihi, Gita; Nouraei, Saeid; Asilian, Ali; Keyvan, Shima; Abtahi-Naeini, Bahareh; Rakhshanpour, Mehrdad; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayed Mohsen

2015-01-01

Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18–55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID:26538695

Elevated cerebrospinal fluid pressure in patients with Alzheimer's disease

PubMed Central

Silverberg, Gerald; Mayo, Martha; Saul, Thomas; Fellmann, Jere; McGuire, Dawn

2006-01-01

Background Abnormalities in cerebrospinal fluid (CSF) production and turnover, seen in normal pressure hydrocephalus (NPH) and in Alzheimer's disease (AD), may be an important cause of amyloid retention in the brain and may relate the two diseases. There is a high incidence of AD pathology in patients being shunted for NPH, the AD-NPH syndrome. We now report elevated CSF pressure (CSFP), consistent with very early hydrocephalus, in a subset of AD patients enrolled in a clinical trial of chronic low-flow CSF drainage. Our objective was to determine the frequency of elevated CSFP in subjects meeting National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for AD, excluding those with signs of concomitant NPH. Methods AD subjects by NINCDS-ADRDA criteria (n = 222), were screened by history, neurological examination, and radiographic imaging to exclude those with clinical or radiographic signs of NPH. As part of this exclusion process, opening CSFP was measured supine under general anesthesia during device implantation surgery at a controlled pCO2 of 40 Torr (40 mmHg). Results Of the 222 AD subjects 181 had pressure measurements recorded. Seven subjects (3.9%) enrolled in the study had CSFP of 220 mmH20 or greater, mean 249 ± 20 mmH20 which was significantly higher than 103 ± 47 mmH2O for the AD-only group. AD-NPH patients were significantly younger and significantly less demented on the Mattis Dementia Rating Scale (MDRS). Conclusion Of the AD subjects who were carefully screened to exclude those with clinical NPH, 4% had elevated CSFP. These subjects were presumed to have the AD-NPH syndrome and were withdrawn from the remainder of the study. PMID:16737542

Clinical characteristics and current treatment of glaucoma.

PubMed

Cohen, Laura P; Pasquale, Louis R

2014-06-02

Glaucoma is a neurodegenerative disorder in which degenerating retinal ganglion cells (RGC) produce significant visual disability. Clinically, glaucoma refers to an array of conditions associated with variably elevated intraocular pressure (IOP) that contributes to RGC loss via mechanical stress, vascular abnormalities, and other mechanisms, such as immune phenomena. The clinical diagnosis of glaucoma requires assessment of the ocular anterior segment with slit lamp biomicroscopy, which allows the clinician to recognize signs of conditions that can produce elevated IOP. After measurement of IOP, a specialized prismatic lens called a gonioscope is used to determine whether the angle is physically open or closed. The structural manifestation of RGC loss is optic nerve head atrophy and excavation of the neuroretinal rim tissue. Treatment is guided by addressing secondary causes for elevated IOP (such as inflammation, infection, and ischemia) whenever possible. Subsequently, a variety of medical, laser, and surgical options are used to achieve a target IOP. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Pathophysiology, prognostic significance and clinical utility of B-type natriuretic peptide in acute coronary syndromes.

PubMed

Wiviott, Stephen D; de Lemos, James A; Morrow, David A

2004-08-16

The natriuretic hormones are a family of vasoactive peptides that can be measured circulating in the blood. Because they serve as markers of hemodynamic stress, the major focus of the use of natriuretic peptide levels [predominantly B-type natriuretic peptide (BNP) and N-terminal (NT)-pro-BNP] has been as an aid to the clinical diagnosis and management of congestive heart failure (CHF). Recently, however, the measurement of natriuretic peptides in the acute coronary syndromes (ACS) has been shown to provide information complementary to traditional biomarkers (of necrosis) such as cardiac troponins and creatine kinase (CK). Studies in several types of acute coronary syndromes [ST-segment elevation myocardial infarction (STEMI), non-ST elevation MI (NSTEMI) and unstable angina (UA)] have shown that elevated levels of natriuretic peptides are independently associated with adverse outcomes, particularly mortality. Additional information is obtained from the use natriuretic peptides in combination with other markers of risk including biomarkers of necrosis and inflammation. This review will summarize the scientific rationale and clinical evidence supporting measurement of natriuretic peptides for risk stratification in acute coronary syndromes. Future research is needed to identify therapies of particular benefit for patients with ACS and natriuretic peptide elevation.

Interrelationships of somatic cell count, mastitis, and milk yield in a low somatic cell count herd.

PubMed

Deluyker, H A; Gay, J M; Weaver, L D

1993-11-01

In a high yielding low SCC herd, changes in milk yield associated with SCC and occurrence of clinical mastitis and differences in SCC with parity, clinical mastitis, and DIM were investigated. Milk yield data were obtained at every milking, and SCC was measured once every 48 h in 117 cows during the first 119 d postpartum. Effects of SCC and clinical mastitis on cumulative milk yield in the first 119 d postpartum were evaluated with least squares linear regression. Repeated measures ANOVA was used to detect changes in SCC. The SCC was highest at lactation onset, and cows with clinical mastitis had significantly higher SCC. During the 10 d prior to onset of clinical mastitis, SCC was higher in affected cows than in matched unaffected controls and surged just prior to diagnosis. During the 10-d period following a mastitis treatment, SCC differences between treated and control cows remained significant but became smaller with time and returned to the premastitis differences. Occurrence of clinical mastitis was associated with 5% milk yield loss. Cows with mean SCC > 245,000 cells/ml over the 119 d showed 6.2% yield loss compared with cows with SCC < or = 90,000 cells/ml. Cows with clinical mastitis had higher SCC prior to and following the end of treatment for mastitis than did controls. Clinical mastitis and SCC were associated with significant yield loss. Milk yield loss attributed to clinical mastitis was greater than that associated with elevated SCC (> 245,000 cells/ml) because a greater percentage of cows (26%) had clinical mastitis than elevated SCC (12.5%).

Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis

PubMed Central

Grove, Tyler B.; Tso, Ivy F.; Chun, Jinsoo; Mueller, Savanna A.; Taylor, Stephan F.; Ellingrod, Vicki L.; McInnis, Melvin G.; Deldin, Patricia J.

2016-01-01

Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychotic disorder not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms. PMID:27416540

Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

PubMed

Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

2016-09-30

Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

PubMed

Bradbury, Rachel A; Lee, Paul; Smith, Howard C

2017-10-01

Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). To investigate the usefulness of an elevated (>40 pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. 141 patients with an elevated AMH and body mass index either <20 kg/m 2 (lean) or >30 kg/m 2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111 ± 73 vs 56 ± 31, P < 0.001) in lean women with FHH compared to those without FHH. PCOS and FHH share common features of elevated AMH levels, oligo-anovulation and polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Associated factors and clinical implications of serum aminotransferase elevation in scrub typhus.

PubMed

Su, Tung-Hung; Liu, Chun-Jen; Shu, Pei-Yun; Fu, Yang-Hsien; Chang, Chi-Hsien; Jao, Ping; Kao, Jia-Horng

2016-12-01

Timely diagnosis and prompt treatment can reduce the complications of scrub typhus. It is thus important to find easy laboratory tests to help in the diagnosis, especially in patients without eschar at initial presentation. Because serum aminotransferase elevation is common in scrub typhus, its associated factors and clinical implications need further investigations. We conducted a retrospective study in Kinmen, Taiwan, to collect clinically suspected scrub typhus patients notified to Taiwan Centers for Disease Control for confirmation during 2005-2010. Scrub typhus was diagnosed and Orientia tsutsugamushi was genotyped by serological or molecular assays. The laboratory data and clinical information were recorded for analysis. Overall, 344 suspected scrub typhus patients were reported to Taiwan Centers for Disease Control and 288 of them were certified scrub typhus. Scrub typhus patients had significantly more thrombocytopenia, serum aminotransferase elevation (76% vs. 54%, p = 0.001), higher frequency of fever, eschar, and lymphadenopathy, compared with nontyphus patients. Hepatic dysfunction in scrub typhus was associated with older age, longer fever duration, and absence of lymphadenopathy, but seemed to be unrelated to the rickettsial genotypes. Multivariate analysis showed that serum aminotransferase elevation (odds ratio: 3.75; p = 0.003; 95% confidence interval: 1.56-9.01) independently predicted scrub typhus. Furthermore, in suspected scrub typhus patients without eschar, 92% of true typhus patients had serum aminotransferase elevation compared with the nontyphus ones (odds ratio: 6.47; p = 0.028, 95% confidence interval: 1.23-34.11). Hepatic dysfunction in scrub typhus patients is associated with older age, longer fever duration, and absence of lymphadenopathy. Serum aminotransferase elevation can aid in the diagnosis of scrub typhus, especially in suspected patients without eschar. Copyright © 2014. Published by Elsevier B.V.

Risk stratification in acute pulmonary embolism with heart-type fatty acid-binding protein: A meta-analysis.

PubMed

Bajaj, Anurag; Rathor, Parul; Sehgal, Vishal; Shetty, Ajay; Kabak, Besher; Hosur, Srikanth

2015-10-01

Heart-type fatty acid-binding protein (H-FABP) has emerged as a new biomarker in risk stratification of patients with acute pulmonary embolism (PE). We performed a meta-analysis of studies in patients with acute PE to assess the prognostic value of elevated H-FABP for short-term adverse outcomes. Two independent reviewers systematically searched PubMed, EMBASE, and Cochrane Database until June 2014. Studies were searched using MeSH word "fatty acid-binding protein" and "pulmonary embolism." Prospective studies were included if those were done on patients with acute PE and if serum H-FABP assay was done. Relevant data on study design, year of publication, patient population, inclusion criteria, exclusion criteria, mean age, sex, type of H-FABP assay, cutoff of H-FABP used, and outcomes were extracted. The primary end point was 30-day complicated clinical course and PE-related mortality. The secondary end point was right ventricular dysfunction (RVD). A random-effects model was used to pool study results. Nine studies, including 1680 patients, reported data on the 30-day complicated clinical course. Elevated H-FABP was significantly associated with the increased risk of 30-day complicated clinical course (odds ratio [OR], 17.67; 95% confidence interval [CI], 6.02-51.89; I(2) = 80%). Similarly, 6 studies, including 676 patients, reported 30-day mortality data. Elevated H-FABP was associated with increased risk of 30-day PE-related mortality (OR, 32.94; 95% CI, 8.80-123.21, I(2) = 53%). The risk of RVD was significantly higher in patients with elevated H-FABP as compared with patients with normal H-FABP (OR, 2.57; 95% CI, 1.05-6.33, I(2) = 57%). The prognostic sensitivity and specificity of H-FABP were 71% and 74% in predicting 30-day complicated clinical course and were 90% and 70% in predicting 30-day mortality. This meta-analysis indicates that elevated H-FABP levels are associated with increased risk of 30-day complicated clinical course, mortality, and RVD. Copyright © 2015 Elsevier Inc. All rights reserved.

HDAC Inhibition Induces Increased Choline Uptake and Elevated Phosphocholine Levels in MCF7 Breast Cancer Cells

PubMed Central

Ward, Christopher S.; Eriksson, Pia; Izquierdo-Garcia, Jose L.; Brandes, Alissa H.; Ronen, Sabrina M.

2013-01-01

Histone deacetylase (HDAC) inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS)-detectable phosphocholine (PC) is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using 13C MRS to monitor [1,2-13C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by 31P MRS (129±7% of control). Furthermore, cellular choline kinase activity was elevated (177±31%), while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively) relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC) increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2) isoforms, resulting in increased PLA2 activity (162±18%) in SAHA-treated cells. Importantly, the levels of total choline (tCho)-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using 1H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow-up diagnostics of HDAC inhibitor treatment. PMID:23626839

The Effectiveness of Cognitive Exposure & Skills Group Manualized Treatments in OIF/OEF Female Veterans

DTIC Science & Technology

2011-04-01

2004). PTSD and somatization in women treated at a VA primary care clinic. Psychosomatics, 45, 291-296. Foa, E. B., Dancu, C. V., Hembree, E...were clinically significant elevations (> 70) on the Demoralization, Somatic Complaints, Low Positive Emotion of the Restructured Clinical scales and... Hypochondriasis , Psych Dev = Psychopathic Deviate, Masc-Fem = Masculinity- Femininity, Psychasth = Psychasthenia, Schizoph = Schizophrenia; Soc Introv

Detection of increased choline compounds with proton nuclear magnetic resonance spectroscopy subsequent to malignant transformation of human prostatic epithelial cells.

PubMed

Ackerstaff, E; Pflug, B R; Nelson, J B; Bhujwalla, Z M

2001-05-01

In this study, a panel of normal human prostate cells (HPCs) and tumor cells derived from metastases were studied by (1)H NMR spectroscopy to determine whether the malignant transformation of HPCs results in the elevation of choline compounds. Although an elevated choline signal has been observed previously in clinical studies, the contribution of the different Cho compounds to this elevation, as well as their quantification, has not been established until now. Here we have shown that HPCs derived from metastases exhibit significantly higher phosphocholine as well as glycerophosphocholine levels compared with normal prostate epithelial and stromal cells. Thus the elevation of the choline peak observed clinically in prostate cancer is attributable to an alteration of phospholipid metabolism and not simply to increased cell density, doubling time, or other nonspecific effects. Androgen deprivation of the androgen receptor-positive cell lines resulted in a significant increase of choline compounds after chronic androgen deprivation of the LNCaP cell line and in a decrease of choline compounds after a more acute androgen deprivation of the LAPC-4 cell line. These data strongly support the use of proton magnetic resonance spectroscopic imaging to detect the presence of prostate cancer for diagnosis, to detect response subsequent to androgen ablation therapy, and to detect recurrence.

Osmotherapy for intracranial hypertension: mannitol versus hypertonic saline.

PubMed

Fink, Matthew E

2012-06-01

Hyperosmolar therapy is one of the core medical treatments for brain edema and intracranial hypertension, but controversy exists regarding the use of the most common agents, mannitol, and hypertonic saline. This article describes the relative merits and adverse effects of these agents using the best available clinical evidence. Mannitol is effective and has been used for decades in the treatment of traumatic brain injury, but it may precipitate acute renal failure if serum osmolarity exceeds 320 mOsm/L. Hypertonic saline appears to be safe, and serum sodium has been elevated to as high as 180 mEq/L in clinical settings without significant neurologic, cardiac, or renal injury. In small comparative trials both agents are effective and no clinically significant difference has been noted, but a properly powered trial has not yet been performed. Both mannitol and hypertonic saline are effective and have an acceptable risk profile for use in the treatment of elevated intracranial pressure secondary to brain edema.

Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

PubMed

Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

2017-01-01

The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study.

PubMed

Patel, Kalyani R; Bertuch, Alison; Sasa, Ghadir S; Himes, Ryan W; Wu, Hao

2017-01-01

Hepatitis-associated aplastic anemia (HAA) is a rare variant of aplastic anemia in which patients present with severe pancytopenia after an episode of acute hepatitis. The marrow failure is often rapid, severe, and usually fatal if untreated. The preceding hepatitis is largely under-studied. Retrospective study of the clinical and histopathologic features of hepatitis in pediatric patients who subsequently developed aplastic anemia and comparison with consecutive cases of acute liver failure and random cases of autoimmune hepatitis during the same time frame. All 7 patients of HAA had significant elevations in aminotransferases and conjugated hyperbilirubinemia at initial presentation. Echoing liver function indices, cholestatic hepatitis with sinusoidal obstruction-type endothelial injury was seen histomorphologically. Autoimmune hepatitis serology such as anti-F-actin, anti-liver/kidney microsome, and hypergammaglobulinemia was negative in all patients. Five of 7 patients (71.4%) had, however, elevated antinuclear antibody, all with a speckled pattern. Hepatitis virus serology was negative in all patients. By immunohistochemical staining, the lobular CD8/CD4 lymphocyte ratio was markedly elevated in all of the initial samples with significant reduction in this ratio (P = 0.03) in 3 patients post treatment (ursodiol, antibiotics, and/or immunosuppressive therapy). Hepatitis preceding HAA is characterized by marked elevation of aminotransferases, conjugated hyperbilirubinemia, elevated antinuclear antibody with a speckled pattern, cholestatic hepatitis with sinusoidal obstruction morphology, and CD8 dominant lobular infiltrates. The present study suggests HAA may result from cytotoxic T-cell-mediated sinusoidal endothelial and hepatocytic injury.

The effects of plane and arc of elevation on electromyography of shoulder musculature in patients with rotator cuff tears.

PubMed

Alenabi, Talia; Dal Maso, Fabien; Tétreault, Patrice; Begon, Mickaël

2016-02-01

Arm elevations in different planes are commonly assessed in clinics and are included in rehabilitation protocols for patients with rotator cuff pathology. The aim of this study was to quantify the effect of plane and angle of elevation on shoulder muscles activity in patients with symptomatic rotator cuff tear to be used for rehabilitation purposes. Eight symptomatic patients with rotator cuff tears were assessed by using EMG (11 surface and 2 fine wire electrodes) synchronized with a motion analysis. The subjects completed five elevations in full can position (arm externally rotated and thumb up) in frontal, scapular and sagittal planes. Muscle activity in three elevation arcs of 20° (from 0° to 60°) was presented as the percentage of mean activity. Data were analyzed by mixed linear models (α=0.003), and Tuckey Post-hoc comparisons for significant effects (α=0.05). The effect of plane was significant for supraspinatus, middle trapezius, anterior, middle, and posterior deltoid, triceps, and pectoralis major (P<0.001). Supraspinatus was more active during abduction than scaption and flexion (P<0.05), and its activity did not increase significantly after 40° of elevation (P>0.05). Infraspinatus had similar activity pattern in the three planes of elevation (P>0.003) with increasing trend in accordance with the elevation angle. In any rehabilitation protocol, if less activity of supraspinatus is desired, active arm elevation should be directed toward flexion and scaption and postponed abduction to prevent high level of activity in this muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparison of the ability of a 4:1 ketogenic diet and a 6.3:1 ketogenic diet to elevate seizure thresholds in adult and young rats.

PubMed

Nylen, Kirk; Likhodii, Sergei; Abdelmalik, Peter A; Clarke, Jasper; Burnham, W McIntyre

2005-08-01

The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.

Time of elevation of head of bed for patients receiving mechanical ventilation and its related factors.

PubMed

Martí-Hereu, L; Arreciado Marañón, A

The semirecumbent position is a widespread recommendation for the prevention of pneumonia associated with mechanical ventilation. To identify the time of elevation of head of bed for patients under mechanical ventilation and the factors related to such elevation in an intensive care unit. An observational, descriptive cross-sectional study. Conducted in an intensive care unit of a tertiary hospital from April to June 2015. The studied population were mechanically ventilated patients. Daily hours in which patients remained with the head of the bed elevated (≥30°), socio-demographic data and clinical variables were recorded. 261 head elevation measurements were collected. The average daily hours that patients remained at ≥30° was 16h28' (SD ±5h38'), equivalent to 68.6% (SD ±23.5%) of the day. Factors related to elevations ≥30° for longer were: enteral nutrition, levels of deep sedation, cardiac and neurocritical diagnostics. Factors that hindered the position were: sedation levels for agitation and abdominal pathologies. Sex, age and ventilation mode did not show a significant relationship with bed head elevation. Although raising the head of the bed is an easy to perform, economical and measurable preventive measure, its compliance is low due to specific factors specific related o the patient's clinical condition. Using innovations such as continuous measurement of the head position helps to evaluate clinical practice and allows to carry out improvement actions whose impact is beneficial to the patient. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

Reaffirming normal: the high risk of pathologizing healthy adults when interpreting the MMPI-2-RF.

PubMed

Odland, Anthony P; Lammy, Andrew B; Perle, Jonathan G; Martin, Phillip K; Grote, Christopher L

2015-01-01

Monte Carlo simulations were utilized to determine the proportion of the normal population expected to have scale elevations on the MMPI-2-RF when multiple scores are interpreted. Results showed that when all 40 MMPI-2-RF scales are simultaneously considered, approximately 70% of normal adults are likely to have at least one scale elevation at or above 65 T, and as many as 20% will have five or more elevated scales. When the Restructured Clinical (RC) Scales are under consideration, 34% of normal adults have at least one elevated score. Interpretation of the Specific Problem Scales and Personality Psychopathology Five Scales--Revised also yielded higher than expected rates of significant scores, with as many as one in four normal adults possibly being miscategorized as having features of a personality disorder by the latter scales. These findings are consistent with the growing literature on rates of apparently abnormal scores in the normal population due to multiple score interpretation. Findings are discussed in relation to clinical assessment, as well as in response to recent work suggesting that the MMPI-2-RF's multiscale composition does not contribute to high rates of elevated scores.

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

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

Nataf, Robert; Skorupka, Corinne; Amet, Lorene

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001).more » Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.« less

Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.

PubMed

Nataf, Robert; Skorupka, Corinne; Amet, Lorene; Lam, Alain; Springbett, Anthea; Lathe, Richard

2006-07-15

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Functional hypothalamic amenorrhea is associated with elevated ghrelin and disordered eating.

PubMed

Schneider, Lisa F; Warren, Michelle P

2006-12-01

To determine whether ghrelin, an orexigen released by the stomach, is elevated in women with hypothalamic amenorrhea who are of normal weight and whether this is associated with abnormal eating behaviors. Controlled clinical study. Healthy volunteers in an academic research environment. Twenty-seven women with functional hypothalamic amenorrhea (FHA) and 42 normally menstruating women. None. Ghrelin and eating behavior. Ghrelin was significantly elevated in FHA (648.4 +/- 92.0 pg/mL vs. controls 596.7 +/- 79.0 pg/mL), while leptin, although lower, was not significantly so (FHA 5.4 +/- 2.8 ng/mL vs. controls 6.4 +/- 3 ng/mL). Eating Attitudes Test (EAT) scores were also significantly elevated in FHA (15.3 +/- 10.6 vs. controls 10.3 +/- 8.4), particularly on the subscale that measured bulimic behaviors. However, FHA patients consumed significantly more kilocalories (1,930 kcal/day vs. 1,588 kcal/day). High ghrelin in women with FHA may be linked to abnormal dietary behaviors, as reflected in high EAT scores yet characterized by normal caloric intake. Ghrelin may act as a restraining metabolic signal preventing a return to cyclicity in women with both disordered eating and FHA, prolonging amenorrhea when leptin has returned to normal.

Use of a Clinical Decision Support System Alert to Prevent Supratherapeutic Vancomycin Concentrations

PubMed Central

Ralph, Rachel; Patel, Jean A.; Postelnick, Michael; Ziauddin, Salma; Flis, Weronika; Galal, Audrey N.

2014-01-01

Background: Alerts issued by clinical decision support systems (CDSS) may be useful to identify and prevent the occurrence of acute kidney injury among patients on nephrotoxic drugs, particularly vancomycin. Objective: The purpose of this instructive study was to determine the effectiveness of using a pharmacist-run CDSS alert of early serum creatinine increases in patients receiving intravenous vancomycin to decrease the proportion of severely elevated vancomycin concentrations. Methods: This was a retrospective study of a prospectively reviewed CDSS alert that triggered in patients with an increase in serum creatinine by 25% from baseline within 24 hours. Severely elevated vancomycin concentrations were divided into a control group (before alert implementation) and a study group (after alert implementation) and considered for study inclusion. The proportion of severely elevated vancomycin concentrations (ie, >30 mg/L) were collected in the control and study groups. Results: There were 1290 and 1501 vancomycin concentrations in the control group and the study group, respectively. A total of 696 CDSS alerts triggered during the study period. The proportion of severely elevated vancomycin troughs decreased from 5.3% (n = 68, median = 36.6 mg/L, interquartile range = 33.75-43.2 mg/L) in the control group to 3.7% (n = 55, median = 34.7 mg/L, interquartile range = 31.3-39.3 mg/L) in the study group. This reflects a statistically significant decrease in the proportion of severely elevated vancomycin concentrations (P = .04). Conclusion: Overall, this instructive analysis on a novel use of CDSS software suggests that the implementation of an alert based on early detection of serum creatinine changes led to a significant decrease in the proportion of severely elevated serum vancomycin concentrations.

Anxiety and psychoactive substance use disorder comorbidity in anorexia nervosa or depression.

PubMed

Jordan, Jennifer; Joyce, Peter R; Carter, Frances A; Horn, Jacqueline; McIntosh, Virginia V W; Luty, Suzanne E; McKenzie, Janice M; Mulder, Roger T; Bulik, Cynthia M

2003-09-01

This study considered whether the prevalence and type of anxiety and psychoactive substance use disorder (PSUD) diagnoses differ between women with spectrum anorexia nervosa (AN) (N=40) and women with major depressive disorder (N = 58) participating in outpatient clinical trials. Anxiety and PSUD diagnoses (according to criteria in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders) were assessed using structured clinical interviews. Comparisons were made between AN subtypes (restricting or binge eating/purging) and by history of depression within the AN sample. A high prevalence of obsessive-compulsive disorder (OCD) was found in women with AN. However, social phobia, simple phobia, and PSUD were significantly elevated in both women with depression and women with AN. Prevalences were similar for anxiety and PSUD diagnoses between AN subtypes. Women with anorexia or depression were comparable in all respects, except for the elevated OCD prevalence in AN, emphasizing the need to use clinical comparison groups to avoid inadvertently attributing elevated prevalences of comorbid conditions to specific disorders. Copyright 2003 by Wiley Periodicals, Inc.

Activity of Tumor Necrosis Factor-alpha (TNF-alpha) and its soluble type I receptor (p55TNF-R) in some drug-induced cutaneous reactions.

PubMed

Chodorowska, Grazyna; Czelej, Dorota; Niewiedzioł, Marta

2003-01-01

Plasma concentration of TNF-alpha and its type I receptor (p55TNF-R) was examined in 126 patients with drug-induced skin reactions using immunoenzymatic ELISA method. Patients were subdivided into 6 groups: maculopapular eruptions (ME), erythema multiforme (EM), erythema multiforme coexisting with erythema nodosum (EMN), hyperergic vasculitis (HV), Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). In the acute clinical stage highly significant (p<0.001) or significant (p<0.01) elevation of mean plasma concentrations of the cytokine and its receptor was found in all examined groups in comparison with the control. Clearing of clinical symptoms was connected with considerable decrease (p<0.001, p<0.01) of mean plasma levels of the both proteins in comparison with the before treatment values. TNF-alpha concentrations still remained significantly more elevated than those observed in the control. The results indicate that plasma activity of TNF-alpha and its p55 receptor change with the clinical course of the examined drug-induced skin reactions, which suggests the partake of both proteins in the pathogenesis of these diseases.

Clinical and Prognostic Effect of Plasma Fibrinogen in Renal Cell Carcinoma: A Meta-Analysis.

PubMed

Tian, Yuejun; Hong, Mei; Jing, Suoshi; Liu, Xingchen; Wang, Hanzhang; Wang, Xinping; Kaushik, Dharam; Rodriguez, Ronald; Wang, Zhiping

2017-01-01

Background . Although numerous studies have shown that plasma fibrinogen is linked to renal cell carcinoma (RCC) risk, the consistency and magnitude of the effect of plasma fibrinogen are unclear. The aim of the study was to explore the association between plasma fibrinogen and RCC prognosis. Methods . An electronic search of Embase, PubMed/MEDLINE, and the Cochrane databases was performed to identify relevant studies published prior to June 1, 2016. Results . A total of 3744 patients with RCC from 7 published studies were included in the meta-analysis. The prognostic and clinical relevance of plasma fibrinogen are evaluated in RCC patients. Statistical significance of the combined hazard ratio (HR) was detected for overall survival, cancer-specific survival, and disease-free survival. Our pooled results showed that elevated plasma fibrinogen was significantly associated with clinical stage and Fuhrman grading. The level of plasma fibrinogen was not found to be associated with tumor type and gender. Conclusions . Elevated plasma fibrinogen is a strong indicator of poorer prognosis of patients with RCC, whereas the plasma fibrinogen is not significantly associated with tumor type. Therefore, plasma fibrinogen could be used in patients with RCC for risk stratification and decision providing a proper therapeutic strategy.

Effect of consuming a purple-fleshed sweet potato beverage on health-related biomarkers and safety parameters in Caucasian subjects with elevated levels of blood pressure and liver function biomarkers: a 4-week, open-label, non-comparative trial

PubMed Central

OKI, Tomoyuki; KANO, Mitsuyoshi; WATANABE, Osamu; GOTO, Kazuhisa; BOELSMA, Esther; ISHIKAWA, Fumiyasu; SUDA, Ikuo

2016-01-01

An open-label study with one treatment arm was conducted to investigate changes in health-related biomarkers (blood pressure and liver enzyme activity) and the safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in Caucasian subjects. Twenty healthy adults, 18–70 years of age, with a body mass index >25 kg/m2, elevated blood pressure and elevated levels of liver function biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml, including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum clinical profile, dipstick urinalysis and blood pressure were determined before consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A trend was found toward lowering systolic blood pressure during the treatment period (p=0.0590). No significant changes were found in diastolic blood pressure throughout the study period. Systolic blood pressure was significantly lower after 4 weeks of consumption compared with before consumption (p=0.0125) and was significantly higher after the 2-week washout period compared with after consumption (p=0.0496). The serum alanine aminotransferase level significantly increased over time, but aspartate aminotransferase and γ-glutamyltransferase levels stayed within the normal range of reference values. Safety parameters of the blood and urine showed no clinically relevant changes. The consumption of a purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically relevant changes in safety parameters of the blood and urine and showed a trend toward lowering systolic blood pressure. PMID:27508114

Clinical and immunological surveys in bee keepers.

PubMed

Bousquet, J; Coulomb, Y; Robinet-Levy, M; Michel, F B

1982-07-01

Two hundred and fifty bee keepers in the South of France, working seasonally, were clinically investigated by means of a questionnaire. Forty-three per cent had presented anaphylactic symptoms and 7.0% toxic reactions when stung by bees. The personal atopic history was found to be significantly (P less than 0.01) elevated in bee keepers who experienced anaphylaxis. Total serum IgE and been venom-specific IgE were titrated in 100 subjects. Total serum IgE was significantly elevated in allergic bee keepers (P = 0.02). Although bee venom-specific IgE were significantly (P less than 0.01) higher in allergic bee keepers this parameter cannot discriminate between allergic and non-allergic bee keepers owing to a considerable overlap. Bee venom-specific IgG was assayed in seventy subjects. Their level was significantly (P less than 0.001) higher in allergic and non-allergic bee keepers as compared with non-allergic blood donors and non-bee-keeping allergic patients. In both bee keeper groups there was no difference in bee venom-specific IgG titres.

Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis.

PubMed

Yamada, Daisuke; Asano, Yoshihide; Takahashi, Takehiro; Masui, Yuri; Aozasa, Naohiko; Akamata, Kaname; Noda, Shinji; Tamaki, Zenshiro; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2012-01-01

Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.

Clinical efficacy of transrectal ultrasound-guided prostate biopsy in men younger than 50 years old with an elevated prostate-specific antigen concentration (>4.0 ng/mL).

PubMed

Lu, Chin-Heng; Lin, Tzu-Ping; Shen, She Huei; Huang, Yi-Hsiu; Chung, Hsiao-Jen; Kuo, Junne-Yih; Huang, William J S; Wu, Howard H H; Chang, Yen-Hwa; Lin, Alex T L; Chen, Kuang-Kuo

2017-07-01

Prostate cancer (PCa) is not commonly found in men younger than 50 years of age. However, serum prostate-specific antigen (PSA) concentration has been examined more frequently at a younger age in Asia partially due to an increased awareness of prostate cancer. The purpose of our study was to investigate the efficacy and complication of PSA-triggered transrectal ultrasonography-guided prostate (TRUSP) biopsies. We retrospectively reviewed TRUSP biopsies in young men with elevated PSA concentration in Taipei Veterans General Hospital. We reviewed the cases of patients younger than 50 years of age with elevated PSA concentration (>4.0 ng/mL), who received 12 cores TRUSP biopsies at TPEVGH from January 2008-December 2013. The age, family history, digital rectal examination (DRE) results, PSA concentration, free/total PSA ratio, total prostate volume, PSA density, lower urinary tract symptoms and complications after the procedure were reviewed. The pathologic findings of TRUSP biopsy and clinical follow-up were reviewed and analyzed according to the Epstein criteria. A total of 77 patients were included and were divided into 2 groups: 1) the younger group consisted of 20 patients <40 years of age; and 2) the elder group had 57 patients who were 40-50 years of age. The overall detection rate of PCa was 11.69% (9/77), and all of the PCa cases were diagnosed in the elder group (group detection rate: 15.8%). There was a significant difference in the severity of lower urinary tract symptoms (LUTS) between these 2 groups. All PCa patients were clinically significant according to the Epstein criteria. Two patients experienced fever (2.60%) after TRUSP biopsy. From our patient cohort, it appears that no benefit was apparent for patients younger than 40 years old who received TRUSP biopsy, even with elevated PSA. However, PCa detected in men between 40 and 50 years of age were all clinically significant. Overall, our results supported current major practice guidelines which recommend an initial PSA checkup at 40 years of age. Copyright © 2017. Published by Elsevier Taiwan LLC.

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.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PubMed

Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

2018-04-01

Guidelines from the NCCN ® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Posttraumatic Stress and Depression in the Nonoffending Caregivers of Sexually Abused Children: Associations with Parenting Practices

PubMed Central

Jobe-Shields, Lisa; Swiecicki, Carole C.; Fritz, Darci R.; Stinnette, Jessica S.; Hanson, Rochelle F.

2016-01-01

Caregiver mental health is a known correlate of parenting practices, and recent research indicated that parental depression following childhood sexual abuse disclosure is associated with concurrent parenting difficulties. The present study extended this line of research by investigating posttraumatic stress symptoms and depression in a sample of caregivers (N=96) of children who experienced sexual abuse recruited from a Children’s Advocacy Center, as well as parenting practices reported by both caregivers and their children (Mean age = 10.79 years, SD = 3.29; 79% female). Twenty four percent of caregivers met criteria for presumptive clinical depression, clinically significant posttraumatic stress, or both. Results indicated elevated caregiver-reported inconsistent parenting in the context of clinically significant distress across symptom groups; children reported particularly elevated inconsistent parenting for caregivers with posttraumatic stress only. Caregiver depression was associated with low self-reported positive parenting and caregiver involvement, in addition to self-reported inconsistencies. Directions for future research are offered to further elucidate the relationships between caregiver mental health and parenting practices following childhood sexual abuse. PMID:26808966

Parent-rated emotional-behavioral and executive functioning in childhood epilepsy.

PubMed

Kavanaugh, Brian C; Scarborough, Vanessa Ramos; Salorio, Cynthia F

2015-01-01

The present study examined clinical and demographic risk factors associated with parent-rated emotional-behavioral and executive functioning in children and adolescents with epilepsy. The medical records of 152 children and adolescents with epilepsy referred for neuropsychological evaluation were reviewed. Results indicated that the sample displayed significantly elevated symptoms across the emotional-behavioral and executive domains assessed. Executive functioning and behavioral symptoms had the highest rates of clinically elevated scores, with lowest rates of elevated scores in internalizing and externalizing emotional problems. Only 34% of those participants with clinically significant emotional-behavioral or executive functioning difficulties had a history of psychological or counseling services, highlighting the underserved mental health needs of this population. In regard to clinical factors, the majority of seizure-related variables were not associated with emotional-behavioral or executive functioning. However, the frequency of seizures (i.e., seizure status) was associated with behavioral regulation aspects of executive functioning, and the age at evaluation was associated with externalizing problems and behavioral symptoms. Family psychiatric history (with the exception of ADHD) was associated with all domains of executive and emotional-behavioral functioning. In summary, emotional-behavioral and executive functioning difficulties frequently co-occur with seizures in childhood epilepsy, with both seizure-related and demographic factors contributing to the presentation of such neurobehavioral comorbidities. The present findings provide treatment providers of childhood epilepsy with important information to assist in better identifying children and adolescents who may be at risk for neurobehavioral comorbidities and may benefit from intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

PubMed

McCormack, S E; Shaham, O; McCarthy, M A; Deik, A A; Wang, T J; Gerszten, R E; Clish, C B; Mootha, V K; Grinspoon, S K; Fleischman, A

2013-02-01

What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

PubMed

Albisinni, S; Aoun, F; Noel, A; El Rassy, E; Lemort, M; Paesmans, M; van Velthoven, R; Roumeguère, T; Peltier, A

2018-01-01

MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of tumor markers and clinicopathological features in serous and mucinous borderline ovarian tumors.

PubMed

Alanbay, I; Aktürk, E; Coksuer, H; Ercan, C M; Karaşahin, E; Dede, M; Yenen, M C; Ozan, H; Dilek, S

2012-01-01

The aim of this study was to assess tumor markers and clinicopathological findings of patients with serous and mucinous borderline ovarian tumor (BOT) features. The study consisted of 50 patients that were diagnosed with and treated for BOT between 2005-2010 in three centers. CA125, CA19-9, and CA125+CA19-9 levels and clinicopathological features were compared in serous and mucinous histotypes. In serous and mucinous BOTs, correlations between tumor markers and demographics such as age, menopausal status, parity, clinical findings (stage, relapse, adjuvant chemotherapy, cytology, lymph node involvement and tumoral morphology (cystic-solid content, papilla, septation) were evaluated. There were no significant differences between serous and mucinous tumors in the clinicopathological features such as stage, tumor markers, age, menopausal status, or cytology. In serous BOTs we found a significant relation between elevated CA125+ CA19-9, CA19-9 and recurrence (p < 0.05). Also there was a significant relation between elevated CA125+ CA19-9, CA19-9 and cytology positivity (p < 0.05). We found a significant relation in serous BOTs between elevated CA125+CA19-9, adjuvant chemotherapy and lymph node metastases (p < 0.05). Also In mucinous BOTs with papilla formation we found a significant relation between elevated CA125 and CA125+ CA19-9 (p < 0.05). There was significant relation between cytology positivity and elevated CA19-9 in mucinous BOTs (p < 0.05). Serum tumor markers of serous and mucinous BOTs were different in relation to their clinicopathological features. This may reflect differences of serous and mucinous BOTs.

Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

PubMed

Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

2017-03-01

Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

A Descriptive Study of Hyperlexia in a Clinically Referred Sample of Children with Developmental Delays.

ERIC Educational Resources Information Center

Grigorenok, Elena L.; Klin, Ami; Pauls, David L.; Senft, Riley; Hooper, Catalina; Volkmar, Fred

2002-01-01

This study of hyperlexia in 80 children with developmental delays found no significant differences in the frequency of hyperlexia in girls compared with boys; a significantly elevated frequency of hyperlexia in children diagnosed with pervasive developmental disorders (PDD) compared with children with non-PDD diagnoses; and a similar range of IQ…

Serum S100B is a useful surrogate marker for long-term outcomes in photochemically-induced thrombotic stroke rat models.

PubMed

Tanaka, Yu; Koizumi, Chie; Marumo, Toshiyuki; Omura, Tomohiro; Yoshida, Shigeru

2007-08-02

In recent years, serum S100B has been used as a secondary endpoint in some clinical trials, in which serum S100B has successfully indicated the benefits or harm done by the tested agents. Compared to clinical stroke studies, few experimental stroke studies report using serum S100B as a surrogate marker for estimating the long-term effects of neuroprotectants. This study sought to observe serum S100B kinetics in PIT stroke models and to clarify the association between serum S100B and both final infarct volumes and long-term neurological outcomes. Furthermore, to demonstrate that early elevations in serum S100B reflect successful neuroprotective treatment, a pharmacological study was performed with a non-competitive NMDA glutamate receptor antagonist, MK-801. Serum S100B levels were significantly elevated after PIT stroke, reaching peak values 48 h after the onset and declining thereafter. Single measurements of serum S100B as early as 48 h after PIT stroke correlated significantly with final infarct volumes and long-term neurological outcomes. Elevated serum S100B was significantly attenuated by MK-801, correlating significantly with long-term beneficial effects of MK-801 on infarct volumes and neurological outcomes. Our results showed that single measurements of serum S100B 48 h after PIT stroke would serve as an early and simple surrogate marker for long-term evaluation of histological and neurological outcomes in PIT stroke rat models.

Evaluation of prolonged fatigue post-West Nile virus infection and association of fatigue with elevated antiviral and proinflammatory cytokines.

PubMed

Garcia, Melissa N; Hause, Anne M; Walker, Christopher M; Orange, Jordan S; Hasbun, Rodrigo; Murray, Kristy O

2014-09-01

This study aimed to characterize fatigue postinfection among study participants with a history of West Nile virus (WNV) infection and determine whether antiviral and pro-inflammatory cytokines were significantly elevated in those reporting prolonged fatigue. We found that 31% (44/140) of study participants experienced prolonged (more than 6 months) fatigue postinfection, with an average length of fatigue duration of 5 years. Females, those younger than 50 years of age, and those with symptomatic clinical WNV disease were significantly more likely to report fatigue. Pro-inflammatory and antiviral cytokines (granulocyte macrophage colony stimulating factor, interferon-γ, interferon-γ inducing protein 10, interleukin 2, interleukin 6, and interleukin 12p70) were significantly elevated in those reporting fatigue postinfection compared to those not reporting fatigue. Clinicians should consider history of WNV infection as a possible factor when evaluating causes of prolonged fatigue following a febrile viral illness in their patients.

Impact of Elevated End-Diastolic Pulmonary Regurgitation Gradient on Worse Clinical Outcomes in Hospitalized Patients With Heart Failure.

PubMed

Honda, Yasuyuki; Nagai, Toshiyuki; Sugano, Yasuo; Honda, Satoshi; Okada, Atsushi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Ogawa, Hisao; Yasuda, Satoshi; Anzai, Toshihisa

2017-02-15

The echo Doppler end-diastolic pulmonary regurgitation (EDPR) gradient correlates well with catheter-derived pulmonary artery diastolic pressure. An elevated EDPR gradient is associated with worse clinical outcomes in patients with stable coronary artery disease. However, the prognostic significance of EDPR gradient in patients with heart failure (HF) is unclear. The aim of the present study was to investigate the prognostic impact of EDPR gradient in HF. We retrospectively examined 751 consecutive hospitalized patients with acute HF. Those with acute coronary syndrome or in-hospital death and those without accessible EDPR gradient data at discharge were excluded. Finally, 265 patients were examined and divided into 2 groups according to EDPR gradient (cutoff 9 mm Hg). Adverse events were defined as worsening HF and death. Patients with elevated EDPR gradient had higher B-type natriuretic peptide, lower age, and lower left ventricular ejection fraction at discharge than those with nonelevated EDPR gradient. During a median follow-up of 429 days, elevated EDPR gradient was independently associated with adverse events (hazard ratio 2.34, 95% CI 1.44 to 3.78, p <0.001) after adjustment for confounders. In conclusion, echo Doppler EDPR gradient might be a noninvasive predictor of clinical outcomes in hospitalized patients with HF. Copyright © 2016 Elsevier Inc. All rights reserved.

Multinomial logistic regression analysis for differentiating 3 treatment outcome trajectory groups for headache-associated disability.

PubMed

Lewis, Kristin Nicole; Heckman, Bernadette Davantes; Himawan, Lina

2011-08-01

Growth mixture modeling (GMM) identified latent groups based on treatment outcome trajectories of headache disability measures in patients in headache subspecialty treatment clinics. Using a longitudinal design, 219 patients in headache subspecialty clinics in 4 large cities throughout Ohio provided data on their headache disability at pretreatment and 3 follow-up assessments. GMM identified 3 treatment outcome trajectory groups: (1) patients who initiated treatment with elevated disability levels and who reported statistically significant reductions in headache disability (high-disability improvers; 11%); (2) patients who initiated treatment with elevated disability but who reported no reductions in disability (high-disability nonimprovers; 34%); and (3) patients who initiated treatment with moderate disability and who reported statistically significant reductions in headache disability (moderate-disability improvers; 55%). Based on the final multinomial logistic regression model, a dichotomized treatment appointment attendance variable was a statistically significant predictor for differentiating high-disability improvers from high-disability nonimprovers. Three-fourths of patients who initiated treatment with elevated disability levels did not report reductions in disability after 5 months of treatment with new preventive pharmacotherapies. Preventive headache agents may be most efficacious for patients with moderate levels of disability and for patients with high disability levels who attend all treatment appointments. Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Patterns of vitamin D, parathyroid hormone and c-terminal telopeptide of collagen type 1 in Caucasian and African descent HIV-infected populations in Central Europe.

PubMed

Noe, Sebastian; Oldenbuettel, Celia; Heldwein, Silke; Jaeger, Hans; Wolf, Eva

2017-10-02

Risk factors for bone loss in HIV patients might differ or have a different impact in African descent compared to Caucasian populations. The aim of the paper is to analyze the relevance of risk factors on surrogate markers of bone metabolism in HIV-infected African descent and Caucasian patients. This is a cross-sectional study in a single HIV-specialized research and clinical care center in Munich, Germany. We included 889 patients in the study, among them 771 Caucasians (86.7%). Only in Caucasians lower vitamin D levels [OR: 2.5 (95CI: 1.6-3.7)], lower calcium levels [OR: 1.8 (1.2-2.8)], and the use of tenofovir disoproxil fumarate [OR: 2.8 (1.8-4.4)] were significantly associated with elevated PTH in multivariate analysis. Likewise, only in Caucasians elevated PTH was significantly associated with elevated markers of c-terminal telopeptides of collagen type 1 (β-CTX) [OR: 1.7 (1.0-3.0)]. Effects of traditional risk factors for secondary hyperparathyroidism and increased markers of bone turn-over seem to be less distinct in African descent HIV patients. The clinical impact and generalizability of this finding as well as the significance of vitamin D supplementation in African descent patients therefore warrants further investigation.

Influence of meteorological conditions on hospital admission in patients with acute coronary syndrome with and without ST-segment elevation: Results of the AIRACOS study.

PubMed

Dominguez-Rodriguez, A; Juarez-Prera, R A; Rodríguez, S; Abreu-Gonzalez, P; Avanzas, P

2016-05-01

Evaluate whether the meterological parameters affecting revenues in patients with ST-segment and non-ST-segment elevation ACS. A prospective cohort study was carried out. Coronary Care Unit of Hospital Universitario de Canarias We studies a total of 307 consecutive patients with a diagnosis of ST-segment and non-ST-segment elevation ACS. We analyze the average concentrations of particulate smaller than 10 and 2.5μm diameter, particulate black carbon, the concentrations of gaseous pollutants and meteorological parameters (wind speed, temperature, relative humidity and atmospheric pressure) that were exposed patients from one day up to 7 days prior to admission. None. Demographic, clinical, atmospheric particles, concentrations of gaseous pollutants and meterological parameters. A total of 138 (45%) patients were classified as ST-segment and 169 (55%) as non-ST-segment elevation ACS. No statistically significant differences in exposure to atmospheric particles in both groups. Regarding meteorological data, we did not find statistically significant differences, except for higher atmospheric pressure in ST-segment elevation ACS (999.6±2.6 vs. 998.8±2.5 mbar, P=.008). Multivariate analysis showed that atmospheric pressure was significant predictor of ST-segment elevation ACS presentation (OR: 1.14, 95% CI: 1.04-1.24, P=.004). In the patients who suffer ACS, the presence of higher number of atmospheric pressure during the week before the event increase the risk that the ST-segment elevation ACS. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Correlation of platelet count and acute ST-elevation in myocardial infarction.

PubMed

Paul, G K; Sen, B; Bari, M A; Rahman, Z; Jamal, F; Bari, M S; Sazidur, S R

2010-07-01

The role of platelets in the pathogenesis of ST-elevation myocardial infarction (STEMI) has been substantiated by studies that demonstrated significant clinical benefits associated with antiplatelet therapy. Initial platelet counts in Acute Myocardial Infarction (AMI) may be a useful adjunct for identifying those patients who may or may not respond to fibrinolytic agents. Patient with acute STEMI has variable level of platelet count and with higher platelet count have poor in hospital outcome. There are many predictors of poor outcome in Acute Myocardial Infarction (AMI) like cardiac biomarkers (Troponin I, Troponin T and CK-MB), C-Reactive Protien (CRP) and WBC (White Blood Cell) counts. Platelet count on presentation of STEMI is one of them. Higher platelet count is associated with higher rate of adverse clinical outcome in ST-Elevation Myocardial Infarction (STEMI), like heart failure, arrhythmia, re-infarction & death. So, categorization of patient with STEMI on the basis of platelet counts may be helpful for risk stratification and management of these patients.

Association of stroke clinical outcomes with coexistence of hyperglycemia and biomarkers of inflammation.

PubMed

Zhou, Jingwen; Wu, Jiahui; Zhang, Jintao; Xu, Tan; Zhang, Huan; Zhang, Yonghong; Zhang, Shaoyan

2015-06-01

To investigate the association of short-term clinical outcomes with coexistence of hyperglycemia and elevated biomarkers of inflammation among acute ischemic stroke (AIS) patients. We performed a retrospective study of 2675 patients diagnosed with AIS from January 2006 to December 2008. The study outcomes were defined as neurologic deficiency (National Institutes of Health Stroke Scale score ≥5) at discharge or death during hospitalization. Compared with normoglycemia and without any elevated biomarkers, patients with hyperglycemia, elevated white blood cell (WBC) count, elevated neutrophils ratio (NEUR), and elevated erythrocyte sedimentation rate (ESR) had higher rates of study outcomes (all P < .05). Furthermore, patients with coexistence of hyperglycemia with any of elevated WBC count, NEUR, or ESR were more likely to have study outcomes (all P < .05). Compared with subjects with normoglycaemia and without any elevated biomarker, multivariate adjusted odds ratios (95% confidence interval) of study outcomes associated with hyperglycemia, elevated WBC count, elevated NEUR, elevated ESR, coexistences of hyperglycemia with elevated WBC count, elevated NEUR, and elevated ESR were 1.492 (1.139-1.955), 1.404 (1.048-1.881), 1.897 (1.411-2.551), 2.184 (1.339-3.564), 1.963 (1.337-2.883), 2.544(1.715- 3.775), and 2.687 (1.347-5.363), respectively. This study indicated that hyperglycemia and elevated biomarkers of inflammation were associated with short-term clinical outcomes, and individuals with coexistence of hyperglycemia and elevated biomarkers of inflammation had higher risk of poor clinical outcomes among AIS patients. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

Patients with elevated serum PSA and indwelling catheter after acute urinary retention: prospective study of 63 patients with 7-year follow-up.

PubMed

Kravchick, Sergey; Bunkin, Igor; Peled, Ronit; Yulish, Eugeny; Ben-Dor, David; Kravchenko, Yakov; Cytron, Shmuel

2007-10-01

Elevated PSA value in the presence of an indwelling catheter is still an enigma. The aims of this prospective study were: to investigate the reliability of elevated PSA levels in patients with normal DRE and indwelling catheter after AUR; to assess the impact of preoperative TRUS-biopsy in detecting prostate cancer in such circumstances; to estimate the crucial duration of follow-up period. 63 patients were included in the study. PSA was assessed 5 days after catheter insertion. All patients failed to void without catheter and have been scheduled for surgery. TRUS-biopsy was performed before operation. All patients underwent surgery at least two weeks after prostate biopsies. Postoperative follow-up visits continued for at least 7 years. Biopsies were taken when indicated by persistently elevated PSA or an abnormal DRE. Mean PSA before catheter insertion differed significantly from PSA obtained on the 5(th) day after AUR (p = 0.001). Mean prostate volume calculated on TRUS was 80.5 +/- 28 ml. Mean duration of indwelling catheter placement was 37.8 +/- 7.97 days. Mean delay in operative treatment as a result of preoperative evaluation was 23.548 +/- 2.487 days. Carcinoma was detected in 13 patients, while clinically insignificant cancer was present in 31% (4 patients). It must be also emphasized that 38% of patients with carcinoma were >70 year-old. Preoperative TRUS-biopsy and postoperative pathologic exam diagnosed carcinoma in 5 patients (2 and 3 respectively). During 42 months of 7-year follow-up cancer was revealed in 8 patients. Mean PSA value in the follow-up period was significantly elevated in patients with carcinoma: 5.99 +/- 3.34 v/s 2.34 +/- 1.68 ng/ml (p = 0.007) and was the strongest predictor for cancer detection (p = 0.001). The detection rate of clinically significant cancer on preoperative biopsies postoperative pathologic exam in patients with AUR and indwelling catheter is low. These patients could be safely operated on without any delay. However, in order to detect clinically important cancer in the peripheral zone a postoperative monitoring period of should be recommended: starting 6 months after operation and continuing subsequently for at least 4 years. Postoperative PSA level is the strongest predictor of cancer detection and could be usefully employed in these patients. AUR and in the patients with large prostate cause elevated PSA. Cancer detection rate on preoperative biopsies is low in these patients. Long postoperative monitoring period should be strongly recommended.

[The clinical significance of the measurement of plasma transferrin as a growth factor. II. The changes in various endocrine status].

PubMed

Matsubara, M; Odagaki, E; Morioka, T; Nakagawa, K

1987-05-20

The clinical significance of the measurement of plasma transferrin (Tf) in patients with hypophysial disorders was reported in our previous papers. In the present study, we determined plasma Tf levels in 55 patients with various endocrine states and considered their clinical significance compared with plasma somatomedin-C (SM-C) levels. Plasma Tf levels decreased significantly in patients with anorexia nervosa (p less than 0.02), hyperthyroidism (p less than 0.05), primary hypothyroidism (p less than 0.05) and Cushing's syndrome (p less than 0.05), while they were elevated significantly in pregnancy (p less than 0.01) or females using estrogens (p less than 0.05). The former two declines were considered a reflection of the malnutritional state of the patients since a significant negative correlation was observed between plasma Tf levels and the percentile deficit from the ideal body weight in patients with anorexia nervosa (p less than 0.01), or between plasma Tf levels and elevated T3 levels which induce hypermetabolism in patients with hyperthyroidism (p less than 0.01). A significant correlation was observed between the SM-C and Tf levels in these subjects (including normal controls and patients with hypophysial disorders) as a whole (r = 0.79, p less than 0.001). These data indicate that plasma Tf is changeable according to the endocrinological and nutritional conditions with good correlation to the SM-C, and it is suggested that Tf also operates as a growth factor in vivo.

African Caribbeans have greater subclinical cerebrovascular disease than Europeans: this is associated with both their elevated resting and ambulatory blood pressure and their hyperglycaemia.

PubMed

Shibata, Dean; Tillin, Therese; Beauchamp, Norman; Heasman, John; Hughes, Alun D; Park, Chloe; Gedroyc, Wady; Chaturvedi, Nish

2013-12-01

Stroke is elevated in people of black African descent, but evidence for excess subclinical cerebrovascular disease is conflicting, and the role of risk factors in determining any ethnic differences observed unexplored. We compared prevalence of brain infarcts, and severe white matter hyperintensities (WMHs) on cerebral MRI, in a community-based sample of men and women aged 58-86 of African Caribbean (214) and European (605) descent, in London, UK. Resting, central and ambulatory blood pressure (BP) were measured; diabetes was assessed by blood testing and questionnaire. Mean age was 70. Multiple (≥4) brain infarcts and severe WMH occurred more frequently in African Caribbeans (18/43%), than Europeans (7/33%, P=0.05/0.008). Separately, clinic and night-time ambulatory BP were significantly associated with severe WMH in both ethnic groups; when both were entered into the model, the association for clinic SBP was attenuated and lost statistical significance [1.00 (0.98-1.02) P=0.9 in Europeans, 1.00 (0.97-1.04) P=0.9 in African Caribbeans], whereas the association for night-time SBP was retained [1.04 (1.02-1.07) P<0.001 in Europeans, 1.08 (1.03-1.12), P=0.001 in African Caribbeans]. The greater age-adjusted and sex-adjusted risk of severe WMH in African Caribbeans compared with Europeans [2.08 (1.15-3.76) P=0.02], was attenuated to 1.45 [(0.74-2.83) P=0.3] on adjustment for clinic and night-time systolic pressure, antihypertensive medication use and glycated haemoglobin. African Caribbeans have a greater burden of subclinical cerebrovascular disease than Europeans. This excess is related to elevated clinic and ambulatory BP, and to hyperglycaemia.

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

PubMed

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

Elevated VGKC-complex antibodies in a boy with fever-induced refractory epileptic encephalopathy in school-age children (FIRES).

PubMed

Illingworth, Marjorie A; Hanrahan, Donncha; Anderson, Claire E; O'Kane, Kathryn; Anderson, Jennifer; Casey, Maureen; de Sousa, Carlos; Cross, J Helen; Wright, Sukvhir; Dale, Russell C; Vincent, Angela; Kurian, Manju A

2011-11-01

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and behavioural difficulties. We describe a case of FIRES in a 4-year-old boy that was associated with elevated voltage-gated potassium channel (VGKC) complex antibodies and a significant clinical and immunological response to immunomodulation. This case, therefore, potentially expands the clinical phenotype of VGKC antibody-associated disease to include that of FIRES. Prior to immunomodulation, neuropsychology assessment highlighted significant attention, memory, and word-finding difficulties. The UK version of the Wechsler Preschool and Primary Scale of Intelligence assessment indicated particular difficulties with verbal skills (9th centile). Immunomodulation was initially administered as intravenous methylprednisolone (followed by maintenance oral prednisolone) and later in the disease course as regular monthly intravenous immunoglobulin infusions and low-dose azathioprine. Now aged 6 years, the seizure burden in this child is much reduced, although increased seizure frequency is observed in the few days before his monthly immunoglobulin infusions. Formal IQ assessment has not been repeated but there is no clinical suggestion of further cognitive regression. VGKC complex antibodies have been reported in a range of central and peripheral neurological disorders (predominantly presenting in adulthood), and the identification of elevated VGKC complex antibodies, combined with the response to immunotherapies in this child, supports an autoimmune pathogenesis in FIRES with potential diagnostic and therapeutic implications. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Assessment of Correlation between Sweat Chloride Levels and Clinical Features of Cystic Fibrosis Patients.

PubMed

Raina, Manzoor A; Khan, Mosin S; Malik, Showkat A; Raina, Ab Hameed; Makhdoomi, Mudassir J; Bhat, Javed I; Mudassar, Syed

2016-12-01

Cystic Fibrosis (CF) is an autosomal recessive disorder and the incidence of this disease is undermined in Northern India. The distinguishable salty character of the sweat belonging to individuals suffering from CF makes sweat chloride estimation essential for diagnosis of CF disease. The aim of this prospective study was to elucidate the relationship of sweat chloride levels with clinical features and pattern of CF. A total of 182 patients, with clinical features of CF were included in this study for quantitative measurement of sweat chloride. Sweat stimulation and collection involved pilocarpine iontophoresis based on the Gibson and Cooks methodology. The quantitative estimation of chloride was done by Schales and Schales method with some modifications. Cystic Fibrosis Trans Membrane Conductance Regulator (CFTR) mutation status was recorded in case of patients with borderline sweat chloride levels to correlate the results and for follow-up. Out of 182 patients having clinical features consistent with CF, borderline and elevated sweat chloride levels were present in 9 (5%) and 41 (22.5%) subjects respectively. Elevated sweat chloride levels were significantly associated with wheeze, Failure To Thrive (FTT), history of CF in Siblings, product of Consanguineous Marriage (CM), digital clubbing and steatorrhoea on univariate analysis. On multivariate analysis only wheeze, FTT and steatorrhoea were found to be significantly associated with elevated sweat chloride levels (p<0.05). Among the nine borderline cases six cases were positive for at least two CFTR mutations and rest of the three cases were not having any mutation in CFTR gene. The diagnosis is often delayed and the disease is advanced in most patients at the time of diagnosis. Sweat testing is a gold standard for diagnosis of CF patients as genetic mutation profile being heterozygous and unlikely to become diagnostic test.

Evaluation of left ventricular Tei index (index of myocardial performance) in healthy dogs and dogs with mitral regurgitation.

PubMed

Teshima, Kenji; Asano, Kazushi; Iwanaga, Koji; Koie, Hiroshi; Uechi, Masami; Kato, Yuka; Kutara, Kenji; Kanno, Nobuyuki; Seki, Mamiko; Edamura, Kazuya; Hasegawa, Atsuhiko; Tanaka, Shigeo

2007-02-01

The left ventricular (LV) Tei index (index of myocardial performance) has been demonstrated to be clinically useful in estimating comprehensive LV function, including the systolic and diastolic performances, in various human cardiac diseases. The purposes of this study were to validate the correlation between the LV Tei index and LV function obtained by cardiac catheterization in healthy dogs, and to evaluate the LV Tei index in dogs with naturally occurring mitral regurgitation (MR). In healthy dogs, the LV Tei index was significantly correlated with the LV peak +dP/dt (r = -0.89) and LV peak -dP/dt (r=0.87). The LV Tei index significantly increased in dogs with MR compared with normal dogs and significantly increased with progressively more severe clinical signs due to heart failure. The elevation of the LV Tei index in dogs with symptomatic MR appears to be associated with shortening of ejection time. The LV Tei index significantly increased with age and was not correlated with heart rate and body weight in normal dogs. In conclusion, our study demonstrated that the LV Tei index was measurable in dogs and not influenced by heart rate and body weight. The LV Tei index significantly increased with the progression of clinical signs in MR dogs. In particular, the elevation of the LV Tei index in dogs with symptomatic MR due to shortening of ejection time may suggest LV systolic dysfunction and the decrement of forward stroke volume.

[Risk factors for elevated serum total bile acid in preterm infants].

PubMed

Song, Yan-Ting; Wang, Yong-Qin; Zhao, Yue-Hua; Zhu, Hai-Ling; Liu, Qian; Zhang, Xiao; Gao, Yi-Wen; Zhang, Wei-Ye; Sang, Yu-Tong

2018-03-01

To study the risk factors for elevated serum total bile acid (TBA) in preterm infants. A retrospective analysis was performed for the clinical data of 216 preterm infants who were admitted to the neonatal intensive care unit. According to the presence or absence of elevated TBA (TBA >24.8 μmol/L), the preterm infants were divided into elevated TBA group with 53 infants and non-elevated TBA group with 163 infants. A univariate analysis and an unconditional multivariate logistic regression analysis were used to investigate the risk factors for elevated TBA. The univariate analysis showed that there were significant differences between the elevated TBA group and the non-elevated TBA group in gestational age at birth, birth weight, proportion of small-for-gestational-age infants, proportion of infants undergoing ventilator-assisted ventilation, fasting time, parenteral nutrition time, and incidence of neonatal respiratory failure and sepsis (P<0.05). The unconditional multivariate logistic regression analysis showed that low birth weight (OR=3.84, 95%CI: 1.53-9.64) and neonatal sepsis (OR=2.56, 95%CI: 1.01-6.47) were independent risk factors for elevated TBA in preterm infants. Low birth weight and neonatal sepsis may lead to elevated TBA in preterm infants.

Serum pro-gastrin-releasing peptide (31-98) in benign prostatic hyperplasia and prostatic carcinoma.

PubMed

Nagakawa, Osamu; Furuya, Yuzo; Fujiuchi, Yasuyoshi; Fuse, Hideki

2002-09-01

To clarify whether serum levels of pro-gastrin-releasing peptide (ProGRP) (31-98) could be a useful marker in patients with prostatic carcinoma. GRP is produced and secreted by prostatic neuroendocrine cells. Serum levels of ProGRP(31-98) were measured by enzyme-linked immunosorbent assay in 20 patients with benign prostatic hyperplasia and 107 patients with prostatic carcinoma. The mean serum levels of ProGRP(31-98) in patients with distant metastasis and hormone-resistant prostate cancer were significantly elevated compared with those in patients with organ-confined disease. Significantly elevated levels of ProGRP(31-98) were detected in 9 patients with prostatic carcinoma before any treatment. During hormone-resistant prostate cancer progression, ProGRP(31-98) levels were elevated in 9 patients (23%). Of the 9 patients with Stage D3 and elevated serum ProGRP, 4 had a normal serum prostate-specific antigen level. ProGRP may be a potential tumor marker for prostate cancer. Additional studies in large groups of patients are needed to define the clinical value of ProGRP.

Elevated plasma migration inhibitory factor in hypertension–hyperlipidemia patients correlates with impaired endothelial function

PubMed Central

Zhou, Boda; Ren, Chuan; Zu, Lingyun; Zheng, Lemin; Guo, Lijun; Gao, Wei

2016-01-01

Abstract Migration inhibitory factor (MIF) has been shown to be critical in the pathology of early artherosclerosis; this article aim to investigate the plasma levels of MIF in hypertension plus hyperlipidemia patients. A total of 39 hypertension plus hyperlipidemia patients without any previous treatment were enrolled (HTN-HLP). Twenty-five healthy subjects were enrolled as the healthy control group (HEALTHY). Plasma MIF was measured by ELISA; laboratory and clinical characteristics were analyzed. HUVECs were treated with pooled plasma from HTN-HLP and HEALTHY groups, and the protein levels of adhesion molecules VCAM-1 and ICAM-1 were determined by ELISA. We found that plasma MIF was significantly elevated in the HTN-HLP group. Serum NO and eNOS levels were significantly lower; serum ET-1 (endothelin) levels were significantly higher in the HTN-HLP group. Furthermore, blood pressure, baPWV (brachial–ankle pulse wave velocity), and serum ET-1 level were significantly positively; serum NO and eNOS levels were negatively correlated with plasma MIF levels. Plasma from HTN-HLP significantly stimulated VCAM-1 and ICAM-1 protein expression on the surface of HUVECs. Plasma MIF was elevated in HTN-HLP patients and correlates with impaired endothelial function. PMID:27787379

Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma.

PubMed

Karlicic, Vukoica; Vukovic, Jelena; Stanojevic, Ivan; Sotirovic, Jelena; Peric, Aleksandar; Jovic, Milena; Cvijanovic, Vlado; Djukic, Mirjana; Banovic, Tatjana; Vojvodic, Danilo

2016-01-01

Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFb1, in tumor microcirculation but not in patient serum samples. IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.

Does specific psychopathology predict development of psychosis in ultra high-risk (UHR) patients?

PubMed

Thompson, Andrew; Nelson, Barnaby; Bruxner, Annie; O'Connor, Karen; Mossaheb, Nilufar; Simmons, Magenta B; Yung, Alison

2013-04-01

Studies have attempted to identify additional risk factors within the group identified as 'ultra high risk' (UHR) for developing psychotic disorders in order to characterise those at highest risk. However, these studies have often neglected clinical symptom types as additional risk factors. We aimed to investigate the relationship between baseline clinical psychotic or psychotic-like symptoms and the subsequent transition to a psychotic disorder in a UHR sample. A retrospective 'case-control' methodology was used. We identified all individuals from a UHR clinic who had subsequently developed a psychotic disorder (cases) and compared these to a random sample of individuals from the clinic who did not become psychotic within the sampling time frame (controls). The sample consisted of 120 patients (60 cases, 60 controls). An audit tool was used to identify clinical symptoms reported at entry to the clinic (baseline) using the clinical file. Diagnosis at transition was assessed using the Operational Criteria for Psychotic Illness (OPCRIT) computer program. The relationship between transition to a psychotic disorder and baseline symptoms was explored using survival analysis. Presence of thought disorder, any delusions and elevated mood significantly predicted transition to a psychotic disorder. When other symptoms were adjusted for, only the presence of elevated mood significantly predicted subsequent transition (hazard ratio 2.69, p = 0.002). Thought disorder was a predictor of transition to a schizophrenia-like psychotic disorder (hazard ratio 3.69, p = 0.008). Few individual clinical symptoms appear to be predictive of transition to a psychotic disorder in the UHR group. Clinicians should be cautious about the use of clinical profile alone in such individuals when determining who is at highest risk.

Serum cholecystokinin and neurotensin during follow-up of pancreas, prostate and medullary thyroid tumors.

PubMed

Pichon, M F; Coquin, G; Fauveau, C; Rey, A

1999-01-01

Growth of pancreatic carcinoma cells is stimulated by cholecystokinin (CCK) and neurotensin (NT). Prostatic carcinoma cells can secrete neurotensin. The CCK gene has been described in thyroid medullary carcinomas (MCT). Serum CCK and NT were measured by RIAs during monitoring of 19 pancreas tumours, 10 prostate adenocarcinomas and 10 thyroid medullary cancers (MCT). No correlations were found between CCK and NT in the three tumour types, nor with CA 19.9, PSA, CEA or calcitonin. In pancreas adenocarcinomas (n = 12), initial median CCK was > 8pg/ml (non significant differences between stages T, N or M). Median NT was > 80 pg/ml in all but M0 and stage I-II cases, and significantly higher in M1 and stages IV (P = 0.002). Non significant differences were found for CCK and NT according to clinical stages. In prostate cancers, median CCK was significantly more elevated after relapse (P = 0.040). Median NT was significantly more elevated in disease-free patients (P = 0.04). In MCT, CCK and NT were not related to clinical stages. In pancreas and prostate cancers serum CCK may follow tumour load and disease progression. NT was lower in progressive disease. The contribution of these peptides in human tumour growth, since they may have therapeutic implication, warrants further investigation.

Clinical and radiographic evaluation of nanocrystalline hydroxyapatite with or without platelet-rich fibrin membrane in the treatment of periodontal intrabony defects

PubMed Central

Elgendy, Enas Ahmed; Abo Shady, Tamer Elamer

2015-01-01

Background: Nano-sized ceramics may represent a promising class of bone graft substitutes due to their improved osseointegrative properties. Nanocrystalline hydroxyapatite (NcHA) binds to bone and stimulate bone healing by stimulation of osteoblast activity. Platelet-rich fibrin (PRF), an intimate assembly of cytokines, glycan chains, and structural glycoproteins enmeshed within a slowly polymerized fibrin network, has the potential to accelerate soft and hard tissue healing. The present study aims to explore the clinical and radiographical outcome of NcHA bone graft with or without PRF, in the treatment of intrabony periodontal defects. Materials and Methods: In a split-mouth study design, 20 patients having two almost identical intrabony defects with clinical probing depth of at least 6 mm were selected for the study. Selected sites were randomly divided into two groups. In Group I, mucoperiosteal flap elevation followed by the placement of NcHA was done. In Group II, mucoperiosteal flap elevation, followed by the placement of NcHA with PRF was done. Clinical and radiographic parameters were recorded at baseline and at 6-month postoperatively. Results: Both treatment groups showed a significant probing pocket depth (PPD) reduction, clinical attachment gain, increase bone density 6-month after surgery compared with baseline. However, there was a significantly greater PPD reduction and clinical attachment gain when PRF was added to NcHA. Conclusion: The NcHA bone graft in combination with PRF demonstrated clinical advantages beyond that achieved by the NcHA alone. PMID:25810595

Cardiotoxicity of Freon among refrigeration services workers: comparative cross-sectional study

PubMed Central

2009-01-01

Background Freon includes a number of gaseous, colorless chlorofluorocarbons. Although freon is generally considered to be a fluorocarbon of relatively low toxicity; significantly detrimental effects may occur upon over exposure. The purpose of the present study is to investigate whether occupational exposure to fluorocarbons can induce arterial hypertension, myocardial ischemia, cardiac arrhythmias, elevated levels of plasma lipids and renal dysfunction. Methods This comparative cross-sectional study was conducted at the cardiology clinic of the Suez Canal Authority Hospital (Egypt). The study included 23 apparently healthy male workers at the refrigeration services workshop who were exposed to fluorocarbons (FC 12 and FC 22) and 23 likewise apparently healthy male workers (unexposed), the control group. All the participants were interviewed using a pre-composed questionnaire and were subjected to a clinical examination and relevant laboratory investigations. Results There were no significant statistical differences between the groups studied regarding symptoms suggesting arterial hypertension and renal affection, although a significantly higher percentage of the studied refrigeration services workers had symptoms of arrhythmias. None of the workers had symptoms suggesting coronary artery disease. Clinical examination revealed that the refrigeration services workers had a significantly higher mean pulse rate compared to the controls, though no significant statistical differences were found in arterial blood pressure measurements between the two study groups. Exercise stress testing of the workers studied revealed normal heart reaction to the increased need for oxygen, while sinus tachycardia was detected in all the participants. The results of Holter monitoring revealed significant differences within subject and group regarding the number of abnormal beats detected throughout the day of monitoring (p < 0.001). There were no significant differences detected in the average heart rate during the monitoring period within subject or group. Most laboratory investigations revealed absence of significant statistical differences for lipid profile markers, serum electrolyte levels and glomerular lesion markers between the groups except for cholesterol and urinary β2-microglobulin (tubular lesion markers) levels which were significantly elevated in freon exposed workers. Conclusions Unprotected occupational exposure to chlorofluorocarbons can induce cardiotoxicity in the form of cardiac arrhythmias. The role of chlorofluorocarbons in inducing arterial hypertension and coronary artery diseases is unclear, although significantly elevated serum cholesterol and urinary β2-microglobulin levels raise a concern. PMID:19594908

Amniotic fluid inflammatory cytokines: potential markers of immunologic dysfunction in autism spectrum disorders.

PubMed

Abdallah, Morsi W; Larsen, Nanna; Grove, Jakob; Nørgaard-Pedersen, Bent; Thorsen, Poul; Mortensen, Erik L; Hougaard, David M

2013-09-01

The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities. AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.

Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure.

PubMed

Kennedy, David J; Shrestha, Kevin; Sheehey, Brendan; Li, Xinmin S; Guggilam, Anuradha; Wu, Yuping; Finucan, Michael; Gabi, Alaa; Medert, Charles M; Westfall, Kristen; Borowski, Allen; Fedorova, Olga; Bagrov, Alexei Y; Tang, W H Wilson

2015-11-01

Plasma levels of cardiotonic steroids are elevated in volume-expanded states, such as chronic kidney disease, but the role of these natriuretic hormones in subjects with heart failure (HF) is unclear. We sought to determine the prognostic role of the cardiotonic steroids marinobufagenin (MBG) in HF, particularly in relation to long-term outcomes. We first measured plasma MBG levels and performed comprehensive clinical, laboratory, and echocardiographic assessment in 245 patients with HF. All-cause mortality, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort, median (interquartile range) MBG was 583 (383-812) pM. Higher MBG was associated with higher myeloperoxidase (r=0.42, P<0.0001), B-type natriuretic peptide (r=0.25, P=0.001), and asymmetrical dimethylarginine (r=0.32, P<0.001). Elevated levels of MBG were associated with measures of worse right ventricular function (RV s', r=-0.39, P<0.0001) and predicted increased risk of adverse clinical outcomes (MBG≥574 pmol/L: hazard ratio 1.58 [1.10-2.31], P=0.014) even after adjustment for age, sex, diabetes mellitus, and ischemic pathogenesis. In mice, a left anterior descending coronary artery ligation model of HF lead to increases in MBG, whereas infusion of MBG into mice for 4 weeks lead to significant increases in myeloperoxidase, asymmetrical dimethylarginine, and cardiac fibrosis. In the setting of HF, elevated plasma levels of MBG are associated with right ventricular dysfunction and predict worse long-term clinical outcomes in multivariable models adjusting for established clinical and biochemical risk factors. Infusion of MBG seems to directly contribute to increased nitrative stress and cardiac fibrosis. © 2015 American Heart Association, Inc.

Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats.

PubMed

Chinnathambi, Vijayakumar; More, Amar S; Hankins, Gary D; Yallampalli, Chandra; Sathishkumar, Kunju

2014-07-01

Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K(+) depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. © 2014 by the Society for the Study of Reproduction, Inc.

Gestational Exposure to Elevated Testosterone Levels Induces Hypertension via Heightened Vascular Angiotensin II Type 1 Receptor Signaling in Rats1

PubMed Central

Chinnathambi, Vijayakumar; More, Amar S.; Hankins, Gary D.; Yallampalli, Chandra; Sathishkumar, Kunju

2014-01-01

ABSTRACT Pre-eclampsia is a life-threatening pregnancy disorder whose pathogenesis remains unclear. Plasma testosterone levels are elevated in pregnant women with pre-eclampsia and polycystic ovary syndrome, who often develop gestational hypertension. We tested the hypothesis that increased gestational testosterone levels induce hypertension via heightened angiotensin II signaling. Pregnant Sprague-Dawley rats were injected with vehicle or testosterone propionate from Gestational Day 15 to 19 to induce a 2-fold increase in plasma testosterone levels, similar to levels observed in clinical conditions like pre-eclampsia. A subset of rats in these two groups was given losartan, an angiotensin II type 1 receptor antagonist by gavage during the course of testosterone exposure. Blood pressure levels were assessed through a carotid arterial catheter and endothelium-independent vascular reactivity through wire myography. Angiotensin II levels in plasma and angiotensin II type 1 receptor expression in mesenteric arteries were also examined. Blood pressure levels were significantly higher on Gestational Day 20 in testosterone-treated dams than in controls. Treatment with losartan during the course of testosterone exposure significantly attenuated testosterone-induced hypertension. Plasma angiotensin II levels were not significantly different between control and testosterone-treated rats; however, elevated testosterone levels significantly increased angiotensin II type 1 receptor protein levels in the mesenteric arteries. In testosterone-treated rats, mesenteric artery contractile responses to angiotensin II were significantly greater, whereas contractile responses to K+ depolarization and phenylephrine were unaffected. The results demonstrate that elevated testosterone during gestation induces hypertension in pregnant rats via heightened angiotensin II type 1 receptor-mediated signaling, providing a molecular mechanism linking elevated maternal testosterone levels with gestational hypertension. PMID:24855104

Prevalence of abnormal serum alanine aminotransferase levels in type 2 diabetic patients in Iran.

PubMed

Meybodi, M A; Afkhami-Ardekani, M; Rashidi, M

2008-09-15

This study was performed to estimate prevalence of transaminase levels in type 2 diabetic patients and identify contributing risk factors. In this cross-sectional study 348 patients with type 2 diabetes, who attended the diabetic clinic of Yazd Diabetes Research Center, were studied from October 2004 to December 2005. Patients with history of viral hepatitis, alcohol abuse and use of drug such as Amiodarone, Bleomycin, methotrexate, tamoxifen and sodium valporate was excluded. To examine the relationships between ALT, AST in individuals with type II diabetes and relation to various metabolic parameters like triglyceride, cholesterol, age, duration of diabetes, gender and BMI. Of 348 patients that entered the study, mean age was 58.8 +/- 11.5. Elevated ALT and AST were found in 10.4 and 3.3% of type 2 diabetic patients, respectively. Although the prevalence of elevated ALT increased with increasing age, FBS and triglyceride levels in subjects, but it was not statistically significant. There was a significant association between elevated ALT and gender as well as diabetes duration. The prevalence of elevated of ALT in type 2 diabetic patients is 1.6 times higher than general population in Iran unrelated to age, BMI, glycemic control, triglyceride levels. Identification risk factors and mechanisms of these elevations are very important and require further evaluation.

Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system

PubMed Central

Tan, Bingyao; MacLellan, Benjamin; Mason, Erik

2018-01-01

Acute elevation of intraocular pressure (IOP) to ischemic and non-ischemic levels can cause temporary or permanent changes in the retinal morphology, function and blood flow/blood perfusion. Previously, such changes in the retina were assessed separately with different methods in clinical studies and animal models. In this study, we used a combined OCT+ ERG system in combination with Doppler OCT and OCT angiography (OCTA) imaging protocols, in order to evaluate simultaneously and correlate changes in the retinal morphology, the retinal functional response to visual stimulation, and the retinal blood flow/blood perfusion, associated with IOP elevation to ischemic and non-ischemic levels in rats. Results from this study suggest that the inner retina responds faster to IOP elevation to levels greater than 30 mmHg with significant reduction of the total retinal blood flow (TRBF), decrease of the capillaries’ perfusion and reduction of the ON bipolar cells contribution to the ERG traces. Furthermore, this study showed that ischemic levels of IOP elevation cause an additional significant decrease in the ERG photoreceptor response in the posterior retina. Thirty minutes after IOP normalization, retinal morphology, blood flow and blood perfusion recovered to baseline values, while retinal function did not recover completely. PMID:29509807

Neurological Nuance: Hodgkin lymphoma presenting with Guillain-BarrÉ syndrome.

PubMed

Anderson, Dustin; Beecher, Grayson; Steve, Trevor A; Jen, Ho; Camicioli, Richard; Zochodne, Douglas W

2017-04-01

Hodgkin lymphoma (HL) is a common lymphoid malignancy rarely associated with Guillain-Barré syndrome (GBS). In most cases, GBS does not precede HL. We describe a patient with acute inflammatory demyelinating polyneuropathy who fulfilled criteria for GBS that heralded undiagnosed HL. Cerebrospinal fluid (CSF) studies revealed albuminocytologic dissociation with significant protein elevation (250 mg/dl). The patient worsened during intravenous immunoglobulin (IVIg) therapy. Constitutional symptoms with elevated inflammatory markers prompted further investigation, and imaging revealed an anterior mediastinal mass confirmed on biopsy to be HL. Chemotherapy yielded early clinical improvement. GBS preceding HL is rare, and this case highlights the importance of considering HL in the setting of GBS. Marked elevations in CSF protein, ongoing deterioration despite administration of IVIg, and constitutional symptoms with elevated inflammatory markers may be clues to possible HL-induced GBS. Muscle Nerve 55: 601-604, 2017. © 2016 Wiley Periodicals, Inc.

Acute coronary syndrome vs nonspecific troponin elevation: clinical predictors and survival analysis.

PubMed

Alcalai, Ronny; Planer, David; Culhaoglu, Afsin; Osman, Aydin; Pollak, Arthur; Lotan, Chaim

2007-02-12

Although troponin is considered a specific marker for the diagnosis of acute coronary syndrome (ACS), recent studies have shown troponin elevation in a variety of nonischemic conditions. Our aim was to determine the predictors for the diagnosis of ACS in the presence of an abnormal troponin level. All patients with abnormal troponin T levels were analyzed. Demographic and clinical data were collected and death was recorded. The study group was divided into 2 subgroups: ACS vs nonthrombotic troponin elevation. A multivariate logistic regression analysis was performed to define variables that predict the diagnosis of ACS. The positive predictive value (PPV) for ACS diagnosis was calculated, and a survival analysis was performed. During the study period, 615 patients had elevated troponin T levels. Only 326 patients (53%) received a main diagnosis of ACS, while 254 (41%) had nonthrombotic troponin elevation; for 35 patients (6%), the diagnosis was not conclusive. Positive predictors for the diagnosis of ACS were age between 40 and 70 years, history of hypertension or ischemic heart disease, normal renal function, and a troponin T level higher than 1.0 ng/mL. The overall PPV of troponin T for ACS diagnosis was only 56% (95% CI, 52%-60%). The PPV of troponin T level higher than 1.0 ng/mL in the presence of normal renal function was 90% but was as low as 27% for values of 0.1 to 1.0 ng/mL for elderly patients with renal failure. In-hospital and long-term survival rates were significantly better (P<.001) for patients with ACS. Nonspecific troponin elevation is a common finding among hospitalized patients and correlates with worse prognosis. The diagnosis of myocardial infarction should still mostly be based on the clinical presentation. The predictors and algorithm suggested in this study might increase the diagnostic accuracy of ACS and direct the appropriate treatment.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma.

PubMed

Magee, Kelsey E; Kelsey, Christina E; Kurzinski, Katherine L; Ho, Jonhan; Mlakar, Logan R; Feghali-Bostwick, Carol A; Torok, Kathryn S

2013-01-01

The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.

Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma

PubMed Central

2013-01-01

Introduction The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. Methods The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). Results IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Conclusions Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS. PMID:24499523

Empirically-Derived MCMI-III Personality Profiles of Incarcerated Female Substance Abusers.

ERIC Educational Resources Information Center

Grabarek, Joanna K.; Bourke, Michael L.; Van Hasselt, Vincent B.

2002-01-01

In the present study, the Millon Clinical Multiaxial Inventory- III (MCMI-III) was administered to 210 female inmates in a jail-based substance abuse prevention program. Analyses resulted in the following three cluster profiles: "normal" (no significant elevations), narcissistic, and antisocial. Hypotheses regarding the personality…

Anger Expression and Blood Pressure in Adolescents

ERIC Educational Resources Information Center

Starner, Tamie M.; Peters, Rosalind M.

2004-01-01

The clinical significance of childhood hypertension is important as elevated pressures during childhood are found to follow a progressively increasing track into adulthood. Little work has been done to examine the relationship of emotions and emotional behavioral factors to the development of hypertension in children. Using the Roy Adaptation…

Exertional rhabdomyolysis: a clinical review with a focus on genetic influences.

PubMed

Landau, Mark E; Kenney, Kimbra; Deuster, Patricia; Campbell, William

2012-03-01

In this review, the clinical and laboratory features of exertional rhabdomyolysis (ER) are discussed in detail, emphasizing the full clinical spectrum from physiological elevations of serum creatine kinase after exertion to life-threatening rhabdomyolysis with acute kidney injury and associated systemic complications. Laboratory markers used to diagnose both ER and rhabdomyolysis are very sensitive, but not very specific, and imperfectly distinguish "subclinical" or asymptomatic from severe, life-threatening illness. However, genetic factors, both recognized and yet to be discovered, likely influence this diverse clinical spectrum of disease and response to exercise. Genetic mutations causative for McArdle disease, carnitine palmitoyl transferase deficiency 2, myoadenylate deaminase deficiency, and malignant hyperthermia have all been associated with ER. Polymorphic variations in the myosin light chain kinase, α-actin 3, creatine kinase-muscle isoform, angiotensin I-converting enzyme, heat shock protein, and interleukin-6 genes have also been associated with either ER or exercise-induced serum creatine kinase elevations typical of ER. The prognosis for ER is significantly better than that for other etiologies of rhabdomyolysis, but the risk of recurrence after an initial episode is unknown. Guidelines for management are provided.

Temporal information processing as a basis for auditory comprehension: clinical evidence from aphasic patients.

PubMed

Oron, Anna; Szymaszek, Aneta; Szelag, Elzbieta

2015-01-01

Temporal information processing (TIP) underlies many aspects of cognitive functions like language, motor control, learning, memory, attention, etc. Millisecond timing may be assessed by sequencing abilities, e.g. the perception of event order. It may be measured with auditory temporal-order-threshold (TOT), i.e. a minimum time gap separating two successive stimuli necessary for a subject to report their temporal order correctly, thus the relation 'before-after'. Neuropsychological evidence has indicated elevated TOT values (corresponding to deteriorated time perception) in different clinical groups, such as aphasic patients, dyslexic subjects or children with specific language impairment. To test relationships between elevated TOT and declined cognitive functions in brain-injured patients suffering from post-stroke aphasia. We tested 30 aphasic patients (13 male, 17 female), aged between 50 and 81 years. TIP comprised assessment of TOT. Auditory comprehension was assessed with the selected language tests, i.e. Token Test, Phoneme Discrimination Test (PDT) and Voice-Onset-Time Test (VOT), while two aspects of attentional resources (i.e. alertness and vigilance) were measured using the Test of Attentional Performance (TAP) battery. Significant correlations were indicated between elevated values of TOT and deteriorated performance on all applied language tests. Moreover, significant correlations were evidenced between elevated TOT and alertness. Finally, positive correlations were found between particular language tests, i.e. (1) Token Test and PDT; (2) Token Test and VOT Test; and (3) PDT and VOT Test, as well as between PDT and both attentional tasks. These results provide further clinical evidence supporting the thesis that TIP constitutes the core process incorporated in both language and attentional resources. The novel value of the present study is the indication for the first time in Slavic language users a clear coexistence of the 'timing-auditory comprehension-attention' relationships. © 2015 Royal College of Speech and Language Therapists.

Resting Heart Rate and Outcomes in Patients with Cardiovascular Disease: Where Do We Currently Stand?

PubMed Central

Menown, Ian BA; Davies, Simon; Gupta, Sandeep; Kalra, Paul R; Lang, Chim C; Morley, Chris; Padmanabhan, Sandosh

2013-01-01

Background Data from large epidemiological studies suggest that elevated heart rate is independently associated with cardiovascular and all-cause mortality in patients with hypertension and in those with established cardiovascular disease. Clinical trial findings also suggest that the favorable effects of beta-blockers and other heart rate–lowering agents in patients with acute myocardial infarction and congestive heart failure may be, at least in part, due to their heart rate–lowering effects. Contemporary clinical outcome prediction models such as the Global Registry of Acute Coronary Events (GRACE) score include admission heart rate as an independent risk factor. Aims This article critically reviews the key epidemiology concerning heart rate and cardiovascular risk, potential mechanisms through which an elevated resting heart rate may be disadvantageous and evaluates clinical trial outcomes associated with pharmacological reduction in resting heart rate. Conclusions Prospective randomised data from patients with significant coronary heart disease or heart failure suggest that intervention to reduce heart rate in those with a resting heart rate >70 bpm may reduce cardiovascular risk. Given the established observational data and randomised trial evidence, it now appears appropriate to include reduction of elevated resting heart rate by lifestyle +/− pharmacological therapy as part of a secondary prevention strategy in patients with cardiovascular disease. PMID:22954325

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

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

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p < .00001), correlating well with age and duration of employment. Thesemore » correlations were stronger for fat (p < .001) than for plasma (p < .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p < .00001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p < .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Clinical and metabolic abnormalities associated with occupational exposure to polychlorinated biphenyls (PCBs)

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

Chase, K.H.; Wong, O.; Thomas, D.

1982-02-01

A cross-sectional study of 120 male workers was conducted to determine the prevalence of increased polychlorinated biphenyl (PCB) absorption as well as the presence of potentially related clinical and metabolic abnormalities. Three exposure categories (''exposed'', ''nominally exposed'', ''nonexposed'') were defined. Complete work histories, clinical histories, physical examinations and laboratory tests, including plasma PCB determinations were obtained. In addition, fat PCB levels were determined in randomly selected subjects in each exposed group. Evidence of dermatotoxicity was observed and elevated PCB levels were noted more frequently in the exposed group (p less than .0001), correlating well with age and duration of employment.more » These correlations were stronger for fat (p less than .001) than for plasma (p less than .01) PCB levels. In the exposed group, significant correlations were found between plasma PCB and serum triglyceride (p less than .0001) and serum glutamic oxaloacetic transaminase (SGOT) levels (p less than .01). These correlations remained significant after controlling for either age or length of employment. No significant correlations were found between PCB levels and levels of cholesterol, high-density lipoprotein cholesterol or levels studied on liver function tests other than SGOT. Further analyses relating frequency of reported direct contact with PCB levels suggested a dermal route of exposure. An analysis by union affiliation demonstrated that those in crafts involving greater direct exposure had correspondingly higher elevations of PCB levels.« less

Reliability of a Bayesian network to predict an elevated aldosterone-to-renin ratio.

PubMed

Ducher, Michel; Mounier-Véhier, Claire; Lantelme, Pierre; Vaisse, Bernard; Baguet, Jean-Philippe; Fauvel, Jean-Pierre

2015-05-01

Resistant hypertension is common, mainly idiopathic, but sometimes related to primary aldosteronism. Thus, most hypertension specialists recommend screening for primary aldosteronism. To optimize the selection of patients whose aldosterone-to-renin ratio (ARR) is elevated from simple clinical and biological characteristics. Data from consecutive patients referred between 1 June 2008 and 30 May 2009 were collected retrospectively from five French 'European excellence hypertension centres' institutional registers. Patients were included if they had at least one of: onset of hypertension before age 40 years, resistant hypertension, history of hypokalaemia, efficient treatment by spironolactone, and potassium supplementation. An ARR>32 ng/L and aldosterone>160 ng/L in patients treated without agents altering the renin-angiotensin system was considered as elevated. Bayesian network and stepwise logistic regression were used to predict an elevated ARR. Of 334 patients, 89 were excluded (31 for incomplete data, 32 for taking agents that alter the renin-angiotensin system and 26 for other reasons). Among 245 included patients, 110 had an elevated ARR. Sensitivity reached 100% or 63.3% using Bayesian network or logistic regression, respectively, and specificity reached 89.6% or 67.2%, respectively. The area under the receiver-operating-characteristic curve obtained with the Bayesian network was significantly higher than that obtained by stepwise regression (0.93±0.02 vs. 0.70±0.03; P<0.001). In hypertension centres, Bayesian network efficiently detected patients with an elevated ARR. An external validation study is required before use in primary clinical settings. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

PubMed

Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

2013-12-01

To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

Lack of utility of measuring serum bilirubin concentration in distinguishing perforation status of pediatric appendicitis.

PubMed

Bonadio, William; Bruno, Santina; Attaway, David; Dharmar, Logesh; Tam, Derek; Homel, Peter

2017-06-01

Pediatric appendicitis is a common, potentially serious condition. Determining perforation status is crucial to planning effective management. Determine the efficacy of serum total bilirubin concentration [STBC] in distinguishing perforation status in children with appendicitis. Retrospective review of 257 cases of appendicitis who received abdominal CT scan and measurement of STBC. There were 109 with perforation vs 148 without perforation. Although elevated STBC was significantly more common in those with [36%] vs without perforation [22%], the mean difference in elevated values between groups [0.1mg/dL] was clinically insignificant. Higher degrees of hyperbilirubinemia [>2mg/dL] were rarely encountered [5%]. Predictive values for elevated STBC in distinguishing perforation outcome were imprecise [sensitivity 38.5%, specificity 78.4%, PPV 56.8%, NPV 63.4%]. ROC curve analysis of multiple clinical and other laboratory factors for predicting perforation status was unenhanced by adding the STBC variable. Specific analysis of those with perforated appendicitis and percutaneously-drained intra-abdominal abscess which was culture-positive for Escherichia coli showed an identical rate of STBC elevation compared to all with perforation. The routine measurement of STBC does not accurately distinguish perforation status in children with appendicitis, nor discern infecting organism in those with perforation and intra-abdominal abscess. Copyright © 2017 Elsevier Inc. All rights reserved.

The dynamics of attachment insecurity and paranoid thoughts: An experience sampling study.

PubMed

Sitko, Katarzyna; Varese, Filippo; Sellwood, William; Hammond, Amy; Bentall, Richard

2016-12-30

It has been proposed that insecure attachment can have adverse effects on the course of psychosis once symptoms have emerged. There is longitudinal evidence that increased insecure attachment is associated with increased severity of psychotic symptoms. The present study examined whether in the flow of daily life attachment insecurity fluctuates, whether elevated stress precedes the occurrence of attachment insecurity, and whether elevated attachment insecurity precedes the occurrence of paranoia. Twenty clinical participants with a psychosis-spectrum diagnosis and twenty controls were studied over six consecutive days using the experience sampling method (ESM). The findings revealed that fluctuations in attachment insecurity were significantly higher in the clinical group, that elevated stress predicted a subsequent increase in attachment insecurity, and that elevated attachment insecurity predicted a subsequent increase in paranoia; this effect was not observed in auditory hallucinations once co-occurring symptoms were controlled for. Finally, although previous ESM studies have shown that low self-esteem precedes the occurrence of paranoia, attachment insecurity continued to predict paranoia even when self-esteem was controlled for. The findings suggest that attachment security may be associated with a lower risk of paranoia, and that psychological interventions should address attachment beliefs and work towards establishing a sense of attachment security. Copyright © 2016. Published by Elsevier Ireland Ltd.

Blastocyst transfer does not improve cycle outcome as compared to D3 transfer in antagonist cycles with an elevated progesterone level on the day of hCG.

PubMed

Demirel, Cem; Aydoğdu, Serkan; Özdemir, Arzu İlknur; Keskin, Gülşah; Baştu, Ercan; Buyru, Faruk

2017-09-01

To evaluate the association between progesterone elevation on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates of gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with the transfer of embryos at different developmental stages (day-3 versus day-5 ETs). This is a retrospective analysis of fresh IVF/ICSI; 194 cycles out of 2676 conducted in a single center. A total of 2676 cycles were analyzed, of which 386 had no progesterone measurements available. Two hundred eighteen cycles had progesterone elevation (p>1.5 ng/mL) giving an overall incidence of 9.5%. Twenty-four cycles were excluded from further analysis. Of the remaining 194 cycles, 151 had day-3 transfers and 43 had blastocyst transfers. There was no statistically significant difference in pregnancy and clinical pregnancy rates per transfer between the D3-ET and D5-ET groups (46% vs. 49%, and 39% vs. 35%, respectively). The results of this study suggest that blastocyst transfer does not improve cycle outcomes compared with D3 transfer in GnRH antagonist cycles with an elevated progesterone level on the day of hCG.

Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

PubMed

Cathcart, Sahara J; Sofronescu, Alina G

2017-08-01

While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis.

PubMed

Murphy, Sabina A; Gibson, Charles Michael; Morrow, David A; Van de Werf, Frans; Menown, Ian B; Goodman, Shaun G; Mahaffey, Kenneth W; Cohen, Marc; McCabe, Carolyn H; Antman, Elliott M; Braunwald, Eugene

2007-09-01

To determine whether the low-molecular weight heparin enoxaparin remains favourable when compared with unfractionated heparin (UFH) among patients with acute coronary syndromes (ACS) when incorporating efficacy and safety of these adjunctive therapies using a net clinical endpoint. We performed a meta-analysis of randomized trials of enoxaparin vs. UFH in ST-elevation-MI (STEMI) or non-ST-elevation-ACS (NSTEACS) (n = 49,088 patients in 12 trials). The net clinical endpoint was defined as death, MI, or major bleeding by 30 days. Death or myocardial infarction (MI) was significantly reduced with enoxaparin when compared with UFH (9.8 vs. 11.4%, OR 0.84, P < 0.001). The net clinical endpoint occurred less frequently with enoxaparin than UFH (12.5 vs. 13.5%, OR 0.90, P = 0.051). Major bleeding was higher with enoxaparin (4.3 vs. 3.4%, OR 1.25, P = 0.019). Among STEMI trials, the net clinical endpoint was significantly lower with enoxaparin (OR 0.84, P = 0.015), but there was no difference in NSTEACS trials (OR 0.97). When compared with UFH, enoxaparin was associated with superior efficacy as adjunctive antithrombin therapy among >49 000 patients across the ACS spectrum. Although bleeding was increased with enoxaparin, this increase was offset by a reduction in death or MI. The net clinical benefit in favour of enoxaparin was evident among the STEMI population and was neutral among the NSTEACS population.

Dermatoglyphic asymmetries and fronto-striatal dysfunction in young-adults reporting non-clinical psychosis

PubMed Central

Mittal, Vijay A.; Dean, Derek J.; Pelletier, Andrea

2012-01-01

Objective Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is know about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. Method A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). Results Participants reporting DAPS (n=16; 7.2%) and no-DAPS (n=205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. Conclusion The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder. PMID:22519833

Evaluation of MicroRNA375 as a Novel Biomarker for Graft Damage in Clinical Islet Transplantation.

PubMed

Kanak, Mazhar A; Takita, Morihito; Shahbazov, Rauf; Lawrence, Michael C; Chung, Wen Yuan; Dennison, Ashley R; Levy, Marlon F; Naziruddin, Bashoo

2015-08-01

Early and sensitive detection of islet graft damage is essential for improving posttransplant outcomes. MicroRNA 375 (miR375) has been reported as a biomarker of pancreatic β-cell death in small animal models. The miR375 levels were measured in purified human islets, sera from patients with autologous and allogeneic islet transplantation as well as total pancreatectomy alone (nontransplanted group). The miR375 levels were also determined in a miniaturized in vitro tube model comprising human islets and autologous blood. The miR375 expression level in islets was dose-dependent (P < 0.001) and significantly elevated after islet damage in plasma in the in vitro model (P = 0.003). Clinical analysis revealed that circulating miR375 levels in both autologous and allogeneic islet recipients were significantly elevated for 7 days after islet infusion, compared with the nontransplanted group (P = 0.005 and <0.001, respectively). Furthermore, miR375 detected the difference in islet graft damage among 3 different anti-inflammatory protocols for clinical autologous transplantation (P < 0.01). Circulating miR375 can be a reliable biomarker to detect graft damage in clinical islet transplantation because serum C-peptide and proinsulin levels are difficult to interpret due to the influence of multiple factors, such as β-cell stress and physiological response.

Electocardiographic findings in adult Nigerians with sickle cell anaemia.

PubMed

Oguanobi, N I; Onwubere, B J C; Ike, S O; Anisiuba, B C; Ejim, E C; Ibegbulam, O G

2010-09-01

Cardiovascular system abnormalities are common causes of morbidity and mortality in sickle cell anaemia. The study aims at determining the pattern of electrocardiographic changes in adult Nigerian sickle cell anaemia patients. A descriptive cross sectional study was done on sixty sickle cell anaemia patients seen at the adult sickle cell clinic of University of Nigeria Teaching Hospital (UNTH) Enugu, and sixty age and sex matched normal controls. All the subjects had clinical evaluation as well as electrocardiographic examination. The mean heart rate, P-wave duration, P-wave dispersion, PR interval, QRS duration, QRS dispersion, QTc interval and QTc dispersion were significantly higher in the patients than in the control group. Electrocardiographic abnormalities identified by this study were: left ventricular hypertrophy (75%; 1.7%), left atrial enlargement (40%; 0%), biventricular hypertrophy (11%; 0), ST-segment elevation (10%; 0%) and increased P-wave and QTc dispersions. ST segment elevation was found more in patients with moderate and severe anaemia (P= 0.02, Spearman correlation r= 0.342; P= 0.007), Sickle cell anaemia is associated with significant electrocardiographic abnormalities. Further prospective studies are recommended to evaluate the prognostic significance of the electrocardiographic intervals dispersion on the long term disease outcome in sickle cell anaemia.

Characterization of women with elevated antimüllerian hormone levels (AMH): correlation of AMH with polycystic ovarian syndrome phenotypes and assisted reproductive technology outcomes.

PubMed

Tal, Reshef; Seifer, David B; Khanimov, Moisey; Malter, Henry E; Grazi, Richard V; Leader, Ben

2014-07-01

Serum Antimüllerian hormone (AMH) levels are elevated in polycystic ovarian syndrome and have been shown to be useful in its diagnosis. However, the clinical significance of extremely high AMH levels is understudied. We aimed to characterize a population of women with elevated AMH (>5 ng/mL). This was a retrospective cohort study of 134 women presenting to our fertility clinic for infertility evaluation and treatment who were found to have random serum AMH over 5 ng/mL. Women were divided into 3 groups according to AMH: 5-10 ng/mL, >10-14 ng/mL, and >14 ng/mL. Endocrine characteristics, polycystic ovarian syndrome (PCOS) phenotypes, fertilization rate, implantation rate, clinical pregnancy, and multiple pregnancy rates were compared between groups. AMH ranged between 5 to 48 ng/mL. Greater than 97% of women with ultrahigh AMH (>10 ng/mL) had PCOS. In addition, women with AMH >10 ng/mL had greater prevalence of polycystic ovarian morphology and oligoamenorrhea than women with AMH 5-10 ng/mL. Moreover, serum AMH correlated positively with luteinizing hormone, total testosterone, and dehydroepiandrosterone sulfate. Furthermore, AMH showed strong predictive ability for the presence of amenorrhea (area under the curve, 0.87; 95% confidence interval, 0.80-0.92; P < .0001). Despite similar age and mean number of transferred embryos, women with AMH >10 ng/mL showed higher rates of ovarian hyperstimulation syndrome and clinical pregnancy rates compared with women with AMH 5-10 ng/mL. These data characterize a population of women with elevated AMH levels, demonstrating that the vast majority of women with AMH >10 ng/mL have PCOS. Increased AMH levels correlated with PCOS severity and are associated with greater ovarian stimulation and higher clinical pregnancy rates following assisted reproductive technology. Copyright © 2014 Mosby, Inc. All rights reserved.

Minnesota Multiphasic Personality Inventory profile in patients with restless legs syndrome.

PubMed

Turkel, Yakup; Oguzturk, Omer; Dag, Ersel; Buturak, S Visal; Ekici, Mehmet S

2015-06-01

Restless legs syndrome (RLS) is associated with psychiatric disorders. We aim to investigate the personality traits of RLS patients using the Minnesota Multiphasic Personality Inventory. Twenty adult patients with RLS (14 females and 6 males) and 20 healthy controls (14 females and 6 males) who were referred to university neurology were enrolled in the present study. Diagnosis of RLS was established using International Restless Legs Syndrome Study Group. Psychometric evaluation was made with the Turkish version of the Minnesota Multiphasic Personality Inventory. RLS patients have significantly higher absolute and clinical elevation scores on hypochondriasis and hysteria, and clinical elevation scores on psychasthenia, compared with the controls. Absolute scores on depression were higher at the border in RLS patients compared with the controls. RLS patients have hypochondriac, hysterical, depressive, and anxious personality traits. © 2014 Wiley Publishing Asia Pty Ltd.

Globalization, Binational Communities, and Imported Food Risks: Results of an Outbreak Investigation of Lead Poisoning in Monterey County, California

PubMed Central

Handley, Margaret A.; Hall, Celeste; Sanford, Eric; Diaz, Evie; Gonzalez-Mendez, Enrique; Drace, Kaitie; Wilson, Robert; Villalobos, Mario; Croughan, Mary

2007-01-01

Objectives. Although the burden of lead poisoning has decreased across developed countries, it remains the most prevalent environmental poison worldwide. Our objective was to investigate the sources of an outbreak of lead poisoning in Monterey County, California. Methods. An investigation in 3 county health department clinics in Monterey County, California, was conducted between 2001 and 2003 to identify risk factors for elevated blood lead levels (≥ 10 μg/dL) among children and pregnant women. Results. The prevalence of elevated blood lead levels was significantly higher in 1 of the 3 clinics (6% among screened children and 13% among prenatal patients). Risk factors included eating imported foods (relative risk [RR]=3.4; 95% confidence interval [CI]=1.2, 9.5) and having originated from the Zimatlan area of Oaxaca, Mexico, compared with other areas of Oaxaca (RR=4.0; 95% CI=1.7, 9.5). Home-prepared dried grasshoppers (chapulines) sent from Oaxaca were found to contain significant amounts of lead. Conclusions. Consumption of foods imported from Oaxaca was identified as a risk factor for elevated blood lead levels in Monterey County, California. Lead-contaminated imported chapulines were identified as 1 source of lead poisoning, although other sources may also contribute to the observed findings. Food transport between binational communities presents a unique risk for the importation PMID:17395841

More inclusive bipolar mixed depression definition by permitting overlapping and non-overlapping mood elevation symptoms.

PubMed

Kim, H; Kim, W; Citrome, L; Akiskal, H S; Goffin, K C; Miller, S; Holtzman, J N; Hooshmand, F; Wang, P W; Hill, S J; Ketter, T A

2016-09-01

The objective of this study was to assess the strengths and limitations of a mixed bipolar depression definition made more inclusive than that of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) by counting not only 'non-overlapping' mood elevation symptoms (NOMES) as in DSM-5, but also 'overlapping' mood elevation symptoms (OMES, psychomotor agitation, distractibility, and irritability). Among bipolar disorder (BD) out-patients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, we assessed prevalence, demographics, and clinical correlates of mixed vs. pure depression, using more inclusive (≥3 NOMES/OMES) and less inclusive DSM-5 (≥3 NOMES) definitions. Among 153 depressed BD, counting not only NOMES but also OMES yielded a three-fold higher mixed depression rate (22.9% vs. 7.2%) and important statistically significant clinical correlates for mixed compared to pure depression (more lifetime anxiety disorder comorbidity, more current irritability, and less current antidepressant use), which were not significant using the DSM-5 threshold. To conclude, further studies with larger numbers of patients with DSM-5 bipolar mixed depression assessing strengths and limitations of more inclusive mixed depression definitions are warranted, including efforts to ascertain whether or not OMES should count toward mixed depression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Globalization, binational communities, and imported food risks: results of an outbreak investigation of lead poisoning in Monterey County, California.

PubMed

Handley, Margaret A; Hall, Celeste; Sanford, Eric; Diaz, Evie; Gonzalez-Mendez, Enrique; Drace, Kaitie; Wilson, Robert; Villalobos, Mario; Croughan, Mary

2007-05-01

Although the burden of lead poisoning has decreased across developed countries, it remains the most prevalent environmental poison worldwide. Our objective was to investigate the sources of an outbreak of lead poisoning in Monterey County, California. An investigation in 3 county health department clinics in Monterey County, California, was conducted between 2001 and 2003 to identify risk factors for elevated blood lead levels (> or = 10 microg/dL) among children and pregnant women. The prevalence of elevated blood lead levels was significantly higher in 1 of the 3 clinics (6% among screened children and 13% among prenatal patients). Risk factors included eating imported foods (relative risk [RR]=3.4; 95% confidence interval [CI]=1.2, 9.5) and having originated from the Zimatlan area of Oaxaca, Mexico, compared with other areas of Oaxaca (RR=4.0; 95% CI=1.7, 9.5). Home-prepared dried grasshoppers (chapulines) sent from Oaxaca were found to contain significant amounts of lead. Consumption of foods imported from Oaxaca was identified as a risk factor for elevated blood lead levels in Monterey County, California. Lead-contaminated imported chapulines were identified as 1 source of lead poisoning, although other sources may also contribute to the observed findings. Food transport between binational communities presents a unique risk for the importation of environmental hazards [corrected

Lidocaine Concentration in Mandibular Bone After Subperiosteal Infiltration Anesthesia Decreases With Elevation of Periosteal Flap and Irrigation With Saline

PubMed Central

Ogawa, Sachie; Watanabe, Masahiro; Kawaai, Hiroyoshi; Tada, Hitoshi; Yamazaki, Shinya

2014-01-01

It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation. PMID:24932978

Elevated troponin predicts long-term adverse cardiovascular outcomes in hypertensive crisis: a retrospective study.

PubMed

Pattanshetty, Deepak J; Bhat, Pradeep K; Aneja, Ashish; Pillai, Dilip P

2012-12-01

Hypertensive crisis is associated with poor clinical outcomes. Elevated troponin, frequently observed in hypertensive crisis, may be attributed to myocardial supply-demand mismatch or obstructive coronary artery disease (CAD). However, in patients presenting with hypertensive crisis and an elevated troponin, the prevalence of CAD and the long-term adverse cardiovascular outcomes are unknown. We sought to assess the impact of elevated troponin on cardiovascular outcomes and evaluate the role of troponin as a predictor of obstructive CAD in patients with hypertensive crisis. Patients who presented with hypertensive crisis (n = 236) were screened retrospectively. Baseline and follow-up data including the event rates were obtained using electronic patient records. Those without an assay for cardiac Troponin I (cTnI) (n = 65) were excluded. Of the remaining 171 patients, those with elevated cTnI (cTnI ≥ 0.12 ng/ml) (n = 56) were compared with those with normal cTnI (cTnI < 0.12 ng/ml) (n = 115) at 2 years for the occurrence of major adverse cardiac or cerebrovascular events (MACCE) (composite of myocardial infarction, unstable angina, hypertensive crisis, pulmonary edema, stroke or transient ischemic attack). At 2 years, MACCE occurred in 40 (71.4%) patients with elevated cTnI compared with 44 (38.3%) patients with normal cTnI [hazard ratio: 2.77; 95% confidence interval (CI): 1.79-4.27; P < 0.001]. Also, patients with elevated cTnI were significantly more likely to have underlying obstructive CAD (odds ratio: 8.97; 95% CI: 1.4-55.9; P < 0.01). In patients with hypertensive crisis, elevated cTnI confers a significantly greater risk of long-term MACCE, and is a strong predictor of obstructive CAD.

Clinical scoring system to detect malignant and premalignant vulval lesions.

PubMed

Tyagi, Shakun; Tripathi, Reva; Batra, Swaraj

2014-02-01

To construct a simple clinical scoring system for evaluation of vulval lesions that will be helpful in clinically detecting the premalignant or malignant lesions of vulva. Seventy women referred for vulval examination at a tertiary care centre in north India were examined over a period of 2 years. Biopsy was performed in 66 consenting women. Association of high-grade vulval lesion with various clinical parameters such as age, duration of symptoms, presenting complaints, the presence of depigmentation, ulceration, hyperkeratosis, acetowhite changes on acetic acid application, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and toluidine blue stain retention was studied. The significantly associated factors were assigned a value of 0 or 1 depending on whether they were present or absent. Score was then formulated for detection of high-grade lesion defined as moderate to severe dysplasia and early malignancy. Histopathology. Out of the various parameters that were studied, duration of symptoms more than 6 months, hyperkeratosis, asymmetrical distribution of the lesion, surface elevation on naked eye or colposcopy, induration on palpation and positive toluidine blue stain retention of the lesion were found to be significantly associated with a malignant or premalignant lesion. It was found that a score of equal to or greater than 3/6 was significantly associated with a malignant or premalignant lesion. This simple scoring system has a potential to identify the high-grade lesions and can be used to identify the vulval lesion requiring a biopsy or further referral to higher centre.

Elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in colorectal cancer

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

Liu, Chenchen; Yue, Ben; Yuan, Chenwei

The THO complex 1 (Thoc1) is a nuclear matrix protein playing vital roles in transcription elongation and mRNA export. Recently, aberrant expression of Thoc1 has been reported in an increasing array of tumor types. However, the clinical significance of Thoc1 expression in colorectal cancer (CRC) is still unknown. The present study aimed to characterize the expression of Thoc1 in human CRC and evaluate its clinical significance. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses showed that the mRNA and protein expression of Thoc1 in CRC specimens was significantly higher than that in adjacent normal colon mucosae. Immunohistochemistry (IHC)more » was conducted to characterize the expression pattern of Thoc1 in 185 archived paraffin-embedded CRC specimens. Statistical analyses revealed that high levels of Thoc1 expression were associated with the clinical stages and tumor differentiation. CRC patients with high levels of Thoc1 expression had poorer overall-survival and disease-free survival, whereas those with lower levels of Thoc1 expression survived longer. Furthermore, multivariate Cox regression analyses demonstrated that Thoc1 expression remained an independent prognostic factor for increased disease recurrence and decreased survival. Our results suggest for the first time that Thoc1 is involved in the development and progression of CRC, and elevated expression of Thoc1 is associated with aggressive phenotype and poor prognosis in CRC. These findings may prove to be clinically useful for developing a new therapeutic target of CRC treatment.« less

Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study.

PubMed

Felker, G Michael; Fiuzat, Mona; Shaw, Linda K; Clare, Robert; Whellan, David J; Bettari, Luca; Shirolkar, Shailesh C; Donahue, Mark; Kitzman, Dalane W; Zannad, Faiez; Piña, Ileana L; O'Connor, Christopher M

2012-01-01

Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. HF-ACTION was a randomized, controlled trial of exercise training in patients with chronic heart failure caused by left ventricular systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher New York Heart Association class, lower systolic blood pressure, higher creatinine, higher amino-terminal proB-type natriuretic peptide (NTproBNP), and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio, 1.14 per 3-ng/mL increase in galectin-3; P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors, and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

Galectin-3 in Ambulatory Patients with Heart Failure: Results from the HF-ACTION Study

PubMed Central

Felker, G. Michael; Fiuzat, Mona; Shaw, Linda K.; Clare, Robert; Whellan, David J.; Bettari, Luca; Shirolkar, Shailesh C.; Donahue, Mark; Kitzman, Dalane W.; Zannad, Faiez; Piña, Ileana L.; O’Connor, Christopher M.

2011-01-01

Background Galectin-3 is a soluble ß-galactoside-binding lectin released by activated cardiac macrophages. Elevated levels of galectin-3 have been found to be associated with adverse outcomes in patients with heart failure. We evaluated the association between galectin-3 and long-term clinical outcomes in ambulatory heart failure patients enrolled in the HF-ACTION study. Methods and Results HF-ACTION was a randomized controlled trial of exercise training in patients with chronic heart failure due to left ventricular (LV) systolic dysfunction. Galectin-3 was assessed at baseline in a cohort of 895 HF-ACTION subjects with stored plasma samples available. The association between galectin-3 and clinical outcomes was assessed using a series of Cox proportional hazards models. Higher galectin-3 levels were associated with other measures of heart failure severity, including higher NYHA class, lower systolic blood pressure, higher creatinine, higher NTproBNP, and lower maximal oxygen consumption. In unadjusted analysis, there was a significant association between elevated galectin-3 levels and hospitalization-free survival (unadjusted hazard ratio = 1.14 per 3 ng/mL increase in galectin-3, P<0.0001). In multivariable modeling, the prognostic impact of galectin-3 was significantly attenuated by the inclusion of other known predictors and galectin-3 was no longer a significant predictor after the inclusion of NTproBNP. Conclusions Galectin-3 is elevated in ambulatory heart failure patients and is associated with poor functional capacity and other known measures of heart failure severity. In univariate analysis, galectin-3 was significantly predictive of long-term outcomes, but this association did not persist after adjustment for other predictors, especially NTproBNP. PMID:22016505

Metformin effects on biochemical recurrence and metabolic signaling in the prostate.

PubMed

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-11-01

Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. © 2015 Wiley Periodicals, Inc.

Metformin Effects on Biochemical Recurrence and Metabolic Signaling in the Prostate

PubMed Central

Winters, Brian; Plymate, Stephen; Zeliadt, Steven B; Holt, Sarah; Zhang, Xiaotun; Hu, Elaine; Lin, Daniel W.; Morrissey, Colm; Wooldridge, Bryan; Gore, John L; Porter, Michael P; Wright, Jonathan L

2015-01-01

Background Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). Methods Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. Results 1,734 men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). ‘Ever’ metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR=0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (p-values all < 0.006). When stratified by metformin use, IGF-1R remained significantly elevated (p=0.01) in men with PCa detected whereas p-AMPK (p=0.05) was elevated only in those without PCa. Conclusion Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use. PMID:26201966

Circulating microparticle levels are reduced in patients with ARDS.

PubMed

Shaver, Ciara M; Woods, Justin; Clune, Jennifer K; Grove, Brandon S; Wickersham, Nancy E; McNeil, J Brennan; Shemancik, Gregory; Ware, Lorraine B; Bastarache, Julie A

2017-05-25

It is unclear how to identify which patients at risk for acute respiratory distress syndrome (ARDS) will develop this condition during critical illness. Elevated microparticle (MP) concentrations in the airspace during ARDS are associated with activation of coagulation and in vitro studies have demonstrated that MPs contribute to acute lung injury, but the significance of MPs in the circulation during ARDS has not been well studied. The goal of the present study was to test the hypothesis that elevated levels of circulating MPs could prospectively identify critically ill patients who will develop ARDS and that elevated circulating MPs are associated with poor clinical outcomes. A total of 280 patients with platelet-poor plasma samples from the prospective Validating Acute Lung Injury biomarkers for Diagnosis (VALID) cohort study were selected for this analysis. Demographics and clinical data were obtained by chart review. MP concentrations in plasma were measured at study enrollment on intensive care unit (ICU) day 2 and on ICU day 4 by MP capture assay. Activation of coagulation was measured by plasma recalcification (clot) times. ARDS developed in 90 of 280 patients (32%) in the study. Elevated plasma MP concentrations were associated with reduced risk of developing ARDS (odds ratio (OR) 0.70 per 10 μM increase in MP concentration, 95% CI 0.50-0.98, p = 0.042), but had no significant effect on hospital mortality. MP concentration was greatest in patients with sepsis, pneumonia, or aspiration as compared with those with trauma or receiving multiple blood transfusions. MP levels did not significantly change over time. The inverse association of MP levels with ARDS development was most striking in patients with sepsis. After controlling for age, presence of sepsis, and severity of illness, higher MP concentrations were independently associated with a reduced risk of developing ARDS (OR 0.69, 95% CI 0.49-0.98, p = 0.038). MP concentration was associated with reduced plasma recalcification time. Elevated levels of circulating MPs are independently associated with a reduced risk of ARDS in critically ill patients. Whether this is due to MP effects on systemic coagulation warrants further investigation.

Behavioral approach and avoidance in schizophrenia: an evaluation of motivational profiles.

PubMed

Felice Reddy, L; Green, Michael F; Rizzo, Shemra; Sugar, Catherine A; Blanchard, Jack J; Gur, Raquel E; Kring, Ann M; Horan, William P

2014-10-01

Schizophrenia is associated with motivational deficits that interfere with a wide range of goal directed activities. Despite their clinical importance, our current understanding of these motivational impairments is limited. Furthermore, different types of motivational problems are commonly seen among individuals within the broad diagnosis of schizophrenia. The goal of the current study was to examine whether clinically meaningful subgroups could be identified based on approach and avoidance motivational tendencies. We measured these tendencies in 151 individuals with schizophrenia. Although prior studies demonstrate elevated BIS sensitivity in schizophrenia at the overall group level, none have explored various combinations of BIS/BAS sensitivities within this disorder. Cluster analyses yielded five subgroups with different combinations of low, moderate, or high BIS and BAS. The subgroups had interpretable differences in clinically rated negative symptoms and self-reported anhedonia/socio-emotional attitudes, which were not detectable with the more commonly used linear BIS/BAS scores. Two of the subgroups had significantly elevated negative symptoms but different approach/avoidance profiles: one was characterized by markedly low BIS, low BAS and an overall lack of social approach motivation; the other had markedly high BIS but moderate BAS and elevated social avoidance motivation. The two subgroups with relatively good clinical functioning showed patterns of BAS greater than BIS. Our findings indicate that there are distinct motivational pathways that can lead to asociality in schizophrenia and highlight the value of considering profiles based on combined patterns of BIS and BAS in schizophrenia. Published by Elsevier B.V.

Interpretation and use of natriuretic peptides in non-congestive heart failure settings.

PubMed

Tsai, Shih-Hung; Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-03-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.

Interpretation and Use of Natriuretic Peptides in Non-Congestive Heart Failure Settings

PubMed Central

Lin, Yen-Yue; Chu, Shi-Jye; Hsu, Ching-Wang; Cheng, Shu-Meng

2010-01-01

Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article. PMID:20191004

The Kinetics and Inhibition of Gamma-Glutamyl Transpeptidase: A Biochemistry Laboratory Experiment.

ERIC Educational Resources Information Center

Splittgerber, A. G.; Sohl, Julie

1988-01-01

Discusses an enzyme kinetics laboratory experiment involving a two substrate system for undergraduate biochemistry. Uses the enzyme gamma-glutamyl transpeptidase as this enzyme in blood serum is of clinical significance. Notes elevated levels are seen in liver disease, alcoholism, and epilepsy. Uses a spectrophotometer for the analysis. (MVL)

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.

Pharmacological and clinical profile of bivalirudin in the treatment of patients with acute coronary syndrome.

PubMed

White, Harvey D

2009-05-01

Bivalirudin is a direct thrombin inhibitor with several pharmacological advantages over heparin. It has been studied extensively in non-ST elevation acute 60 coronary syndromes (NSTE-ACS) and in percutaneous coronary intervention. Bivalirudin has also recently been investigated in patients with ST-elevation myocardial infarction (STEMI) treated with primary angioplasty and stenting. More than 27,000 patients were randomized in these trials. To provide an overview of the pharmacological properties of bivalirudin and its efficacy and safety profile in patients across the spectrum of acute coronary syndromes (ACS). All published, peer-reviewed clinical trials were reviewed and as relevant were included. Bivalirudin with provisional IIb/IIIa antagonists provides consistent results across the full spectrum of ACS, with similar or non-inferior protection from ischemic events and significantly reduces bleeding complications compared with heparin and IIb/IIIa antagonists. In STEMI, mortality at 30 days and 1 year is significantly reduced. The unique pharmacokinetic profile of bivalirudin allows for simultaneous reductions in both ischemic and hemorrhagic events and makes it an appropriate alternative to heparin.

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

PubMed

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-08-01

α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

Effect of particle size on calcium release and elevation of pH of endodontic cements.

PubMed

Saghiri, Mohammad Ali; Asatourian, Armen; Orangi, Jafar; Lotfi, Mehrdad; Soukup, Jason W; Garcia-Godoy, Franklin; Sheibani, Nader

2015-06-01

Elevation of pH and calcium ion release are of great importance in antibacterial activity and the promotion of dental soft and hard tissue healing process. In this study, we evaluated the effect of particle size on the elevation of pH and the calcium ion release from calcium silicate-based dental cements. Twelve plastic tubes were divided into three groups, filled with white mineral trioxide aggregate (WMTA), WMTA plus 1% methylcellulose, and nano-modified WMTA (nano-WMTA), and placed inside flasks containing 10 ml of distilled water. The pH values were measured using a pH sensor 3, 24, 72, and 168 h after setting of the cements. The calcium ion release was measured using an atomic absorption spectrophotometer with same sample preparation method. Data were subjected to two-way analysis of variance (anova) followed by post hoc Tukey tests with significance level of P < 0.05. Nano-WMTA showed significant pH elevation only after 24 h (P < 0.05) compared with WMTA, and after 3, 24, and 72 h compared with WMTA plus 1% methylcellulose (P < 0.05). Nano-WMTA showed significantly higher calcium ion release values compared to the other two groups (P < 0.05). Nano-modification of WMTA remarkably increased the calcium ion release at all time intervals postsetting, which can significantly influence the osteogenic properties of human dental pulp cells and as a consequence enhance mineralized matrix nodule formation to achieve desirable clinical outcomes. However, the increase in pH values mainly occurred during the short time postsetting. Addition of 1% methylcellulose imposed a delay in elevation of pH and calcium ion release by WMTA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Postoperative elevation in creatine kinase and its impact on renal function in patients undergoing complex partial nephrectomy.

PubMed

Sidana, Abhinav; Walton-Diaz, Annerleim; Truong, Hong; Siddiqui, M Minhaj; Miao, Ning; Shih, Johanna; Mannes, Andrew; Bratslavsky, Gennady; Linehan, W Marston; Metwalli, Adam R

2016-07-01

To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN). Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as >2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR. From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation >2000 U/L. Factors associated with postoperative elevation of CK > 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p < 0.001). Although CK > 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p < 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months. In our cohort, a significant proportion of patients developed CK elevations >2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.

Serum CA125 predicts extrauterine disease and survival in uterine carcinosarcoma

PubMed Central

Huang, Gloria S.; Chiu, Lydia G.; Gebb, Juliana S.; Gunter, Marc J.; Sukumvanich, Paniti; Goldberg, Gary L.; Einstein, Mark H.

2009-01-01

Objective The purpose of this study was to determine the clinical utility of CA125 measurement in patients with uterine carcinosarcoma (CS). Methods Ninety-five consecutive patients treated for CS at a single institution were identified. All 54 patients who underwent preoperative CA125 measurement were included in the study. Data were abstracted from the medical records. Tests of association between preoperative CA125 and previously identified clinicopathologic prognostic factors were performed using Fisher’s exact test and Pearson chi-square test. To evaluate relationship of CA125 elevation and survival, a Cox proportional hazard model was used for multivariate analysis, incorporating all of prognostic factors identified by univariate analysis. Results Preoperative CA125 was significantly associated with the presence of extrauterine disease (P<0.001), deep myometrial invasion (P<0.001), and serous histology of the epithelial component (P=0.005). Using univariate survival analysis, stage (HR=1.808, P=0.004), postoperative CA125 level (HR=9.855, P<0.001), and estrogen receptor positivity (HR=0.314, P=0.029) were significantly associated with survival. In the multivariate model, only postoperative CA125 level remained significantly associated with poor survival (HR=5.725, P=0.009). Conclusion Preoperative CA125 elevation is a marker of extrauterine disease and deep myometrial invasion in patients with uterine CS. Postoperative CA125 elevation is an independent prognostic factor for poor survival. These findings indicate that CA125 may be a clinically useful serum marker in the management of patients with CS. PMID:17935762

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

PubMed

Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-06-03

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

Elevated Liver Enzymes

MedlinePlus

Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

Clinical Significance of Postvoid Residual Volume in Older Ambulatory Women

PubMed Central

Huang, Alison J.; Brown, Jeanette S.; Boyko, Edward J.; Moore, Elya E.; Scholes, Delia; Walter, Louise C.; Lin, Feng; Vittinghoff, Eric; Fihn, Stephan D.

2013-01-01

Objectives To examine the prevalence, natural history, and clinical significance of elevations in postvoid residual (PVR) volume in ambulatory older women Design Prospective cohort study Setting Group health plan in Washington state Participants 987 ambulatory women aged 55 to 75 years Measurements PVR was measured by bladder ultrasonography at baseline, 1 year, and 2 years. Participants completed questionnaires about urinary symptoms and provided urine samples for microbiologic evaluation. Results Of the 987 participants, 79% had a PVR <50 mL, 10% had a PVR of 50–99 mL, 6% had a PVR of 100–199 mL, and 5% had a PVR ≥200 mL at baseline. Of women with a PVR <50, 66% reported at least one urinary symptom at baseline. Of women with a PVR ≥200 mL, 27% reported no significant symptoms at baseline. In adjusted analyses using data from all study visits, women with a PVR ≥100 mL were more likely to report urinating >8 times during the day (OR=1.42, CI=1.07–1.87), and women with a PVR ≥200 mL were more likely to report weekly urgency incontinence (OR=1.50, CI=1.03–2.18), versus those with a PVR <50 mL. Elevated PVR was not associated with increased risk of stress incontinence, nocturnal frequency, or urinary tract infection in adjusted analyses. Forty-six percent of those with a PVR ≥200 mL and 63% of those with a PVR of 100–199 mL at baseline had a PVR <50 mL at 2 years. Conclusion Over 10% of ambulatory older women may have a PVR ≥100 mL associated with increased risk of some urinary symptoms, but many with elevated PVR are asymptomatic, and elevations in PVR frequently resolve within 2 years. Symptom-guided management of urinary symptoms may be more appropriate than PVR-guided management in this population. PMID:21806559

Clues for early detection of autoimmune Addison's disease - myths and realities.

PubMed

Saevik, Å B; Åkerman, A-K; Grønning, K; Nermoen, I; Valland, S F; Finnes, T E; Isaksson, M; Dahlqvist, P; Bergthorsdottir, R; Ekwall, O; Skov, J; Nedrebø, B G; Hulting, A-L; Wahlberg, J; Svartberg, J; Höybye, C; Bleskestad, I H; Jørgensen, A P; Kämpe, O; Øksnes, M; Bensing, S; Husebye, E S

2018-02-01

Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L -1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L -1 [2-442]) than in those without (81 nmol L -1 [1-668], P < 0.001). The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Neisseria gonorrhoeae antimicrobial resistance among men who have sex with men and men who have sex exclusively with women: the Gonococcal Isolate Surveillance Project, 2005-2010.

PubMed

Kirkcaldy, Robert D; Zaidi, Akbar; Hook, Edward W; Holmes, King K; Holmes, King H; Soge, Olusegun; del Rio, Carlos; Hall, Geraldine; Papp, John; Bolan, Gail; Weinstock, Hillard S

2013-03-05

Gonorrhea treatment has been complicated by antimicrobial resistance in Neisseria gonorrhoeae. Gonococcal fluoroquinolone resistance emerged more rapidly among men who have sex with men (MSM) than men who have sex exclusively with women (MSW). To determine whether N. gonorrhoeae urethral isolates from MSM were more likely than isolates from MSW to exhibit resistance to or elevated minimum inhibitory concentrations (MICs) of antimicrobials used to treat gonorrhea. 6 years of surveillance data from the Gonococcal Isolate Surveillance Project. Publicly funded sexually transmitted disease clinics in 30 U.S. cities. Men with a total of 34 600 episodes of symptomatic urethral gonorrhea. Percentage of isolates exhibiting resistance or elevated MICs and adjusted odds ratios for resistance or elevated MICs among isolates from MSM compared with isolates from MSW. In all U.S. regions except the West, isolates from MSM were significantly more likely to exhibit elevated MICs of ceftriaxone and azithromycin than isolates from MSW (P < 0.050). Isolates from MSM had a high prevalence of resistance to ciprofloxacin, penicillin, and tetracycline and were significantly more likely to exhibit antimicrobial resistance than isolates from MSW (P < 0.001). Sentinel surveillance may not be representative of all patients with gonorrhea. HIV status, travel history, and antimicrobial use data were missing for some patients. Men who have sex with men are vulnerable to the emerging threat of antimicrobial-resistant N. gonorrhoeae. Because antimicrobial susceptibility testing is not routinely done in clinical practice, clinicians should monitor for treatment failures among MSM diagnosed with gonorrhea. Strengthened prevention strategies for MSM and new antimicrobial treatment options are needed.

Metabolic syndrome and subclinical carotid atherosclerosis among Chinese elderly people living in a rural community.

PubMed

Yan, Zhongrui; Liang, Yajun; Jiang, Hui; Cai, Chuanzhu; Sun, Binglun; Qiu, Chengxuan

2014-06-01

The relationship between the metabolic syndrome and subclinical atherosclerosis among elderly people remains controversial. We seek to investigate the associations of metabolic syndrome and its components with subclinical carotid atherosclerosis in older people living in rural China. This cross-sectional study included 911 participants (age ≥60 years, 59.4% women) of the community-based Confucius Hometown Aging Project in Shandong, China, who were free of clinical cardiovascular disease. In 2010-2011, data were collected through interviews, clinical examinations, and laboratory tests. Carotid intima media thickness (cIMT) and carotid artery plaque were assessed using ultrasonography. Metabolic syndrome was defined by four sets of criteria. Data were analyzed with multiple general linear and logistic regression models. Carotid plaque was detected in 514 (56.4%) persons. Depending on the defining criteria, prevalence of metabolic syndrome ranged from 30.6% to 56.9%. Hypertension, elevated blood pressure (≥130/85 mmHg), diabetes/prediabetes, and high fasting plasma glucose (≥5.6 mmol/L) were significantly associated with an increased likelihood of carotid plaque, whereas an increased cIMT was associated with elevated blood pressure and hypertension (P<0.05). Obesity, high triglycerides, and dyslipidemia were not associated with carotid artery plaque or cIMT. The significant association of metabolic syndrome with an increased likelihood of carotid plaque disappeared when elevated blood pressure and high plasma glucose were added to the models. Metabolic syndrome was not associated with cIMT. Metabolic syndrome is associated with subclinical carotid plaque among Chinese elderly people, driven primarily by elevated blood pressure and hyperglycemia. Older adults with metabolic syndrome, especially those with high blood pressure and hyperglycemia, may benefit from evaluation for subclinical atherosclerosis.

Circulating Branched-chain Amino Acid Concentrations Are Associated with Obesity and Future Insulin Resistance in Children and Adolescents

PubMed Central

McCormack, Shana E.; Shaham, Oded; McCarthy, Meaghan A.; Deik, Amy A.; Wang, Thomas J.; Gerszten, Robert E.; Clish, Clary B.; Mootha, Vamsi K.; Grinspoon, Steven K.; Fleischman, Amy

2012-01-01

Background Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. Objective To determine whether pediatric obesity is associated with elevations in fasting circulating concentrations of branched-chain amino acids (isoleucine, leucine, and valine), and whether these elevations predict future insulin resistance. Research Design and Methods Sixty-nine healthy subjects, ages 8 to18 years, were enrolled as a cross-sectional cohort. A subset who were pre- or early-pubertal, ages 8 to 13 years, were enrolled in a prospective longitudinal cohort for 18 months (n=17 with complete data). Results Elevations in the concentrations of BCAA’s were significantly associated with BMI Z-score (Spearman’s Rho 0.27, p=0.03) in the cross-sectional cohort. In the subset of subjects followed longitudinally, baseline BCAA concentrations were positively associated with HOMA-IR measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex, and pubertal stage (p=0.046). Conclusions Elevations in the concentrations of circulating branched-chain amino acids are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance. PMID:22961720

Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants.

PubMed

Moya-Alvarez, Violeta; Mireku, Michael Osei; Ayotte, Pierre; Cot, Michel; Bodeau-Livinec, Florence

2016-01-01

Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. At 12 months, the mean BLL of infants was 7.41 μg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 μg/dL. Lead poisoning, defined as BLL>10 μg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa.

Ordering pattern and performance of biochemical tests for diagnosing pheochromocytoma between 2000 and 2008.

PubMed

Yu, Run

2009-01-01

To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation.

Polyclonal and allergen-induced cytokine responses in children with elevated immunoglobulin E but no atopic disease.

PubMed

Smart, J M; Tang, M L K; Kemp, A S

2002-11-01

Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease. To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared. We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years). Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls. The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.

Complex PTSD as proposed for ICD-11: validation of a new disorder in children and adolescents and their response to Trauma-Focused Cognitive Behavioral Therapy.

PubMed

Sachser, Cedric; Keller, Ferdinand; Goldbeck, Lutz

2017-02-01

To evaluate whether the symptoms of children and adolescents with clinically significant posttraumatic stress symptoms (PTSS) form classes consistent with the diagnostic criteria of complex PTSD (CPTSD) as proposed for the ICD-11, and to relate the emerging classes with treatment outcome of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Latent classes analysis (LCA) was used to explore the symptom profiles of the clinical baseline assessment of N = 155 children and adolescents participating in a randomized controlled trial of TF-CBT. The treatment outcomes of patients with posttraumatic stress disorder (PTSD) and of patients with CPTSD were compared by a t-test for depended samples and a repeated-measures ANOVA. The LCA revealed two distinct classes: a PTSD class characterized by elevated core symptoms of PTSD (n = 62) and low symptoms of disturbances in self-organization versus a complex PTSD class with elevated PTSD core symptoms and elevated symptoms of disturbances in self-organization (n = 93). The Group × Time interaction regarding posttraumatic stress symptoms was not significant. Pre-post effect sizes regarding posttraumatic stress symptoms were large for both groups (PTSD: d = 2.81; CPTSD: d = 1.37). For disturbances in self-organization in the CPTSD class, we found medium to large effect sizes (d = 0.40-1.16) after treatment with TF-CBT. The results provide empirical evidence of the ICD-11 CPTSD and PTSD distinction in a clinical sample of children and adolescents. In terms of relative improvement from their respective baseline posttraumatic stress symptoms, patients with PTSD and CPTSD responded equally to TF-CBT; however, those with CPTSD ended treatment with clinically and statistically greater symptoms than those with PTSD. © 2016 Association for Child and Adolescent Mental Health.

CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

PubMed Central

English, Brett A.; Dortch, Marcus; Ereshefsky, Larry; Jhee, Stanford

2014-01-01

In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting. PMID:22707017

The Basic Metabolic Profile in Heart Failure-Marker and Modifier.

PubMed

Elfar, Ahmed; Sambandam, Kamalanathan K

2017-08-01

The physiologic determinants of each of the components of the basic metabolic profile in patients with heart failure will be explored. Additionally, the review will discuss the prognostic value of alterations in the basic metabolic profile as well as their effects on management. Abnormalities in the basic metabolic profile have significant correlation with clinical outcomes and can modify treatment in heart failure. Hypochloremia has recently received increased attention for these reasons. Elevated creatinine, increased blood urea nitrogen, hyponatremia, and hypochloremia correlate with worse mortality and diuretic resistance in heart failure. Hypokalemia, even when mild, has proven to be a worse clinical indicator than modest elevations in serum potassium. Hypochloremia is mechanistically linked to hyponatremia and metabolic alkalosis, but recent compelling data suggests that it can provide more discriminating prognostic information. Knowledge of the physiologic basis for each of these alterations informs their management.

Cerebrospinal fluid markers before and after shunting in patients with secondary and idiopathic normal pressure hydrocephalus

PubMed Central

Tullberg, Mats; Blennow, Kaj; Månsson, Jan-Eric; Fredman, Pam; Tisell, Magnus; Wikkelsö, Carsten

2008-01-01

Background The aim of this study was to explore biochemical changes in the cerebrospinal fluid (CSF) induced by shunt surgery and the relationship between these changes and clinical improvement. Methods We measured clinical symptoms and analysed lumbar CSF for protein content, neurodegeneration and neurotransmission markers in patients with secondary (SNPH, n = 17) and idiopathic NPH (INPH, n = 18) before and 3 months after shunt surgery. Patients were divided into groups according to whether or not there was improvement in clinical symptoms after surgery. Results Preoperatively, the only pathological findings were elevated neurofilament protein (NFL), significantly more so in the SNPH patients than in the INPH patients, and elevated albumin content. Higher levels of NFL correlated with worse gait, balance, wakefulness and neuropsychological performance. Preoperatively, no differences were seen in any of the CSF biomarkers between patients that improved after surgery and those that did not improve. Postoperatively, a greater improvement in gait and balance performance correlated with a more pronounced reduction in NFL. Levels of albumin, albumin ratio, neuropeptide Y, vasoactive intestinal peptide and ganglioside GD3 increased significantly after shunting in both groups. In addition, Gamma amino butyric acid increased significantly in SNPH and tau in INPH. Conclusion We conclude that a number of biochemical changes occur after shunt surgery, but there are no marked differences between the SNPH and INPH patients. The results indicate that NFL may be a marker that can predict a surgically reversible state in NPH. PMID:18439296

Serum levels of matrix metalloproteinases: implications in clinical neurology.

PubMed

Romi, Fredrik; Helgeland, Geir; Gilhus, Nils Erik

2012-01-01

Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in remodeling extracellular matrix and cell-matrix interactions. A pathogenic role of MMPs in neurological disorders is likely. This paper focuses on serological clinical aspects only. In multiple sclerosis, higher serum MMP-3 is seen during relapses. Lower serum MMP-8 and -9 levels correlate with fewer contrast-enhanced T(2)-weighted MRI lesions, and serum MMP-9 can be used in monitoring treatment. In myasthenia gravis, serum MMP-2, -3, and -9 levels are elevated in both generalized and ocular diseases. A proportion of the patients have markedly increased serum MMP-3. In acute stroke, higher serum MMP-9 correlates with larger infarct volume, stroke severity, and worse functional outcome, and serum MMP-3 is significantly lower than in several other neurological disorders and healthy controls. In amyotrophic lateral sclerosis, serum MMP-2 correlates with disease progression, and both serum MMP-1 and -2 are elevated. In Alzheimer's disease, serum MMP-3, -9, and -10 are elevated. In migraine, serum MMP-2 is elevated, and also MMP-9 in those patients with migraine without aura. MMP-9 is implicated in the pathogenesis of experimental epilepsy. A pathogenic role of MMPs in these conditions could be related to their ability to degrade extracellular matrix. MMPs may also facilitate autoimmunity. Copyright © 2012 S. Karger AG, Basel.

Early clinical and radiological outcomes of reverse shoulder arthroplasty with an eccentric all-polyethylene glenosphere to treat failed hemiarthroplasty and the sequelae of proximal humeral fractures.

PubMed

Merolla, Giovanni; Tartarone, Antonio; Sperling, John W; Paladini, Paolo; Fabbri, Elisabetta; Porcellini, Giuseppe

2017-01-01

The aim of this study was to assess the effectiveness of reverse total shoulder arthroplasty (RTSA) with an all-polyethylene glenosphere in patients with failed hemiarthroplasty (HH) or the sequelae of proximal humeral fractures. Thirty-six patients were assessed at a mean follow-up of 36 months using clinical scores and recording shoulder range of movement (ROM). Active anterior elevation (p < 0.001), lateral elevation (p < 0.001) and internal rotation (p < 0.0001) improved significantly, whereas improvement in external rotation was not significant. The mean Constant score rose significantly from 8.5 ± 7.6 to 40.7 ± 15.7 (p < 0.001) and the Simple Shoulder Test score from 0.42 ± 0.85 to 5.5 ± 2.6 (p < 0.001). Pain improved significantly from 8.7 ± 0.9 to 2.3 ± 1.2 (p < 0.001). Implant radiographic survivorship was 84.6 %. Scapular notching was detected in 7/36 patients (17.5 %). There were five complications: one (stiffness) among patients with fracture sequelae and four among those with failed HH (instability, n = 2; humeral component disassembly, n = 1; pain, n = 1). The two groups did not exhibit significant differences in pain, clinical scores or ROM. RTSA with an all-polyethylene glenosphere may have the potential to reduce the risk of biological notching due to polyethylene osteolysis. Further long-term studies are required to assess its efficacy. The good clinical performance and reasonable rate of notching of the polyethylene glenosphere support its use in primary and revision shoulder arthroplasty. Level 4, retrospective therapeutic case series.

Circulating intestinal fatty acid-binding protein (I-FABP) levels in acute decompensated heart failure.

PubMed

Kitai, Takeshi; Kim, Yong-Hyun; Kiefer, Kathryn; Morales, Rommel; Borowski, Allen G; Grodin, Justin L; Tang, W H Wilson

2017-06-01

Venous congestion has become increasingly recognized as a potential contributor to end-organ dysfunction in heart failure. Elevated I-FABP, which is excreted specifically from damaged intestinal epithelial cells, has been found in patients with abdominal hypertension and intestinal ischemia. We hypothesize that elevated intestinal fatty acid-binding protein (I-FABP) levels would identify patients with more advanced heart failure who have venous and intestinal congestion. Baseline serum I-FABP levels were measured in 69 acute decompensated heart failure (ADHF) patients admitted to the intensive care unit for invasive hemodynamic monitoring and tailored medical therapy. Comprehensive echocardiography examinations were performed in all study patients, and clinical outcomes (death, cardiac transplant or left ventricular assist device placement) were assessed. The median circulating I-FABP level was 853pg/ml (interquartile range: 533 to 1448pg/ml). Age, gender, race, and baseline comorbidities were comparable between patients with low and high I-FABP levels. Although there were no significant correlations between I-FABP levels and invasively-measured hemodynamic parameters nor echocardiographic parameters, patients with higher I-FABP levels (≥853g/ml) had significantly worse clinical outcomes compared to those with lower I-FABP levels (<853pg/ml, P=0.025). Circulating I-FABP levels had no association with invasively-measured hemodynamic parameters, but were associated with adverse clinical outcomes in patients with ADHF with systolic dysfunction. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Short-Term Moderately Elevated Intraocular Pressure Is Associated With Elevated Scotopic Electroretinogram Responses

PubMed Central

Choh, Vivian; Gurdita, Akshay; Tan, Bingyao; Prasad, Ratna C.; Bizheva, Kostadinka; Joos, Karen M.

2016-01-01

Purpose Moderately elevated intraocular pressure (IOP) is a risk factor for open-angle glaucoma. Some patients suffer glaucoma despite clinically measured normal IOPs. Fluctuations in IOP may have a significant role since IOPs are higher during sleep and inversion activities. Controlled transient elevations of IOPs in rats over time lead to optic nerve structural changes that are similar to the early changes observed in constant chronic models of glaucoma. Because early intervention decreases glaucoma progression, this study was done to determine if early physiological changes to the retina could be detected with noninvasive electrophysiological and optical imaging tests during moderately elevated IOP. Methods Intraocular pressures were raised to moderately high levels (35 mm Hg) in one eye of Sprague-Dawley rats while the other (control) eye was untreated. One group of rats underwent scotopic threshold response (STR) and electroretinogram (ERG) testing, while another 3 groups underwent optical coherence tomography (OCT) imaging, Western blot, or histologic evaluation. Results The amplitudes of the STR and ERG responses in eyes with moderately elevated IOPs were enhanced compared to the values before IOP elevation, and compared to untreated contralateral eyes. Structural changes to the optic nerve also occurred during IOP elevation. Conclusions Although ischemic IOP elevations are well-known to globally reduce components of the scotopic ERG, acute elevation in rats to levels often observed in untreated glaucoma patients caused an increase in these parameters. Further exploration of these phenomena may be helpful in better understanding the mechanisms mediating early retinal changes during fluctuating or chronically elevated IOP. PMID:27100161

Prognostic Implications of Single-Sample Confirmatory Testing for Undiagnosed Diabetes: A Prospective Cohort Study.

PubMed

Selvin, Elizabeth; Wang, Dan; Matsushita, Kunihiro; Grams, Morgan E; Coresh, Josef

2018-06-19

Current clinical definitions of diabetes require repeated blood work to confirm elevated levels of glucose or hemoglobin A1c (HbA1c) to reduce the possibility of a false-positive diagnosis. Whether 2 different tests from a single blood sample provide adequate confirmation is uncertain. To examine the prognostic performance of a single-sample confirmatory definition of undiagnosed diabetes. Prospective cohort study. The ARIC (Atherosclerosis Risk in Communities) study. 13 346 ARIC participants (12 268 without diagnosed diabetes) with 25 years of follow-up for incident diabetes, cardiovascular outcomes, kidney disease, and mortality. Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and HbA1c (≥6.5%) from a single blood sample. Among 12 268 participants without diagnosed diabetes, 978 had elevated levels of fasting glucose or HbA1c at baseline (1990 to 1992). Among these, 39% had both (confirmed undiagnosed diabetes), whereas 61% had only 1 elevated measure (unconfirmed undiagnosed diabetes). The confirmatory definition had moderate sensitivity (54.9%) but high specificity (98.1%) for identification of diabetes cases diagnosed during the first 5 years of follow-up, with specificity increasing to 99.6% by 15 years. The 15-year positive predictive value was 88.7% compared with 71.1% for unconfirmed cases. Confirmed undiagnosed diabetes was significantly associated with cardiovascular and kidney disease and mortality, with stronger associations than unconfirmed diabetes. Lack of repeated measurements of fasting glucose and HbA1c. A single-sample confirmatory definition of diabetes had a high positive predictive value for subsequent diagnosis and was strongly associated with clinical end points. Our results support the clinical utility of using a combination of elevated fasting glucose and HbA1c levels from a single blood sample to identify undiagnosed diabetes in the population. National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.

Hydroxyapatite paste Ostim, without elevation of full-thickness flaps, improves alveolar healing stimulating BMP- and VEGF-mediated signal pathways: an experimental study in humans.

PubMed

Canuto, R A; Pol, R; Martinasso, G; Muzio, G; Gallesio, G; Mozzati, M

2013-08-01

Tooth extraction is considered as the starting point of jaw atrophy via osteoclast activity stimulation. The maintenance of dental alveolar bone depends on surgery procedure and use of materials to maintain prior space favoring bone regeneration. Among substitutes used in dentistry to fill bone defects, Ostim-Pastes (Ostim) is a nanocrystalline paste tested for treatment of severe clinical conditions. This research first investigated the effect of Ostim on alveolar healing, comparing in the same healthy subjects, an Ostim-filled socket with a not-filled one. Moreover, it also proposed a new surgical protocol for the post-extractive socket treatment using the graft materials without elevation of full-thickness flaps. Fourteen patients were enrolled to bilateral maxillary or mandibular extraction that was performed without elevation of full-thickness flaps. In each patient, one socket was filled using Ostim, and the other one was allowed to undergo natural healing. No suture was carried out. Clinical and biologic parameters were screened at 1, 7, and 14 days. Obtained results evidenced that nanocrystalline hydroxyapatite supports bone regeneration, increasing the synthesis of pro-osteogenic factors as bone morphogenetics protein (BMP)-4, BMP-7, alkaline phosphatase, and osteocalcin. Moreover, filling post-extractive socket with nanocrystalline hydroxyapatite paste leads to a complete epithelialization already at 7 days after extraction, despite the fact that the teeth were extracted without elevation of full-thickness flaps . The improved epithelialization is mediated by increased vascular endothelial growth factor (VEGF) expression. No significant change was observed in inflammatory parameters, with exception of an early and transient IL-1β induction, that could trigger and improve alveolar healing. Clinical and biomolecular observations of this explorative study evidenced that nanocrystalline hydroxyapatite improves alveolar socket healing, increasing angiogenesis, epithelialization, and osteogenesis, also in absence of elevation of full-thickness flaps. © 2011 John Wiley & Sons A/S.

A stand-alone lateral condyle-elevating trochlear osteotomy leads to high residual instability but no excessive increase in patellofemoral osteoarthritis at 12-year follow-up.

PubMed

Tigchelaar, S; van Sambeeck, J; Koeter, S; van Kampen, A

2018-04-01

Trochlear osteotomy is a rarely performed procedure, only indicated in selected cases. Due to its nature, it can potentially lead to cartilage damage and subsequent early osteoarthritis. Satisfactory short-term results from lateral condyle-elevating osteotomy have previously been reported. The long-term effects of this procedure on clinical outcomes, patellar stability and radiological osteoarthritis are reported here. Sixteen patients (19 knees) with patellar instability due to trochlear dysplasia were included. An isolated lateral condyle-elevating trochlear osteotomy was performed between 1995 and 2002. All patients were re-examined at a minimum of 12-year follow-up. Three patients were lost to follow-up, and one patient underwent a patellofemoral arthroplasty 3 years post-operatively due to progressive osteoarthritis. Complete follow-up was therefore available in 12 patients (15 knees). Recurrent instability, VAS pain, WOMAC, Lysholm and Kujala scores were used as outcome measures. Radiological osteoarthritis was recorded using the Iwano and the Kellgren-Lawrence classifications. A repeated-measures ANOVA was used to test for repeated measures (pre-operative, 2-year and final follow-up), and Spearman's correlation coefficient for relationships between osteoarthritis and functional scores. At final follow-up, VAS pain showed a non-significant improvement from 52 to 25, and the median Kujala score was 78. Median Lysholm (54-71, p = 0.021) and WOMAC (78-96, p = 0.021) scores improved from the pre-operative assessment to final follow-up. There was no significant difference observed between clinical scores at the 2-year and final follow-up. Residual patellar instability was reported in four out of 15 knees. Three knees showed no patellofemoral osteoarthritis, eight knees had grade 1 and four knees grade 2. No correlation between VAS pain, Lysholm, WOMAC or Kujala scores and osteoarthritis could be identified (n.s.). A stand-alone lateral condyle-elevating trochleoplasty results in the significant improvement of most clinical scores; however, when performed as a stand-alone procedure, it leads to a high percentage of residual instability. In contrast to general belief, the development of patellofemoral osteoarthritis at 12-year follow-up did not exceed the findings from other trochleoplasty case series. Case series with no comparison group, Level IV.

Identifying potential barriers to physical activity adherence: anxiety sensitivity and body mass as predictors of fear during exercise.

PubMed

Smits, Jasper A J; Tart, Candyce D; Presnell, Katherine; Rosenfield, David; Otto, Michael W

2010-01-01

A growing body of work suggests that obese adults are less likely to adhere to exercise than normal-weight adults because they experience greater levels of discomfort and distress during exercise sessions. The present study introduces and provides a preliminary test of the hypothesis that the distress experienced during exercise among persons with elevated body mass index is particularly high among those who fear somatic arousal (i.e. elevated anxiety sensitivity [AS]). Young adults were randomly assigned to complete 20 min of treadmill exercise (at 70% of their age-adjusted predicted maximum heart rate) or 20 min of rest. Body mass, AS, and negative affect were measured at baseline, and fear was measured at 4-min intervals during the experimental phase. Consistent with the authors' hypothesis, there was a significant Exercise x BMI x ASI interaction (sr(2) = .08), suggesting that the greatest fear levels during exercise were observed among participants with high body mass, but only if they also had elevated AS. These findings offer a new approach for identifying specific vulnerable individuals and have clear clinical implications, given that the amplification factor of AS can be modified with clinical intervention.

Serial 1H-MRS in GM2 gangliosidoses.

PubMed

Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola

2008-03-01

GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations.

Elevation of Autoantibody in Patients with Ischemic Stroke.

PubMed

Yoshida, Yoichi; Hiwasa, Takaki; Machida, Toshio; Kobayashi, Eiichi; Mine, Seiichiro; Matsushima, Jun; Takiguchi, Masaki; Iwadate, Yasuo

2018-05-31

Recent clinical research has revealed a significant correlation between atherosclerosis, one of the primary etiologies of ischemic stroke, and the immune system. Assuming that "disease-specific autoantibodies are produced in the sera of patients with ischemic stroke," we investigated multiple arteriosclerosis-related antibodies using the serological identification of antigens by recombinant cDNA expression cloning (SEREX), an established method for identifying antigenic proteins. We either screened a human aortic endothelial cell cDNA library or conducted protein array screening using the sera from patients with ischemic stroke, such as carotid artery stenosis or transient ischemic attack (TIA). Next, we measured serum antibody levels using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in patient/healthy donor (HD) cohorts and identified several antigens, the antibody levels of which were significantly higher in patients with ischemic stroke than in HDs. This review introduced the method of identifying antigens by the SEREX and protein microarray and summarized antigenic proteins. In particular, it focused on anti-replication protein A2 antibody and anti-programmed cell death 11 antibody, which are significantly related to atherosclerotic plaque and ischemic brain tissue, respectively, and proposed the mechanism of elevated autoantibody levels against them. Furthermore, this review suggests a possibility of clinical application as an atherosclerotic disease diagnostic marker for TIA or cerebral infarction.

Depression and anxiety symptoms in bronchiectasis: associations with health-related quality of life.

PubMed

Olveira, Casilda; Olveira, Gabriel; Gaspar, Inmaculada; Dorado, Antonio; Cruz, Ivette; Soriguer, Federico; Quittner, Alexandra L; Espildora, Francisco

2013-04-01

Bronchiectasis causes pulmonary infections and loss of lung function, resulting in chronic respiratory symptoms and worsening health-related quality of life. The aims of this study were to measure symptoms of depression and anxiety in a sample of patients with bronchiectasis and evaluate their relationship to health outcomes and health-related quality of life. This cross-sectional study included adolescents and adults with bronchiectasis. Patients completed the hospital anxiety and depression scale and the St. George respiratory questionnaire. Health outcome data, including clinical, radiological and spirometric values, were recorded from medical charts. Ninety-three participants with bronchiectasis of any aetiology were recruited: 20 % had elevated depression-related scores and 38 % had elevated anxiety-related scores. Increased symptoms of depression and anxiety were significantly associated with age; anxiety was associated with more frequent exacerbations. Regression analyses indicated that after controlling for demographic (gender and age) and clinical variables (exacerbations frequency, daily sputum, aetiology and spirometry), both depression and anxiety symptoms predicted significantly worse health-related quality of life. In comparison with other predictors, psychological symptoms explained the largest amount of variance in health-related quality of life. Symptoms of depression and anxiety were significant predictors of health-related quality of life in patients with bronchiectasis, independently of respiratory involvement, gender, age or other variables.

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer.

PubMed

Shigeyasu, Kunitoshi; Okugawa, Yoshinaga; Toden, Shusuke; Miyoshi, Jinsei; Toiyama, Yuji; Nagasaka, Takeshi; Takahashi, Naoki; Kusunoki, Masato; Takayama, Tetsuji; Yamada, Yasuhide; Fujiwara, Toshiyoshi; Chen, Leilei; Goel, Ajay

2018-06-21

Adenosine-to-inosine (A-to-I) RNA editing, a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family, is a recently discovered epigenetic modification dysregulated in human cancers. However, the clinical significance and the functional role of RNA editing in colorectal cancer (CRC) remain unclear. We have systematically and comprehensively investigated the significance of the expression status of ADAR1 and of the RNA editing levels of antizyme inhibitor 1 (AZIN1), one of the most frequently edited genes in cancers, in 392 colorectal tissues from multiple independent CRC patient cohorts. Both ADAR1 expression and AZIN1 RNA editing levels were significantly elevated in CRC tissues when compared with corresponding normal mucosa. High levels of AZIN1 RNA editing emerged as a prognostic factor for overall survival and disease-free survival and were an independent risk factor for lymph node and distant metastasis. Furthermore, elevated AZIN1 editing identified high-risk stage II CRC patients. Mechanistically, edited AZIN1 enhances stemness and appears to drive the metastatic processes. We have demonstrated that edited AZIN1 functions as an oncogene and a potential therapeutic target in CRC. Moreover, AZIN1 RNA editing status could be used as a clinically relevant prognostic indicator in CRC patients.

Consecutive monitoring of faecal calprotectin during mesalazine suppository therapy for active rectal inflammation in ulcerative colitis.

PubMed

Yamamoto, T; Shimoyama, T; Matsumoto, K

2015-09-01

No studies have monitored the levels of faecal calprotectin (FC) during mesalazine suppository therapy for proctitis in ulcerative colitis (UC). To evaluate the value of consecutive monitoring of FC in patients with UC during mesalazine suppository therapy. One hundred and sixty patients with active inflammation limited to the rectum were treated with mesalazine 1 g suppository once daily for 8 weeks. Patients who achieved clinical remission were advised to maintain the treatment, and were followed up for further 40 weeks. FC levels were measured every 8 weeks during the study. At week 8, 118 patients (74%) went into clinical remission, of whom 88 achieved endoscopic healing. The median FC level significantly decreased in patients with clinical and endoscopic remission (both P < 0.0001), while it did not change significantly in those without remission. Eighty (68%) of the 118 patients with remission continued the treatment. Twenty-four patients (30%) relapsed during the 40-week follow-up. In patients with clinical relapse, the median FC level elevated already 8 weeks before the diagnosis of relapse. In contrast, in patients who maintained remission it remained at a low level and did not significantly change during the follow-up. Elevated FC level (≥55 μg/g) was useful for the early diagnosis of relapse (88% sensitivity and 80% specificity). Faecal calprotectin may represent a useful biomarker for the assessment of disease activity in UC patients treated with mesalazine suppositories. Serial monitoring of faecal calprotectin appears to be valuable for the prediction and early diagnosis of relapse during maintenance therapy. © 2015 John Wiley & Sons Ltd.

Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

PubMed Central

O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

2016-01-01

Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

PubMed

O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

2016-10-01

Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Utilization of small changes in serum creatinine with clinical risk factors to assess the risk of AKI in critically lll adults.

PubMed

Cruz, Dinna N; Ferrer-Nadal, Asunción; Piccinni, Pasquale; Goldstein, Stuart L; Chawla, Lakhmir S; Alessandri, Elisa; Belluomo Anello, Clara; Bohannon, Will; Bove, Tiziana; Brienza, Nicola; Carlini, Mauro; Forfori, Francesco; Garzotto, Francesco; Gramaticopolo, Silvia; Iannuzzi, Michele; Montini, Luca; Pelaia, Paolo; Ronco, Claudio

2014-04-01

Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient's clinical course. We set out to assess the performance of this combination approach. A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1-0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit. Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001). Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.

Effect of sex difference in clinical presentation (stable coronary artery disease vs unstable angina pectoris or non-ST-elevation myocardial infarction vs ST-elevation myocardial infarction) on 2-year outcomes in patients undergoing percutaneous coronary intervention.

PubMed

Tang, Xiao-Fang; Song, Ying; Xu, Jing-Jing; Ma, Yuan-Liang; Zhang, Jia-Hui; Yao, Yi; He, Chen; Wang, Huan-Huan; Jiang, Ping; Jiang, Lin; Liu, Ru; Gao, Zhan; Zhao, Xue-Yan; Qiao, Shu-Bin; Xu, Bo; Yang, Yue-Jin; Gao, Run-Lin; Yuan, Jin-Qing

2018-02-01

To determine whether there is a difference in 2-year prognosis among patients across the spectrum of coronary artery disease undergoing percutaneous coronary intervention (PCI). We analyzed all consecutive patients undergoing PCI at a single center from 1/1-12/31/2013. Clinical presentations were compared between sexes according to baseline clinical, angiographic, and procedural characteristics and 2-year (mean 730 ± 30-day) outcomes. We grouped 10 724 consecutive patients based on sex and clinical presentation. Among patients with ST-elevation myocardial infarction (STEMI), rates of all-cause death (6.7% vs 1.4%) and cardiac death (3.8% vs 1.1%) were significantly higher in women than in men (P < 0.05), but these rates did not differ between men and women with stable coronary artery disease (SCAD) and non-ST-elevation acute coronary syndrome ((NSTE-ACS). Incidence of major bleeding was greater than in men only in those women presenting with ACS. After multivariable adjustment, female sex was not an independent predictor of outcomes in STEMI (hazard ratio [HR] for all-cause death: 1.33, 95% confidence interval [CI]:0.52-3.38; P = 0.55; HR for cardiac death: 0.69, 95%CI: 0.23-2.09, P = 0.51], but was still an independent predictor of bleeding in STEMI (HR: 3.53, 95%CI: 1.26-9.91, P = 0.017). Among STEMI patients, women had worse 2-year mortality after PCI therapy, but female sex was not an independent predictor of mortality after adjustment for baseline characteristics. In STEMI patients, women were at higher bleeding risk than men after PCI, even after multivariable adjustment. © 2017, Wiley Periodicals, Inc.

Long-Term Outcomes of Non-ST-Elevation Myocardial Infarction Without Creatine Kinase Elevation　- The J-MINUET Study.

PubMed

Ishihara, Masaharu; Nakao, Koichi; Ozaki, Yukio; Kimura, Kazuo; Ako, Junya; Noguchi, Teruo; Fujino, Masashi; Yasuda, Satoshi; Suwa, Satoru; Fujimoto, Kazuteru; Nakama, Yasuharu; Morita, Takashi; Shimizu, Wataru; Saito, Yoshihiko; Hirohata, Atsushi; Morita, Yasuhiro; Inoue, Teruo; Okamura, Atsunori; Uematsu, Masaaki; Hirata, Kazuhito; Tanabe, Kengo; Shibata, Yoshisato; Owa, Mafumi; Tsujita, Kenichi; Funayama, Hiroshi; Kokubu, Nobuaki; Kozuma, Ken; Tobaru, Tetsuya; Oshima, Shigeru; Nakai, Michikazu; Nishimura, Kunihiro; Miyamoto, Yoshihiro; Ogawa, Hisao

2017-06-23

According to troponin-based criteria of myocardial infarction (MI), patients without elevation of creatine kinase (CK), formerly classified as unstable angina (UA), are now diagnosed as non-ST-elevation MI (NSTEMI), but little is known about their outcomes.Methods and Results:Between July 2012 and March 2014, 3,283 consecutive patients with MI were enrolled. Clinical follow-up data were obtained up to 3 years. The primary endpoint was a composite of all-cause death, non-fatal MI, non-fatal stroke, cardiac failure and urgent revascularization for UA. There were 2,262 patients with ST-elevation MI (STEMI), 563 NSTEMI with CK elevation (NSTEMI+CK) and 458 NSTEMI without CK elevation (NSTEMI-CK). From day 0, Kaplan-Meier curves for the primary endpoint began to diverge in favor of NSTEMI-CK for up to 30 days. The 30-day event rate was significantly lower in patients with NSTEMI-CK (3.3%) than in STEMI (8.6%, P<0.001) and NSTEMI+CK (9.9%, P<0.001). Later, the event curves diverged in favor of STEMI. The event rate from 31 days to 3 years was significantly lower in patients with STEMI (19.8%) than in NSTEMI+CK (33.6%, P<0.001) and NSTEMI-CK (34.2%, P<0.001). Kaplan-Meier curves from 31 days to 3 years were almost identical between NSTEMI+CK and NSTEMI-CK (P=0.91). Despite smaller infarct size and better short-term outcomes, long-term outcomes of NSTEMI-CK after convalescence were as poor as those for NSTEMI+CK and worse than for STEMI.

Influence of patient race and ethnicity on clinical assessment in patients with affective disorders.

PubMed

Gara, Michael A; Vega, William A; Arndt, Stephan; Escamilla, Michael; Fleck, David E; Lawson, William B; Lesser, Ira; Neighbors, Harold W; Wilson, Daniel R; Arnold, Lesley M; Strakowski, Stephen M

2012-06-01

Rates of clinical diagnoses of schizophrenia in African American individuals appear to be elevated compared with other ethnic groups in the United States, contradicting population rates derived from epidemiologic surveys. To determine whether African American individuals would continue to exhibit significantly higher rates of clinical diagnoses of schizophrenia, even after controlling for age, sex, income, site, and education, as well as the presence or absence of serious affective disorder, as determined by experts blinded to race and ethnicity. A secondary objective was to determine if a similar pattern occurred in Latino subjects. Ethnicity-blinded and -unblinded diagnostic assessments were obtained in 241 African American individuals (mean [SD] age, 34.3 [8.1] years; 57% women), 220 non-Latino white individuals (mean [SD] age, 32.7 [8.5] years; 53% women), and 149 Latino individuals (mean [SD] age, 33.5 [8.0] years; 58% women) at 6 US sites. Logistic regression models were used to determine whether elevated rates of schizophrenia in African American individuals would persist after controlling for various confounding variables including blinded expert consensus diagnoses of serious affective illness. Six academic medical centers across the United States. Six hundred ten psychiatric inpatients and outpatients. Relative odds of unblinded clinical diagnoses of schizophrenia in African American compared with white individuals. A significant ethnicity/race effect (χ(2)(2)=10.4, P=.01) was obtained when schizophrenia was narrowly defined, controlling for all other predictors. The odds ratio comparing African American with non-Latino white individuals was significant (odds ratio=2.7; 95% CI, 1.5-5.1). Similar differences between African American and white individuals occurred when schizophrenia was more broadly defined (odds ratio=2.5; 95% CI, 1.4-4.5). African American individuals did not differ significantly from white individuals in overall severity of manic and depressive symptoms but did evidence more severe psychosis. African American individuals exhibited significantly higher rates of clinical diagnoses of schizophrenia than non-Latino white subjects, even after controlling for covariates such as serious affective disorder.

Eosinophilic Endotype of Asthma.

PubMed

Aleman, Fernando; Lim, Hui Fang; Nair, Parameswaran

2016-08-01

Asthma is a heterogeneous disease that can be classified into different clinical endotypes, depending on the type of airway inflammation, clinical severity, and response to treatment. This article focuses on the eosinophilic endotype of asthma, which is defined by the central role that eosinophils play in the pathophysiology of the condition. It is characterized by elevated sputum and/or blood eosinophils on at least 2 occasions and by a significant response to treatments that suppress eosinophilia. Histopathologic demonstration of eosinophils in the airways provides the most direct diagnosis of eosinophilic asthma; but it is invasive, thus, impractical in clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

The relationships between perfectionism, pathological worry and generalised anxiety disorder.

PubMed

Handley, Alicia K; Egan, Sarah J; Kane, Robert T; Rees, Clare S

2014-04-02

The relationships between perfectionism, pathological worry and generalised anxiety disorder (GAD) were investigated in a clinical sample presenting for treatment of perfectionism. This study explored the utility of perfectionism in predicting pathological worry in a sample of individuals with elevated perfectionism and GAD (n = 36). Following this, the study examined whether perfectionism could predict a principal GAD diagnosis in the full sample (n = 42). Scores on the perfectionism dimensions Concern over Mistakes, Personal Standards, and Clinical Perfectionism significantly predicted pathological worry among participants with GAD after controlling for gender and depression. The perfectionism dimension Doubts about Actions significantly predicted whether individuals from the full sample received a principal diagnosis of GAD. These findings support certain dimensions of perfectionism having significant associations with pathological worry and GAD.

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

PubMed

Luetkemeyer, Annie; Hare, C Bradley; Stansell, John; Tien, Phyllis C; Charlesbois, Edwin; Lum, Paula; Havlir, Diane; Peters, Marion

2006-01-01

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.

GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients

PubMed Central

Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

2013-01-01

α-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as “incurable” diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy. PMID:24179708

Husbandry stress exacerbates mycobacterial infections in adult zebrafish, Danio rerio (Hamilton)

USGS Publications Warehouse

Ramsay, J.M.; Watral, Virginia G.; Schreck, C.B.; Kent, M.L.

2009-01-01

Mycobacteria are significant pathogens of laboratory zebrafish, Danio rerio (Hamilton). Stress is often implicated in clinical disease and morbidity associated with mycobacterial infections but has yet to be examined with zebrafish. The aim of this study was to examine the effects of husbandry stressors on zebrafish infected with mycobacteria. Adult zebrafish were exposed to Mycobacterium marinum or Mycobacterium chelonae, two species that have been associated with disease in zebrafish. Infected fish and controls were then subjected to chronic crowding and handling stressors and examined over an 8-week period. Whole-body cortisol was significantly elevated in stressed fish compared to non-stressed fish. Fish infected with M. marinum ATCC 927 and subjected to husbandry stressors had 14% cumulative mortality while no mortality occurred among infected fish not subjected to husbandry stressors. Stressed fish, infected with M. chelonae H1E2 from zebrafish, were 15-fold more likely to be infected than non-stressed fish at week 8 post-injection. Sub-acute, diffuse infections were more common among stressed fish infected with M. marinum or M. chelonae than non-stressed fish. This is the first study to demonstrate an effect of stress and elevated cortisol on the morbidity, prevalence, clinical disease and histological presentation associated with mycobacterial infections in zebrafish. Minimizing husbandry stress may be effective at reducing the severity of outbreaks of clinical mycobacteriosis in zebrafish facilities. ?? 2009 Blackwell Publishing Ltd.

Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy.

PubMed

Rödel, Franz; Steinhäuser, Kerstin; Kreis, Nina-Naomi; Friemel, Alexandra; Martin, Daniel; Wieland, Ulrike; Rave-Fränk, Margret; Balermpas, Panagiotis; Fokas, Emmanouil; Louwen, Frank; Rödel, Claus; Yuan, Juping

2018-02-01

RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS). We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012). These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Chromogranin A as a useful neuroendocrine marker in patients with autoimmune Addison's disease.

PubMed

El Ali, Z; Fichna, M; Piniewska, J; Kosowicz, J; Grzymisławski, M

2010-03-01

Antiparietal cells antibodies (APC-Ab) are commonly found in patients with autoimmune Addison's disease (AAD), usually pointing to autoimmune atrophic gastritis and pernicious anemia. The autoaggression to the gastric proton pumpmay result in a long-term hypergastrinemia, which predisposes to enterochromaffin-like cell hyper/dysplasia and gastric carcinoids. We evaluated the clinical utility of assessing serum chromogranin A levels in patients with AAD. Serum chromogranin A, gastrin, and gastric APC-Ab levels were determined in 40 patients with AAD using commercially available kits. Serum chromogranin A and gastrin levels were found to be elevated in 27.5 and 22.5% of patients with AAD, respectively. The Addison's patients with elevated APC-Ab had significantly higher chromogranin A and gastrin levels, as compared to individuals with normal APC-Ab (chromogranin A: 128.00+/-123.08 vs 57.68+/-36.50 ng/ml, p=0.0036; gastrin: 141.38+/-191.43 vs 49.50+/-75.36 muU/ml, p=0.003). Additionally, the patients with AAD and coexisting elevated serum APC-Ab, contrary to those with normal levels, showed a significant correlation between the chromogranin A and gastrin concentrations (r=0.52, p=0.0092 vs r=0.211, p=0.43). Serum chromogranin A appeared also significantly correlated with APC-Ab levels (r=0.431, p=0.005). In patients with autoimmune Addison's disease hyperchromograninemia and hypergastrinemia occur with a prevalence of 27.5 and 22.5%, respectively. Addison's patients with coexisting elevated gastric APC-Ab, particularly with elevated gastrin levels, are at risk of enterochromaffin-like cells hyper/dysplasia. Serum chromogranin A assessment may complement histology for the early diagnosis of gastric carcinoid in these patients.

Clinical Significance of Serum Ferritin at Diagnosis in Patients With Acute Myeloid Leukemia: A YACHT Multicenter Retrospective Study.

PubMed

Tachibana, Takayoshi; Andou, Taiki; Tanaka, Masatsugu; Ito, Satomi; Miyazaki, Takuya; Ishii, Yoshimi; Ogusa, Eriko; Koharazawa, Hideyuki; Takahashi, Hiroyuki; Motohashi, Kenji; Aoki, Jun; Nakajima, Yuki; Matsumoto, Kenji; Hagihara, Maki; Hashimoto, Chizuko; Taguchi, Jun; Fujimaki, Katsumichi; Fujita, Hiroyuki; Fujisawa, Shin; Kanamori, Heiwa; Nakajima, Hideaki

2018-06-01

A multicenter retrospective analysis was performed to evaluate the clinical significance of serum ferritin at diagnosis in patients with acute myeloid leukemia (AML). The study cohort included 305 patients who were newly diagnosed with AML from 2000 to 2015 and received standard induction chemotherapy. Transplantation was performed in 168 patients. The median ferritin value was 512 ng/mL (range, 8-9475 ng/mL). Ferritin correlated with lactate dehydrogenase, C-reactive protein, white blood cell count, and blast count, and elevation of ferritin was associated with poor performance status. The median follow-up period was 58 months (range, 4-187 months) among survivors. The high ferritin group (≥ 400 ng/mL) demonstrated inferior event-free survival (EFS) at the 5-year interval (30% vs. 40%; P = .033) compared to the low ferritin group. Multivariate analysis in the high-risk karyotype revealed that high ferritin levels predicted worse EFS (hazard ratio = 2.07; 95% confidence interval, 1.28-3.33; P = .003). Elevated ferritin at diagnosis may indicate tumor burden in patients with AML and predict worse EFS in the high-risk group. Copyright © 2018 Elsevier Inc. All rights reserved.

Canine pancreatic lipase immunoreactivity concentrations associated with intervertebral disc disease in 84 dogs.

PubMed

Schueler, R O; White, G; Schueler, R L; Steiner, J M; Wassef, A

2018-05-01

To determine the differences in serum canine pancreatic lipase immunoreactivity between dogs with intervertebral disc herniation and healthy control dogs. Eighty-four client-owned dogs with intervertebral disc herniation, diagnosed by neurologic examination and imaging, and 18 healthy control dogs. Samples of whole blood were collected within 90 minutes of admission. Serum canine pancreatic lipase immunoreactivity concentrations were measured by a commercial immunoassay and evaluated for association with intervertebral disc herniation, signalment, neurolocalisation and the preadmission administration of glucocorticosteriods or non-steroidal anti-inflammatory drugs. Serum canine pancreatic lipase immunoreactivity concentrations were statistically increased in dogs with intervertebral disc herniation (P<0·01, n=38). A subgroup of dogs (19/38) with elevated canine pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and 4 weeks later, and 15 had resolution of clinical signs and values less than 200 μg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not significantly correlated with clinical gastrointestinal disease, neurolocalisation or the preadmission administration of corticosteroids or non-steroidal anti-inflammatory drugs. These results suggest that serum canine pancreatic lipase immunoreactivity concentrations are significantly elevated in dogs with intervertebral disc herniation. © 2018 British Small Animal Veterinary Association.

The magnitude of elevated maternal serum human chorionic gonadotropin and pregnancy complications.

PubMed

Sharony, Reuven; Zipper, Oren; Amichay, Keren; Wiser, Amir; Kidron, Debora; Biron-Shental, Tal; Maymon, Ron

2017-07-01

This study assessed the correlation between the magnitude of the elevation in maternal serum human chorionic gonadotropin (MShCG) levels and pregnancy complications. Among 80,716 screened pregnancies, 120 with moderately elevated MShCG (3.00-5.99 MoM) were compared to 84 with extremely elevated MShCG >6.00 MoM. A control series of 120 women with normal MShCG (<3.00 MoM) were matched. Rates of intrauterine growth restriction, preterm labour, antepartum foetal death (APFD), pre-eclampsia, and placental abruption were analysed. We found that the study group had more adverse outcomes than the control group (73/204 [36%] vs. 18/120 [15%]; p < .0001). The rate was higher in the extremely elevated group than in the moderately elevated group (43/84 [51%] vs. 30/120 [25%]; p < .0001). All 12 cases of APFD (14%) occurred among the extremely elevated series. In conclusion, adverse pregnancy outcomes are more common in women with extremely elevated MShCG. The patients should receive counselling regarding this trend and undergo close pregnancy monitoring. Impact statement • What is already known on this subject?In addition to its contribution to Down syndrome (DS) screening, maternal serum human chorionic gonadotropin (MShCG) levels are a marker for pregnancy complications such as intrauterine growth restriction (IUGR), preterm labour (PTL), antepartum fatal death (APFD), pre-eclampsia (PE), placental abruption (PA) and fetal malformations with or without chromosomal aberrations. • What the results of this study add? We found that in the presence of elevated MShCG levels, the incidence of IUGR and PTL increased. PE increased clinically, but statistical significance was seen only when MShCG was extremely elevated (≥ 6.00 MoM). APFD and PA were associated with very high MShCG levels only. • What the implications are of these findings for clinical practice and/or further research? Women with high MShCG levels should be counselled. In case of very high levels (≥ 6.00 MoM), the risk of APFD and PA should be discussed. The pregnancy should be monitored for IUGR, PTL and PE. In view of the limited number of enrolled patients with very high levels of MShCG, the experience of other institutions is needed to corroborate these findings.

Elevation of blood lead levels in emergency department patients with extra-articular retained missiles.

PubMed

Nguyen, Ann; Schaider, Jeffrey J; Manzanares, Mariah; Hanaki, Roy; Rydman, Robert J; Bokhari, Faran

2005-02-01

Patients who survive gunshot wounds often have retained missiles. Unlike intra-articular retained missiles, extra-articular retained missiles (EARMs) are not routinely removed. Cases of lead toxicity from EARMs have been described. This study seeks to determine whether blood lead levels are elevated in emergency department patients with EARMs compared with matched controls, whether clinical symptoms of lead toxicity are more prevalent in patients with EARMs than in controls, and whether longer missile retention times or recent hypermetabolic conditions are associated with higher blood lead levels. One hundred twenty adults with EARMs and 120 age- and gender-matched controls with no history of gunshot wound were prospectively enrolled on presentation to a large urban emergency department. Whole blood lead (WBL), zinc protoporphyrin, and hemoglobin levels were obtained. Patients completed a questionnaire regarding time since gunshot injury; symptoms of lead toxicity; and occurrence within 30 days of any surgery, alcohol abuse, illicit drug abuse, diabetic ketoacidosis, hyperthyroidism, infection, fracture, pregnancy, or lactation. Five EARM patients (4%) and no control patients (0%) had WBL greater than our threshold for medical follow-up (20 microg/dL). Mean WBL was 6.71 microg/dL (95% confidence interval [CI], 5.68-7.74 microg/dL) in EARM patients and 3.16 mug/dL (95% CI, 2.79-3.53 microg/dL) in controls. This difference was statistically significant when analyzed by matched pairs t test (p = 0.0001). There was no difference in the number of symptoms associated with lead toxicity that were noted by EARM patients versus controls (p = 0.377). Longer duration of missile retention was not associated with higher blood lead levels (r = 0.125, p = 0.172). Of the five hypermetabolic conditions analyzed, only fractures were associated with elevated blood lead levels (9.95 microg/dL [95% CI, 5.77-14.13 microg/dL] in EARM patients with fractures vs. 6.23 microg/dL [95% CI, 5.23-7.23 microg/dL] in EARM patients without fractures). Patients with EARMs have significantly elevated blood lead levels compared with matched controls. The occurrence of a bony fracture within the past 30 days is associated with a higher lead level. In 96% of patients with EARMs, elevated lead levels were not clinically significant and did not change patient management.

Optimization of the precordial leads of the 12-lead electrocardiogram may improve detection of ST-segment elevation myocardial infarction.

PubMed

Scott, Peter J; Navarro, Cesar; Stevenson, Mike; Murphy, John C; Bennett, Johan R; Owens, Colum; Hamilton, Andrew; Manoharan, Ganesh; Adgey, A A Jennifer

2011-01-01

For the assessment of patients with chest pain, the 12-lead electrocardiogram (ECG) is the initial investigation. Major management decisions are based on the ECG findings, both for attempted coronary artery revascularization and risk stratification. The aim of this study was to determine if the current 6 precordial leads (V(1)-V(6)) are optimally located for the detection of ST-segment elevation in ST-segment elevation myocardial infarction (STEMI). We analyzed 528 (38% anterior [200], 44% inferior [233], and 18% lateral [95]) patients with STEMI with both a 12-lead ECG and an 80-lead body surface map (BSM) ECG (Prime ECG, Heartscape Technologies, Bangor, Northern Ireland). Body surface map was recorded within 15 minutes of the 12-lead ECG during the acute event and before revascularization. ST-segment elevation of each lead on the BSM was compared with the corresponding 12-lead precordial leads (V(1)-V(6)) for anterior STEMI. In addition, for lateral STEMI, leads I and aVL of the BSM were also compared; and limb leads II, III, aVF of the BSM were compared with inferior unipolar BSM leads for inferior STEMI. Leads with the greatest mean ST-segment elevation were selected, and significance was determined by analysis of variance of the mean ST segment. For anterior STEMI, leads V(1), V(2), 32, 42, 51, and 57 had the greatest mean ST elevation. These leads are located in the same horizontal plane as that of V(1) and V(2). Lead 32 had a significantly greater mean ST elevation than the corresponding precordial lead V(3) (P = .012); and leads 42, 51, and 57 were also significantly greater than corresponding leads V(4), V(5), V(6), respectively (P < .001). Similar findings were also found for lateral STEMI. For inferior STEMI, the limb leads of the BSM (II, III, and aVF) had the greatest mean ST-segment elevation; and lead III was significantly superior to the inferior unipolar leads (7, 17, 27, 37, 47, 55, and 61) of the BSM (P < .001). Leads placed on a horizontal strip, in line with leads V(1) and V(2), provided the optimal placement for the diagnosis of anterior and lateral STEMI and appear superior to leads V(3), V(4), V(5), and V(6). This is of significant clinical interest, not only for ease and replication of lead placement but also may lead to increased recruitment of patients eligible for revascularization with none or borderline ST-segment elevation on the initial 12-lead ECG. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

PubMed

Crary, Michael A; Carnaby, Giselle D; Shabbir, Yasmeen; Miller, Leslie; Silliman, Scott

2016-02-01

Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

In-hospital delay in ST-segment-elevation myocardial infarction after Manchester Triage.

PubMed

Trigo, Joana; Gago, Paula; Mimoso, Jorge; Santos, Walter; Marques, Nuno; Gomes, Veloso

2008-10-01

In ST-segment elevation myocardial infarction (STEMI), time to reperfusion influences morbidity and mortality, and reducing in-hospital delay (IHD) continues to be important. Doubts have been expressed whether the Manchester Triage System (MTS) contributes to this objective. To evaluate the effectiveness of the MTS in classifying STEMI patients and its effect on IHD. We analyzed 278 patients with STEMI admitted to the Coronary Care Unit through the Emergency Department between January 13 2005 and November 26 2006. The patients were divided into two groups according to their MTS classification: Group A--emergent and very urgent patients; Group B--urgent and standard patients. The two groups were compared in terms of clinical and demographic characteristics, pre-hospital delay (PHD), IHD and door-to-needle (DNT) and door-to-balloon (DBT) times. The mean age of the patients studied was 68 +/- 14 years, and 184 patients (65.7%) were male. Group A comprised 220 patients (79%) and Group B 58 patients (21%). There were no significant differences between the two groups in clinical or demographic characteristics or in PHD. IHD, DNT and DBT were significantly longer in Group B. 1) Although the majority of STEMI patients were classified as emergent or very urgent, the percentage not classified as such by the MTS was excessively high. 2) This could not be explained by clinical characteristics or by PHD. 3) The incorrect classification by the MTS of patients with STEMI resulted in significantly increased IHD in a large proportion of patients, limiting prompt access to reperfusion therapy.

Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: A pro- and retrospective analysis

PubMed Central

Janik, Stefan; Bekos, Christine; Hacker, Philipp; Raunegger, Thomas; Ghanim, Bahil; Einwallner, Elisa; Beer, Lucian; Klepetko, Walter; Müllauer, Leonhard; Ankersmit, Hendrik J.; Moser, Bernhard

2017-01-01

Objective Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs. Results Pretreatment CRP serum concentrations were significantly elevated in patients with TETs, particularly TCs and metastatic TETs. After complete tumor resection CRP serum concentrations were decreased (p = 0.135) but increased significantly in case of tumor recurrence (p = 0.001). High pretreatment CRP was associated with significantly worse 5- and 10-year freedom-from recurrence (FFR) (p = 0.010) and was a negative prognostic factor for FFR (HR 3.30; p = 0.015). IL-6 (not IL-1β) serum concentrations were significantly elevated in patients with TETs but we did not detect CRP tissue expression in TETs. Materials and Methods Pretreatment CRP serum concentrations were retrospectively analyzed from 128 surgical patients (1990–2015). In a subset of 68 patients longitudinal analysis of CRP was performed. Additionally, immunohistochemical tumor CRP expression and serum concentrations of interleukin (IL)-6 and IL-1β were measured. Conclusions Hence, diagnostic measurement of serum CRP might be useful to indicate highly aggressive TETs and to make doctors consider tumor recurrences during oncological follow-up. PMID:28514756

Hemodynamics and Vascular Hypertrophy in African Americans and Caucasians With High Blood Pressure.

PubMed

Hill, LaBarron K; Sherwood, Andrew; Blumenthal, James A; Hinderliter, Alan L

2016-12-01

Hypertension in African Americans is characterized by greater systemic vascular resistance (SVR) compared with Caucasian Americans, but the responsible mechanisms are not known. The present study sought to determine if peripheral vascular hypertrophy is a potential mechanism contributing to elevated SVR in African Americans with high blood pressure (BP). In a biracial sample of 80 men and women between the ages of 25 and 45 years, with clinic BP in the range 130/85-160/99mm Hg, we assessed cardiac output and SVR, in addition to BP. Minimum forearm vascular resistance (MFVR), a marker of vascular hypertrophy, also was assessed. SVR was elevated in African Americans compared with Caucasians (P < 0.001). Regression models indicated that age, body mass index, 24-hour diastolic BP, and ethnicity were significant predictors of SVR. There was also a significant interaction between ethnicity and MFVR in explaining SVR in the study sample. In particular, there was a significant positive association between MFVR and SVR among African Americans (P = 0.002), whereas the association was inverse and not statistically significant among Caucasians (P = 0.601). Hypertrophy of the systemic microvasculature may contribute to the elevated SVR that is characteristic of the early stages of hypertension in African American compared with Caucasians. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Pain Coping Skills Training for Patients with Elevated Pain Catastrophizing who are Scheduled for Knee Arthroplasty: A Quasi-Experimental Study

PubMed Central

Riddle, Daniel L.; Keefe, Francis J.; Nay, William T.; McKee, Daphne; Attarian, David E.; Jensen, Mark P.

2011-01-01

Objectives To (1) describe a behavioral intervention designed for patients with elevated pain catastrophizing who are scheduled for knee arthroplasty, and (2) use a quasi-experimental design to evaluate the potential efficacy of the intervention on pain severity, catastrophizing cognitions, and disability. Design Quasi-experimental non-equivalent control group design with a 2 month follow-up. Setting Two university-based Orthopedic Surgery departments. Participants Adults scheduled for knee replacement surgery who reported elevated levels of pain catastrophizing. Patients were recruited from two clinics and were assessed prior to surgery and 2 months following surgery. Intervention A group of 18 patients received a psychologist directed pain coping skills training intervention comprising 8 sessions and the other group, a historical cohort of 45 patients, received usual care. Main Outcome Measures WOMAC Pain and Disability scores as well as scores on the Pain Catastrophizing Scale. Results Two months following surgery, the patients who received pain coping skills training reported significantly greater reductions in pain severity and catastrophizing, and greater improvements in function as compared to the usual care cohort. Conclusion Pain catastrophizing is known to increase risk of poor outcome following knee arthroplasty. The findings provide preliminary evidence that the treatment may be highly efficacious for reducing pain, catastrophizing, and disability, in patients reporting elevated catastrophizing prior to knee arthroplasty. A randomized clinical trial is warranted to confirm these effects. PMID:21530943

Vitamin C treatment reduces elevated C-reactive protein

PubMed Central

Block, Gladys; Jensen, Christopher D.; Dalvi, Tapashi B.; Norkus, Edward P.; Hudes, Mark; Crawford, Patricia B.; Holland, Nina; Fung, Ellen B.; Schumacher, Laurie; Harmatz, Paul

2009-01-01

Plasma C-reactive protein (CRP) is an inflammatory biomarker that predicts cardiovascular disease. We investigated whether vitamins C or E could reduce CRP. Healthy nonsmokers (n=396) were randomized to three groups:1000 mg/day vitamin C, 800 IU/day vitamin E, or placebo, for two months. Median baseline CRP was low, 0.85 mg/L. No treatment effect was seen when all participants are included. However, significant interaction was found, indicating that treatment effect depends on baseline CRP concentration. Among participants with CRP indicative of elevated cardiovascular risk (≥1.0 mg/L), vitamin C reduced median CRP by 25.3% vs. Placebo (p=0.02), (median reduction in the vitamin C group, 0.25 mg/L, 16.7%). These effects are similar to those of statins. The vitamin E effect was not significant. In summary, treatment with vitamin C but not E significantly reduced CRP among individuals with CRP ≥ 1.0 mg/L. Among the obese, 75% had CRP ≥ 1.0 mg/L. These data extend previous results in smokers, and identify CRP levels susceptible to reductions. Research is needed to determine whether reducing this inflammatory biomarker with vitamin C could reduce diseases associated with obesity. But research on clinical benefits of antioxidants should limit participants to persons with elevations in the target biomarkers. PMID:18952164

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

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

Bian, Yong, E-mail: drbiany@126.com; Yu, Yun; Wang, Shanshan

2015-08-07

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDACmore » patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.« less

Infection-induced anaemia: a cross-sectional study of 14,636 German travellers aged 20-49 years.

PubMed

Herbinger, K-H; Metzner, M; Schmidt, V; Beissner, M; Nothdurft, H D; von Sonnenburg, F; Löscher, T

2013-12-01

Anaemia is a frequently diagnosed condition which can develop as a consequence of numerous factors, including infectious diseases (IDs). Travelling, especially in sub-/tropical regions, leads to an elevated risk of contracting IDs. The aim of our study was to assess the epidemiological significance of IDs in inducing anaemia among a large cohort of returned travellers. This was a cross-sectional study in which data on 17,009 returned travellers aged 20-49 years who consulted the travel medicine clinic of the University of Munich between 1999 and 2011 were retrieved and analysed. Of the returned travellers, 8.3 % (6.0 % of males/10.4 % of females) were diagnosed with anaemia. The prevalence of anaemia was significantly elevated among patients of African (21.4/28.3 %) and Asian (11.6/15.7 %) origin. When the study population was restricted to the 14,636 travellers of German origin, 7.1 % of the returned travellers (4.6/9.6 %) were diagnosed with anaemia. The prevalence was significantly elevated among patients who travelled for >30 days (5.7 of males/10.6 % of females) and for male travellers visiting friends and relatives (7.7 %). However, these correlations were confounded by malaria. The prevalence of anaemia was significantly elevated only among returned travellers diagnosed with malaria (36.1 of males/26.9 % of females) and with symptomatic intestinal Entamoeba histolytica infections (30.0/33.3 %). Following the exclusion of confounding by malaria from the statistical analysis, the prevalence of anaemia was found to be significantly elevated among patients of African and Asian origin, and among patients of German origin who had travelled for >30 days, it could be mainly attributable to chronic, long-lasting causes. Although more than 550 travel-associated IDs were assessed in our study, only symptomatic intestinal Entamoeba histolytica infections and, to an even larger extent, malaria were determined to be of epidemiological significance for inducing anaemia among travellers.

Elevated serum levels of TPS and CYFRA 21-1 predict poor prognosis in advanced non-small-cell lung cancer patients treated with gefitinib.

PubMed

Chen, Fengsheng; Luo, Xi; Zhang, Jinbiao; Lu, Yang; Luo, Rongcheng

2010-09-01

Serum concentrations of tissue polypeptide-specific antigen (TPS) and Cytokeratin-19-Fragments (CYFRA 21-1) before operation or chemotherapy have been proved to be a useful prognostic tool for patients with NSCLC, but the related data for advanced NSCLC patients treated with gefitinib are limited. We retrospectively reviewed 122 advanced NSCLC patients treated with gefitinib between April 2002 and August 2007. Multiple clinical factors including pretreatment serum levels of TPS and CYFRA 21-1, age, gender, performance status (PS), smoking history, stage, histology, the number of prior chemotherapy and the patients' clinical outcomes were analyzed. Patients without elevated serum TPS levels had a more RR (36.8%) than those with elevated serum TPS levels (18.5%) (P = 0.023), nevertheless, a similar result was not seen in patients with normal CYFRA 21-1 levels. For patients with normal vs. high TPS levels, the median survival times (MSTs) were 15.9 vs. 7.3 months (P = 0.001). For patients with normal vs. high CYFRA 21-1, the MSTs were 15.4 vs. 7.5 months (P = 0.003). Moreover, for patients with both elevated, vs. one elevated and both normal TPS and CYFRA 21-1 levels, the MSTs were 5.4 vs. 11.4 months (P = 0.001), and 16.5 months (P < 0.001), respectively. In multivariate analysis, TPS (P = 0.001) and CYFRA 21-1 (P = 0.005) alone or combination (P < 0.001) remained significant correlation to survival. In NSCLC patients with gefitinib therapy, pretreatment serum levels of TPS and CYFRA 21-1 alone or combined might be independent prognostic factors, and the pretreatment serum TPS level may predict the tumor response.

Effect of the percentage of body fat on surgical, clinical and pathological outcomes in women with endometrial cancer.

PubMed

Kerimoglu, Ozlem Secilmis; Pekin, Aybike; Yilmaz, Setenay Arzu; Yavas, Guler; Beyhekim, Fatma; Demirtaş, Ayşe Ayda; Dogan, Nasuh Utku; İlhan, Tolgay Tuyan; Celik, Cetin

2015-03-01

This study used the measure of percentage of body fat (%BF) to define obesity and evaluated the effect of percentage of %BF on clinical, surgical and pathological features in women with endometrial cancer. Between 2011 and 2013, bioelectrical impedance analysis and body size measurements of 94 patients whose endometrial biopsy revealed endometrial cancer were obtained. Patients were divided into two groups according to body mass index (BMI) (normal, < 30 kg/m(2); elevated, ≥ 30 kg/m(2)), and also classified by %BF (normal, < 32%; elevated, ≥ 32%). The patients' mean age was 55.0 ± 10.9 years. Mean %BF and BMI were 40.8% ± 9.8% and 32.9 ± 7.5, respectively. Eighty-three (88%) patients were obese according to %BF; 54 (57%) were obese according to BMI. Patients with elevated %BF were more likely to have less than 50% myometrial invasion (P = 0.004). Significantly more para-aortic lymph nodes were retrieved in patients with normal %BF or BMI (P < 0.001, P < 0.001). Patients with elevated %BF had longer operating times (P = 0.043) and were more likely to have stage I disease than patients with normal %BF (P < 0.001). Endometrial cancer patients with an elevated %BF are more likely to have stage I disease and less than 50% myometrial invasion than patients with normal %BF. Defining obesity by BF may provide better estimation of obesity prevalence in patients with endometrial cancer and further understanding the relationship between BF with endometrial cancer may give more information about the effects of obesity on endometrial cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

McPherson, Stuart; Henderson, Elsbeth; Burt, Alastair D; Day, Christopher P; Anstee, Quentin M

2014-05-01

A third of the population are estimated to have NAFLD of varying severity. Serum immunoglobulins are frequently elevated in patients with chronic liver disease, but little is known about serum immunoglobulin levels in patients with NAFLD. Aim of this study was to evaluate serum immunoglobulin levels (IgA, IgG, and IgM) in a large cohort of patients with biopsy-proven NAFLD and determine if immunoglobulin levels are associated with clinical or histological features. Patients seen in a tertiary fatty liver clinic between 1999 and 2009 were included. Liver biopsies were assessed using the Kleiner score. Immunoglobulin levels and other blood tests were taken at time of biopsy. 285 patients (110 simple steatosis and 175 NASH) had serum immunoglobulins measured within 6months of liver biopsy. 130 (46%) patients had elevated (>1× upper limit of normal) serum IgA levels, 28 (10%) patients had elevated IgG and 22 (8%) raised IgM. Serum IgA levels were elevated more frequently in patients with NASH compared with subjects with simple steatosis (55% vs. 31%, p<0.001). Overall, 55 (19%) patients had advanced liver fibrosis (Kleiner stage 3-4). There was a significant positive association between serum IgA levels and the stage of fibrosis (p<0.001). Serum IgA, age, platelets, AST/ALT ratio and BMI were all independently with advanced fibrosis following multivariate analysis. A model constructed from these independent predictors accurately predicted advanced fibrosis (AUROC 0.87). The serum IgA level was frequently elevated in patients with NAFLD and was an independent predictor of advanced fibrosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Impact of low level of high-density lipoprotein-cholesterol sampled in overnight fasting state on the clinical outcomes in patients with acute myocardial infarction (difference between ST-segment and non-ST-segment-elevation myocardial infarction).

PubMed

Ji, Mi Seon; Jeong, Myung Ho; Ahn, Young Keun; Kim, Young Jo; Chae, Shung Chull; Hong, Taek Jong; Seong, In Whan; Chae, Jei Keon; Kim, Chong Jin; Cho, Myeong Chan; Rha, Seung-Woon; Bae, Jang Ho; Seung, Ki Bae; Park, Seung Jung

2015-01-01

Despite good treatment, there are residual risks in acute myocardial infarction (AMI) patients, and low level of high-density lipoprotein-cholesterol (HDL) has drawn attention as a possible cause. However, the impact of low HDL on ST-segment-elevation myocardial infarction (STEMI) compared with non-ST-segment-elevation myocardial infarction (NSTEMI) is not clear. Our aim was to evaluate the impact of low HDL on clinical outcomes in patients with STEMI or NSTEMI. We included 9270 AMI patients undergoing successful percutaneous coronary intervention. They were grouped into STEMI and NSTEMI, and subdivided into two groups according to HDL level sampled in overnight fasting state. Primary end point was in-hospital death. Secondary end point was a composite of major adverse cardiac events (MACE) in hospital survivors during one-year follow-up. In the STEMI population, low HDL group showed significantly higher in-hospital death rate [4.6% vs. 1.4%, hazard ratio (HR): 2.380, 95% confidence interval (CI): 1.143-4.956, p=0.020] than normal HDL group. In NSTEMI population, there was no significant difference between two groups (1.8% vs. 0.9%, HR: 1.231, 95% CI: 0.649-2.335, p=0.525), but in subgroup analysis, very low HDL subgroup showed higher in-hospital mortality rate compared with normal HDL group (4.0% vs. 0.9%, respectively, p=0.009). In 12-month MACE rates, there was no significant difference between two groups in both populations. Low HDL was associated with significantly higher risk of in-hospital mortality in STEMI patients, but not in NSTEMI patients. Thus, more aggressive treatment should be considered in STEMI patients with low HDL. Copyright © 2014. Published by Elsevier Ltd.

Adjunctive 5-hydroxytryptophan slow-release for treatment-resistant depression: Clinical and pre-clinical rationale

PubMed Central

Jacobsen, Jacob P.R.; Krystal, Andrew D.; Krishnan, K. Ranga R.; Caron, Marc G.

2017-01-01

Serotonin transporter (SERT) inhibitors treat depression by elevating brain extracellular 5-hydroxytryptamine (5-HTExt). However, only one-third of patients respond adequately. Treatment-resistant depression (TRD) is a major unmet need. Interestingly, elevating 5-HTExt beyond what is achieved by a SERT inhibitor appears to treat TRD. Adjunctive administration of 5-hydroxytryptophan (5-HTP) safely elevates 5-HTExt beyond the SERT inhibitor effect in humans; but, 5-HTP cannot be a clinically viable drug because of its poor pharmacokinetics. A slow-release (SR) delivery mode would be predicted to overcome the pharmacokinetic limitations of 5-HTP, substantially enhance the pharmacological action, and transform 5-HTP into a clinically viable drug. Animal studies bear out this prediction. Thus, adjunct 5-HTP SR could be an important new treatment for TRD. Here we review the clinical and preclinical evidence. PMID:27692695

Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography.

PubMed

Peretti, Charles-Siegfried; Peretti, Charles Roger; Kozora, Elizabeth; Papathanassiou, Dimitri; Chouinard, Virginie-Anne; Chouinard, Guy

2012-01-01

Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography (SPECT). 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% (0/23) of controls. SLE women also had significantly greater cognitive dysfunction (mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction. Copyright © 2012 S. Karger AG, Basel.

Kinematic analysis of dynamic shoulder motion in patients with reverse total shoulder arthroplasty.

PubMed

Kwon, Young W; Pinto, Vivek J; Yoon, Jangwhon; Frankle, Mark A; Dunning, Page E; Sheikhzadeh, Ali

2012-09-01

Reverse total shoulder arthroplasty (rTSA) has been used to treat patients with irreparable rotator cuff dysfunction. Despite the proven clinical efficacy, there is minimal information regarding the underlying changes to the shoulder kinematics associated with this construct. Therefore, we sought to examine the kinematics of dynamic shoulder motion in patients with well-functioning rTSA. We tested 12 healthy subjects and 17 patients with rTSA. All rTSA patients were able to elevate their arms to at least 90° and received the implant as the primary arthroplasty at least 6 months before testing. On average, the rTSA patients elevated their arms to 112° ± 12° (mean ± SD) and reported an American Shoulder and Elbow Surgeons outcome score of 90.6 ± 6.3. A 3-dimensional electromagnetic motion capture device was used to detect the dynamic motion of the trunk, scapula, and humerus during bilateral active shoulder elevation along the sagittal, scapular, and coronal planes. In both healthy and rTSA shoulders, the majority of the humeral-thoracic motion was provided by the glenohumeral motion. Therefore, the ratio of glenohumeral to scapulothoracic (ST) motion was always greater than 1.62 during elevation along the scapular plane. In comparison to healthy subjects, however, the contribution of ST motion to overall shoulder motion was significantly increased in the rTSA shoulders. This increased contribution was noted in all planes of shoulder elevation and was maintained when weights were attached to the arm. Kinematics of the rTSA shoulders are significantly altered, and more ST motion is used to achieve shoulder elevation. Copyright © 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Epidermal Dysfunction Leads to an Age-Associated Increase in Levels of Serum Inflammatory Cytokines.

PubMed

Hu, Lizhi; Mauro, Theodora M; Dang, Erle; Man, George; Zhang, Jing; Lee, Dale; Wang, Gang; Feingold, Kenneth R; Elias, Peter M; Man, Mao-Qiang

2017-06-01

Even though elderly populations lack visible or other clinical signs of inflammation, their serum cytokine and C-reactive protein levels typically are elevated. However, the origin of age-associated systemic inflammation is unknown. Our previous studies showed that abnormalities in epidermal function provoke cutaneous inflammation, and because intrinsically aged skin displays compromised permeability barrier homeostasis and reduced stratum corneum hydration, we hypothesized here that epidermal dysfunction could contribute to the elevations in serum cytokines in the elderly. Our results show first that acute disruption of the epidermal permeability barrier in young mice leads not only to a rapid increase in cutaneous cytokine mRNA expression but also an increase in serum cytokine levels. Second, cytokine levels in both the skin and serum increase in otherwise normal, aged mice (>12 months). Third, expression of tumor necrosis factor-α and amyloid A mRNA levels increased in the epidermis, but not in the liver, in parallel with a significant elevation in serum levels of cytokines. Fourth, disruption of the permeability barrier induced similar elevations in epidermal and serum cytokine levels in normal and athymic mice, suggesting that T cells play a negligible role in the elevations in cutaneous and serum inflammatory cytokines induced by epidermal dysfunction. Fifth, correction of epidermal function significantly reduced cytokine levels not only in the skin but also in the serum of aged mice. Together, these results indicate that the sustained abnormalities in epidermal function in chronologically aged skin contribute to the elevated serum levels of inflammatory cytokines, potentially predisposing the elderly to the subsequent development or exacerbation of chronic inflammatory disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Elevated depressive symptoms are associated with hypertriglyceridemia in Japanese male workers.

PubMed

Kamezaki, Fumihiko; Sonoda, Shinjo; Nakata, Sei; Okazaki, Masahiro; Tamura, Masahito; Abe, Haruhiko; Takeuchi, Masaaki; Otsuji, Yutaka

2011-01-01

The aim of this study was to determine whether elevated depressive symptoms are associated with metabolic syndrome and its components in the Japanese population. Out of 1,386 male workers who underwent measurements of variables of metabolic syndrome components in their health checkup, 1,186 subjects (44.5 ± 9.6 years) completed the Zung self-rating depression scale (ZSDS) (response rate 85.6%). In this study, metabolic syndrome was defined according to the joint scientific statement proposed by 6 major organizations, including the International Diabetes Federation. The overall frequency of elevated depressive symptoms (ZSDS scores ≥40) was 42.1% (n=499). The incidence of metabolic syndrome was significantly higher in subjects with elevated depressive symptoms than in those without (13.2% vs. 8.9%, p<0.05). Of all the metabolic syndrome components, mean triglyceride levels were significantly higher in subjects with elevated depressive symptoms than in those without [124.7 (95% confidence interval (CI): 117.8-131.7) mg/dL vs. 111.5 (95% CI: 107.2-115.9) mg/dL, p<0.05]. Consequently, hypertriglyceridemia (28.9% vs. 21.0%, p<0.01) was the main component correlated with the between-group difference of metabolic syndrome incidence. In the logistic regression analysis after adjustment for potential confounders, the odds ratio of the total ZSDS scores for the diagnosis of hypertriglyceridemia was 1.52 (95% CI: 1.13-2.04; p<0.01), and the major depressive symptom was psychomotor agitation (odds ratio: 1.47; 95% CI: 1.10-1.94; p<0.01). This study showed that elevated depressive symptoms were associated with hypertriglyceridemia in Japanese male workers, which affected the clinical diagnosis of metabolic syndrome.

Evaluation of serum lysyl oxidase as a blood test for colorectal cancer.

PubMed

Ward, S T; Weston, C J; Hepburn, E; Damery, S; Hejmadi, R K; Morton, D G; Middleton, G; Ismail, T; Adams, D H

2014-06-01

Lysyl oxidase (LOX) expression is elevated in colorectal cancer (CRC) tissue and associated with disease progression. A blood test may form a more acceptable diagnostic test for CRC although LOX has not previously been measured in the serum. We therefore sought to determine the clinical usefulness of a serum LOX test for CRC in a symptomatic population. Adult patients referred to a hospital colorectal clinic with bowel symptoms completed a questionnaire and provided a blood sample for serum LOX measurement. Associations between presenting symptoms, serum LOX concentrations and outcomes of investigations were tested by univariate and multivariate analyses to determine if serum LOX was clinically useful in the prediction of CRC. LOX expression in CRC and adjacent colon biopsies was evaluated by ELISA and immunohistochemistry. Thirty-one cases of colorectal cancer and 16 high-risk polyps were identified from a total of 962 participants. There was no association between serum LOX concentration and the presence of CRC, high-risk polyps or cancers at any site. LOX expression was significantly increased in CRC tissue compared to adjacent colon. Despite overexpression of LOX in CRC tissue, elevated serum levels could not be demonstrated. Serum LOX measurement is therefore not a clinically useful test for CRC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Late myocardial ischemia with ST-segment elevation after negative dobutamine stress echocardiography in a patient with normal coronary arteries.

PubMed

Cabani, Enrico; Lattanzi, Fabio; Paci, Anna Maria; Pieroni, Andrea; Baria, Luca; Tommasi, Salvatore Mario De

2009-04-01

Late complications after pharmacological stress echocardiography are infrequent but potentially dreadful events. We report the case of a 80-year-old woman admitted to hospital for rest chest pain with trivial troponin increase, normal left ventricular function and no significant ECG changes. A dobutamine stress echocardiography was performed for diagnostic purpose, with a negative result. About 30 min after the end of dobutamine infusion, she developed ST-segment elevation in inferior leads associated with chest pain and left ventricular dyssynergy, promptly resolved by sublingual nitrates. Subsequently, angiography documented the absence of significant coronary stenoses. The following clinical course was uneventful. Transient myocardial ischemia was likely due to dobutamine-induced coronary spasm. The case emphasizes the utility of routine, long-lasting monitoring of patients after stress echocardiography, even if negative, to counteract possible late life-threatening complications.

Effect of preseasonal enzyme potentiated desensitisation (EPD) on plasma-IL-6 and IL-10 of grass pollen-sensitive asthmatic children.

PubMed

Ippoliti, F; Ragno, V; Del Nero, A; McEwen, L M; McEwen, H; Businco, L

1997-05-01

EPD is a method of preventive immunotherapy which employs b-glucuronidase as a biological response modifier. Plasma IL-6 and IL-10 were measured before a single injection of EPD, 24 hours later and 15 days after in a group of 17 children suffering from grass pollen asthma. 17 normal untreated children were used as controls. Although the study was conducted before the grass pollen season when the allergic children were free of symptoms, their plasma IL-6 and IL-10 were significantly elevated before the injection of EPD. 24 hours after treatment the plasma IL-10 had increased significantly and there was also a slight rise in IL-6. 15 days after treatment IL-6 had fallen to normal but IL-10 was still elevated. These findings suggest antigen-specific and non-specific mechanisms by which EPD may produce clinical improvement.

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

PubMed Central

Montezano, Augusto C.

2014-01-01

Abstract Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redox-sensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20, 164–182. PMID:23600794

Thyroid Autoantibodies and the Clinical Presentation of Moyamoya Disease: A Prospective Study.

PubMed

Lanterna, Luigi A; Galliani, Silvia; Zangari, Rosalia; Conti, Luciano; Brembilla, Carlo; Gritti, Paolo; Colleoni, Maria Luisa; Bernucci, Claudio

2018-05-01

Moyamoya is a rare cerebrovascular disease characterized by the progressive occlusion of the intracranial carotid artery. Thyroid autoantibodies have been found to be associated with the disease, but their clinical significance has never been studied. The objective of this study was to investigate the relationship between thyroid autoantibodies and the clinical presentation of moyamoya. This is a prospective study including 37 patients with moyamoya disease (MMD) or unilateral moyamoya (uMM). Thyroid function and thyroid autoantibodies (e.g., antithyroperoxidase and antithyroglobulin) were investigated. We studied the effect of gender, age, type of moyamoya (uMM versus MMD), and thyroid autoantibodies on the clinical presentation, dichotomized into aggressive (hemorrhage, major stroke, or frequent transient ischemic attack [TIA]) and nonaggressive presentation (headache, rare TIAs, and incidental diagnosis) according to the criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis. Of the 37 patients included in the study, the autoantibodies were elevated in 9 (24.3%). An aggressive presentation occurred in 21 patients (hemorrhage in 11, major stroke in 9, frequent TIAs in 1). The autoantibodies were elevated in 8 of the 21 patients (38.09%) with an aggressive presentation and in 1 of those presenting with minor symptoms (6.2%). The presence of elevated autoantibodies was the only variable associated with an aggressive presentation in the multivariate logistic analysis (P = .048). When the serum concentration of the thyroid autoantibodies is increased, the patients have a higher risk of an aggressive presentation. Our results support the hypothesis that activation of immune-mediated processes affects the moyamoya physiopathology. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level.

PubMed

Chua, Michael E; Tanseco, Patrick P; Mendoza, Jonathan S; Castillo, Josefino C; Morales, Marcelino L; Luna, Saturnino L

2015-04-01

To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis.

The relationship between prolactin response and clinical efficacy of risperidone in acute psychotic inpatients.

PubMed

Lee, Bun-Hee; Kim, Yong-Ku

2006-06-01

Hyperprolactinemia can be induced by dopamine D2 receptor-binding drugs such as antipsychotic drugs. The author investigated the relationship between changes in prolactin (PRL) and clinical efficacy of risperidone. In this study, 27 acute psychotic inpatients completed a 12-week trial of risperidone. At baseline and at 2, 4, 8, and 12 weeks after beginning medication, the author measured PRL, assessed hyperprolactinemia-related symptoms, and administered the Brief Psychotic Rating Scale (BPRS). Risperidone treatment significantly elevated serum PRL level (range: 26.9 ng/ml-320.0 ng/ml). The increases of PRL in females were higher than males. The changes in serum PRL levels were not significantly correlated with the improvements in total BPRS scores. PRL-related symptoms such as irregular menstruation, galactorrhea, or erectile dysfunction occurred in nine subjects (7 females and 2 males) whose serum PRL levels increase very highly after 2 weeks of risperidone. In conclusion, our study suggests that the changes in serum PRL levels were not significantly correlated with clinical efficacy of risperidone.

Schizotypal traits in a non-clinical sample from Hawai'i.

PubMed

Schiffman, Jason

2004-03-01

Most research investigating schizotypal traits, and linking schizotypal personality disorder (SPD) to later schizophrenia, has used Caucasian samples. The lack of cross-cultural comparisons on SPD trait scales inhibits confidence in generalizing the link between SPD and schizophrenia to non-Caucasian populations. The few studies investigating cross-cultural rates of schizotypal traits in non-clinical samples report mixed findings with respect to cultural variation. This study report rates of schizotypal traits in an ethnically and culturally diverse non-clinical sample (N = 353) in the state of Hawaii using the Schizotypai Personality Disorder Questionnaire-B (SPQ-B). Analyses did not detect significantly elevated rates between ethnic groups on the Cognitive/Perceptual, Disorganized, or Total SPQ Score Scales. Significant differences between Caucasians and Asians, as well as between Caucasians and Mixed Ethnicity on the SPQ-B Interpersonal Scale suggest relatively less shyness and more sociability in the Caucasian group. Generally, findings of no significant differences between ethnic groups on the SPQ-B suggest that rates of schizotypy are similar across ethnic groups in Hawaii.

Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea.

PubMed

Niu, Yawen; Zhao, Guiqiu; Li, Cui; Lin, Jing; Jiang, Nan; Che, Chengye; Zhang, Jie; Xu, Qiang

2018-01-01

To determine the role of protease-activated receptor-2 (PAR-2) in cornea infected by Aspergillus fumigatus. PAR-2 was tested in normal and infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A. fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was documented by clinical score and photographs with a slit lamp. PCR, Western blot, and ELISA tested expression of PAR-2, IL-1β, TNF-α, IFN-γ, MIP-2, and p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and immunofluorescent staining. PAR-2 expression was significantly elevated by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY-NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and proinflammatory cytokine expression compared with infected control. In PMNs, PAR-2 expression was also significantly increased by A. fumigatus, which was significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited proinflammatory cytokine protein expression, as compared with that in infected control cells, which may be modified by p-ERK1/2. These data provide evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN infiltration, and proinflammatory cytokine expression through PAR-2, which may be modified by p-ERK1/2.

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer

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

Chan, D.W.; Waud, J.M.; Hsu, T.H.

1983-06-01

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T/sub 4/ derivative that does not bind significantly to the thyroxine-binding proteins. This RIA was evaluated for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T/sub 4/ assay was expressed as coefficient of variation. The correlation coefficients (r) of a dialysis method and a free thyroxine index were 0.871 and 0.911, respectively. Free T/sub 4/ correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition,more » 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T/sub 4/, very low T/sub 3/, and elevated rT/sub 3/. We found this free T/sub 4/ assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.« less

Nonsteroidal mineralocorticoid antagonists in diabetic kidney disease.

PubMed

Dojki, Farheen K; Bakris, George

2017-09-01

Current data highlight the pathological aspects of excess aldosterone in promoting glomerular hypertrophy, glomerulosclerosis, and proteinuria in diabetic kidney disease (DKD). The role of nonsteroidal mineralocorticoid receptor antagonists (MRAs) in DKD is being evaluated in ongoing clinical trials. Recent studies demonstrate beneficial effects of adding MRAs to the treatment regimen of patients with type 2 diabetes with nephropathy. The MRAs spironolactone and eplerenone can protect against organ damage caused by elevated levels of serum aldosterone in patients with heart failure and DKD but are limited by their side effects, for example, hyperkalemia. Finerenone is more selective for the mineralocorticoid receptor than spironolactone and has greater affinity for the mineralocorticoid receptor than eplerenone. It reduces the concentration of aldosterone without causing significant elevation in serum potassium. MRAs have a clear role in reducing albuminuria when used with other renin-angiotensin system blockers in DKD; however, hyperkalemia limits their use. This article provides an overview of clinical studies with a novel MRA, finerenone, and several nonsteroidal MRAs being studied for treatment in DKD.

Video game violence use among "vulnerable" populations: the impact of violent games on delinquency and bullying among children with clinically elevated depression or attention deficit symptoms.

PubMed

Ferguson, Christopher J; Olson, Cheryl K

2014-01-01

The issue of children's exposure to violent video games has been a source of considerable debate for several decades. Questions persist whether children with pre-existing mental health problems may be influenced adversely by exposure to violent games, even if other children are not. We explored this issue with 377 children (62 % female, mixed ethnicity, mean age = 12.93) displaying clinically elevated attention deficit or depressive symptoms on the Pediatric Symptom Checklist. Results from our study found no evidence for increased bullying or delinquent behaviors among youth with clinically elevated mental health symptoms who also played violent video games. Our results did not support the hypothesis that children with elevated mental health symptoms constitute a "vulnerable" population for video game violence effects. Implications and suggestions for further research are provided.

Elevated Plasma Soluble CD14 and Skewed CD16+ Monocyte Distribution Persist despite Normalisation of Soluble CD163 and CXCL10 by Effective HIV Therapy: A Changing Paradigm for Routine HIV Laboratory Monitoring?

PubMed Central

Castley, Alison; Berry, Cassandra; French, Martyn; Fernandez, Sonia; Krueger, Romano; Nolan, David

2014-01-01

Objective We investigated plasma and flow cytometric biomarkers of monocyte status that have been associated with prognostic utility in HIV infection and other chronic inflammatory diseases, comparing 81 HIV+ individuals with a range of treatment outcomes to a group of 21 healthy control blood donors. Our aim is to develop and optimise monocyte assays that combine biological relevance, clinical utility, and ease of adoption into routine HIV laboratory practice. Design Cross-sectional evaluation of concurrent plasma and whole blood samples. Methods A flow cytometry protocol was developed comprising single-tube CD45, CD14, CD16, CD64, CD163, CD143 analysis with appropriately matched isotype controls. Plasma levels of soluble CD14 (sCD14), soluble CD163 (sCD163) and CXCL10 were measured by ELISA. Results HIV status was associated with significantly increased expression of CD64, CD143 and CD163 on CD16+ monocytes, irrespective of the virological response to HIV therapy. Plasma levels of sCD14, sCD163 and CXCL10 were also significantly elevated in association with viremic HIV infection. Plasma sCD163 and CXCL10 levels were restored to healthy control levels by effective antiretroviral therapy while sCD14 levels remained elevated despite virological suppression (p<0.001). Conclusions Flow cytometric and plasma biomarkers of monocyte activation indicate an ongoing systemic inflammatory response to HIV infection, characterised by persistent alterations of CD16+ monocyte expression profiles and elevated sCD14 levels, that are not corrected by antiretroviral therapy and likely to be prognostically significant. In contrast, sCD163 and CXCL10 levels declined on antiretroviral therapy, suggesting multiple activation pathways revealed by these biomarkers. Incorporation of these assays into routine clinical care is feasible and warrants further consideration, particularly in light of emerging therapeutic strategies that specifically target innate immune activation in HIV infection. PMID:25544986

Clinical relevance and discriminatory value of elevated liver aminotransferase levels for dengue severity.

PubMed

Lee, Linda K; Gan, Victor C; Lee, Vernon J; Tan, Adriana S; Leo, Yee Sin; Lye, David C

2012-01-01

Elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is prominent in acute dengue illness. The World Health Organization (WHO) 2009 dengue guidelines defined AST or ALT ≥ 1000 units/liter (U/L) as a criterion for severe dengue. We aimed to assess the clinical relevance and discriminatory value of AST or ALT for dengue hemorrhagic fever (DHF) and severe dengue. We retrospectively studied and classified polymerase chain reaction positive dengue patients from 2006 to 2008 treated at Tan Tock Seng Hospital, Singapore according to WHO 1997 and 2009 criteria for dengue severity. Of 690 dengue patients, 31% had DHF and 24% severe dengue. Elevated AST and ALT occurred in 86% and 46%, respectively. Seven had AST or ALT ≥ 1000 U/L. None had acute liver failure but one patient died. Median AST and ALT values were significantly higher with increasing dengue severity by both WHO 1997 and 2009 criteria. However, they were poorly discriminatory between non-severe and severe dengue (e.g., AST area under the receiver operating characteristic [ROC] curve=0.62; 95% confidence interval [CI]: 0.57-0.67) and between dengue fever (DF) and DHF (AST area under the ROC curve=0.56; 95% CI: 0.52-0.61). There was significant overlap in AST and ALT values among patients with dengue with or without warning signs and severe dengue, and between those with DF and DHF. Although aminotransferase levels increased in conjunction with dengue severity, AST or ALT values did not discriminate between DF and DHF or non-severe and severe dengue.

Clinical significance of stress-related increase in blood pressure: current evidence in office and out-of-office settings.

PubMed

Munakata, Masanori

2018-05-29

High blood pressure is the most significant risk factor of cardiovascular and cerebrovascular diseases worldwide. Blood pressure and its variability are recognized as risk factors. Thus, hypertension control should focus not only on maintaining optimal levels but also on achieving less variability in blood pressure. Psychosocial stress is known to contribute to the development and worsening of hypertension. Stress is perceived by the brain and induces neuroendocrine responses in either a rapid or long-term manner. Moreover, endothelial dysfunction and inflammation might be further involved in the modulation of blood pressure elevation associated with stress. White-coat hypertension, defined as high clinic blood pressure but normal out-of-office blood pressure, is the most popular stress-related blood pressure response. Careful follow-up is necessary for this type of hypertensive patients because some show organ damage or a worse prognosis. On the other hand, masked hypertension, defined as high out-of-office blood pressure but normal office blood pressure, has received considerable interest as a poor prognostic condition. The cause of masked hypertension is complex, but evidence suggests that chronic stress at the workplace or home could be involved. Chronic psychological stress could be associated with distorted lifestyle and mental distress as well as long-lasting allostatic load, contributing to the maintenance of blood pressure elevation. Stress issues are common in patients in modern society. Considering psychosocial stress as the pathogenesis of blood pressure elevation is useful for achieving an individual-focused approach and 24-h blood pressure control.

Moderate acute pancreatitis with pleural effusion and impaired kidney functions

NASA Astrophysics Data System (ADS)

Lumbantoruan, O. H.; Dairi, L. B.

2018-03-01

Acute pancreatitis is a pancreatic inflammatory reaction that is clinically characterized by acute abdominal pain accompanied by elevated amylase and lipase enzymes. A 57-year-old female patient came to the emergency department with the main complaint of localized pain in the epigastric region within the last three days. Blood pressure 130/90mmHg, pulse 90x/i, RR 20x/i, temperature 37°C, sub-icteric on the eyes and tenderness in the epigastric region. Laboratory findings were leukocytosis, increased amylase, and lipase, elevated liver enzymes, hypoalbuminemia, elevated Kidney Functions, acidosis, and hypoglycemia. Abdominal CT-Scan revealed a partially lobulated edge with solid and necrotic components of the caput pancreas and widespread suspicion to the pancreatic corpus. The mass appeared to cause widening of the biliary and intrahepatic systems with minimal right pleural effusion. The liverwas slightly enlarged. The patient was with acute pancreatitis and treated with the installation of an open nasogastric tube, and resuscitated with ringer lactate fluid followed by IVFD D5%. Patients fasted for three days before giving a low fat, protein diet, antibiotic and proton pump inhibitors for seven days. After nine days, amylase and lipase levels decreased with significant clinical improvement. The next three days, the patient was discharged.

Continued cannabis use at one year follow up is associated with elevated mood and lower global functioning in bipolar I disorder.

PubMed

Kvitland, Levi Roestad; Melle, Ingrid; Aminoff, Sofie Ragnhild; Demmo, Christine; Lagerberg, Trine Vik; Andreassen, Ole Andreas; Ringen, Petter Andreas

2015-02-05

There is limited knowledge about how environmental factors affect the course of bipolar disorder (BD). Cannabis has been proposed as a potential risk factor for poorer course of illness, but the role of cannabis use has not been studied in a first treatment BD I sample. The present study examines the associations between course of illness in first treatment BD I and continued cannabis use, from baseline to one year follow up. Patients (N = 62) with first treatment DSM-IV BD I were included as part of the Thematically Organized Psychosis study (TOP), and completed interviews and self-report questionnaires at both baseline and follow up. Cannabis use within the last six months at baseline and use between baseline and follow up ("continued use") was recorded. After controlling for confounders, continued cannabis use was significantly associated with elevated mood (YMRS) and inferior global functioning (GAF-F) at follow up. Elevated mood mediated the effect of cannabis use on global functioning. These results suggest that cannabis use has clinical implications for the early course of BD by increasing mood level. More focus on reducing cannabis use in clinical settings seems to be useful for improving outcome in early phase of the disorder.

Emotional Triggers and Psychopathology Associated with Suicidal Ideation in Urban Children with Elevated Aggressive-Disruptive Behavior

ERIC Educational Resources Information Center

Wyman, Peter A.; Gaudieri, Patricia A.; Schmeelk-Cone, Karen; Cross, Wendi; Brown, C. Hendricks; Sworts, Luke; West, Jennifer; Burke, Katharine C.; Nathan, Janaki

2009-01-01

8.6% suicidal ideation (SI) was found among 349 urban 6-9 year olds in the top tercile of aggressive-disruptive behavior. SI was associated with more self-reported depression, ODD, conduct problems, and ADHD symptoms (ES 0.70-0.97) and 3.5-5 times more clinically significant symptoms. Parents rated more symptoms in older children associated with…

Sleep disturbance and depressive affect in patients treated with haemodialysis.

PubMed

Maung, Stephanie; Sara, Ammar El; Cohen, Danielle; Chapman, Cherylle; Saggi, Subodh; Cukor, Daniel

2017-03-01

Sleep disorders and depression are prevalent conditions in patients with end-stage kidney disease. These co-morbidities have significant overlap and compounded morbidity and mortality burden. This overlap presents challenges to optimal clinical assessment and treatment. The goal of this study was to assess the prevalence of sleep disturbance in patients on maintenance haemodialysis, and to assess the impact of depressive affect. This was a single-site, single group, cross-sectional study of 69 English-speaking patients undergoing maintenance haemodialysis. Self-reported assessments included those of sleep quality (Pittsburgh Sleep Quality Index), depression (Beck Depression Inventory), daytime sleepiness (Epworth's Sleepiness Scale), a dialysis-specific sleep questionnaire, and standard laboratory values. No objective sleep information was collected. All participants were well dialysed, and represented all four daily shifts. Fifty-eight per cent reported clinically significant sleep difficulty, with elevated yet sub-threshold daytime sleepiness. Mean depressive affect was also elevated, yet sub-diagnostic and was positively correlated with increased age. Participants scoring above the diagnostic threshold for depression had significantly more disturbed sleep quality, more daytime sleepiness and had more problems sleeping due to restless leg syndrome than people with minimal depressive affect. Poor sleep quality is prevalent in patients on maintenance haemodialysis, and is associated with increased daytime sleepiness. Depression further compounds this relationship, and is significantly associated with increased daytime sleepiness and restless leg syndrome. © 2016 European Dialysis and Transplant Nurses Association/European Renal Care Association.

The relationships between perfectionism, pathological worry and generalised anxiety disorder

PubMed Central

2014-01-01

Background The relationships between perfectionism, pathological worry and generalised anxiety disorder (GAD) were investigated in a clinical sample presenting for treatment of perfectionism. Method This study explored the utility of perfectionism in predicting pathological worry in a sample of individuals with elevated perfectionism and GAD (n = 36). Following this, the study examined whether perfectionism could predict a principal GAD diagnosis in the full sample (n = 42). Results Scores on the perfectionism dimensions Concern over Mistakes, Personal Standards, and Clinical Perfectionism significantly predicted pathological worry among participants with GAD after controlling for gender and depression. The perfectionism dimension Doubts about Actions significantly predicted whether individuals from the full sample received a principal diagnosis of GAD. Conclusions These findings support certain dimensions of perfectionism having significant associations with pathological worry and GAD. PMID:24693946

Trace element reference intervals in the blood of healthy green sea turtles to evaluate exposure of coastal populations.

PubMed

Villa, C A; Flint, M; Bell, I; Hof, C; Limpus, C J; Gaus, C

2017-01-01

Exposure to essential and non-essential elements may be elevated for green sea turtles (Chelonia mydas) that forage close to shore. Biomonitoring of trace elements in turtle blood can identify temporal trends over repeated sampling events, but any interpretation of potential health risks due to an elevated exposure first requires a comparison against a baseline. This study aims to use clinical reference interval (RI) methods to produce exposure baseline limits for essential and non-essential elements (Na, Mg, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, Ba, and Pb) using blood from healthy subadult turtles foraging in a remote and offshore part of the Great Barrier Reef. Subsequent blood biomonitoring of three additional coastal populations, which forage in areas dominated by agricultural, urban and military activities, showed clear habitat-specific differences in blood metal profiles relative to the those observed in the offshore population. Coastal turtles were most often found to have elevated concentrations of Co, Mo, Mn, Mg, Na, As, Sb, and Pb relative to the corresponding RIs. In particular, blood from turtles from the agricultural site had Co concentrations ranging from 160 to 840 μg/L (4-25 times above RI), which are within the order expected to elicit acute effects in many vertebrates. Additional clinical blood biochemistry and haematology results indicate signs of a systemic disease and the prevalence of an active inflammatory response in a high proportion (44%) of turtles from the agricultural site. Elevated Co, Sb, and Mn in the blood of these turtles significantly correlated with elevated markers of acute inflammation (total white cell counts) and liver dysfunction (alkaline phosphatase and total bilirubin). The results of this study support the notion that elevated trace element exposures may be adversely affecting the health of nearshore green sea turtles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Significance of the E3 ubiquitin protein UBR5 as an oncogene and a prognostic biomarker in colorectal cancer

PubMed Central

Xu, Xiaowen; Zhu, Yan; Guo, Aizhen; Shen, Xian; Cao, Fuao; Chang, Wenjun

2017-01-01

The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An in vivo animal model further confirmed that UBR5 knockdown reduced the growth of CRC tumors. In conclusion, our study is the first to systematically investigate the clinical and biological significance of UBR5 and to conclude that an elevated UBR5 level plays an oncogenic role and may be a potential prognostic marker in CRC. PMID:29296225

Hyperhomocysteinemia following a methionine load in patients with non-insulin-dependent diabetes mellitus and macrovascular disease.

PubMed

Munshi, M N; Stone, A; Fink, L; Fonseca, V

1996-01-01

In the setting of an outpatient diabetic clinic, we determined whether macrovascular disease in patients with diabetes mellitus is associated with hyperhomocysteinemia (elevated plasma homocysteine [H(e)] concentrations) following a methionine load. Methionine-load tests were performed in 18 healthy controls, 11 diabetics without vascular disease (five insulin-dependent [IDDM] and six non-insulin-dependent [NIDDM]); and 17 diabetics with vascular disease (five IDDM and 12 NIDDM). All subjects were male, and there was no significant difference in mean age among the three groups. We measured plasma H(e) concentrations before and 2, 4, 6, 8, and 24 hours after an oral methionine load. Hyperhomocysteinemia (peak plasma H(e) concentration > control mean +/- 2 SD) occurred with significantly greater frequency (seven of 18, 39%) in patients with NIDDM as compared with age-matched controls (7%), being more common in those with macrovascular disease (five of 12, 41%). The area under the curve (AUC) over 24 hours, reflecting the total period of exposure to H(e), was also elevated with greater frequency in patients with NIDDM and macrovascular disease (33%) as compared with controls (0%). We conclude that hyperhomocysteinemia is associated with macrovascular disease in a significant proportion of patients with NIDDM. Further investigation of this association may determine whether hyperhomocysteinemia contributes to the increased frequency and accelerated clinical course of vascular disease in patients with diabetes mellitus.

TNF-alpha and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects.

PubMed

Kamer, Angela R; Craig, Ronald G; Pirraglia, Elizabeth; Dasanayake, Ananda P; Norman, Robert G; Boylan, Robert J; Nehorayoff, Andrea; Glodzik, Lidia; Brys, Miroslaw; de Leon, Mony J

2009-11-30

The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.

An elevated amniotic fluid prostaglandin F2α concentration is associated with intra-amniotic inflammation/infection, and clinical and histologic chorioamnionitis, as well as impending preterm delivery in patients with preterm labor and intact membranes.

PubMed

Park, Jee Yoon; Romero, Roberto; Lee, JoonHo; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun

2016-01-01

To determine whether an elevated amniotic fluid concentration of prostaglandin F2α (PGF2α) is associated with intra-amniotic inflammation/infection and adverse pregnancy outcomes in patients with preterm labor and intact membranes. The retrospective cohort study included 132 patients who had singleton pregnancies with preterm labor (< 35 weeks of gestation) and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as for genital mycoplasmas. Intra-amniotic inflammation was defined by an elevated amniotic fluid matrix metalloproteinase-8 (MMP-8) concentration (>23 ng/mL). PGF2α was measured with a sensitive and specific immunoassay. The amniotic fluid PGF2α concentration was considered elevated when it was above the 95th percentile among pregnant women at 15-36 weeks of gestation who were not in labor (≥170 pg/mL). (1) The prevalence of an elevated amniotic fluid PGF2α concentration was 40.2% (53/132) in patients with preterm labor and intact membranes; (2) patients with an elevated amniotic fluid PGF2α concentration had a significantly higher rate of positive amniotic fluid culture [19% (10/53) versus 5% (4/79); p = 0.019], intra-amniotic inflammation/infection [49% (26/53) versus 20% (16/79); p = 0.001], spontaneous preterm delivery, clinical and histologic chorioamnionitis, and funisitis, as well as a higher median amniotic fluid MMP-8 concentration and amniotic fluid white blood cell count and a shorter amniocentesis-to-delivery interval than those without an elevated concentration of amniotic fluid PGF2α (p < 0.05 for each); and (3) an elevated amniotic fluid PGF2α concentration was associated with a shorter amniocentesis-to-delivery interval after adjustment for the presence of intra-amniotic inflammation/infection [hazard ratio 2.1, 95% confidence interval (CI) 1.4-3.1; p = 0.001]. The concentration of PGF2α was elevated in the amniotic fluid of 40.2% of patients with preterm labor and intact membranes and is an independent risk factor for intra-amniotic inflammation/infection, impending preterm delivery, chorioamnionitis, and funisitis.

Anxiety Independently Contributes to Elevated Inflammation in Humans with Obesity

PubMed Central

Pierce, Gary L.; Kalil, Graziela Z.; Ajibewa, Tiwaloluwa; Holwerda, Seth W.; Persons, Jane; Moser, David J.; Fiedorowicz, Jess G.

2016-01-01

Objective Anxious and depressive states are associated with increased cardiovascular disease (CVD) risk and a proinflammatory phenotype, although the latter appears to be at least partially explained by adiposity. We hypothesized that depression and anxiety would be associated with elevated inflammation independent of adiposity in persons with obesity at high risk of CVD. Methods We explored the relation between baseline anxiety as measured by the Beck Anxiety Inventory (BAI) and depression as measured by the Beck Depression Inventory-II (BDI-II), and baseline serum c-reactive protein (CRP) in a cross-sectional sample of 100 participants [mean (SD) age 57.8 (7.7) years; 64% female] with obesity [mean (SD) body mass index, BMI 37.3 (5.5) kg/m2] enrolled in a clinical trial for pharmacological weight loss interventions. Results BAI, but not BDI-II, scores were significantly correlated with CRP (rho=0.28, p=0.005). BMI was also highly correlated with CRP (rho=0.42, p<0.0001). In multivariate models, the relation between anxiety and CRP remained significant (p=0.038), independent of BMI, age and sex. Conclusion Anxiety, but not depression, is associated with elevated inflammation in persons with obesity beyond that attributable to higher BMI. Further study is warranted to assess whether anxiety represents a potential therapeutic target to mitigate corresponding CVD risk associated with elevated inflammation in persons with obesity. PMID:28000423

Preliminary evaluation of serum total cholesterol concentrations in dogs with osteosarcoma.

PubMed

Leeper, H; Viall, A; Ruaux, C; Bracha, S

2017-10-01

To determine if total serum cholesterol concentrations were altered in dogs with osteosarcoma. To evaluate association of total serum cholesterol concentration with clinical outcomes in dogs with appendicular osteosarcoma. Retrospective, multi-institutional study on 64 dogs with osteosarcoma. Control population consisted of dogs with traumatic bone fractures (n=30) and healthy patients of similar age and weight as those of the osteosarcoma cases (n=31). Survival analysis was done on 35 appendicular osteosarcoma patients that received the current standard of care. Statistical associations were assessed by univariable and multi-variable analysis. Information about age, sex, primary tumour location, total cholesterol concentration, monocytes and lymphocyte counts and alkaline phosphatase were also included. Total cholesterol was elevated above the reference interval (3·89 to 7·12 mmol/L) (150 to 275 mg/dL) in 29 of 64 (45·3%) osteosarcoma-bearing dogs, whereas similar elevations were found in only 3 of 30 (10%) fracture controls (P<0·0001) and 2 of 31 (6·5%) similar age/weight controls (P=0·0002). Elevated total cholesterol was significantly associated with a reduced hazard ratio (0·27, P=0·008) for overall mortality in dogs with osteosarcoma. These results suggest that elevated total cholesterol is associated with canine osteosarcoma and may have prognostic significance. © 2017 British Small Animal Veterinary Association.

Creatine kinase elevation, lactacidemia, and metabolic myopathy in adult patients with diabetes mellitus.

PubMed

Frank, Marlies; Finsterer, Josef

2012-01-01

To determine the frequency of elevated creatine kinase (CK) levels among patients with diabetes mellitus and to determine how often elevated CK is attributable to primary myopathy. In this prospective study, we investigated how often CK, aspartate amino-transferase, alanine aminotransferase, and resting lactate were elevated among consecutive diabetic patients attending our clinic. Those with elevated CK values were offered a neurologic workup. Ninety-nine patients with diabetes mellitus, aged 19 to 87 years, were assessed between May 2008 and April 2010. Seven patients had type 1 diabetes and 92 patients had type 2 diabetes. CK, aspartate aminotransferase, alanine aminotransferase, and resting lactate were elevated in 19 of 99, 25 of 99, 22 of 99, and 24 of 98 patients, respectively. Eleven of 19 patients with increased CK were self-injecting insulin. Ten of 24 patients with elevated serum lactate took metformin. Seven of 19 patients with elevated CK consented to neurologic workup. Two of the 7 had elevated resting lactate. In all 7 patients, the findings from neurologic investigation were indicative of a metabolic defect and further diagnostic evaluation was recommended. In diabetic patients attending our clinic, elevated CK levels occur in one-fifth and lactacidemia occurs in one-quarter. Elevated CK levels are attributable to a primary metabolic myopathy in most cases. Elevated CK levels in the setting of diabetes mellitus require further neurologic evaluation.

Cardiac output in idiopathic normal pressure hydrocephalus: association with arterial blood pressure and intracranial pressure wave amplitudes and outcome of shunt surgery

PubMed Central

2011-01-01

Background In patients with idiopathic normal pressure hydrocephalus (iNPH) responding to shunt surgery, we have consistently found elevated intracranial pressure (ICP) wave amplitudes during diagnostic ICP monitoring prior to surgery. It remains unknown why ICP wave amplitudes are increased in these patients. Since iNPH is accompanied by a high incidence of vascular co-morbidity, a possible explanation is that there is reduced vascular compliance accompanied by elevated arterial blood pressure (ABP) wave amplitudes and even altered cardiac output (CO). To investigate this possibility, the present study was undertaken to continuously monitor CO to determine if it is correlated to ABP and ICP wave amplitudes and the outcome of shunting in iNPH patients. It was specifically addressed whether the increased ICP wave amplitudes seen in iNPH shunt responders were accompanied by elevated CO and/or ABP wave amplitude levels. Methods Prospective iNPH patients (29) were clinically graded using an NPH grading scale. Continuous overnight minimally-invasive monitoring of CO and ABP was done simultaneously with ICP monitoring; the CO, ABP, and ICP parameters were parsed into 6-second time windows. Patients were assessed for shunt surgery on clinical grade, Evan's index, and ICP wave amplitude. Follow-up clinical grading was performed 12 months after surgery. Results ICP wave amplitudes but not CO or ABP wave amplitude, showed good correlation with the response to shunt treatment. The patients with high ICP wave amplitude did not have accompanying high levels of CO or ABP wave amplitude. Correlation analysis between CO and ICP wave amplitudes in individual patients showed different profiles [significantly positive in 10 (35%) and significantly negative in 16 (55%) of 29 recordings]. This depended on whether there was also a correlation between ABP and ICP wave amplitudes and on the average level of ICP wave amplitude. Conclusions These results gave no evidence that the increased levels of ICP wave amplitudes seen in iNPH shunt responders prior to surgery were accompanied by elevated levels of ABP wave amplitudes or elevated CO. In the individual patients the correlation between CO and ICP wave amplitude was partly related to an association between ABP and ICP wave amplitudes which can be indicative of the state of cerebrovascular pressure regulation, and partly related to the ICP wave amplitude which can be indicative of the intracranial compliance. PMID:21349148

Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression.

PubMed

Pagliaccio, David; Pine, Daniel S; Barch, Deanna M; Luby, Joan L; Leibenluft, Ellen

2018-05-01

Cross-sectional, longitudinal, and genetic associations exist between irritability and depression. Prior studies have examined developmental trajectories of irritability, clinical outcomes, and associations with child and familial depression. However, studies have not integrated neurobiological measures. The present study examined developmental trajectories of irritability, clinical outcomes, and cortical structure among preschoolers oversampled for depressive symptoms. Beginning at 3 to 5 years old, a sample of 271 children enriched for early depressive symptoms were assessed longitudinally by clinical interview. Latent class mixture models identified trajectories of irritability severity. Risk factors, clinical outcomes, and cortical thickness were compared across trajectory classes. Cortical thickness measures were extracted from 3 waves of magnetic resonance imaging at 7 to 12 years of age. Three trajectory classes were identified among these youth: 53.50% of children exhibited elevated irritability during preschool that decreased longitudinally, 30.26% exhibited consistently low irritability, and 16.24% exhibited consistently elevated irritability. Compared with other classes, the elevated irritability class exhibited higher rates of maternal depression, early life adversity, later psychiatric diagnoses, and functional impairment. Further, elevated baseline irritability predicted later depression beyond adversity and personal and maternal depression history. The elevated irritability class exhibited a thicker cortex in the left superior frontal and temporal gyri and the right inferior parietal lobule. Irritability manifested with specific developmental trajectories in this sample enriched for early depression. Persistently elevated irritability predicted poor psychiatric outcomes, higher risk for later depression, and decreased overall function later in development. Greater frontal, temporal, and parietal cortical thickness also was found, providing neural correlates of this risk trajectory. Copyright © 2018 American Academy of Child and Adolescent Psychiatry. All rights reserved.

Intrathecal Th17- and B cell-associated cytokine and chemokine responses in relation to clinical outcome in Lyme neuroborreliosis: a large retrospective study.

PubMed

Gyllemark, Paula; Forsberg, Pia; Ernerudh, Jan; Henningsson, Anna J

2017-02-01

B cell immunity, including the chemokine CXCL13, has an established role in Lyme neuroborreliosis, and also, T helper (Th) 17 immunity, including IL-17A, has recently been implicated. We analysed a set of cytokines and chemokines associated with B cell and Th17 immunity in cerebrospinal fluid and serum from clinically well-characterized patients with definite Lyme neuroborreliosis (group 1, n = 49), defined by both cerebrospinal fluid pleocytosis and Borrelia-specific antibodies in cerebrospinal fluid and from two groups with possible Lyme neuroborreliosis, showing either pleocytosis (group 2, n = 14) or Borrelia-specific antibodies in cerebrospinal fluid (group 3, n = 14). A non-Lyme neuroborreliosis reference group consisted of 88 patients lacking pleocytosis and Borrelia-specific antibodies in serum and cerebrospinal fluid. Cerebrospinal fluid levels of B cell-associated markers (CXCL13, APRIL and BAFF) were significantly elevated in groups 1, 2 and 3 compared with the reference group, except for BAFF, which was not elevated in group 3. Regarding Th17-associated markers (IL-17A, CXCL1 and CCL20), CCL20 in cerebrospinal fluid was significantly elevated in groups 1, 2 and 3 compared with the reference group, while IL-17A and CXCL1 were elevated in group 1. Patients with time of recovery <3 months had lower cerebrospinal fluid levels of IL-17A, APRIL and BAFF compared to patients with recovery >3 months. By using a set of markers in addition to CXCL13 and IL-17A, we confirm that B cell- and Th17-associated immune responses are involved in Lyme neuroborreliosis pathogenesis with different patterns in subgroups. Furthermore, IL-17A, APRIL and BAFF may be associated with time to recovery after treatment.

High-Mobility Group Box 1 (HMGB1) Is Elevated Systemically in Persons with Acute or Chronic Traumatic Spinal Cord Injury.

PubMed

Papatheodorou, Angelos; Stein, Adam; Bank, Matthew; Sison, Cristina P; Gibbs, Katie; Davies, Peter; Bloom, Ona

2017-02-01

Inflammation in traumatic spinal cord injury (SCI) has been proposed to promote damage acutely and oppose functional recovery chronically. However, we do not yet understand the signals that initiate or prolong inflammation in persons with SCI. High-Mobility Group Box 1 (HMGB1) is a potent systemic inflammatory cytokine-or damage-associated molecular pattern molecule (DAMP)-studied in a variety of clinical settings. It is elevated in pre-clinical models of traumatic spinal cord injury (SCI), where it promotes secondary injury, and strategies that block HMGB1 improve functional recovery. To investigate the potential translational relevance of these observations, we measured HMGB1 in plasma from adults with acute (≤ 1 week post-SCI, n = 16) or chronic (≥ 1 year post-SCI, n = 47) SCI. Plasma from uninjured persons (n = 51) served as controls for comparison. In persons with acute SCI, average HMGB1 levels were significantly elevated within 0-3 days post-injury (6.00 ± 1.8 ng/mL, mean ± standard error of the mean [SEM]) or 4-7 (6.26 ± 1.3 ng/mL, mean ± SEM), compared with controls (1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.001 and p ≤ 0.01, respectively). In persons with chronic SCI who were injured for 15 ± 1.5 years (mean ± SEM), HMGB1 also was significantly elevated, compared with uninjured persons (3.7 ± 0.69 vs. 1.26 ± 0.24 ng/mL, mean ± SEM; p ≤ 0.0001). Together, these data suggest that HMGB1 may be a common, early, and persistent danger signal promoting inflammation in individuals with SCI.

Hypertensive crisis. Clinical presentation, comorbidities, and target organ involvement.

PubMed

Al-Bannay, Rashed; Husain, Aysha A

2010-08-01

To evaluate the clinical presentation and comorbidities of hypertensive crisis in our own population. In this cohort based study, we investigate the clinical presentation and comorbidities of hypertensive crisis by evaluating the data collected between January and April 2009. We included 154 patients admitted with systolic and diastolic blood pressure of >179 mm Hg and >119 mm Hg (based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria) in the Department of Internal Medicine, Salmaniya Medical Complex, Kingdom of Bahrain. In the study population, 64.3% had hypertensive urgency (blood pressure elevation without end organ damage) and 35.7% had hypertensive emergency (blood pressure elevation with end organ damage). The mean age group was 45-65 years (56% of the study population) and more men were affected than women (100:54). Shortness of breath and neurological deficits had a strong statistical association with hypertensive emergency, and headache and blurring of vision had the same tendency toward hypertensive urgency. Diabetes mellitus was an independent risk factor for hypertensive crisis. Most of the studied patients were known hypertensive. Diabetes mellitus is powerful predictor for hypertensive crisis. Dyspnea and neurological deficits have significant statistical correlation with hypertensive emergencies.

A non-pregnant woman with elevated beta-HCG: A case of para-neoplastic syndrome in ovarian cancer.

PubMed

Goldstein, Jennifer; Pandey, Prasamsa; Fleming, Nicole; Westin, Shannon; Piha-Paul, Sarina

2016-08-01

There is a broad range of possible diagnoses for an elevated beta human chorionic gonadotropin (β-hCG) in the absence of intrauterine or ectopic pregnancy. When women of child bearing potential undergo evaluation for clinical trial, it is often unclear what course of evaluation to take when a pregnancy test is positive. We describe the clinical course of a patient with widely metastatic mucinous ovarian carcinoma with metastasis to the peritoneum, lymph nodes and liver. The patient was found to have a mildly elevated β-hCG during initial evaluation for clinical trial. Extensive work up for ectopic pregnancy, trophoblastic disease, and phantom β-hCG were negative. The patient's β-hCG levels continued to rise until initiation of therapy. She was treated on a phase I protocol with restaging scans revealing a partial response. The β-hCG was retested and declined in conjunction with her response, consistent with paraneoplastic β-hCG. Here, we propose a decision making algorithm to evaluate a patient with an elevated β-hCG undergoing assessment for clinical trial.

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.

Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?

PubMed

Dohrn, M F; Othman, A; Hirshman, S K; Bode, H; Alecu, I; Fähndrich, E; Karges, W; Weis, J; Schulz, J B; Hornemann, T; Claeys, K G

2015-05-01

Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1-deoxy-sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined. The plasma profile of 12 sphingoid bases in patients with DSPN and T2DM(n = 39) were cross-sectionally compared to other nerve disorders including chronic inflammatory demyelinating polyneuropathy (CIDP) (n = 13), transthyretin-related familial amyloid polyneuropathy (FAP) (n = 10), amyotrophic lateral sclerosis (ALS) (n = 13) and small fibre neuropathy (n = 12) by liquid chromatography mass spectrometry. Correlations to the DSPN stage were additionally performed. Furthermore, the sphingoid base distribution in sural nerve specimens was measured in patients with DSPN (n = 6) compared to CIDP (n = 3). A significantly increased amount of 1-deoxy-sphingolipids [1-deoxy-sphinganine (0.11 ± 0.06 μmol/l), 1-deoxy-sphingosine (0.24 ± 0.16 μmol/l)] in patients with DSPN was observed compared to age-matched healthy controls (0.06 ± 0.03 μmol/l; 0.12 ± 0.05 μmol/l) and to the other groups. (Para)clinical parameters including sensory loss, neuropathic pain, weakness, vibration perception, nerve conduction velocity, sensory nerve action potentials (sural nerve) and duration of T2DM did not correlate with plasma 1-deoxy-sphingolipid levels, neither did the clinical stage according to the Dyck classification for DSPN. Sphingolipid levels in sural nerve biopsies showed no differences between DSPN and CIDP. Contrarily, patients with a small fibre neuropathy had decreased C₂₀-sphingosine plasma levels. 1-deoxy-sphingolipid plasma levels are significantly elevated in DSPN. They are already detectable in early disease stages but do not correlate with the clinical course. Further knowledge on 1-deoxy-sphingolipids might lead to a better pathophysiological understanding and future treatment options in DSPN. © 2015 EAN.

Preoperative serum HER2 extracellular domain levels in primary invasive breast cancer.

PubMed

Lee, Sae Byul; Lee, Jong Won; Yu, Jong Han; Ko, Beom Seok; Kim, Hee Jeong; Son, Byung Ho; Gong, Gyungyub; Lee, Hee Jin; Kim, Sung-Bae; Jung, Kyung Hae; Ahn, Jin-Hee; Lee, Woochang; Sung, Joohon; Ahn, Sei-Hyun

2014-12-10

Despite the preclinical outcomes and biologic significance of the presence of the human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD), there is little evidence supporting the measurement of ECD levels in any clinical setting. The aim of this study was to determine the prevalence of elevated serum HER2 ECD levels, the association between these levels and tissue HER2 overexpression, and the potential clinical prognostic value of HER2 ECD in primary invasive breast cancer. Serum HER2 ECD levels were examined preoperatively in 2,862 consecutive stage I-III primary breast cancer patients between 2007 and 2009. Serum HER2 ECD levels were measured by chemiluminescence immunoassay (ADVIA Centaur), and the tissue HER2 status was assessed by immunohistochemistry and fluorescence in situ hybridization. The cutoff value for the serum level of HER2 ECD was set at 15.2 ng/ml. Among the 2,862 patients, 126 (4.4%) had elevated serum HER2 ECD levels, and HER2 was overexpressed in the tumor tissue of 692 patients (24.2%), with a concordance of 78.7%. Multivariate analysis revealed that elevated serum HER2 ECD was a significant independent prognostic factor for worse distant-metastasis-free survival [DMFS; hazard ratio (HR) = 2.50, 95% confidence interval (CI) = 1.5-4.3, P = 0.001] and breast-cancer-specific survival (BCSS; HR = 2.0, 95% CI = 1.1-3.8, P = 0.036), which were much stronger in patients with tissue HER2-positive tumors (DMFS: HR = 3.8, 95% CI = 2.0-7.0, P < 0.001; BCSS: HR = 2.6, 95% CI = 1.2-5.3, P = 0.012). Given the prevalence of HER2 expression, its measurement as an independent prognostic factor can be clinically useful, particularly in patients with tissue HER2-positive tumors.

Elevated soluble CD30 correlates with development of bronchiolitis obliterans syndrome following lung transplantation.

PubMed

Fields, Ryan C; Bharat, Ankit; Steward, Nancy; Aloush, Aviva; Meyers, Brian F; Trulock, Elbert P; Chapman, William C; Patterson, G Alexander; Mohanakumar, Thalachallour

2006-12-27

The long-term function of lung transplants is limited by chronic rejection (bronchiolitis obliterans syndrome, BOS). Due to lack of specific markers, BOS is diagnosed clinically. Because there is strong evidence that alloimmunity plays a significant role in the pathogenesis of BOS, we investigated whether soluble CD30 (sCD30), a T-cell activation marker, would correlate with BOS. Sera collected serially from BOS+ (n = 20) and matched BOS- (n = 20) lung transplant (LT) patients were analyzed for sCD30 by enzyme-linked immunosorbent assay. Pretransplant sera and sera from normal donors were also analyzed. PreLT levels were comparable to normal subjects. However, posttransplant there was a significant elevation in sCD30 levels during BOS development in all BOS+ patients, compared to BOS- (mean 139.8+/-10.7 vs. 14.8+/-2.7 U/ml, P < 0.001). sCD30 levels declined in the BOS+ patients but were still elevated compared to BOS- (48.52+/-5.04 vs. 7.19+/-2.9, P < 0.0001). We conclude that sCD30 may represent a novel marker to monitor the development of BOS.

Efficacy of sequential use of fluoxetine for smoking cessation in elevated depressive symptom smokers.

PubMed

Brown, Richard A; Abrantes, Ana M; Strong, David R; Niaura, Raymond; Kahler, Christopher W; Miller, Ivan W; Price, Lawrence H

2014-02-01

Fluoxetine, a selective serotonin reuptake inhibitor, was examined in the treatment of smokers with elevated depressive symptoms. Specifically, this randomized, open-label clinical trial was designed to evaluate the efficacy of three logical, real-world alternatives for providing smoking cessation treatment to smokers with elevated depressive symptoms. In a sample of 216 smokers (mean Center for Epidemiological Studies Depression Scale score = 11.41), participants were randomly assigned to (a) transdermal nicotine patch (TNP), beginning on quit date and continuing for 8 weeks thereafter; (b) standard administration of antidepressant pharmacotherapy with fluoxetine (20mg), beginning 2 weeks before quit date and continuing for 8 weeks following quit date + TNP (ST-FLUOX); or (c) sequential administration of fluoxetine (20mg), beginning 8 weeks before quit date and continuing for 8 weeks following quit date + TNP (SEQ-FLUOX). All participants received 5 sessions of brief behavioral smoking cessation treatment. Findings indicate that SEQ-FLUOX resulted in significantly higher point prevalence abstinence than ST-FLUOX at 6-month follow-up (OR = 2.35; 95% CI = 1.10-5.02, p < .03), a difference that was reduced at the 12-month assessment. Furthermore, sequential fluoxetine treatment, compared with standard fluoxetine treatment, resulted in significantly lower levels of depressive symptoms throughout smoking cessation treatment (p < .025) and significantly lower nicotine withdrawal-related negative affect (p < .004) immediately after quitting. Findings suggest that if one is going to prescribe fluoxetine for smoking cessation in smokers with elevated depressive symptoms, it is best to begin prescribing fluoxetine well before the target quit date.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

PubMed

Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

2017-08-01

Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

The value of HCG serum concentrations after trigger in predicting pregnancy and live birth rates in IVF-ICSI.

PubMed

Zhou, Jianjun; Wang, Shanshan; Wang, Bin; Wang, Junxia; Chen, Hua; Zhang, Ningyuan; Hu, Yali; Sun, Haixiang

2015-06-01

The aim of this study was to determine if an association existed between serum human chorionic gonadotrophin (HCG) level at 12 h after trigger and IVF and intracytoplasmic sperm (ICSI) treatment outcomes. Women undergoing initial IVF-ICSI and embryo transfer treatment using the long luteal phase gonadotrophin-releasing hormone agonist protocol between April 2012 and March 2013 for tubal factor were included (n = 699). In the clinical pregnancy group, HCG after trigger was significantly elevated (276.0 ± 5.1 versus 198.5 ± 6.1 mIU/mL; P < 0.001). The optimal cut-off value proposed by the receiver operating characteristic analysis (area under curve = 0.730) for HCG was 201.2 mIU/ml. Compared with the lower HCG group, the clinical pregnancy rate in the higher HCG group was increased in obese and non-obese patients (77.8% versus 57.3%, P < 0.05; 85.6% versus 53.0%, P < 0.01, respectively). Adjusted for age and body mass index, an increase of HCG was associated with a better IVF-ICSI treatment outcome (OR 4.39, 95% CI 2.99 to 6.45). Clinical pregnancy rate was significantly higher across increasing quartiles of HCG. An elevated level of serum HCG at 12 h after trigger was associated with a better IVF-ICSI outcome. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Soluble ST2 and N-terminal pro-brain natriuretic peptide combination. Useful biomarker for predicting outcome of childhoodpulmonary arterial hypertension.

PubMed

Chida, Ayako; Sato, Hiroki; Shintani, Masaki; Nakayama, Tomotaka; Kawamura, Yoichi; Furutani, Yoshiyuki; Inai, Kei; Saji, Tsutomu; Matsuoka, Rumiko; Nonoyama, Shigeaki; Nakanishi, Toshio

2014-01-01

Some potential biomarkers have been reported recently in patients with pulmonary arterial hypertension (PAH), but the most clinically useful among these potential biomarkers, especially in childhood PAH, has not been identified. Therefore, this study investigated which biomarker is useful in assessing severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable PAH (HPAH). Fifty-nine patients who were younger than 16 years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates were quantified: high-sensitivity troponin T, human heart fatty acid-binding protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3, soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated well with New York Heart Association class. On area under the receiver operating characteristic curve analysis, sST2 had a significantly good relationship with prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated sST2 and NT-proBNP level predicted poor outcome of the present patients with childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP. The sST2 and NT-proBNP combination is a useful biomarker to predict clinical condition and outcome in patients with childhood IPAH/HPAH.  

Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.

PubMed

Redfield, Margaret M; Chen, Horng H; Borlaug, Barry A; Semigran, Marc J; Lee, Kerry L; Lewis, Gregory; LeWinter, Martin M; Rouleau, Jean L; Bull, David A; Mann, Douglas L; Deswal, Anita; Stevenson, Lynne W; Givertz, Michael M; Ofili, Elizabeth O; O'Connor, Christopher M; Felker, G Michael; Goldsmith, Steven R; Bart, Bradley A; McNulty, Steven E; Ibarra, Jenny C; Lin, Grace; Oh, Jae K; Patel, Manesh R; Kim, Raymond J; Tracy, Russell P; Velazquez, Eric J; Anstrom, Kevin J; Hernandez, Adrian F; Mascette, Alice M; Braunwald, Eugene

2013-03-27

Studies in experimental and human heart failure suggest that phosphodiesterase-5 inhibitors may enhance cardiovascular function and thus exercise capacity in heart failure with preserved ejection fraction (HFPEF). To determine the effect of the phosphodiesterase-5 inhibitor sildenafil compared with placebo on exercise capacity and clinical status in HFPEF. Multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial of 216 stable outpatients with HF, ejection fraction ≥50%, elevated N-terminal brain-type natriuretic peptide or elevated invasively measured filling pressures, and reduced exercise capacity. Participants were randomized from October 2008 through February 2012 at 26 centers in North America. Follow-up was through August 30, 2012. Sildenafil (n = 113) or placebo (n = 103) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks. Primary end point was change in peak oxygen consumption after 24 weeks of therapy. Secondary end points included change in 6-minute walk distance and a hierarchical composite clinical status score (range, 1-n, a higher value indicates better status; expected value with no treatment effect, 95) based on time to death, time to cardiovascular or cardiorenal hospitalization, and change in quality of life for participants without cardiovascular or cardiorenal hospitalization at 24 weeks. Median age was 69 years, and 48% of patients were women. At baseline, median peak oxygen consumption (11.7 mL/kg/min) and 6-minute walk distance (308 m) were reduced. The median E/e' (16), left atrial volume index (44 mL/m2), and pulmonary artery systolic pressure (41 mm Hg) were consistent with chronically elevated left ventricular filling pressures. At 24 weeks, median (IQR) changes in peak oxygen consumption (mL/kg/min) in patients who received placebo (-0.20 [IQR, -0.70 to 1.00]) or sildenafil (-0.20 [IQR, -1.70 to 1.11]) were not significantly different (P = .90) in analyses in which patients with missing week-24 data were excluded, and in sensitivity analysis based on intention to treat with multiple imputation for missing values (mean between-group difference, 0.01 mL/kg/min, [95% CI, -0.60 to 0.61]). The mean clinical status rank score was not significantly different at 24 weeks between placebo (95.8) and sildenafil (94.2) (P = .85). Changes in 6-minute walk distance at 24 weeks in patients who received placebo (15.0 m [IQR, -26.0 to 45.0]) or sildenafil (5.0 m [IQR, -37.0 to 55.0]; P = .92) were also not significantly different. Adverse events occurred in 78 placebo patients (76%) and 90 sildenafil patients (80%). Serious adverse events occurred in 16 placebo patients (16%) and 25 sildenafil patients (22%). Among patients with HFPEF, phosphodiesterase-5 inhibition with administration of sildenafil for 24 weeks, compared with placebo, did not result in significant improvement in exercise capacity or clinical status. clinicaltrials.gov Identifier: NCT00763867.

Associates of an elevated natriuretic peptide level in stable heart failure patients: implications for targeted management.

PubMed

Jan, Aftab; Dawkins, Ian; Murphy, Niamh; Collier, Patrick; Baugh, John; Ledwidge, Mark; McDonald, Kenneth; Watson, Chris J

2013-01-01

Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population. In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured. Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates. Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

Clinical benefit of drugs targeting mitochondrial function as an adjunct to reperfusion in ST-segment elevation myocardial infarction: A meta-analysis of randomized clinical trials.

PubMed

Campo, Gianluca; Pavasini, Rita; Morciano, Giampaolo; Lincoff, A Michael; Gibson, C Michael; Kitakaze, Masafumi; Lonborg, Jacob; Ahluwalia, Amrita; Ishii, Hideki; Frenneaux, Michael; Ovize, Michel; Galvani, Marcello; Atar, Dan; Ibanez, Borja; Cerisano, Giampaolo; Biscaglia, Simone; Neil, Brandon J; Asakura, Masanori; Engstrom, Thomas; Jones, Daniel A; Dawson, Dana; Ferrari, Roberto; Pinton, Paolo; Ottani, Filippo

2017-10-01

To perform a systematic review and meta-analysis of randomized clinical trials (RCT) comparing the effectiveness of drugs targeting mitochondrial function vs. placebo in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical coronary reperfusion. Inclusion criteria: RCTs enrolling STEMI patients treated with primary percutaneous coronary intervention (PCI) and comparing drugs targeting mitochondrial function vs. placebo. Odds ratios (OR) were computed from individual studies and pooled with random-effect meta-analysis. Fifteen studies were identified involving 5680 patients. When compared with placebo, drugs targeting mitochondrial component/pathway were not associated with significant reduction of cardiovascular and all-cause mortality (OR 0.9, 95% CI 0.7-1.17 and OR 0.92, 95% CI 0.69-1.23, respectively). However, these agents significantly reduced hospital admission for heart failure (HF) (OR 0.64; 95% CI 0.45-0.92) and increased left ventricular ejection fraction (LVEF) (OR 1.44; 95% CI 1.15-1.82). After analysis for subgroups according to the mechanism of action, drugs with direct/selective action did not reduce any outcome. Conversely, those with indirect/unspecific action showed a significant effect on cardiovascular mortality (0.65, 95% CI 0.46-0.92), all-cause mortality (OR 0.69, 95% CI 0.52-0.92), hospital readmission for HF (OR 0.41, 95% CI 0.28-0.6) and LVEF (OR 1.49, 95% CI 1.09-2.05). Administration of drugs targeting mitochondrial function in STEMI patients undergoing primary PCI appear to have no effect on mortality, but may reduce hospital readmission for HF. The drugs with a broad-spectrum mechanism of action seem to be more effective in reducing adverse events. Copyright © 2017 Elsevier B.V. All rights reserved.

Ketonuria and HELLP syndrome

PubMed Central

Gubbala, Phanendra Kumar; Karoshi, Mahantesh; Zakaria, Faris

2009-01-01

We recently managed a patient with the HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelet count) where there was a delay in diagnosis due to gastroenteritis. This case also reiterates the varied or lack of symptomatology in patients developing HELLP and obscuring the initial diagnosis. Patients with HELLP syndrome have significant maternal morbidity and mortality, hence clinical vigilance and high suspicion play a key role in the diagnosis and subsequent management. PMID:21686464

Ketonuria and HELLP syndrome.

PubMed

Gubbala, Phanendra Kumar; Karoshi, Mahantesh; Zakaria, Faris

2009-01-01

We recently managed a patient with the HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelet count) where there was a delay in diagnosis due to gastroenteritis. This case also reiterates the varied or lack of symptomatology in patients developing HELLP and obscuring the initial diagnosis. Patients with HELLP syndrome have significant maternal morbidity and mortality, hence clinical vigilance and high suspicion play a key role in the diagnosis and subsequent management.

Do children with gender dysphoria have intense/obsessional interests?

PubMed

VanderLaan, Doug P; Postema, Lori; Wood, Hayley; Singh, Devita; Fantus, Sophia; Hyun, Jessica; Leef, Jonathan; Bradley, Susan J; Zucker, Kenneth J

2015-01-01

This study examined whether children clinically referred for gender dysphoria (GD) show increased symptoms of autism spectrum disorder (ASD). Circumscribed preoccupations or intense interests were considered as overlapping symptoms expressed in GD and ASD. In gender-referred children (n = 534; 82.2% male) and their siblings (n = 419; 57.5% male), we examined Items 9 and 66 on the Child Behavior Checklist, which measure obsessions and compulsions, respectively. Non-GD clinic-referred (n = 1,201; 48.5% male) and nonreferred (n = 1,201; 48.5% male) children were also examined. Gender-referred children were elevated compared to all other groups for Item 9, and compared to siblings and nonreferred children for Item 66. A gender-related theme was significantly more common for gender-referred boys than male siblings on Item 9 only. A gender-related theme was not significantly more common for gender-referred girls compared to their female siblings on either item. The findings for Item 9 support the idea that children with GD show an elevation in obsessional interests. For gender-referred boys in particular, gender-related themes constituted more than half of the examples provided by their mothers. Intense/obsessional interests in children with GD may be one of the factors underlying the purported link between GD and ASD.

Elevated high-sensitive troponin T in negative stress test individuals.

PubMed

Brzezinski, Rafael Y; Fisher, Eyal; Ehrenwald, Michal; Shefer, Gabi; Stern, Naftali; Shapira, Itzhak; Zeltser, David; Berliner, Shlomo; Shenhar-Tsarfaty, Shani; Milwidsky, Assi; Rogowski, Ori

2018-06-01

The exercise ECG stress test (EST) is still the first step of work-up in intermediate risk patients in many clinical scenarios. High-sensitive cardiac troponin T (hs-cTnT) elevation is related to future cardiovascular events in the general population and in patients with ischaemic heart disease. The relation between these 2 tests is not well described. A total of 2780 participants from the Tel-Aviv Medical Center Inflammation Survey cohort (mean age 49 years, 79% men) were analysed. Multiple physiologic and metabolic parameters including hs-cTnT were collected. All participants completed an EST manually reviewed by a cardiologist. A positive EST was documented in 224 subjects (8%). The majority (91%) of participants with hs-cTnT levels of 5-14 ng/L had a negative EST as well as 89.3% of subjects with levels >14 ng/L. The proportion of subjects with a positive EST and detectable hs-cTnT levels (>5 ng/L) was not significantly greater compared to those with a negative EST (53.1% vs 46.2%, respectively, P = .09). Among subjects referred for EST as part of an annual health survey, we found no significant association between EST results to hs-cTnT detection. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

A latent profile analysis of childhood trauma in women with bulimia nervosa: Associations with borderline personality disorder psychopathology.

PubMed

Utzinger, Linsey M; Haukebo, Justine E; Simonich, Heather; Wonderlich, Stephen A; Cao, Li; Lavender, Jason M; Mitchell, James E; Engel, Scott G; Crosby, Ross D

2016-07-01

The aim of this study was to empirically examine naturally occurring groups of individuals with bulimia nervosa (BN) based on their childhood trauma (CT) histories and to compare these groups on a clinically relevant external validator, borderline personality disorder (BPD) psychopathology. This study examined the relationship between CT and BPD psychopathology among 133 women with BN using latent profile analysis (LPA) to classify participants based on histories of CT. Participants completed the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P), the Diagnostic Interview for Borderlines-Revised (DIB-R), and the Childhood Trauma Questionnaire (CTQ). The LPA revealed four trauma profiles: low/no trauma, emotional trauma, sexual trauma, and polytrauma. Results indicated that the sexual and polytrauma profiles displayed significantly elevated scores on the DIB-R and that the low/no and emotional trauma profiles did not differ significantly on the DIB-R. Secondary analyses revealed elevated levels of a composite CT score among those with both BN and BPD psychopathology compared to those with BN only. These findings suggest that both childhood sexual abuse and the additive effects of childhood polytrauma may be linked to BPD psychopathology in BN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:689-694). © 2016 Wiley Periodicals, Inc.

Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia.

PubMed

Ricotta, Daniel N; Frishman, William

2012-01-01

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.

The relationship between increased levels of Anti-dsDNA with clinical manifestation in patients with SLE in Haji Adam Malik General Hospital Medan

NASA Astrophysics Data System (ADS)

Marpaung, B.; Patrick, J.

2018-03-01

Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease characterized by widespread inflammation and affects any organism the body. Many autoimmune diseases result in autoantibody production, but Anti-dsDNA antibodies are highly specific to SLE. Previous study found that Anti-dsDNA antibodies are associated with severe clinical manifestations of lupus. The aim of this study was to examine the relationship between anti-dsDNA level with clinical features and laboratory findings in SLE patients. This cross-sectional study was conducted in Hospital Haji Adam Malik Medan in May-October 2016.We examine anti-dsDNA, clinical features and kidney laboratory profile in all patient. Data were statistically analyzed.81 SLE patients with median level of anti-dsDNA 294 (6.1-1317). There was no significant relationship between increased level of Anti-dsDNA with clinical manifestations (p>0.05). There were significant relationships between increased level of Anti-dsDNA with renal impairment (p=0.049), urea level (p=0.016), urine protein (p=0.042) and hematology disorder (p=0.005). Arthritis is the most frequent clinical manifestation (96.3%) followed by malar rash (77.8%). Elevated anti-dsDNA level was not related with clinical manifestations but there was significant relationship with hematology disorder, urea, creatinine, and proteinuria in SLE patents.

Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: A post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial.

PubMed

Mantovani, Alessandro; Targher, Giovanni; Temporelli, Pier Luigi; Lucci, Donata; Gonzini, Lucio; Nicolosi, Gian Luigi; Marchioli, Roberto; Tognoni, Gianni; Latini, Roberto; Cosmi, Franco; Tavazzi, Luigi; Maggioni, Aldo Pietro

2018-06-01

The prognostic impact of hyperuricemia on long-term clinical outcomes in patients with chronic heart failure (HF) has been investigated in observational registries and clinical trials, but the results have been often inconclusive. We examined the prognostic impact of elevated serum uric acid levels on long-term clinical outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial. CLINICALTRIALS. NCT00336336. We assessed the rates of all-cause death, cardiovascular death, cardiovascular hospitalization and the composite of all-cause death or cardiovascular hospitalization over a median follow-up of 3.9 years among 6683 ambulatory patients with chronic HF. Patients in the 3rd serum uric acid tertile (>7.2 mg/dl) had a nearly 1.8-fold increased risk of both all-cause death and cardiovascular death, and a nearly 1.5-fold increased risk of cardiovascular hospitalization and of the composite endpoint compared to those in the 1st uric acid tertile (<5.7 mg/dl). Beyond serum uric acid ≥ 7 mg/dl the risk of outcomes increased sharply and linearly. The significant association between elevated serum uric acid levels and adverse outcomes persisted after adjustment for multiple established cardiovascular risk factors, HF etiology, left ventricular ejection fraction, medication use and other potential confounders, with an adjusted hazard ratio of 1.37 (95% CI 1.22-1.55) for all-cause death, 1.48 (1.29-1.69) for cardiovascular death, 1.19 (1.09-1.30) for cardiovascular hospitalization and 1.21 (1.11-1.31) for the composite endpoint, respectively. Elevated serum uric acid levels are independently associated with poor long-term survival and increased risk of cardiovascular hospitalization in patients with chronic HF. Copyright © 2018 Elsevier Inc. All rights reserved.

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

PubMed

Burgess, Sarah; Abu-Laban, Riyad B; Slavik, Richard S; Vu, Erik N; Zed, Peter J

2016-04-01

To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures. © The Author(s) 2016.

High levels of vitamin D in relation to reduced risk of schizophrenia with elevated C-reactive protein.

PubMed

Zhu, Dao-min; Liu, Yong; Zhang, Ai-guo; Chu, Zhao-xue; Wu, Qing; Li, Hui; Ge, Jin-fang; Dong, Yi; Zhu, Peng

2015-08-30

There is growing evidence on the novel role of vitamin D in reducing inflammation. This study aimed to examine the hypothesis that vitamin D is inversely associated with C-reactive protein (CRP) in patients with schizophrenia, and high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP. Ninety-three patients with schizophrenia and 93 family-matched controls were recruited in this cross-sectional study. Plasma concentrations of CRP and 25-hydroxyvitamin D [25(OH)D] were measured using commercial kits. Information about demographic characteristics and clinic data were obtained by interviews or medical records. Mean levels of CRP and 25(OH)D were 43.3% higher and 26.7% lower for patients compared to controls, respectively. 25(OH)D were inversely associated with CRP in the patients, but not in the controls. The proportions of patients significantly increased with increasing quartiles of CRP, while significantly decreased with increasing quartiles of 25(OH)D. Among individuals with high CRP, participants with high 25(OH)D have significantly lower proportion (adjusted OR =0.217, 95% CI 0.063, 0.751) of schizophrenia compared to those with low 25(OH)D. The evidence suggested that high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The Predictive Prognostic Values of Serum TNF-α in Comparison to SOFA Score Monitoring in Critically Ill Patients

PubMed Central

Yousef, Ayman Abd Al-Maksoud; Suliman, Ghada Abdulmomen

2013-01-01

Background. The use of inflammatory markers to follow up critically ill patients is controversial. The short time frame, the need for frequent and serial measurement of biomarkers, the presence of soluble receptor and their relatively high cost are the major drawbacks. Our study's objective is to compare the prognostic values of serum TNF-α and SOFA score monitoring in critically ill patients. Patients and Methods. A total of ninety patients were included in the study. Forty-five patients developed septic complication (sepsis group). Forty-five patients were critically ill without evidence of infectious organism (SIRS group). Patients' data include clinical status, central venous pressure, and laboratory analysis were measured. A serum level of TNF-α and SOFA score were monitored. Results. Monitoring of TNF-α revealed significant elevation of TNF-α at 3rd and 5th days of ICU admission in both groups. Monitoring of SOFA score revealed significant elevation of SOFA scores in both groups throughout their ICU stay, particularly in nonsurvivors. Positive predictive ability of SOFA score was demonstrated in critically ill patients. Conclusion. Transient significant increase in serum levels of TNF-α were detected in septic patients. Persistent elevation of SOFA score was detected in nonsurvivor septic patients. SOFA score is an independent prognostic value in critically ill patients. PMID:24175285

Prevalence of hypothyroidism in rheumatoid arthritis and its correlation with disease activity.

PubMed

Joshi, Prakash; Agarwal, Abhishek; Vyas, Sony; Kumar, Ravindra

2017-01-01

To analyse the prevalence of hypothyroidism in rheumatoid arthritis (RA) patients and to elucidate its correlation with disease activity. A total of 52 RA patients were enrolled in this study. All patients were assessed fully clinically and underwent routine laboratory investigation including thyroid function testing. Hypothyroidism (defined as having a TSH level >4.20 μIU/mL) was observed in 20/52 (38.4%). Erythrocyte sedimentation rates (ESR) were found significantly elevated in patients with hypothyroidism compared to those without (36.3 ± 24.2 vs. 24.6 ± 9.0 mm/h). Disease activity parameters such as DAS-28-ESR, tender joint count; VAS scores were also significantly higher in the former. A significant correlation with serum TSH levels was observed with ESR and DAS-28-ESR. Thyroid function test should be included in clinical evaluation of RA patients. © The Author(s) 2016.

Unexplained high thyroid stimulating hormone: a "BIG" problem.

PubMed

Mendoza, Heidi; Connacher, Alan; Srivastava, Rajeev

2009-01-01

Macro-hormones and macro-enzymes are high molecular weight conjugates of hormones or enzymes, respectively, often with immunoglobulins. These are referred to as macromolecular complexes, and may cause artefactually elevated biochemical tests results. Macro enzymes of the most commonly measured serum enzymes have been identified and are recognised as a source of elevated measurements that may cause diagnostic confusion; macro-creatine kinase and macro-amylase are the two better known macro-enzymes in clinical practice. Literature on macro-hormones is largely restricted to macro-prolactin. We present a case of a clinically euthyroid patient, who had persistently elevated thyroid stimulating hormone (TSH) but free thyroxine within the reference limits. She underwent repeated thyroid investigations and thyroid hormone interference studies, until macro-TSH was identified as the most likely cause of unexplained elevated TSH. Following the identification and characterisation of this biochemical abnormality, she is no longer subject to repeated blood tests for assessment of thyroid function; the patient currently remains clinically euthyroid.

[Development of Diagrammatic Recording System for Choledochoscope and Its Clinical Application].

PubMed

Xue, Zhao; Hu, Liangshuo; Tang, Bo; Zhang, Xiaogang; Lyu, Yi

2017-11-30

To develop a diagrammatic recording system for choledochoscopy and evaluate the system with clinical application. To match the real-time image and procedure illustration during choledochoscopy examination, we combined video-image capture and speech recognition technology to quickly generate personalized choledochoscopy images and texts records. The new system could be used in sharing territorial electronic medical records, telecommuting, scientific research and education, et al. In the clinical application of 32 patients, the choledochoscopy diagrammatic recording system could significantly improve the surgeons' working efficiency and patients' satisfaction. It could also meet the design requirement of remote information interaction. The choledochoscopy diagrammatic recording system which is recommended could elevate the quality of medical service and promote academic exchange and training.

The Prevalence of Obesity and Elevated Blood Pressure in Adolescent Student Athletes From the State of Mississippi

PubMed Central

Stiefel, Eric C.; Field, Larry; Replogle, William; McIntyre, Louis; Igboechi, Oduche; Savoie, Felix H.

2016-01-01

Background: Over the past 30 years, there has been a dramatic increase in the prevalence of childhood obesity and hypertension in the United States. The prevalence of these diagnoses among individuals participating in school-sanctioned sports has not been clearly defined. Purpose: To identify the prevalence of obesity and elevated blood pressure (BP) among student athletes and investigate associations between race, sex, type and number of sports played, and the prevalence of these diseases. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Pre–sports participation medical examinations (N = 7705) performed between 2009 and 2013 were reviewed to identify the prevalence of obesity and elevated BP and examine relationships between the type of sports played, participation in multiple sports versus a single sport, and the athlete’s body weight and body mass index (BMI). Results: The prevalence of obesity was 23.5%. There was a significant association (P < .001) between the number of sports played by the student and BMI. The risk of obesity among single-sport athletes was more than 2-fold the risk (relative risk [RR], 2.13) compared with ≥3-sport athletes and 1.42 times greater compared with 2-sport athletes (RR, 1.42). The prevalence of elevated BP was 21.2%. There was a significant association (P < .001) between the number of sports played by the student and elevated BP. The risk of elevated BP among single-sport athletes was 1.59 times greater (RR, 1.59) than ≥3-sport athletes and 1.30 times greater compared with 2-sport athletes (RR, 1.30). Finally, obese students were 2.40 times more likely to have elevated BP compared with nonobese students (P < .001). Conclusion: The result of this study confirms the progressive nature of the obesity epidemic and identifies the contribution of obesity to the worsening cardiometabolic profiles in student athletes. The study also identifies that participation in multiple sports and running sports decreases the individual’s risk for obesity and hypertension. Clinical Relevance: The present study emphasizes the importance of screening for obesity and elevated blood pressure during the athlete’s preparticipation physical examination. PMID:26962540

MMPI-2 validity, clinical and content scales, and the Fake Bad Scale for personal injury litigants claiming idiopathic environmental intolerance.

PubMed

Staudenmayer, Herman; Phillips, Scott

2007-01-01

Idiopathic environmental intolerance (IEI) is a descriptor for nonspecific complaints that are attributed to environmental exposure. The Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was administered to 50 female and 20 male personal injury litigants alleging IEI. The validity scales indicated no overreporting of psychopathology. Half of the cases had elevated scores on validity scales suggesting defensiveness, and a large number had elevations on Fake Bad Scale (FBS) suggesting overreporting of unauthenticated symptoms. The average T-score profile for females was defined by the two-point code type 3-1 (Hysteria-Hypochondriasis), and the average T-score profile for males was defined by the three-point code type 3-1-2 (Hysteria, Hypochondriasis-Depression). On the content scales, Health Concerns (HEA) scale was significantly elevated. Idiopathic environmental intolerance litigants (a) are more defensive about expressing psychopathology, (b) express distress through somatization, (c) use a self-serving misrepresentation of exaggerated health concerns, and (d) may exaggerate unauthenticated symptoms suggesting malingering.

Aged Chinese-origin rhesus macaques infected with SIV develop marked viremia in absence of clinical disease, inflammation or cognitive impairment.

PubMed

Bissel, Stephanie J; Gurnsey, Kate; Jedema, Hank P; Smith, Nicholas F; Wang, Guoji; Bradberry, Charles W; Wiley, Clayton A

2018-02-01

Damage to the central nervous system during HIV infection can lead to variable neurobehavioral dysfunction termed HIV-associated neurocognitive disorders (HAND). There is no clear consensus regarding the neuropathological or cellular basis of HAND. We sought to study the potential contribution of aging to the pathogenesis of HAND. Aged (range = 14.7-24.8 year) rhesus macaques of Chinese origin (RM-Ch) (n = 23) were trained to perform cognitive tasks. Macaques were then divided into four groups to assess the impact of SIVmac251 infection (n = 12) and combined antiretroviral therapy (CART) (5 infected; 5 mock-infected) on the execution of these tasks. Aged SIV-infected RM-Ch demonstrated significant plasma viremia and modest CSF viral loads but showed few clinical signs, no elevations of systemic temperature, and no changes in activity levels, platelet counts or weight. Concentrations of biomarkers of acute and chronic inflammation such as soluble CD14, CXCL10, IL-6 and TNF-α are known to be elevated following SIV infection of young adult macaques of several species, but concentrations of these biomarkers did not shift after SIV infection in aged RM-Ch and remained similar to mock-infected macaques. Neither acute nor chronic SIV infection or CART had a significant impact on accuracy, speed or percent completion in a sensorimotor test. Viremia in the absence of a chronic elevated inflammatory response seen in some aged RM-Ch is reminiscent of SIV infection in natural disease resistant hosts. The absence of cognitive impairment during SIV infection in aged RM-Ch might be in part attributed to diminishment of some facets of the immunological response. Additional study encompassing species and age differences is necessary to substantiate this hypothesis.

Relationship between ketamine-induced developmental neurotoxicity and NMDA receptor-mediated calcium influx in neural stem cell-derived neurons.

PubMed

Wang, Cheng; Liu, Fang; Patterson, Tucker A; Paule, Merle G; Slikker, William

2017-05-01

Ketamine, a noncompetitive NMDA receptor antagonist, is used as a general anesthetic and recent data suggest that general anesthetics can cause neuronal damage when exposure occurs during early brain development. To elucidate the underlying mechanisms associated with ketamine-induced neurotoxicity, stem cell-derived models, such as rodent neural stem cells harvested from rat fetuses and/or neural stem cells derived from human induced pluripotent stem cells (iPSC) can be utilized. Prolonged exposure of rodent neural stem cells to clinically-relevant concentrations of ketamine resulted in elevated NMDA receptor levels as indicated by NR1subunit over-expression in neurons. This was associated with enhanced damage in neurons. In contrast, the viability and proliferation rate of undifferentiated neural stem cells were not significantly affected after ketamine exposure. Calcium imaging data indicated that 50μM NMDA did not cause a significant influx of calcium in typical undifferentiated neural stem cells; however, it did produce an immediate elevation of intracellular free Ca 2+ [Ca 2+ ] i in differentiated neurons derived from the same neural stem cells. This paper reviews the literature on this subject and previous findings suggest that prolonged exposure of developing neurons to ketamine produces an increase in NMDA receptor expression (compensatory up-regulation) which allows for a higher/toxic influx of calcium into neurons once ketamine is removed from the system, leading to neuronal cell death likely due to elevated reactive oxygen species generation. The absence of functional NMDA receptors in cultured neural stem cells likely explains why clinically-relevant concentrations of ketamine did not affect undifferentiated neural stem cell viability. Published by Elsevier B.V.

Elevated serum uric acid levels are independent risk factors for diabetic foot ulcer in female Chinese patients with type 2 diabetes.

PubMed

Ye, Xiao; Cao, Ying; Gao, Fang; Yang, Qunying; Zhang, Qian; Fu, Xiajun; Li, Jimin; Xue, Yaoming

2014-01-01

To investigate the relationship between elevated serum uric acid levels and the presence of diabetic foot ulcer (DFU) in Chinese patients with type 2 diabetes (T2D). A retrospective study was performed on 829 outpatients with T2D (478 men, 351 women) who visited the Diabetes Clinic (Nanfang Hospital, Southern Medical University) from January 2007 to December 2009. Information regarding their clinical history, anthropometric measurements, and laboratory data were collected. Potential confounding variables with P < 0.10 were adjusted for in multivariate logistic regression analysis. In univariate analyses, there was a significant difference in serum uric acid levels between female patients with and without DFU (370 ± 128 vs. 313 ± 107 μmol/L, respectively; P < 0.05), but not between male patients with and without DFU (317 ± 100 vs. 348 ± 111 μmol/L, respectively; P = 0.643). The prevalence of DFU among quintiles of uric acid levels (from 1-20% to 80-100%) was 5.3%, 3.9%, 7.7%, 5.5%, and 16.7%, respectively. Using uric acid level as a continuous variable, the multivariate-adjusted odds ratio for diabetic foot ulcer in female patients was 1.004 (95% confidence interval 1.001-1.008; P < 0.05). Elevated uric acid levels are a significant and independent risk factor for diabetic foot ulcer in female Chinese patients with T2D. Whether serum uric acid is involved in the pathogenesis of DFU in female patients remains to be investigated. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients

PubMed Central

Ghitza, Udi E.; Preston, Kenzie L.; Epstein, David H.; Kuwabara, Hiroto; Endres, Christopher J.; Bencherif, Badreddine; Boyd, Susan J.; Copersino, Marc L.; Frost, J. James; Gorelick, David A.

2010-01-01

Background Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown. Methods We determined whether regional brain mOR binding before treatment correlates with outcome and compared it to standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine-abstinence reinforcement whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography (PET) with [11C] carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment, 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology. Results Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sub-lobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use. Conclusions Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction. PMID:20579973

Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia syndrome patients correlate with body mass index, interleukin-6, interleukin-8, erythrocyte sedimentation rate.

PubMed

Xiao, Yangming; Haynes, Wanda L; Michalek, Joel E; Russell, I Jon

2013-05-01

The levels of several inflammatory cytokines are abnormal in many patients with the fibromyalgia syndrome (FMS) and may play a role in its pathogenesis. The inflammatory marker C-reactive protein (CRP) is associated with the disease activity in patients with inflammatory rheumatic diseases, but its role in FMS is unknown. We undertook this study to determine whether high-sensitivity CRP (hsCRP) is elevated in FMS and whether its levels relate to key biologic or clinical measures. One hundred and five patients with FMS (1990 ACR criteria) and 61 healthy normal controls (HNC) at a ratio of 2:1 were recruited. The serum concentrations of hsCRP, interleukin-8 (IL-8), and interleukin-6 (IL-6) were assessed using enzyme-linked immunosorbent assays. The hsCRP levels were marginally higher in FMS than in HNC (p = 0.06) and its abnormality rate (>1.5 SD above the HNC mean) was significantly higher in FMS (25 %) compared with HNC (6.8 %) (p = 0.03). Serum IL-8 levels, IL-6 levels, and erythrocyte sedimentation rate (ESR) in FMS did not differ from those in HNC. Body mass index (BMI), ESR, IL-8, and IL-6 levels correlated with hsCRP levels in FMS. No associations were found between hsCRP and age, gender, ethnicity, or other clinical measures. Serum CRP levels were higher in FMS and significantly correlated with BMI, ESR, IL-8, and IL-6 levels, suggesting that inflammation may contribute to the symptoms in some FMS patients, particularly those who are obese. Weight loss and therapies directed against inflammation may be useful in the management of FMS patients with elevated hsCRP.

Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

PubMed

Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

2017-09-09

Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The Impact of Progesterone Level on Day Of hCG Injection in IVF Cycles on Clinical Pregnancy Rate.

PubMed

Ashmita, Jawa; Vikas, Swarankar; Swati, Garg

2017-01-01

Premature progesterone rise (PPR) has long been implicated as contributing to implantation failure. Despite the use of gonadotropin-releasing hormone (GnRH) analogues, subtle increases in serum progesterone ( P 4 ) levels beyond a threshold progesterone concentration were observed on the day of trigger in controlled ovarian hyperstimulation cycles. The purpose of the study was to evaluate the incidence of PPR on the day of trigger in conventional IVF/ICSI cycles and its impact on clinical pregnancy rate. A total of 235 patients undergoing conventional IVF/IVF-ICSI by fresh embryo transfer cycles from January 2016 to December 2016 at the infertility unit of a tertiary care hospital were prospectively analyzed. Patients included in the study were subjected to GnRH agonist long/antagonist protocol. Ovulation induction was given with rFSH and/or HMG in both the protocols. The cutoff for defining PPR was P 4 ≥ 1.5 ng/ml, and an analysis of the role of P 4 on clinical pregnancy rate was performed. Statistical analysis was performed with the Statistical Package for the Social Sciences trial version 23.0 software for Windows and Primer software. The overall clinical pregnancy rate per embryo transfer was 30.6%. The clinical pregnancy rate in the patients with P 4 <1.5 ng/ml was significantly higher than those with elevated levels, P 4 ≥ 1.5 ng/ml (33.3% vs. 12.9%; P = 0.037). Premature progesterone elevation in ART cycles is possibly associated with lower clinical pregnancy rates.

Relation of the aortic stiffness with the GRACE risk score in patients with the non ST-segment elevation myocardial infarction

PubMed Central

Omer, Gedikli; Gokhan, Aksan; Adem, Uzun; Sabri, Demircan; Korhan, Soylu

2014-01-01

Background: Current guidelines recommend clinical risk scoring systems for the patients diagnosed and determinated treatment strategy with in Non-ST-elevation elevation myocardial infarction (NSTEMI). Previous studies demonstrated association between aortic elasticity properties, stiffness and severity CAD. However, the associations between Aortic stiffness, elasticity properties and clinical risk scores have not been investigated. In the present study we have evaluated the relation between the Global Registry of Acute Coronary Events (GRACE) risk score and aortic stiffness in patients with NSTEMI. Method: We prospectively analyzed 87 consecutive patients with NSTEMI. Aortic elastic parameter and stiffness parameter were calculated from the echocardiographically derived thoracic aortic diameters (mm/m2), and the measurement of pulse pressure obtained by cuff sphygmomanometry. We have categorized the patients in to two groups as low ((n = 45) (GRACE risk score ≤ 140)) and high ((n = 42) (GRACE risk score > 140)) risk group according to GRACE risk score and compare the both groups. Results: Table 1 shows baseline characteristics of patients. Our study showed that Aortic strain was significantly low (3.5 ± 1.4, 7.9 ± 2.3 respectively, p < 0.001) and aortic stiffness index was significantly high (3.9 ± 0.38; 3 ± 0.35, respectively, p < 0.001) in the high risk group values compared to those with low risk group. The aortic stiffness index was the only independent predictor of GRACE risk score (OR: 119.390; 95% CI: 2.925-4872.8; p = 0.011) in multivariate analysis. Conclusion: We found a significant correlation between aortic stiffness, impaired elasticity and GRACE risk score. Aortic stiffness index was the only independent variable of the high GRACE risk score. The inclusion of aortic stiffness into the GRACE risk score could allow improved risk classification of patients with ACS at admission and this may be important in the diagnosis, follow up and treatment of the patients. PMID:25356178

Relation of the aortic stiffness with the GRACE risk score in patients with the non ST-segment elevation myocardial infarction.

PubMed

Omer, Gedikli; Gokhan, Aksan; Adem, Uzun; Sabri, Demircan; Korhan, Soylu

2014-01-01

Current guidelines recommend clinical risk scoring systems for the patients diagnosed and determinated treatment strategy with in Non-ST-elevation elevation myocardial infarction (NSTEMI). Previous studies demonstrated association between aortic elasticity properties, stiffness and severity CAD. However, the associations between Aortic stiffness, elasticity properties and clinical risk scores have not been investigated. In the present study we have evaluated the relation between the Global Registry of Acute Coronary Events (GRACE) risk score and aortic stiffness in patients with NSTEMI. We prospectively analyzed 87 consecutive patients with NSTEMI. Aortic elastic parameter and stiffness parameter were calculated from the echocardiographically derived thoracic aortic diameters (mm/m(2)), and the measurement of pulse pressure obtained by cuff sphygmomanometry. We have categorized the patients in to two groups as low ((n = 45) (GRACE risk score ≤ 140)) and high ((n = 42) (GRACE risk score > 140)) risk group according to GRACE risk score and compare the both groups. Table 1 shows baseline characteristics of patients. Our study showed that Aortic strain was significantly low (3.5 ± 1.4, 7.9 ± 2.3 respectively, p < 0.001) and aortic stiffness index was significantly high (3.9 ± 0.38; 3 ± 0.35, respectively, p < 0.001) in the high risk group values compared to those with low risk group. The aortic stiffness index was the only independent predictor of GRACE risk score (OR: 119.390; 95% CI: 2.925-4872.8; p = 0.011) in multivariate analysis. We found a significant correlation between aortic stiffness, impaired elasticity and GRACE risk score. Aortic stiffness index was the only independent variable of the high GRACE risk score. The inclusion of aortic stiffness into the GRACE risk score could allow improved risk classification of patients with ACS at admission and this may be important in the diagnosis, follow up and treatment of the patients.

Maxillary sinus floor augmentation using a beta-tricalcium phosphate (Cerasorb) alone compared to autogenous bone grafts.

PubMed

Zijderveld, Steven A; Zerbo, Ilara R; van den Bergh, Johan P A; Schulten, Engelbert A J M; ten Bruggenkate, Chris M

2005-01-01

A prospective human clinical study was conducted to determine the clinical and histologic bone formation ability of 2 graft materials, a beta-tricalcium phosphate (Cerasorb; Curasan, Kleinostheim, Germany) and autogenous chin bone, in maxillary sinus floor elevation surgery. Ten healthy patients underwent a bilateral (n = 6) or unilateral (n = 4) maxillary sinus floor elevation procedure under local anesthesia. In each case, residual posterior maxillary bone height was between 4 and 8 mm. In cases of bilateral sinus floor elevation, the original bone was augmented with a split-mouth design with 100% beta-tricalcium phosphate on the test side and 100% chin bone on the contralateral control side. The unilateral cases were augmented with 100% beta-tricalcium phosphate. After a healing period of 6 months, ITI full body screw-type implants (Straumann, Waldenburg, Switzerland) were placed. At the time of implant surgery, biopsy samples were removed with a 3.5-mm trephine drill. Sixteen sinus floor elevations were performed. Forty-one implants were placed, 26 on the test side and 15 on the control side. The clinical characteristics at the time of implantation differed, especially regarding clinical appearance and drilling resistance. The increase in height was examined radiographically prior to implantation and was found to be sufficient in all cases. After a mean of nearly 1 year of follow-up, no implant losses or failures had occurred. The promising clinical results of the present study and the lack of implant failures are probably mainly the result of requiring an original bone height of at least 4 mm at the implant location. Although autogenous bone grafting is still the gold standard, according to the clinical results, the preimplantation sinus floor elevation procedure used, which involved a limited volume of beta-tricalcium phosphate, appeared to be a clinically reliable procedure in this patient population.

Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

PubMed

Ohyama, Katsuhiro; Inoue, Michiko

2016-01-01

Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

Comparison of long-term mortality of acute ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome patients after percutaneous coronary intervention

PubMed Central

Ren, Lihui; Ye, Huiming; Wang, Ping; Cui, Yuxia; Cao, Shichang; Lv, Shuzheng

2014-01-01

Background and aims: This study is to compare the short-term and long-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI). Methods and results: A total of 266 STEMI patients and 140 NSTE-ACS patients received PCI. Patients were followed up by telephone or at medical record or case statistics center and were followed up for 4 years. Descriptive statistics and multivariate survival analyses were employed to compare the mortality in STEMI and NSTE-ACS. All statistical analyses were performed by SPSS19.0 software package. NSTE-ACS patients had significantly higher clinical and angiographic risk profiles at baseline. During the 4-year follow-up, all-cause mortality in STEMI was significantly higher than that in NSTE-ACS after coronary stent placement (HR 1.496, 95% CI 1.019-2.197). In a landmark analysis no difference was seen in all-cause mortality for both STEMI and NSTE-ACS between 6 month and 4 years of follow-up (HR 1.173, 95% CI 0.758-1.813). Conclusions: Patients with STEMI have a worse long-term prognosis compared to patients with NSTE-ACS after PCI, due to higher short-term mortality. However, NSTE-ACS patients have a worse long-term survival after 6 months. PMID:25664077

Correlation between hematologic profile and transaminase enzymes with hospitalization duration dengue

NASA Astrophysics Data System (ADS)

Tinambunan, E.; Suryani; Katu, S.; Halim, R.; Mubin, A. H.; Sahyuddin

2018-03-01

Dengue is an infectious disease that can be found from mild to severe andaffected the clinical spectrum of the disease. Various hematologic profiles and transaminase enzymes are thought to reflect the severity of the disease thus affecting the hospitalization duration. For determining the correlation between hematological profile and transaminase enzyme to the hospitalization duration in dengue patients, an observational design study with the cross-sectional approach on dengue subjects was from 2 hospitals in Makassar. Hemoglobin, leukocyte, thrombocyte, AST, ALT, PT, and APTT were examined for hospitalization duration. There were 65 samples (34 men, 31 women) with the length of stay <5 days 34 people and ≥ 5 days 31 people. The result of the analysis showed that there was a low correlation of leukocyte value (p = 0.036) and APTT prolongation (p = 0.023) with hospitalization duration of dengue patients. There was no correlation between the elevated of hematocrit value (p = 0.429), thrombocytopenia (p = 1.000), elevated of AST (p = 0.456) and ALT (p = 0.285) on hospitalization duration. In conclusion, low leukocyte values and APTT prolongation correlate with hospitalization duration but did not correlate significantly with hospitalization duration for elevated hematocrit, thrombocytopenia, elevated AST, and ALT.

An Assessment of Psychological Need in Emergency Medical Staff in the Northern Health and Social Care Trust Area.

PubMed

Aisling, McAleese; Aisling, Diamond; David, Curran

2016-05-01

Psychological stress is increasingly recognised within emergency medicine, given the environmental and clinical stressors associated with the specialism. The current study assessed whether psychological distress is experienced by emergency medical staff and if so, what is the expressed need within this population? Participants included ambulance personnel, nursing staff, doctors and ancillary support staff within two Accident and Emergency (A&E) departments and twelve ambulance bases within one Trust locality in NI (N = 107). The General Health Questionnaire (GHQ-12, Goldberg, 1972, 1978), Secondary Traumatic Stress Scale (STSS, Bride, 2004) and an assessment of need questionnaire were completed and explored using mixed method analysis. Results showed elevated levels of psychological distress within each profession except ambulance service clinical support officers (CSOs). Elevated levels of secondary trauma symptomatology were also found; the highest were within some nursing grades and junior doctors. Decreased enjoyment in job over time was significantly associated with higher scores. Analysis of qualitative data identified sources of stress to include low morale. A total of 65% of participants thought that work related stressors had negatively affected their mental health. Participants explored what they felt could decrease psychological distress including improved resources and psychoeducation. There were elevated levels of distress and secondary traumatic stress within this population as well as an expressed level of need, on both systemic and support levels.

Ubiquitous Multicriteria Clinic Recommendation System.

PubMed

Chen, Toly

2016-05-01

Advancements in information, communication, and sensor technologies have led to new opportunities in medical care and education. Patients in general prefer visiting the nearest clinic, attempt to avoid waiting for treatment, and have unequal preferences for different clinics and doctors. Therefore, to enable patients to compare multiple clinics, this study proposes a ubiquitous multicriteria clinic recommendation system. In this system, patients can send requests through their cell phones to the system server to obtain a clinic recommendation. Once the patient sends this information to the system, the system server first estimates the patient's speed according to the detection results of a global positioning system. It then applies a fuzzy integer nonlinear programming-ordered weighted average approach to assess four criteria and finally recommends a clinic with maximal utility to the patient. The proposed methodology was tested in a field experiment, and the experimental results showed that it is advantageous over two existing methods in elevating the utilities of recommendations. In addition, such an advantage was shown to be statistically significant.

Elevated preoperative blood pressures in adult surgical patients are highly predictive of elevated home blood pressures.

PubMed

Schonberger, Robert B; Nwozuzu, Adambeke; Zafar, Jill; Chen, Eric; Kigwana, Simon; Monteiro, Miriam M; Charchaflieh, Jean; Sophanphattana, Sophisa; Dai, Feng; Burg, Matthew M

2018-04-01

Blood pressure (BP) measurement during the presurgical assessment has been suggested as a way to improve longitudinal detection and treatment of hypertension. The relationship between BP measured during this assessment and home blood pressure (HBP), a better indicator of hypertension, is unknown. The purpose of the present study was to determine the positive predictive value of presurgical BP for predicting elevated HBP. We prospectively enrolled 200 patients at a presurgical evaluation clinic with clinic blood pressures (CBPs) ≥130/85 mm Hg, as measured using a previously validated automated upper-arm device (Welch Allyn Vital Sign Monitor 6000 Series), to undergo daily HBP monitoring (Omron Model BP742N) between the index clinic visit and their day of surgery. Elevated HBP was defined, per American Heart Association guidelines, as mean systolic HBP ≥135 mm Hg or mean diastolic HBP ≥85 mm Hg. Of the 200 participants, 188 (94%) returned their home blood pressure monitors with valid data. The median number of HBP recordings was 10 (interquartile range, 7-14). Presurgical CBP thresholds of 140/90, 150/95, and 160/100 mm Hg yielded positive predictive values (95% confidence interval) for elevated HBP of 84.1% (0.78-0.89), 87.5% (0.81-0.92), and 94.6% (0.87-0.99), respectively. In contrast, self-reported BP control, antihypertensive treatment, availability of primary care, and preoperative pain scores demonstrated poor agreement with elevated HBP. Elevated preoperative CBP is highly predictive of longitudinally elevated HBP. BP measurement during presurgical assessment may provide a way to improve longitudinal detection and treatment of hypertension. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

PubMed

Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

2011-11-01

To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

Effects of royal jelly supplementation on glycemic control and oxidative stress factors in type 2 diabetic female: a randomized clinical trial.

PubMed

Pourmoradian, Samira; Mahdavi, Reza; Mobasseri, Majid; Faramarzi, Elnaz; Mobasseri, Mehrnoosh

2014-05-01

It has been proposed that royal jelly has antioxidant properties and may improve oxidative stress and glycemic control. Therefore, we investigated the effects of royal jelly supplementation in diabetic females. In this pilot, parallel design randomized clinical trial, 50 female volunteers with type 2 diabetes were randomly allocated to the supplemented (25, cases) and placebo (25, cases) groups, based on random block procedure produced by Random Allocation Software, given a daily dose of 1,000 mg royal jelly soft gel or placebo, respectively, for 8 weeks. Before and after intervention, glycemic control indices, antioxidant and oxidative stress factors were measured. After royal jelly supplementation, the mean fasting blood glucose decreased remarkably (163.05±42.51 mg/dL vs. 149.68±42.7 mg/dL). Royal jelly supplementation resulted in significant reduction in the mean serum glycosylated hemoglobin levels (8.67%±2.24% vs. 7.05%±1.45%, P=0.001) and significant elevation in the mean insulin concentration (70.28±29.16 pmol/L vs. 86.46±27.50 pmol/L, P=0.01). Supplementation significantly increased erythrocyte superoxidase dismutase and glutathione peroxidase activities and decreased malondialdehyde levels (P<0.05). At the end of study, the mean total antioxidant capacity elevated insignificantly in both groups. On the basis of our findings, it seems that royal jelly supplementation may be beneficial in controlling diabetes outcomes. Further studies with larger sample size are warranted.

Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide

PubMed Central

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J.; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A.; Taylor, Matthew R. G.; Lowes, Brian D.; Fuller, Maria; Benjamin, Elfrida R.; Sweetman, Lawrence

2014-01-01

Background Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X‐linked lysosomal disorder that is a risk factor for most types of heart disease. Methods and Results We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α‐galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow‐up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). Conclusions In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near‐term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. Clinical Trial Registration URL: clinicaltrials.gov. Unique Identifier: NCT01019629. PMID:24496231

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

PubMed

Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

2017-12-01

Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

The relation among steroid hormone levels, lipid profile and menopausal symptom severity.

PubMed

Kaya, Cihan; Cengiz, Hüseyin; Yeşil, Ali; Ekin, Murat; Yaşar, Levent

2017-12-01

Many postmenopausal women experience hot flashes, night sweats, non-specific emotional and psychological distresses. Our aim was to investigate the relation among steroid hormone levels, lipid profile and menopausal symptom severity using the menopause rating scale (MRS). A cross-sectional study was performed at our outpatient clinic with natural postmenopausal women. A total of 444 women were included in this study. The basic characteristics of the study population, such as age, gravidity, parity, time to menopause onset and body mass index (BMI) were recorded. Venous blood samples were collected from subjects after overnight fasting. The levels of high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglyceride (TG), fasting plasma glucose, C-reactive protein, thyroid-stimulating hormone (TSH), cortisol, estradiol (E2), progesterone, testosterone and dehydroepiandrostenedione sulfate (DHEA-S) were analyzed. The MRS questionnaire validated for the Turkish population was used to assess the menopausal symptoms. There was a statistically significant difference between mild and severe total symptom scores for TG, and elevated TG levels were observed in the severe group (p = 0.04). Elevated testosterone levels were observed with severe psychological symptom and total symptom scores. There were significant differences in progesterone level in psychological, urogenital, and total scores and lower levels were seen in severe symptom groups. There was a significant negative correlation between urogenital symptom scores and progesterone levels (p < 0.001). Elevated levels of testosterone were related to severe psychological symptom and total menopausal symptom scores. A decrease in progesterone levels was related to high psychological, urogenital and total menopausal symptom scores. Elevated TG levels were also related to the total severe symptom scores.

Severe Acinetobacter baumannii Sepsis Is Associated with Elevation of Pentraxin 3

PubMed Central

Ketter, Patrick M.; Guentzel, M. Neal; Schaffer, Beverly; Herzig, Maryanne; Wu, Xiaowu; Montgomery, Robbie K.; Parida, Bijaya K.; Fedyk, Chriselda G.; Yu, Jieh-Juen; Jorgensen, James; Chambers, James P.; Cap, Andrew P.

2014-01-01

Multidrug-resistant Acinetobacter baumannii is among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated intravascular coagulation have been reported following fulminant A. baumannii sepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge with A. baumannii strains ATCC 19606 and clinical isolates (CI) 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL/6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3 in vivo. A. baumannii strain CI 79 exhibited significantly (P < 0.0005) increased mortality, with an approximate 50% lethal dose (LD50) of 105 CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines (KC, MCP-1, and RANTES) and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitment/activation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 (1,561 ng/ml versus 145 ng/ml), with concomitant severe pathology (liver and spleen) and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis. PMID:25001601

Clinical and Laboratory Associations with Persistent Hyperferritinemia in 373 Black Hemochromatosis and Iron Overload Screening Study Participants.

PubMed

Barton, James C; Barton, J Clayborn; Adams, Paul C

2017-01-01

373 black participants had elevated screening and post-screening serum ferritin (SF) (> 300 μg/L men; > 200 μg/L women). We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF > 1,000 and ≤ 1,000 μg/L and performed regressions on SF. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF > 1,000 μg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion > 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p < 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF > 1,000 μg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

Periodic limb movements of sleep: empirical and theoretical evidence supporting objective at-home monitoring

PubMed Central

Moro, Marilyn; Goparaju, Balaji; Castillo, Jelina; Alameddine, Yvonne; Bianchi, Matt T

2016-01-01

Introduction Periodic limb movements of sleep (PLMS) may increase cardiovascular and cerebrovascular morbidity. However, most people with PLMS are either asymptomatic or have nonspecific symptoms. Therefore, predicting elevated PLMS in the absence of restless legs syndrome remains an important clinical challenge. Methods We undertook a retrospective analysis of demographic data, subjective symptoms, and objective polysomnography (PSG) findings in a clinical cohort with or without obstructive sleep apnea (OSA) from our laboratory (n=443 with OSA, n=209 without OSA). Correlation analysis and regression modeling were performed to determine predictors of periodic limb movement index (PLMI). Markov decision analysis with TreeAge software compared strategies to detect PLMS: in-laboratory PSG, at-home testing, and a clinical prediction tool based on the regression analysis. Results Elevated PLMI values (>15 per hour) were observed in >25% of patients. PLMI values in No-OSA patients correlated with age, sex, self-reported nocturnal leg jerks, restless legs syndrome symptoms, and hypertension. In OSA patients, PLMI correlated only with age and self-reported psychiatric medications. Regression models indicated only a modest predictive value of demographics, symptoms, and clinical history. Decision modeling suggests that at-home testing is favored as the pretest probability of PLMS increases, given plausible assumptions regarding PLMS morbidity, costs, and assumed benefits of pharmacological therapy. Conclusion Although elevated PLMI values were commonly observed, routinely acquired clinical information had only weak predictive utility. As the clinical importance of elevated PLMI continues to evolve, it is likely that objective measures such as PSG or at-home PLMS monitors will prove increasingly important for clinical and research endeavors. PMID:27540316

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy (ECT)

PubMed Central

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A.; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J. Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B.; Zorumski, Charles F.; Conway, Charles; Nagele, Peter

2017-01-01

Background While electroconvulsive therapy (ECT) is widely regarded as a life-saving and safe procedure, evidence regarding its effects on myocardial cell injury are sparse. The objective of this investigation was to determine incidence and magnitude of new cardiac troponin elevation after ECT using a novel high-sensitivity cardiac troponin I (hscTnI) assay. Methods This was a prospective cohort study in adult patients undergoing ECT in a single academic center (up to three ECT treatments per patient). The primary outcome was new hscTnI elevation after ECT, defined as an increase of hscTnI >100% after ECT compared to baseline with at least one value above the limit of quantification (10 ng/L). 12-lead ECG and hscTnI values were obtained prior to and 15–30 minutes after ECT; in a subset of patients an additional 2-hour hscTnI value was obtained. Results The final study population was 100 patients and a total of 245 ECT treatment sessions. Eight patients (8/100, 8%) experienced new hscTnI elevation after ECT with a cumulative incidence of 3.7% (9/245 treatments; one patient had two hscTnI elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2/245, 0.8%). Median hscTnI concentrations did not increase significantly after ECT. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of ECT treatments. Conclusions ECT appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with pre-existing cardiovascular risk factors, however, may develop new cardiac troponin elevation after ECT, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia. PMID:28166110

The evaluation of the effect of body positioning on intra-abdominal pressure measurement and the effect of intra-abdominal pressure at different body positioning on organ function and prognosis in critically ill patients.

PubMed

Yi, Min; Leng, Yuxin; Bai, Yu; Yao, Gaiqi; Zhu, Xi

2012-04-01

Current literatures confirmed the widespread and frequent development of both intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) among the critically ill with a significant associated risk of organ failure and increased mortality. The 2004 International ACS Consensus Conference committee proposed that intra-abdominal pressure (IAP) be measured in complete supine position; however, the supine position of intensive care unit (ICU) patients (<30° of bed increase) presented a significant risk for ventilator-associated pneumonia. Therefore, the potential contribution of head of bed (HOB) position in elevating IAP should be considered. The purpose of this study was to evaluate the effect of body positioning on IAP measurement and the effect of IAP at different body positions on organ function and prognosis in critically ill patients. A prospective cohort study to investigate the effect of different patient positioning on IAP, organ function, and prognosis was conducted on 88 patients admitted to a medical-surgical ICU. On admission, patients' epidemiological data and risk factors for IAH were studied; daily mean IAPs, abdominal perfusion pressure, filtration gradient, Acute Physiology and Chronic Health Evaluation II score, sequential organ failure assessment score, and multiple organ dysfunction scores were registered; next, conventional hemodynamic variables, intrathoracic blood volume index, global end-diastolic volume index and extravascular lung water using the pulse contour cardiac output system were recorded. Intra-abdominal pressures were recorded through a bladder catheter every 4 hours on the first day. Intra-abdominal pressure was measured with the patient HOB increases from 0° to 45°. Mean arterial pressure was recorded simultaneously, whereas abdominal perfusion pressure and filtration gradient (FG) were also calculated simultaneously. The main results of this study were the incidence of IAH (28.4%) and ACS (2.3%) in ICU patients; the significant and independent relationship between IAP and HOB increases. Considering the absolute numbers of IAP, the HOB of 10° and 20° showed slight differences, whereas that of 30° and 45° showed clinically significant differences; HOB elevation was associated with clinically significant decreases in abdominal perfusion pressure and FG; patients with IAH were prone to the development of shock and multiple organ dysfunction syndrome and exhibited significantly lower intrathoracic blood volume index and global end-diastolic volume index and higher extravascular lung water. There is a significant and independent relationship between IAP and HOB positioning in critically ill patients, with the HOB of 30° and 45° showing significant difference. Abdominal perfusion pressure and FG are significantly decreased when the patient's HOB is elevated. The potential contribution of body position in elevating IAP should be considered in critically ill patients with the risk of IAH and ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

[Clinical significance of early percutaneous coronary intervention in patients with Braunwald III-B type unstable angina pectoris].

PubMed

Nozaki, Katsuhiro; Nakao, Koichi; Horiuchi, Kenji; Kasanuki, Hiroshi; Honda, Takashi

2003-06-01

To assess the efficacy of early invasive strategy for the treatment of Braunwald III-B type unstable angina pectoris. This study included 573 consecutive patients of whom 267 underwent percutaneous coronary intervention (PCI) (312 lesions). The patients were divided into two groups, 95 treated with the early invasive strategy of coronary angiography within 24 hr of admission (Group PCI-I) and the remaining 172 treated with the early conservative strategy of coronary angiography 24 hr after admission (Group PCI-C). No significant differences were noted in the baseline characteristics of the two groups except for ST segment elevation on electrocardiography at presentation, which occurred significantly less frequently in Group PCI-C (36.8% vs 8.1%, p < 0.0001). The initial success rate of percutaneous coronary intervention was sufficiently high in both groups (Group PCI-I: 96.9% vs Group PCI-C: 97.7%, NS). Acute myocardial infarction occurred in six patients of Group PCI-C (3.5%) because of the side branch occlusion. There was no in-hospital death or emergent coronary artery bypass grafting. During the 6-month follow-up, there were no significant differences in the death rates (2.1% vs 1.7%), the death or myocardial infarction rates (5.3% vs 5.8%) and the target lesion revascularization ratio (26.0% vs 25.7%) between Group PCI-I and Group PCI-C. The clinical outcomes of the early invasive strategy for unstable angina pectoris were almost equivalent to those of the early conservative strategy, despite more frequent ST segmental elevation at admission in Group PCI-I. These findings suggest that the early invasive strategy for unstable angina pectoris may be acceptable even in the current Japanese clinical setting without the use of GP IIb/IIIa receptor antagonist, low molecular weight heparin or clopidogrel.

Evaluation of efficacy and safety of glycopyrrolate - xylazine - propofol anesthesia in buffalo calves

PubMed Central

Potliya, Sandeep; Kumar, Ashok; Kumar, Sandeep; Singh, Sukhbir; Kumar, Sarvan

2015-01-01

Aim: To evaluate the efficacy and safety of glycopyrrolate - xylazine - propofol anesthesia in buffalo calves. Materials and Methods: The study was conducted on six clinically healthy male buffalo calves, 6-12 months of age, and weighing between 130 and 170 kg. In all the animals; glycopyrrolate (0.01 mg/kg, IM), xylazine (0.1 mg/kg, IM) and 1% propofol as single bolus (1.5 mg/kg, intravenous), were administered. The parameters observed included behavioral changes, physiological; hematological and blood biochemical parameters. Results: Muzzle and nostrils became dry in all the animals after glycopyrrolate administration. A decrease in spontaneous activity and mild cutaneous analgesia was noticed after xylazine administration. After administration of propofol, loss of swallowing reflex, palpebral reflex, corneal reflexes, periosteal reflex and complete analgesia was observed. There was no significant change in rectal temperature and heart rate. However, heart rate remained elevated during anesthesia. Respiratory rate decreased significantly after propofol administration. There was a significant increase in plasma glucose after the xylazine and propofol administration which remained elevated till recovery. A significant decrease in chloride level was seen after propofol administration. Conclusions: Glycopyrrolate - xylazine - propofol anesthetic combination may safely be used for short duration anesthesia in buffalo calves. PMID:27047082

Obesity Cardiometabolic Comorbidity Prevalence in Children in a Rural Weight-Management Program.

PubMed

O'Hara, Valerie; Browne, Nancy; Fathima, Samreen; Sorondo, Barbara; Bayleran, Janet; Johnston, Starr; Hastey, Kathrin

2017-01-01

This descriptive study examines the prevalence of obesity-related cardiometabolic (CM) risk factors using CM laboratory metrics, in 3 to 19 year olds presenting to a rural American Academy of Pediatrics stage 3 multidisciplinary weight management clinic based on gender, age ranges, and obesity classes. From 2009 to 2016, 382 children (body mass index ≥85th percentile) enrolled. Multiple logistic regression determined the effects of age, gender, or obesity class on CM risk factors. Odds of elevated insulin were more significant in 15 to 19 year olds than in 3 to 5 year olds, or in 6 to 11 year olds. Obesity class III had higher odds than class II, class I, and overweight in having elevated insulin; twice likely than class II for having low high-density lipoprotein; and twice as likely than class I for high triglycerides. Adolescents and obesity class III categories have significant CM risk but the burden in younger and less severe obesity cohorts cannot be underestimated.

Neuronal exosomes reveal Alzheimer’s disease biomarkers in Down syndrome

PubMed Central

Hamlett, Eric D.; Goetzl, Edward J.; Ledreux, Aurélie; Vasilevko, Vitaly; Boger, Heather A.; LaRosa, Angela; Clark, David; Carroll, Steven L.; Iragui, Maria Carmona; Fortea, Juan; Mufson, Elliott J.; Sabbagh, Marwan; Mohammed, Abdul H.; Hartley, Dean; Doran, Eric; Lott, Ira T.; Granholm, Ann-Charlotte

2018-01-01

INTRODUCTION Individuals with Down syndrome (DS) exhibit Alzheimer’s disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non-AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid-beta (Aβ) peptides and phosphorylated-Tau (P-Tau) in neuronal exosomes may document preclinical AD. METHODS AD neuropathogenic proteins Aβ1-42, P-T181-Tau and P-S396-Tau were quantified by enzyme-linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age-matched controls. RESULTS Neuronal exosome levels of Aβ1-42, P-T181-Tau and P-S396-Tau were significantly elevated in individuals with DS compared to age-matched controls at an early age. No significant gender differences were observed. DISCUSSION These early increases in Aβ1-42, P-T181-Tau, and P-S396-Tau in individuals with DS may provide a basis for early intervention as targeted treatments become available. PMID:27755974

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

PubMed

Fu, Xiaohong; Yang, Jihong; Fan, Zhaoxin; Chen, Xianguang; Wu, Jie; Li, Jie; Wu, Hua

2016-02-01

To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

Change in Periodontitis during Pregnancy and Risk of Preterm Birth and Low Birthweight

PubMed Central

Michalowicz, Bryan S.; Hodges, James S.; Novak, M. John; Buchanan, William; DiAngelis, Anthony J.; Papapanou, Panos N.; Mitchell, Dennis A.; Ferguson, James E.; Lupo, Virginia R.; Bofill, James; Matseoane, Stephen

2009-01-01

Aim Determine if periodontitis progression during pregnancy is associated with adverse birth outcomes. Materials and Methods We used clinical data and birth outcomes from the OPT Study, which randomized women to receive periodontal treatment before 21 weeks gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow-up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as ≥ 3mm loss of clinical attachment. Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls. Results The distribution of gestational age at the end of pregnancy (P > 0.1) and mean birthweight (3295 versus 3184 grams, P = 0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percent of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (P > 0.05). Conclusions In these women with periodontitis and within this study’s limitations, disease progression was not associated with increased risk for delivering a preterm or low birthweight infant. Clinical Relevance Scientific Rationale Maternal periodontitis and disease progression during pregnancy have been associated with elevated risk for preterm birth. We used data from a recent clinical trial to explore possible associations between progressive periodontitis and birth outcomes. Principal Findings The distribution of gestational age at delivery and mean birthweights did not differ significantly between women who experienced progressive periodontitis and those who did not. Clinical Implication While it is important to treat dental diseases, including periodontitis, during pregnancy, women whose periodontal condition worsens during pregnancy are not at elevated risk for adverse pregnancy outcomes. PMID:19426177

Homocysteine enhances the predictive value of the GRACE risk score in patients with ST-elevation myocardial infarction.

PubMed

Fan, Yan; Wang, Jianjun; Zhang, Sumei; Wan, Zhaofei; Zhou, Dong; Ding, Yanhong; He, Qinli; Xie, Ping

2017-09-01

The present study aims to investigate whether the addition of homocysteine level to the Global Registry of Acute Coronary Events (GRACE) risk score enhances its predictive value for clinical outcomes in ST-elevation myocardial infarction (STEMI). A total of 1143 consecutive patients with STEMI were included in this prospective cohort study. Homocysteine was detected, and the GRACE score was calculated. The predictive power of the GRACE score alone or combined with homocysteine was assessed by the receiver operating characteristic (ROC) analysis, methods of net reclassification improvement (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 36.7 months, 271 (23.7%) patients reached the clinical endpoints. It showed that the GRACE score and homocysteine could independently predict all-cause death [GRACE: HR=1.031 (1.024-1.039), p<0.001; homocysteine: HR=1.023 (1.018-1.028), p<0.001] and MACE [GRACE: HR=1.008 (1.005-1.011), p<0.001; homocysteine: HR=1.022 (1.018-1.025), p<0.001]. When they were used in combination to assess the clinical outcomes, the area under the ROC curve significantly increased from 0.786 to 0.884 (95% CI=0.067-0.128, Z=6.307, p<0.001) for all-cause death and from 0.678 to 0.759 (95% CI=0.055-0.108, Z=5.943, p<0.001) for MACE. The addition of homocysteine to the GRACE model improved NRI (all-cause death: 0.575, p<0.001; MACE: 0.621, p=0.008) and IDI (all-cause death: 0.083, p<0.001; MACE: 0.130, p=0.016), indicating effective discrimination and reclassification. Both the GRACE score and homocysteine are significant and independent predictors for clinical outcomes in patients with STEMI. A combination of them can develop a more predominant prediction for clinical outcomes in these patients.

UTE-T2* mapping detects sub-clinical meniscus injury after anterior cruciate ligament tear

PubMed Central

Williams, A.; Qian, Y.; Golla, S.; Chu, C.R.

2018-01-01

SUMMARY Objective Meniscus tear is a known risk factor for osteoarthritis (OA). Quantitative assessment of meniscus degeneration, prior to surface break-down, is important to identification of early disease potentially amenable to therapeutic interventions. This work examines the diagnostic potential of ultrashort echo time-enhanced T2* (UTE-T2*) mapping to detect human meniscus degeneration in vitro and in vivo in subjects at risk of developing OA. Design UTE-T2* maps of 16 human cadaver menisci were compared to histological evaluations of meniscal structural integrity and clinical magnetic resonance imaging (MRI) assessment by a musculoskeletal radiologist. In vivo UTE-T2* maps were compared in 10 asymptomatic subjects and 25 ACL-injured patients with and without concomitant meniscal tear. Results In vitro, UTE-T2* values tended to be lower in histologically and clinically normal meniscus tissue and higher in torn or degenerate tissue. UTE-T2* map heterogeneity reflected collagen disorganization. In vivo, asymptomatic meniscus UTE-T2* values were repeatable within 9% (root-mean-square average coefficient of variation). Posteromedial meniscus UTE-T2* values in ACL-injured subjects with clinically diagnosed medial meniscus tear (n = 10) were 87% higher than asymptomatics (n = 10, P < 0.001). Posteromedial menisci UTE-T2* values of ACL-injured subjects without concomitant medial meniscal tear (n = 15) were 33% higher than asymptomatics (P = 0.001). Posterolateral menisci UTE-T2* values also varied significantly with degree of joint pathology (P = 0.001). Conclusion Significant elevations of UTE-T2* values in the menisci of ACL-injured subjects without clinical evidence of subsurface meniscal abnormality suggest that UTE-T2* mapping is sensitive to subclinical meniscus degeneration. Further study is needed to determine whether elevated subsurface meniscus UTE-T2* values predict progression of meniscal degeneration and development of OA. PMID:22306000

Correlation of Admission Heart Rate With Angiographic and Clinical Outcomes in Patients With Right Coronary Artery ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: HORIZONS-AMI (The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) Trial.

PubMed

Kosmidou, Ioanna; McAndrew, Thomas; Redfors, Björn; Embacher, Monica; Dizon, José M; Mehran, Roxana; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W

2017-07-19

Bradycardia on presentation is frequently observed in patients with right coronary artery ST-segment elevation myocardial infarction, but it is largely unknown whether it predicts poor angiographic or clinical outcomes in that patient population. We sought to determine the prognostic implications of admission heart rate (AHR) in patients with ST-segment elevation myocardial infarction and a right coronary artery culprit lesion. We analyzed 1460 patients with ST-segment elevation myocardial infarction and a right coronary artery culprit lesion enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial who underwent primary percutaneous coronary intervention. Patients presenting with high-grade atrioventricular block were excluded. Outcomes were examined according to AHR range (AHR <60, 61-79, 80-99, and ≥100 beats per minute). Baseline and procedural characteristics did not vary significantly with AHR except for a more frequent history of diabetes mellitus, longer symptom-to-balloon time, more frequent cardiogenic shock, and less frequent restoration of thrombolysis in myocardial infarction 3 flow in patients with admission tachycardia (AHR >100 beats per minute). Angiographic analysis showed no significant association between AHR and lesion location or complexity. On multivariate analysis, admission bradycardia (AHR <60 beats per minute) was not associated with increased 1-year mortality (hazard ratio 1.33; 95% CI 0.41-4.34, P =0.64) or major adverse cardiac events (hazard ratio 1.08; 95% CI 0.62-1.88, P =0.78), whereas admission tachycardia was a strong independent predictor of mortality (hazard ratio 5.02; 95% CI 1.95-12.88, P =0.0008) and major adverse cardiac events (hazard ratio 2.20; 95% CI 1.29-3.75, P =0.0004). In patients with ST-segment elevation myocardial infarction and a right coronary artery culprit lesion undergoing primary percutaneous coronary intervention, admission bradycardia was not associated with increased mortality or major adverse cardiac events at 1 year. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00433966. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Investigation of Central Pain Processing in Post-Operative Shoulder Pain and Disability

PubMed Central

Valencia, Carolina; Fillingim, Roger B.; Bishop, Mark; Wu, Samuel S.; Wright, Thomas W.; Moser, Michael; Farmer, Kevin; George, Steven Z.

2014-01-01

Measures of central pain processing like conditioned pain modulation (CPM), and suprathreshold heat pain response (SHPR) have been described to assess different components of central pain modulatory mechanisms. Central pain processing potentially play a role in the development of postsurgical pain, however, the role of CPM and SHPR in explaining postoperative clinical pain and disability is still unclear. Seventy eight patients with clinical shoulder pain were included in this study. Patients were examined before shoulder surgery, at 3 months, and 6 months after surgery. The primary outcome measures were pain intensity and upper extremity disability. Analyses revealed that the change score (baseline – 3 months) of 5th pain rating of SHPR accounted for a significant amount of variance in 6 month postsurgical clinical pain intensity and disability after age, sex, preoperative pain intensity, and relevant psychological factors were considered. The present study suggests that baseline measures of central pain processing were not predictive of 6 month postoperative pain outcome. Instead, the 3 month change in SHPR might be a relevant factor in the transition to elevated 6-month postoperative pain and disability outcomes. In patients with shoulder pain, the 3 month change in a measure of central pain processing might be a relevant factor in the transition to elevated 6-month postoperative pain and disability scores. PMID:24042347

Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

PubMed

Thurlow, Vanessa R; Asafu-Adjaye, Michelle; Agalou, Stamatina; Rahman, Yusof

2010-05-01

There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

MR imaging of the hippocampus in normal pressure hydrocephalus: correlations with cortical Alzheimer's disease confirmed by pathologic analysis.

PubMed

Savolainen, S; Laakso, M P; Paljärvi, L; Alafuzoff, I; Hurskainen, H; Partanen, K; Soininen, H; Vapalahti, M

2000-02-01

MR studies have shown hippocampal atrophy to be a sensitive diagnostic feature of Alzheimer's disease (AD). In this study, we measured the hippocampal volumes of patients with a clinical diagnosis of normal pressure hydrocephalus (NPH), a potentially reversible cause of dementia when shunted. Further, we examined the relationship between the hippocampal volumes and cortical AD pathologic findings, intracranial pressure, and clinical outcomes in cases of NPH. We measured hippocampal volumes from 37 patients with a clinical diagnosis of NPH (27 control volunteers and 24 patients with AD). The patients with NPH underwent biopsy, and their clinical outcomes were followed for a year. Compared with those for control volunteers, the findings for patients with NPH included a minor left-side decrease in the hippocampal volumes (P < .05). Compared with those for patients with AD, the findings for patients with NPH included significantly larger hippocampi on both sides. Although not statistically significant, trends toward larger volumes were observed in patients with NPH who had elevated intracranial pressure, who benefited from shunting, and who did not display cortical AD pathologic findings. Measurements of hippocampal volumes among patients with a clinical diagnosis of NPH have clear clinical implications, providing diagnostic discrimination from AD and possibly prediction of clinical outcome after shunting.

Factors associated with overweight and obesity in schizophrenia, schizoaffective and bipolar disorders.

PubMed

Chouinard, Virginie-Anne; Pingali, Samira M; Chouinard, Guy; Henderson, David C; Mallya, Sonal G; Cypess, Aaron M; Cohen, Bruce M; Öngür, Dost

2016-03-30

Evidence suggests abnormal bioenergetic status throughout the body in psychotic disorders. The present study examined predictors of elevated body mass index (BMI) across diagnostic categories of schizophrenia, schizoaffective and bipolar disorders. In a cross-sectional study, we studied demographic and clinical risk factors for overweight and obesity in a well-characterized sample of 262 inpatients and outpatients with schizophrenia (n=59), schizoaffective disorder (n=81) and bipolar I disorder (n=122). Across the three diagnostic categories, the prevalence of overweight (29.4%) and obesity (33.2%) combined was 62.6% (164/262). Logistic regression analyses, adjusted for age, sex and ethnicity, showed that schizoaffective disorder, lifetime major depressive episode, presence of prior suicide attempt, and more than 5 lifetime hospitalizations were significantly associated with BMI≥25. Patients with schizophrenia had significantly lower risk for overweight and obesity. Overall, we found that affective components of illness were associated with elevated BMI in our cross-diagnostic sample. Our results show that patients with schizoaffective disorder have a greater risk for obesity. Identifying predictors of elevated BMI in patients with psychotic and mood disorders will help prevent obesity and related cardiovascular and cerebral complications. Future studies are needed to elucidate the mechanistic nature of the relationship between obesity and psychiatric illness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Elevated troponin in patients with acute stroke - Is it a true heart attack?

PubMed

Dous, George V; Grigos, Angela C; Grodman, Richard

2017-09-01

Although the prognostic value of a positive troponin in an acute stroke patient is still uncertain, it is a commonly encountered clinical situation given that Ischemic Heart Disease (IHD) and cerebrovascular disease (CVD) frequently co-exist in the same patient and share similar risk factors. Our objectives in this review are to (1) identify the biologic relationship between acute cerebrovascular stroke and elevated troponin levels, (2) determine the pathophysiologic differences between positive troponin in the setting of acute stroke versus acute myocardial infarction (AMI), and (3) examine whether positive troponin in the setting of acute stroke has prognostic significance. We also will provide an insight analysis of some of the available studies and will provide guidance for a management approach based on the available data according to the current guidelines.

Assessment of periodontal bone level revisited: a controlled study on the diagnostic accuracy of clinical evaluation methods and intra-oral radiography.

PubMed

Christiaens, Véronique; De Bruyn, Hugo; Thevissen, Eric; Koole, Sebastiaan; Dierens, Melissa; Cosyn, Jan

2018-01-01

The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2). The study sample included 49 interdental sites in 17 periodontitis patients. Evaluation methods included vertical relative probing attachment level (RAL-V), analogue and digital intra-oral radiography and bone sounding without and with flap elevation. The latter was considered the true bone level. Five examiners evaluated all radiographs. Significant underestimation of the true bone level was observed for all evaluation methods pointing to 2.7 mm on average for analogue radiography, 2.5 mm for digital radiography, 1.8 mm for RAL-V and 0.6 mm for bone sounding without flap elevation (p < 0.001). Radiographic underestimation of the true bone level was higher in the (pre)molar region (p ≤ 0.047) and increased with defect depth (p < 0.001). Variation between clinicians was huge (range analogue radiography 2.2-3.2 mm; range digital radiography 2.1-3.0 mm). All evaluation methods significantly underestimated the true bone level. Bone sounding was most accurate, whereas intra-oral radiographs were least accurate. Deep periodontal defects in the (pre)molar region were most underrated by intra-oral radiography. Bone sounding had the highest accuracy in assessing interdental bone level.

Optimal optic nerve sheath diameter threshold for the identification of elevated opening pressure on lumbar puncture in a Chinese population.

PubMed

Wang, Lijuan; Feng, Liangshu; Yao, Yan; Wang, Yuzhi; Chen, Ying; Feng, Jiachun; Xing, Yingqi

2015-01-01

Ultrasonography of the optic nerve sheath diameter (ONSD) is a non-invasive and rapid method that might be helpful in the identification of increased intracranial pressure (ICP). The use of an ONSD greater than 5 mm on ultrasound as an indicator of increased ICP in a Caucasian population has been studied. However, the cut-off point of this predictor in Chinese patients has not been established. Thus, we conducted this study to identify the ONSD criterion for the detection of elevated opening pressure on lumbar puncture (LP) in a Chinese population and to investigate the influencing factors. This study was a blind cross-sectional study. Patients who presented with suspected increased ICP were included. The opening pressure on LP of each participant was confirmed. We analyzed the clinical differences between the groups of patients with abnormal and normal opening pressures on LP. A receiver operating characteristic curve was constructed to determine the ONSD cut-off point for the identification of abnormal opening pressure on LP. In total, 279 patients were recruited, and 101 patients presented with elevated opening pressure on LP. ONSD was a significant independent predictor of elevated opening pressure on LP (p<0.001). However, no statistical significance was observed regarding the factors that might have affected this relationship including gender, age, body mass index, waistline, head circumference, hypertension and pathological subtype. The ONSD cut-off point for the identification of elevated opening pressure on LP was 4.1 mm; this cut-off yielded a sensitivity of 95% and a specificity of 92%. ONSD is a strong and accurate predictor of elevated opening pressure on LP. The cut-off point of this predictor in a Chinese population was remarkably lower than that found in a Caucasian population. Thus, ethnic differences should be noted when using the ONSD as an indicator of increased ICP.

B Lymphocyte Stimulator Levels in Systemic Lupus Erythematosus: Higher Circulating Levels in African American Patients and Increased Production after Influenza Vaccination in Patients with Low Baseline Levels

PubMed Central

Ritterhouse, Lauren L.; Crowe, Sherry R.; Niewold, Timothy B.; Merrill, Joan T.; Roberts, Virginia C.; Dedeke, Amy B.; Neas, Barbara R.; Thompson, Linda F.; Guthridge, Joel M.; James, Judith A.

2011-01-01

Objective Examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels. Clinical and serologic features of SLE that are associated with elevated BLyS levels will also be investigated. Methods Clinical history, disease activity measurements and blood specimens were collected from sixty SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum IFN-α activity, 25-hydroxyvitamin D, and humoral responses to influenza vaccination. Results Thirty percent of SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than European American patients (p=0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (p=0.863), and BLyS levels increased post-vaccination only in the subset of patients in the lowest quartile of BLyS levels (p=0.0003). Elevated BLyS levels were associated with increased disease activity as measured by SLEDAI, PGA, and SLAM in European Americans (p=0.035, p=0.016, p=0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nRNP (p=0.0003) and decreased 25(OH)D (p=0.018). Serum IFN-α activity was a significant predictor of elevated BLyS in a multivariate analysis (p=0.002). Conclusion African American SLE patients have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination. PMID:22127709

Elevated Peak Postoperative B-type Natriuretic Peptide Predicts Decreased Longer-Term Physical Function after Primary Coronary Artery Bypass Graft Surgery

PubMed Central

Fox, Amanda A.; Marcantonio, Edward R.; Collard, Charles D.; Thoma, Mathis; Perry, Tjorvi E.; Shernan, Stanton K.; Muehlschlegel, Jochen D.; Body, Simon C.

2011-01-01

Background Elevated peak postoperative B-type natriuretic peptide (BNP) is associated with increased major adverse cardiovascular events and all-cause mortality after coronary artery bypass graft (CABG) surgery. Whether elevated postoperative BNP predicts worse post-discharge physical function (PF) is unknown. We hypothesized that peak postoperative BNP associates with PF assessed up to 2 years after CABG surgery, even after adjusting for clinical risk factors including preoperative PF. Methods This two institution prospective cohort study included patients undergoing primary CABG surgery with cardiopulmonary bypass. Short Form-36 questionnaires were administered to subjects preoperatively and 6 months, 1 and 2 years postoperatively. Short Form-36 PF domain scores were calculated using the Short Form-36 norm based scoring algorithm. Plasma BNP concentrations measured preoperatively and on postoperative days 1–5 were log10 transformed before analysis. To determine whether peak postoperative BNP independently predicts PF scores 6 months through 2 years after CABG surgery, multivariable longitudinal regression analysis of the postoperative PF scores was performed, adjusting for important clinical risk factors. Results 845 subjects (mean age±SD: 65±10 years) were analyzed. Peak postoperative BNP was significantly associated with postoperative PF (effect estimate for log10 peak BNP = −7.66 PF score points; 95% CI = −9.68, −5.64; P=<0.0001). After multivariable adjustments, peak postoperative BNP remained independently associated with postoperative PF (effect estimate for log10 peak BNP =−3.06 PF score points; 95% CI = −5.15, −0.97; P=0.004). Conclusions Elevated peak postoperative BNP independently associates with worse longer-term physical function after primary CABG surgery. Future studies are needed to determine whether medical management targeted towards reducing elevated postoperative BNP can improve PF after CABG surgery. PMID:21427536

Elevated IL-17A and IL-22 regulate expression of inducible CD38 and Zap-70 in chronic lymphocytic leukemia.

PubMed

Kouzegaran, Samaneh; Siroosbakht, Soheila; Farsad, Bahram Fariborz; Rezakhaniha, Bijan; Dormanesh, Banafshe; Behnod, Vahid; Tanha, Amir Saber

2018-01-01

In this study, we investigated the role and expression of interleukin (IL)-17A and IL-22 in chronic lymphocytic leukemia. We evaluated the expression of markers above on CLL by ELISA, qRT-PCR, flow cytometric analysis and nonparametric Kruskal-Wallis test. Quantitative RT-PCR revealed that the mRNA levels of IL-17A and IL-22 in PBMCs of CLL patients were upregulated compared with those from healthy subjects (mean ± SD: 1.96 ± 0.232 vs.0.72 ± 0.15, P < 0.001 and mean ± SD: 2.45 ± 0.534 vs.0.81 ± 0.26, P < 0.001, respectivily). In addition, findings showed that the IL-17A and IL-22 plasma level was significantly elevated than that from healthy control group (P  < 0.001). The median IL-17A and IL-22 in CLL patients and healthy control group were 48.28 ± 17.2 pg mL -1 ; 20.01 ± 11.16 pg mL -1 and 58.68 ± 23.4 pg mL -1 ;16.47 ± 10.31 P < 0.001, respectively. The levels of IL-17A and IL-22 was not significantly associated with the different stages of disease (Rai stages; Kruskal-Wallis test P > 0.05).No significant relationship was found between expression of CD38 and higher median serum levels of IL-17A in patients, but patients with negative expression of ZAP-70 showed a significant association with higher median serum levels of IL-17A compared with healthy subjects. (57.84 pg mL -1 vs. 31.67 pg mL -1 ; P = 0.016). IL-22 is elevated and associated with CD38 and Zap-70 expression in patients with CLL. No significant correlation was found between expression of CD38 and increased levels of IL-17A, negative expression of ZAP-70 showed a significant association with increased levels of IL-17A. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Associations Between Vitamin D Levels and Depressive Symptoms in Later Life: Evidence From the English Longitudinal Study of Ageing (ELSA).

PubMed

de Oliveira, Cesar; Hirani, Vasant; Biddulph, Jane P

2017-06-22

A possible role of vitamin D in depression has received considerable attention, especially given the significant disability, mortality, and healthcare costs associated to depression and the high prevalence of vitamin D deficiency. We investigated the cross-sectional associations between serum 25-hydroxyvitamin D (25OHD) levels and depressive symptoms (CES-D) in 5,607 older adults from the English Longitudinal Study of Ageing (ELSA). Overall, there was a significant association between low 25OHD levels and elevated depressive symptoms (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.20-2.07 for the lowest quartile; OR = 1.45, 95% CI = 1.15-1.83 for <30 nmol/L cut-off and OR = 1.34, 95% CI = 1.10-1.62 for the ≤50 nmol/L cut-off) after adjustment for a wide range of covariates of clinical significance. Fully adjusted models showed that women in the lowest (OR = 1.67, 95% CI = 1.20-2.34) and second lowest (OR = 1.68, 95% CI = 1.20-2.35) quartiles of 25OHD as well as those with 25OHD levels <30 nmol/L (OR = 1.40, 95% CI = 1.06-1.86) and ≤50 nmol/L (OR = 1.35, 95% CI = 1.07-1.72) were more likely to report elevated depressive symptoms. For men, however, this association only remained significant for those with 25OHD levels of <30 nmol/L (OR = 1.60, 95% CI = 1.06-2.42) in the fully adjusted models. The independent and inverse association found between low 25OHD levels and elevated depressive symptoms suggests that vitamin D deficiency may be a risk factor for late-life depression, particularly among women. Whether our findings have any clinical meaning or not, additional data are needed from well-designed randomized controlled trials of vitamin D for the prevention and treatment of late-life depression. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins.

PubMed

Ebersole, Jeffrey L; Cappelli, David; Mathys, Erik C; Steffen, Michelle J; Singer, Robert E; Montgomery, Michael; Mott, Glen E; Novak, M John

2002-12-01

The acute phase response (APR) represents a systemic counterpart to the localized inflammatory response. This report describes patient-oriented and non-human primate model studies to determine the effect of periodontal disease on systemic acute phase proteins (APP). Patient-oriented studies included comparison of the levels of APP, using enzyme-linked immunosorbent assay (ELISA), with the presence and severity of periodontitis in localized chronic periodontitis (LCP), generalized aggressive periodontitis (GAP), and Sjogren's syndrome (SS) patients. The non-human primate experiments evaluated the serum level of APPs under natural conditions, following mechanical hygiene, experimental gingivitis, and during ligature-induced periodontitis. Analysis of the LCP population showed what appeared to be a threshold of periodontal disease severity required for elevating the C-reactive protein (CRP) and haptoglobin (HG). The results demonstrated a significant elevation in CRP in the GAP versus the control groups, as well as lower levels of all mediators in healthy non-smokers (HNS) versus smokers (HS), suggesting that these systemic inflammatory markers were altered in response to challenge by noxious materials from smoking. Significantly different levels of CRP, HG, and alpha1-antiproteinase were noted in the SS patients suggesting that the autoimmune aspects of Sjögren's syndrome may impact upon oral health and systemic responses. Parallel evidence was also obtained from the primate studies. Providing mechanical oral hygiene, which significantly lowered clinical inflammation and bleeding of the gingiva, decreased the serum APP levels. Both CRP and fibrinogen were significantly elevated during progressing periodontitis, which also appeared to have an impact on serum lipids and lipoproteins. These findings supported results relating chronic oral infections and the inflammation of periodontitis as contributors to and/or triggers for systemic inflammatory responses. Finally, similarities in the clinical and microbiological parameters of gingival inflammation and periodontitis between humans and non-human primates was extended to identification of changes in serum APP in the non-human primates that appeared to be in direct response to the induction of progressing periodontitis. These systemic changes provide additional evidence for the biological plausibility of periodontal infections contributing to various systemic diseases.

Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies

PubMed Central

Powers, Robert W.; Jeyabalan, Arun; Clifton, Rebecca G.; Van Dorsten, Peter; Hauth, John C.; Klebanoff, Mark A.; Lindheimer, Marshall D.; Sibai, Baha; Landon, Mark; Miodovnik, Menachem

2010-01-01

Background Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2-fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women. PMID:20948996

Childhood Attention-Deficit/Hyperactivity Disorder and Homelessness: A 33-Year Follow-Up Study.

PubMed

García Murillo, Lourdes; Ramos-Olazagasti, Maria A; Mannuzza, Salvatore; Castellanos, Francisco Xavier; Klein, Rachel G

2016-11-01

To examine whether childhood attention-deficit/hyperactivity disorder (ADHD) predicts homelessness in adulthood, and whether the persistence of childhood ADHD through adolescence influences the likelihood of homelessness. A 33-year prospective, controlled, follow-up was performed of clinic-referred, 6- to 12-year-old boys of white ethnicity with ADHD (probands; mean = 8), at a mean age of 41 years (follow-up [FU] = 41). Comparisons, children without ADHD from the same medical center, were matched for age and socioeconomic status (SES). Both groups were evaluated at a mean age of 18 years (FU18). Homelessness was assessed at FU41 in 134 of 207 probands (65%) and 136 of 178 (76%) comparisons. We tested the following: the relationship between childhood ADHD and homelessness; whether adolescent dysfunctions (conduct disorder, non-alcohol substance use disorder, arrests, and school dropout) accounted for this relationship, if found; and whether ADHD that persisted through FU18 elevated probands' homelessness rate. Probands had significantly higher rates of homelessness than comparisons (23.7% vs. 4.4%; χ 2 1  = 21.15, df = 1, p < .001). In a multivariate analysis, including childhood ADHD and covariates, the probands' significant elevation of homelessness remained (odds ratio [OR] = 3.60, 95% CI = 1.32-9.76, p = .01). Probands with persistent ADHD through adolescence had significantly more homelessness than remitted probands (χ 2 1  = 12.73, p < .001), but this relationship was no longer significant when conduct disorder at FU18 was controlled (OR = 1.97, 95% CI = 0.89-4.38, p = .09). Among boys of white ethnicity who were followed into adulthood, childhood ADHD was associated with an elevated rate of homelessness. Findings point to the need for clinical monitoring of childhood ADHD through adolescence, even when ADHD does not persist, in hopes of mitigating a cascade of malfunction that includes homelessness. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

The Price of a Neglected Zoonosis: Case-Control Study to Estimate Healthcare Utilization Costs of Human Brucellosis.

PubMed

Vered, Oded; Simon-Tuval, Tzahit; Yagupsky, Pablo; Malul, Miki; Cicurel, Assi; Davidovitch, Nadav

2015-01-01

Human brucellosis has reemerged as a serious public health threat to the Bedouin population of southern Israel in recent years. Little is known about its economic implications derived from elevated healthcare utilization (HCU). Our objective was to estimate the HCU costs associated with human brucellosis from the insurer perspective. A case-control retrospective study was conducted among Clalit Health Services (CHS) enrollees. Brucellosis cases were defined as individuals that were diagnosed with brucellosis at the Clinical Microbiology Laboratory of Soroka University Medical Center in the 2010-2012 period (n = 470). Control subjects were randomly selected and matched 1:3 by age, sex, clinic, and primary physician (n = 1,410). HCU data, demographic characteristics and comorbidities were obtained from CHS computerized database. Mean±SD age of the brucellosis cases was 26.6±17.6 years. 63% were male and 85% were Bedouins. No significant difference in Charlson comorbidity index was found between brucellosis cases and controls (0.41 vs. 0.45, respectively, P = 0.391). Before diagnosis (baseline), the average total annual HCU cost of brucellosis cases was slightly yet significantly higher than that of the control group ($439 vs. $382, P<0.05), however, no significant differences were found at baseline in the predominant components of HCU, i.e. hospitalizations, diagnostic procedures, and medications. At the year following diagnosis, the average total annual HCU costs of brucellosis cases was significantly higher than that of controls ($1,327 vs. $380, respectively, P<0.001). Most of the difference stems from 7.9 times higher hospitalization costs (p<0.001). Additional elevated costs were 3.6 times higher laboratory tests (P<0.001), 2.8 times higher emergency room visits (P<0.001), 1.8 times higher medication (P<0.001) and 1.3 times higher diagnostic procedures (P<0.001). We conclude that human brucellosis is associated with elevated HCU costs. Considering these results in cost-effective analyses may be crucial for both reducing health inequities and optimal allocation of health systems' scarce resources.

A common factor suppresses thickening in young women with malar area port wine stains and delays low density lipoprotein elevation: is it estrogen?

PubMed

Klapman, M H; Sosa, V B; Yao, J F

2014-06-01

Port wine stains in the malar area of the face can develop thickening in early adult life. We began a study with a hypothesis that this thickening can be associated with elevation of low density lipoprotein. In a retrospective review, we divided 53 subjects with malar port wine stains into 4 groups, adults 25-39 years of age with thickening, that age group without thickening, adults 40+ years of age with thickening, and that age group without thickening. Low density lipoprotein levels in the subjects were compared to age and sex matched controls randomly selected from the general Dermatology clinic. The younger subjects with thickening demonstrated significantly higher low density lipoprotein levels than their controls (p .0082) and without thickening lower low density lipoprotein levels than their controls with great significance (p .00058). The subjects without thickening also consisted mainly of women. The low density lipoprotein levels in the older age groups, whether thickened or not, demonstrated no significant difference in low density lipoprotein levels between subjects and controls. This led to a new hypothesis that there is a factor in a subgroup of young adult women with malar port wine stains that suppresses thickening and delays the elevation of low density lipoprotein and that this factor might be estrogen. The implications of this hypothesis are that it could define a marker for a subset of the population that might be protected from the diseases associated with early elevation of low density lipoprotein and provide a source of cutaneous tissue for studying the basic science of this protection (although limited by cosmetic considerations). Future laboratory research to test the new hypothesis might include testing blood of women with malar port wine stains with or without thickening for estrogen and other sex hormones. It might also include skin biopsies to study receptors for estrogen, other sex hormones, and angiogenic factors in malar port wine stains with or without thickening. Future clinical research might include a long term prospective project to study the development of low density lipoprotein related diseases in women with malar port wine stains with or without thickening over years. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oxidative Stress and Inflammation Differentially Elevated in Objective Versus Habitual Subjective Reduced Sleep Duration in Obstructive Sleep Apnea

PubMed Central

DeMartino, Theresanne; Ghoul, Rawad El; Wang, Lu; Bena, James; Hazen, Stanley L.; Tracy, Russel; Patel, Sanjay R.; Auckley, Dennis; Mehra, Reena

2016-01-01

Study Objectives: Data have demonstrated adverse health effects of sleep deprivation. We postulate that oxidative stress and systemic inflammation biomarkers will be elevated in relation to short-term and long-term sleep duration reduction. Methods: We analyzed data from the baseline examination of a randomized controlled trial involving participants with moderate to severe obstructive sleep apnea (OSA). Baseline polysomnography provided the total sleep time (PSG-TST, primary predictor); self-reported habitual sleep duration (SR-HSD) data was collected. Morning measures of oxidative stress and systemic inflammation included: myeloperoxidase (MPO, pmol/L), oxidized low-density lipoprotein (ox-LDL, U/L), F2-isoprostane (ng/mg), paraoxonase 1 (PON1, nmol·min−1·mL−1), and aryl esterase (μmol·min−1·mL−1). Linear models adjusted for age, sex, race, body mass index (BMI), cardiovascular disease (CVD), smoking, statin/anti-inflammatory medications, and apnea-hypopnea index were utilized (beta estimates and 95% confidence intervals). Results: One hundred forty-seven participants comprised the final analytic sample; they were overall middle-aged (51.0 ± 11.7 y), obese (BMI = 37.3 ± 8.1 kg/m2), and 17% had CVD. Multivariable models demonstrated a significant inverse association of PSG-TST and MPO (β [95% CI] = −20.28 [−37.48, −3.08], P = 0.021), i.e., 20.3 pmol/L MPO reduction per hour increase PSG-TST. Alternatively, a significant inverse association with ox-LDL and SR-HSD was observed (β [95% CI] = 0.98 [0.96, 0.99], P = 0.027), i.e., 2% ox-LDL reduction per hour increase SR-HSD. Conclusions: Even after consideration of obesity and OSA severity, inverse significant findings were observed such that reduced PSG-TST was associated with elevated MPO levels and SR-HSD with ox-LDL, suggesting differential up-regulation of oxidative stress and pathways of inflammation in acute versus chronic sleep curtailment. Clinical Trial Registration: NIH clinical trials registry number NCT00607893. Citation: DeMartino T, Ghoul RE, Wang L, Bena J, Hazen SL, Tracy R, Patel SR, Ackley D, Mehra R. Oxidative stress and inflammation differentially elevated in objective versus habitual subjective reduced sleep duration in obstructive sleep apnea. SLEEP 2016;39(7):1361–1369. PMID:27091532

Parkinson's disease and occupation: differences in associations by case identification method suggest referral bias.

PubMed

Teschke, Kay; Marion, Stephen A; Tsui, Joseph K C; Shen, Hui; Rugbjerg, Kathrine; Harris, M Anne

2014-02-01

We used a population-based sample of 403 Parkinson's disease cases and 405 controls to examine risks by occupation. Results were compared to a previous clinic-based analysis. With censoring of jobs held within 10 years of diagnosis, the following had significantly or strongly increased risks: social science, law and library jobs (OR = 1.8); farming and horticulture jobs (OR = 2.0); gas station jobs (OR = 2.6); and welders (OR = 3.0). The following had significantly decreased risks: management and administration jobs (OR = 0.70); and other health care jobs (OR = 0.44). These results were consistent with other findings for social science and farming occupations. Risks for teaching, medicine and health occupations were not elevated, unlike our previous clinic-based study. This underscores the value of population-based over clinic-based samples. Occupational studies may be particularly susceptible to referral bias because social networks may spread preferentially via jobs. © 2013 Wiley Periodicals, Inc.

Elevated red blood cell distribution width is associated with liver function tests in patients with primary hepatocellular carcinoma.

PubMed

Wei, Ting-Ting; Tang, Qing-Qin; Qin, Bao-Dong; Ma, Ning; Wang, Li-Li; Zhou, Lin; Zhong, Ren-Qian

2016-11-25

Red blood cell distribution width (RDW), a routinely tested parameter of the complete blood count (CBC), has been reported to be increased in various cancers and correlated with the patients' clinical characteristics. However, the significance of RDW in primary hepatocellular carcinoma (pHCC) is largely unknown. The aim of this study was to evaluate the associations between RDW and the clinical characteristics of pHCC patients. Medical records of 110 treatment-naive pHCC patients were retrospectively reviewed. Their clinical characteristics on admission, including RDW, liver function tests and tumor stage, were extracted, and their relationships were analyzed using Spearman correlation and Kruskal-Wallis test. Sixty-eight healthy individuals were set as controls. RDW was significantly increased in pHCC patients and correlated with the liver function tests. However, no correlation between RDW and tumor stage was found. RDW may be used to assess the liver function, but not the tumor stage in pHCC patients.

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.

Blood Pressure Control and Risk of Stroke or Systemic Embolism in Patients With Atrial Fibrillation: Results From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

PubMed

Rao, Meena P; Halvorsen, Sigrun; Wojdyla, Daniel; Thomas, Laine; Alexander, John H; Hylek, Elaine M; Hanna, Michael; Bahit, M Cecilia; Lopes, Renato D; De Caterina, Raffaele; Erol, Cetin; Goto, Shinya; Lanas, Fernando; Lewis, Basil S; Husted, Steen; Gersh, Bernard J; Wallentin, Lars; Granger, Christopher B

2015-12-01

Patients with atrial fibrillation (AF) and hypertension are at high risk for stroke. Previous studies have shown elevated risk of stroke in patients with AF who have a history of hypertension (regardless of blood pressure [BP] control) and in patients with elevated BP. We assessed the association of hypertension and BP control on clinical outcomes. In ARISTOTLE (n=18 201), BP was evaluated as history of hypertension requiring treatment and elevated BP (systolic ≥140 and/or diastolic ≥90 mm Hg) at study entry and any point during the trial. Hazard ratios (HRs) were derived from Cox proportional hazards models including BP as a time-dependent covariate. A total of 15 916 (87.5%) patients had a history of hypertension requiring treatment. In patients with elevated BP measurement at any point during the trial, the rate of stroke or systemic embolism was significantly higher (HR, 1.53; 95% confidence interval [CI], 1.25-1.86), as was hemorrhagic stroke (HR 1.85; 95% CI, 1.26-2.72) and ischemic stroke (HR, 1.50; 95% CI, 1.18-1.90). Rates of major bleeding were lower in patients with a history of hypertension (HR, 0.80; 95% CI, 0.66-0.98) and nonsignificantly lower in patients with elevated BP at study entry (HR, 0.89; 95% CI, 0.77-1.03). The benefit of apixaban versus warfarin on preventing stroke or systemic embolism was consistent among patients with and without a history of hypertension (P interaction=0.27), BP control at baseline (P interaction=0.43), and BP control during the trial (P interaction=0.97). High BP measurement at any point during the trial was independently associated with a substantially higher risk of stroke or systemic embolism. These results strongly support efforts to treat elevated BP as an important strategy to optimally lower risk of stroke in patients with AF. URL: https://ClinicalTrials.gov/. Unique identifier: NCT00412984. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

A Low-Effort, Clinic-Wide Intervention Improves Attendance for HIV Primary Care

PubMed Central

Gardner, Lytt I.; Marks, Gary; Craw, Jason A.; Wilson, Tracey E.; Drainoni, Mari-Lynn; Moore, Richard D.; Mugavero, Michael J.; Rodriguez, Allan E.; Bradley-Springer, Lucy A.; Holman, Susan; Keruly, Jeanne C.; Sullivan, Meg; Skolnik, Paul R.; Malitz, Faye; Metsch, Lisa R.; Raper, James L.; Giordano, Thomas P.

2012-01-01

Background. Retention in care for human immunodeficiency virus (HIV)–infected patients is a National HIV/AIDS Strategy priority. We hypothesized that retention could be improved with coordinated messages to encourage patients' clinic attendance. We report here the results of the first phase of the Centers for Disease Control and Prevention/Health Resources and Services Administration Retention in Care project. Methods. Six HIV-specialty clinics participated in a cross-sectionally sampled pretest-posttest evaluation of brochures, posters, and messages that conveyed the importance of regular clinic attendance. 10 018 patients in 2008–2009 (preintervention period) and 11 039 patients in 2009–2010 (intervention period) were followed up for clinic attendance. Outcome variables were the percentage of patients who kept 2 consecutive primary care visits and the mean proportion of all primary care visits kept. Stratification variables were: new, reengaging, and active patients, HIV RNA viral load, CD4 cell count, age, sex, race or ethnicity, risk group, number of scheduled visits, and clinic site. Data were analyzed by multivariable log-binomial and linear models using generalized estimation equation methods. Results. Clinic attendance for primary care was significantly higher in the intervention versus preintervention year. Overall relative improvement was 7.0% for keeping 2 consecutive visits and 3.0% for the mean proportion of all visits kept (P < .0001). Larger relative improvement for both outcomes was observed for new or reengaging patients, young patients and patients with elevated viral loads. Improved attendance among the new or reengaging patients was consistent across the 6 clinics, and less consistent across clinics for active patients. Conclusion. Targeted messages on staying in care, which were delivered at minimal effort and cost, improved clinic attendance, especially for new or reengaging patients, young patients, and those with elevated viral loads. PMID:22828593

Targeted temperature management in neurological intensive care unit

PubMed Central

Muengtaweepongsa, Sombat; Srivilaithon, Winchana

2017-01-01

Targeted temperature management (TTM) shows the most promising neuroprotective therapy against hypoxic/ischemic encephalopathy (HIE). In addition, TTM is also useful for treatment of elevated intracranial pressure (ICP). HIE and elevated ICP are common catastrophic conditions in patients admitted in Neurologic intensive care unit (ICU). The most common cause of HIE is cardiac arrest. Randomized control trials demonstrate clinical benefits of TTM in patients with post-cardiac arrest. Although clinical benefit of ICP control by TTM in some specific critical condition, for an example in traumatic brain injury, is still controversial, efficacy of ICP control by TTM is confirmed by both in vivo and in vitro studies. Several methods of TTM have been reported in the literature. TTM can apply to various clinical conditions associated with hypoxic/ischemic brain injury and elevated ICP in Neurologic ICU. PMID:28706860

Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study.

PubMed

Prakash, Shiva; Sen, Ramesh Kumar; Tripathy, Sujit Kumar; Sen, Indu Mohini; Sharma, R R; Sharma, Sadhna

2013-07-01

A few animal studies have shown that IL-6 can serve as an early marker of fat embolism syndrome. The degree to which this is true in human trauma victims is unknown. In this clinical study, we sought to determine (1) whether elevated serum IL-6 levels at 6, 12, and 24 hours in patients with skeletal trauma were associated with the development of fat embolism syndrome (FES) within 72 hours after injury, and (2) at what time after trauma peak IL-6 levels are observed. Forty-eight patients between 16 and 40 years old who presented to our tertiary trauma center within 6 hours of injury with long bone and/or pelvic fractures were included in this study. Serum IL-6 levels were measured at 6, 12, and 24 hours after injury. The patients were observed clinically and monitored for 72 hours for development of FES symptoms. Gurd's criteria were used to diagnose FES. Elevated serum IL-6 levels 12 hours after trauma correlated with an increased likelihood of having FES develop; no significant relationship was observed between IL-6 levels at 6 or 24 hours and the development of FES. Patients with FES had a mean IL-6 level of 131 pg/mL, whereas those without FES had a mean IL-6 level of 72 pg/mL. Peak IL-6 levels were observed at 12 hours. An elevated serum IL-6 level may be useful as an early marker of FES in patients with isolated skeletal trauma. Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Clinical Characteristics and Outcome of Hepatic Sarcoidosis: A Population-Based Study 1976-2013.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Simonetto, Douglas A; Matteson, Eric L

2017-10-01

Data on clinical manifestations and outcome of hepatic sarcoidosis are scarce. This study aimed to use a population-based cohort of patients with incident sarcoidosis to better describe the characteristics of hepatic sarcoidosis. A cohort of incident cases of sarcoidosis in Olmsted County, MN, USA, from 1976 to 2013 was identified from the database. Diagnosis was verified by individual medical record review. Confirmed cases of sarcoidosis were then reviewed for liver involvement. Data on clinical manifestations, imaging study, liver biochemical tests, treatment, and outcome were collected. Cumulative incidence of cirrhosis adjusted for the competing risk of death was estimated. A total of 345 cases of incident sarcoidosis were identified. Of these, 19 cases (6%) had liver involvement (mean age 46.1 years, 53% female and 79% Caucasian). Most patients had asymptomatic liver disease and were discovered in pursuit of abnormal biochemical tests and imaging studies. Alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were elevated in the majority of patients (88 and 90%, respectively). Elevated transaminases were less common and less severe. About half of patients had abnormal imaging study with hypodense nodular lesions being the most common abnormality (six patients) followed by hepatomegaly (three patients). Liver biopsy revealed non-caseating granuloma in 88% (14 of 16 patients). A total of four patients developed cirrhosis. Involvement of the liver by sarcoidosis was seen in 6% of patients with sarcoidosis. The majority of patients were asymptomatic. Elevated ALP and GGT were the most common abnormal biochemical tests. Liver biopsy revealed non-caseating granuloma in almost all cases. Cirrhosis was seen in a significant number of patients. Generalizability of the observations to other populations may be limited, as the studied population was predominantly Caucasian. The prevalence of liver disease may be higher in more diverse populations.

Changes in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure in men and women with primary open angle glaucoma.

PubMed

Marjanović, Ivan; Martinez, Antonio; Marjanović, Marija; Kontić, Djordje; Hentova-Senćanić, Paraskeva; Marković, Vujica; Bozić, Marija

2013-01-01

An altered perfusion of the optic nerve head has been proposed as a pathogenic factor of glaucoma. The aim of this study was to evaluate the changes of the hemodynamic parameters in the retrobulbar arterial circulation after decrease of the elevated intraocular pressure (IOP) in women and men with primary open angle glaucoma. The study included 60 patients (33 males and 27 females) older than 50 years, with diagnosed and treated primary open angle glaucoma (77 eyes of 39 patients had increased IOP, > 25 mm Hg).They were examined at the Clinic of Eye Diseases (complete ophthalmologic exam) and Clinic of Neurology, Clinical Center of Serbia, Belgrade, from December 2009 to December 2010. Imaging of hemodynamic parameters of three retrobulbar arterial vessels: ophthalmic, central retinal and posterior ciliary arteries with color Doppler was performed. Among women, hemodynamic arterial parameter of the peak-systolic velocity was increased in the central retinal artery and decreased in the ophthalmic artery and posterior ciliary arteries; end-diastolic velocity was increased in all three retrobulbar vascular levels; Pourcelot resistivity index was increased, but pulsatility index was decreased in all three vessels. Among men, peak-systolic velocity, end-diastolic velocity and pulsatility index were decreased in all three vessels; resistivity index was increased in the ophthalmic artery, but decreased in the central retinal artery and posterior ciliary arteries. There was a significant change of the ophthalmic artery pulsatility index in women, and the end-diastolic velocity of the ophthalmic artery in men. There was a difference of the retrobulbar arterial circulation between women and men with primary open angle glaucoma after decrease of the elevated intraocular pressure.The role of vascular factors in the supply of the optic disc neuroretinal rim is important.

Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non-ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial.

PubMed

Yong, Gerald; Rankin, Jamie; Ferguson, Louise; Thom, Jim; French, John; Brieger, David; Chew, Derek P; Dick, Ron; Eccleston, David; Hockings, Bernard; Walters, Darren; Whelan, Alan; Eikelboom, John W

2009-01-01

There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI). We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography. Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome. These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.

Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue.

PubMed

Kogelnik, Andreas M; Loomis, Kristin; Hoegh-Petersen, Mette; Rosso, Fernando; Hischier, Courtney; Montoya, Jose G

2006-12-01

Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression. We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir. Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study. Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients. These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.

Clinical Interpretation of Elevated CA 19-9 Levels in Obstructive Jaundice Following Benign and Malignant Pancreatobiliary Disease.

PubMed

Kim, Min Seong; Jeon, Tae Joo; Park, Ji Young; Choi, Jeongmin; Shin, Won Chang; Park, Seong Eun; Seo, Ji Young; Kim, Young Moon

2017-08-25

Elevated carbohydrate antigen (CA) 19-9 level may be unable to differentiate between benign and malignant pancreatobiliary disease with obstructive jaundice. The study aims to determine the clinical interpretation and the diagnostic value of CA 19-9 level in pancreatobiliary diseases with coexistent obstructive jaundice. We retrospectively reviewed the data of 981 patients who underwent biliary drainage due to obstructive jaundice following pancreatobiliary disease at Sanggye Paik Hospital for 5 years. 114 patients with serial follow-up data for CA 19-9 level were included in this study (80 patients with malignancy and 34 patients with benign diseases). We compared the levels of CA 19-9 levels and the biochemical value before and after biliary drainage. The rate of CA 19-9 elevation (>37 U/mL) was significantly different between the benign group and the malignant group (59% vs. 90%, p=0.001). Despite the decrease in serum bilirubin after biliary drainage, CA 19-9 levels remained elevated in 12% of patients in the benign group and in 63% of patients in the malignant group (p<0.001). Finally, 12% of patients in the benign group turned out to have malignant disease. A receiver operating characteristic analysis provided a cut-off value of 38 U/mL for differentiating benign disease from malignant disease after biliary drainage (area under curve, 0.787; 95% confidence interval, 0.703 to 0.871; sensitivity, 62%; specificity, 88%). This study suggested that we should consider the possibility of malignant causes if the CA 19-9 levels remain high or are more than 38 U/mL after resolution of biliary obstruction.

Low sensitivity of anion gap to detect clinically significant lactic acidosis in the emergency department.

PubMed

Xu, Q; HowlettClyne, S; Fuezery, A; Cembrowski, G S

2017-12-01

Lactic acidosis represents the pathologic accumulation of lactate and hydrogen ions. It is important to efficiently diagnose lactic acidosis as delayed treatment will lead to poor patient outcomes. As plasma lactate levels may not be rapidly available, some physicians may use elevated anion gaps to test for the need to measure lactate. All Edmonton metropolitan hospitals have Radiometer blood gas/electrolyte instruments in the ED or close by. As lactate is measured for each set of electrolytes, we were able to determine the effectiveness of a screening anion gap for lactic acidosis. Two years of emergency department lactates and electrolytes from Edmonton's 5 metropolitan hospitals were analyzed. We determined the sensitivity, specificity and positive predictive value of detecting an elevated lactate, defined as ≥2.5mmol/L or ≥4mmol/L. Depending on the elevated anion gap cut-off and the definition of elevated lactate, between 40-80% of elevated lactates are missed. In general, the positive predictive value approaches 40% for AGs ≥12mmol/L and 60% for AGs ≥16mmol/L. Anion gap is an inadequate marker of lactic acidosis. We recommend that lactate be done with each set of electrolytes and/or blood gases. In this way lactic acidosis will not be missed. Copyright © 2017. Published by Elsevier Inc.

Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

PubMed

Humbert, M; Segal, E S; Kiely, D G; Carlsen, J; Schwierin, B; Hoeper, M M

2007-08-01

After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.

The Melbourne Pre-Diabetes Study: prediction of type 1 diabetes mellitus using antibody and metabolic testing.

PubMed

Colman, P G; McNair, P; Margetts, H; Schmidli, R S; Werther, G A; Alford, F P; Ward, G M; Tait, B D; Honeyman, M C; Harrison, L C

1998-07-20

To determine the utility of various autoantibodies in predicting progression to clinical diabetes in first-degree relatives of patients with type 1 diabetes mellitus. 3315 first-degree relatives of patients with type 1 diabetes (1161 parents, 1206 siblings and 948 offspring) recruited through diabetes clinics, private endocrinologists, Diabetes Australia and the Juvenile Diabetes Foundation. Prevalence of islet cell antibodies (ICA) levels > or = 20 JDFu, insulin autoantibodies (IAA) levels > 100 nU/mL, and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase IA2 (IA2Ab); change in beta cell function over time; and development of clinical diabetes. 2.6% of relatives had elevated ICA levels, 1.3% had elevated IAA levels and 0.3% had both. High ICA levels were significantly more frequent in siblings than in offspring or parents, and were more frequent in relatives younger than 20 years. GADAb were detected in 68% and IA2Ab in 57% of relatives with elevated ICA and/or IAA levels. Diabetes developed in 33 relatives (25 siblings, 2 offspring and 6 parents). Before diagnosis of clinical diabetes, high ICA levels were detected in 18 (58%), high IAA levels in 7 (23%), both in 5 (15%), and either in 19 (61%); GADAb were detected in 26 (84%), IA2Ab in 13 (42%), both in 11 (35%), and either in 28 (90%). First phase insulin release (FPIR) less than 50 mU/L was very strongly associated with progression to diabetes. In relatives with FPIR initially greater than 50 mU/L who eventually developed diabetes, there was a gradual and continuous reduction in FPIR over time before diagnosis. Type 1 diabetes can be diagnosed in the preclinical stage. The recently described antibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 appear superior to ICA as screening tools for the preclinical diagnosis of type 1 diabetes.

Aneurysmal subarachnoid hemorrhage lead to systemic upregulation of IL-23/IL-17 inflammatory axis.

PubMed

Chaudhry, Shafqat Rasul; Güresir, Erdem; Vatter, Hartmut; Kinfe, Thomas M; Dietrich, Dirk; Lamprecht, Alf; Muhammad, Sajjad

2017-09-01

IL-23 and IL-17 are pro-inflammatory cytokines. IL-23 is secreted by activated macrophages and dendritic cells, while IL-17 by Th17 cells. Serum IL-23 and IL-17 are known to be elevated in numerous inflammatory diseases including neurodegenerative diseases. The role of serum IL-23 and IL-17 in aneurysmal subarachnoid hemorrhage (aSAH) has still not been investigated. The present work investigates the serum IL-23 and IL-17 levels and their association with post hemorrhagic complications and clinical outcome in patients with aSAH. In this study, 80 patients with aSAH (Hunt and Hess grade I-V) were prospectively recruited. We enrolled 24 control patients with lumbar spinal stenosis. Peripheral venous blood was withdrawn from controls and from aSAH patients at day 1 and day 7, allowed to clot and centrifuged to obtain serum. Enzyme linked immunoassay kits were employed to quantify the serum levels of IL-23 and IL-17 by applying 50µL of serum samples. Post hemorrhagic complications and clinical outcome were documented prospectively from patient's hospital record. Serum IL-23 and IL-17 levels were significantly elevated in aSAH patients at day 1 and day 7 (n=80) as compared to control patients (n=24). Further analysis after dichotomy of patients who suffered from post hemorrhagic complications including cerebral vasospasm, chronic hydrocephalus, seizures, cerebral ischemia, delayed neurological deficits showed differential correlations with different post hemorrhagic complications (Table 1). Serum IL-23 and IL-17 levels did not correlate with clinical outcome. Serum IL-23 and IL-17 levels were elevated in patients with aSAH showing upregulation of IL-23/IL-17 inflammatory axis after aSAH. Serum IL-23 and IL-17 showed differential correlations with post hemorrhagic complications and no correlation with clinical outcome. Copyright © 2017 Elsevier Ltd. All rights reserved.

improbable molecular results and the need to reevaluate a priori genetic risks: A report of 2 neuromuscular disorders

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

Giardine, R.M.; Rose, N.C.; Fischbeck, K.H.

Case 1: A 27-year-old woman whose brother and deceased father were diagnosed with myotonic dystrophy presented for preconceptional counseling. Three other first and second degree relatives were judged clinically affected on the basis of myotonia by positive electromyelograms (EMGs). The proband appeared to be clinically affected with mild percussion myotonia and a positive EMG. Initial studies by linkage analysis required postulation that the at-risk chromosome 19 inherited by the patient and her brother had undergone recombination in the brother between 2 very closely linked RFLP markers. Conclusion: Molecular testing did not support a unifying diagnosis for myotonia in this family.more » In addition to one classic example of myotonic dystrophy, it is possible a milder form of myotonia is also segregating in this pedigree. Case 2: The maternal aunt of a young man with Becker`s muscular dystrophy (BMD) presented for reproductive counseling. Serum CK values were elevated in her mother, who shared an X chromosome haplotype with the affected grandson and was judged an obligate carrier. The aunt was judged a likely carrier because of elevated serum CK values. Three maternal uncles, including ones with the same X chromosome haplotype as the affected nephew, were clinically normal. Finally, dosage analysis for dystrophin exons deleted in the grandson showed the grandmother and aunt to be non-carriers, but the mother of the affected boy to be a somatic carrier. The grandmother and aunt are not BMD carriers. Since the elevated CK levels do not segregate with the affected X chromosome, they may reflect autosomal inheritance or nongenetic influences; in either case their clinical significance is uncertain. These cases reinforce the importance of periodic reevaluation of initial genetic assignments, particularly when rare events must be invoked to explain molecular studies.« less

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

PubMed

Shi, Xiulin; Lin, Mingzhu; Liu, Changqin; Xiao, Fangsen; Liu, Yongwen; Huang, Peiying; Zeng, Xin; Yan, Bing; Liu, Suhuan; Li, Xiaoying; Yang, Shuyu; Li, Xuejun; Li, Zhibin

2016-07-29

Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Increased circulating blood cell counts in combat-related PTSD: Associations with inflammation and PTSD severity.

PubMed

Lindqvist, Daniel; Mellon, Synthia H; Dhabhar, Firdaus S; Yehuda, Rachel; Grenon, S Marlene; Flory, Janine D; Bierer, Linda M; Abu-Amara, Duna; Coy, Michelle; Makotkine, Iouri; Reus, Victor I; Aschbacher, Kirstin; Bersani, F Saverio; Marmar, Charles R; Wolkowitz, Owen M

2017-12-01

Inflammation is reported in post-traumatic stress disorder (PTSD). Few studies have investigated circulating blood cells that may contribute to inflammation. We assessed circulating platelets, white blood cells (WBC) and red blood cells (RBC) in PTSD and assessed their relationship to inflammation and symptom severity. One-hundred and sixty-three male combat-exposed veterans (82 PTSD, 81 non-PTSD) had blood assessed for platelets, WBC, and RBC. Data were correlated with symptom severity and inflammation. All cell counts were significantly elevated in PTSD. There were small mediation effects of BMI and smoking on these relationships. After adjusting for these, the differences in WBC and RBC remained significant, while platelet count was at trend level. In all subjects, all of the cell counts correlated significantly with inflammation. Platelet count correlated with inflammation only in the PTSD subjects. Platelet count, but none of the other cell counts, was directly correlated with PTSD severity ratings in the PTSD group. Combat PTSD is associated with elevations in RBC, WBC, and platelets. Dysregulation of all three major lineages of hematopoietic cells in PTSD, as well as their significant correlation with inflammation, suggest clinical significance of these changes. Copyright © 2017 Elsevier B.V. All rights reserved.

Does pain take holidays? Non-attendance rates at a hospital-based pain clinic are elevated during the Jewish high-holidays.

PubMed

Ratmansky, Motti; Hai, Nitzan; Schlossberg, Tzion; Mimouni-Bloch, Aviva; Schweiger, Avraham

2017-01-01

Patient non-attendance is an expensive and persistent problem worldwide with rates between 5-39% reported in the literature. The objective of the study was to assess whether there is a higher incidence of non-attendance in a hospital-based pain clinic during the period of the Jewish High Holidays (Rosh-Hashanah to Sukkot) and whether this is further compounded by other factors, such as demographic characteristics and previous visits to the clinic. Records were taken from the Lowenstein Rehabilitation Hospital appointment scheduling system. Data was gathered from two time-periods: High-Holidays and Control for each year, over a total of 6 years 2008-2013. Non-attendance was analyzed by period, by age, by gender and by previous visits to the clinic. In the entire population studied (666 distinct records), the non-attendance rate was higher during the High-Holidays as compared to the Control period (32 vs. 24.1%; p  = 0.030). Non-attendance rates were significantly higher during the Holidays among repeating patients (28.6 vs. 14.8%; p  = 0.002) and among women (34.6 vs. 20.7%; p  = 0.004). Our data suggest that non-attendance is elevated during the High-Holidays in specific groups of patients, namely, repeating patients and women. Despite no direct inquiry into the reasons for non-attendance, we speculate that the elevated well-being and familial support during the holidays contribute to the patients' ability to cope with persistent pain and possibly directly reduce the amount of pain, leading to patients missing their pain clinic appointments. Our results, provided they can be corroborated by larger-scale studies, can assist in scheduling policy adjustments such as avoidance of appointments during the High-holidays for specific patient populations and more rigorous reminder efforts during these times of the year that may lead to reduction in overall non-attendance rates in the pain clinic. Further, our data provide an impetus for further studies of non-attendance patterns among pain clinic patients, in order to acquire a better understanding of the reasons for non-attendance and develop strategies to reduce it and thus contribute to the continuous improvement of the Israeli health systems as well as others worldwide.

On the value of routine prothrombin time screening in elective neurosurgical procedures.

PubMed

Dützmann, Stephan; Gessler, Florian; Marquardt, Gerhard; Seifert, Volker; Senft, Christian

2012-11-01

The authors performed a study to evaluate whether preoperative assessment of prothrombin time (PT) is mandatory in patients undergoing routinely planned neurosurgical procedures. The charts of all patients admitted to general wards of the authors' department for routinely planned surgery (excluding trauma and ICU patients) between 2006 and 2010 were retrospectively reviewed. The authors assessed preoperative PT and the clinical courses of all patients, with special consideration for patients receiving coagulation factor substitution. All cases involving hemorrhagic complications were analyzed in detail with regard to pre- and postoperative PT abnormalities. Prothrombin time was expressed as the international normalized ratio, and values greater than 1.28 were regarded as elevated. Clinical courses and PT values of 4310 patients were reviewed. Of these, 33 patients (0.7%) suffered hemorrhagic complications requiring repeat surgery. Thirty-one patients (94%) had a normal PT before the initial operation, while 2 patients had slightly elevated PT values of 1.33 and 1.65, which were anticipated based on the patient's history. In the latter 2 cases, surgery was performed without prior correction of PT. Preoperatively, PT was elevated in 78 patients (1.8%). In 73 (93.6%) of the 78 patients, the PT elevation was expected and explained by each patient's medical history. In only 5 (0.1%) of 4310 patients did we find an unexpected PT elevation (mean 1.53, range 1.37-1.74). All 5 patients underwent surgery without complications, while 2 had received coagulation factor substitution preoperatively, as requested by the surgeon, because of an estimated risk of bleeding complications. None of the 5 patients received coagulation factor substitution postoperatively, and later detailed laboratory studies ruled out single coagulation factor deficiencies. There was no statistically significant association between preoperatively elevated PT levels and the occurrence of hemorrhagic complications (p = 0.12). Before the second procedure but not before the initial operation, 4 (12%) of the 33 patients had elevated PT. The findings suggest that the value of preoperative PT testing is limited in patients in whom a normal history can be ascertained. Close postoperative PT control is necessary in every neurosurgical patient, and better tests need to be developed to identify patients who are prone to hemorrhagic complications.

Treatment of Pediatric Graves' Disease Is Associated with Excessive Weight Gain

PubMed Central

van Veenendaal, Nicole R.

2011-01-01

Context: Little information is available about changes in body weight and body mass index in children before, during, and after treatment for Graves' disease (GD). Objective: Our objective was to examine changes in body weight after treatment for GD in children as related to clinical features. Design: The medical records of 43 pediatric patients with GD [35 girls and eight boys, aged 4.0–18.5 (mean 10.9) yr] were examined. Patients were included if clinical data were available for 1 yr before and after the diagnosis of GD. Main Outcome Measures: Weight, height, body mass index (BMI) z-scores, and thyroid hormone levels were assessed. Results: Overall, patients presented with an average BMI z-score of −0.02 ± 1.05 that was not different from the normal population (P = 0.921) or their premorbid values (P = 0.07). However, in the subset of patients who were initially overweight or obese in the premorbid state, the BMI decreased significantly during the development of hyperthyroidism (P < 0.05). After initiation of treatment, patients gained significant amounts of weight over the first 6 months leading to elevated BMI z-scores (P < 0.0001), and elevations in BMI persisted in about 25% of the patients. Conclusion: Excessive weight gain within 6 months of treatment is seen in children treated for GD, and the gain in weight can persist. PMID:21849528

Hepatic manifestations of telomere biology disorders.

PubMed

Patnaik, Mrinal M; Kamath, Patrick S; Simonetto, Douglas A

2018-06-07

A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical portosystemic shunt. Approximately seven years after the initial presentation, the patient developed progressive dyspnoea and a diagnosis of idiopathic pulmonary fibrosis was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder was suspected. A flow-fluorescence in situ hybridisation analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to the patient's death nine years after his initial presentation with portal hypertension. During those nine years two brothers also developed idiopathic pulmonary fibrosis. The questions that arise from this case include. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Psychological characteristics of patients with asthma.

PubMed

Bulcun, Emel; Turkel, Yakup; Oguztürk, Omer; Dag, Ersel; Visal Buturak, S; Ekici, Aydanur; Ekici, Mehmet

2018-01-01

Psychological distress of patients with asthma may be reduced when they learned to live with their illness. Asthma can change the psychological and personality characteristics. We aim to investigate the psychological and personality characteristics of patients with asthma using MMPI (Minnesota Multiphasic Personality Inventory). Thirty-three adult patients with asthma (23 female and 10 male) and 20 healthy controls (14 females and 6 males) were enrolled in this study. Psychometric evaluation was made with the Turkish version of the MMPI. The patients were separated into two groups according to the duration of symptoms (recent-onset asthma < 10 years, long-standing asthma ≥10 years). Patients with asthma compared with control group had significantly higher the rate of clinical elevation on depression, hysteria, psychasthenia and social introversion. Patients with recent-onset asthma compared with long-standing asthma have significantly higher the rate of clinical elevation on depression, hysteria, psychopathic deviate, psychasthenia and social introversion. MMPI mean t score in patients with recent-onset asthma was higher than patients with long-standing asthma. MMPI mean t score in patients with asthma was negatively associated with the symptom duration in multivariate model. Patients with asthma have relatively more inactivity, anergia, guilt, pessimism, nonspecific physical complaints, irrational fears and introvert. Patients with long-standing asthma have less psychological distress, suggesting that learned to cope with his illness. © 2016 John Wiley & Sons Ltd.

Resting and post-exercise serum biomarkers of cardiac and skeletal muscle damage in adolescent runners.

PubMed

Nie, J; Tong, T K; George, K; Fu, F H; Lin, H; Shi, Q

2011-10-01

This study examined the response of serum biomarkers of cardiac and skeletal muscle damage at rest and after a routine workout of 21 km run in 12 male adolescent (16.2±0.6 years) long-distance runners. Biomarkers of cardiac [troponins (cTnT, cTnI), creatine kinase MB mass (CK-Mbmass)] and skeletal muscle [creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hydroxybutyrate dehydrogenase (HBD)] damage were assayed at rest, 2, 4 and 24 h post-exercise. At rest, cTnT and cTnI were not detectable; however, CK, CK-MBmass, AST, ALT and HBD were above corresponding clinical cut-off values. Post-exercise significant elevations above rest were observed for all biomarkers, except ALT, 2 and 4 h following the run, and remained elevated in cTnI, CK, CK-MBmass, LDH and AST 24 h post-workout. A significant increase in data points above clinical cut-off values from rest to post-exercise was reported for cTnT, cTnI and CK at 2 and 4 h, and in cTnI and CK 24 h post-exercise. In conclusion, a 21 km run in adolescent runners increased post-exercise biomarkers of cardiac and skeletal muscle damage. © 2010 John Wiley & Sons A/S.

Clinical role for a superantigen in Yersinia pseudotuberculosis infection.

PubMed Central

Abe, J; Onimaru, M; Matsumoto, S; Noma, S; Baba, K; Ito, Y; Kohsaka, T; Takeda, T

1997-01-01

Yersinia pseudotuberculosis is an enteric pathogen that causes a variety of clinical symptoms in the human. Recently, we reported the production of a superantigen (Y. pseudotuberculosis-derived mitogen, YPM) by this organism and characterized the gene structure of ypm. To further study the potential pathogenic role of YPM in Y. pseudotuberculosis infection, we assayed IgG anti-YPM antibodies and T cell antigen receptor-Vbeta expression of the T cells in peripheral blood and in mesenteric lymph node in patients acutely infected with Y. pseudotuberculosis. 20 out of 33 patients (61%) had an elevated antibody titer compared with healthy controls (P = 0.0001). Patients with systemic symptoms such as lymphadenopathy, transient renal dysfunction, and arthritis had significantly higher titers of anti-YPM than patients with gastrointestinal tract symptoms alone. T cells bearing the Vbeta3 gene segment were significantly increased (P = 0.009) among acute phase patients compared with healthy children. During the convalescence phase of the illness, there was a reduction in the abnormal level of Vbeta3 T cells. Moreover, in the mesenteric lymph node, an elevated level of Vbeta3 T cells compared with peripheral blood and a sequence diversity in the junctional region of the T cell antigen receptor beta-chain containing Vbeta3 element was observed in one patient. Together, these findings suggest that YPM was produced in vivo and played an important role in the pathogenesis of Y. pseudotuberculosis infection. PMID:9109426

Female gender: an independent factor in ST-elevation myocardial infarction.

PubMed

Trigo, Joana; Mimoso, Jorge; Gago, Paula; Marques, Nuno; Faria, Ricardo; Santos, Walter; Candeias, Rui; Pereira, Salomé; Marques, Vasco; Brandão, Victor; Camacho, Ana; de Jesus, Ilídio; Gomes, Veloso

2010-09-01

Cardiovascular disease is the leading cause of death in women. In ST-elevation myocardial infarction (STEMI) in particular, the question has been raised whether specific characteristics of women confer a worse prognosis. To evaluate the differences in STEMI patients between the genders in cardiovascular risk profile, clinical presentation, therapeutic approach and in-hospital and 6-month mortality rates. We analyzed 1578 patients admitted consecutively with STEMI during a 7-year period (from January 13, 2002 to December 31, 2008). The patients were divided into two groups according to gender, and compared in terms of baseline clinical and demographic characteristics, pre-hospital and in-hospital delay, clinical presentation on admission, reperfusion therapy, severity of coronary disease and in-hospital and 6-month mortality. Of the 1578 patients, 26% were female. Women were older (by 8 years), and had a higher cardiovascular risk profile. On admission, their clinical presentation was more severe, with a higher frequency of anterior myocardial infarction and acute heart failure symptoms. Women had longer ischemic times and lower rates of reperfusion therapy. Mortality in women was significantly higher than in men, both in-hospital (17.5 vs. 5.3%) and at 6 months (23.5% vs. 8.2%). After adjustment in multivariate analysis, mortality in women remained higher. The adverse demographic and clinical profile could partially explain the worse prognosis of STEMI in women. This, together with longer pre-hospital delays, led to underuse of reperfusion therapy. Even so, female gender by itself had a negative and independent influence on mortality in STEMI patients.

Clinical features of Epstein-Barr virus-associated infectious mononucleosis in hospitalized Korean children

PubMed Central

Son, Keun Hyung

2011-01-01

Purpose Few studies have been conducted on the recent status of infectious mononucleosis (IM) in Korean children. The aim of this study was to evaluate the recent trend in the clinical manifestations of Epstein-Barr virus (EBV)-associated IM as well as the clinical differences according to age. Methods A retrospective study was performed on 81 children hospitalized with EBV-associated IM who fulfilled the serological criteria for the diagnosis of EBV infection (viral capsid antigen immunoglobulin M positive). The patients were divided into 3 age groups: <5 years, 5 to 9 years, and ≥10 years. We evaluated the recent trend in clinical manifestations and the differences in clinical and laboratory findings among the 3 age groups. Results Thirty (37%) children were under 5 years of age, 38 (46.9%) were 5 to 9 years of age, and 13 (16%) were 10 years of age or older. The differences in the symptoms and signs among the 3 age groups were not statistically significant, except for headache. The mean duration of fever was 7.7 days (range, 0 to 18 days). A comparison of liver enzyme elevation among the age groups showed an association with advancing age (26.6%, 63.1%, and 76.9%, respectively, P=0.04) Conclusion This study showed that EBV-associated IM in Korean children continues to occur mostly in children under 10 years of age. In children with EBV-associated IM, the incidence of headache and liver enzyme elevation, the duration of fever, and the proportion of females to males were all positively associated with advancing age. PMID:22232623

A comparison of technologies used for estimation of body temperature.

PubMed

Mangat, Jasdip; Standley, Thomas; Prevost, Andrew; Vasconcelos, Joana; White, Paul

2010-09-01

Body temperature measurement is an important clinical parameter. The performance of a number of non-invasive thermometers was measured by comparing intra- and inter-operator variability (n = 100) and clinical accuracy (n = 61). Variability was elevated in febrile compared to normothermic subjects for axillary and oral electronic contact thermometer measures and a temporal artery thermometer (p < 0.001 for both). Temporal artery thermometry and one mode of an infrared tympanic thermometer demonstrated significant clinical inaccuracy (p < 0.001 for both). Electronic contact thermometer repeatability and reproducibility are highly variable in febrile adults both in the axilla and oral cavity. Infrared thermometry of the skin over the superficial temporal artery is unreliable for measuring core body temperature, particularly in febrile subjects and patients in theatre. The infrared tympanic thermometers tested are acceptable for clinical practice; however, care should be exercised with the different modes of operation offered.

Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma

PubMed Central

Ma, Ming; Zhang, Shanshan; Zhang, Yongmeng; Yuan, Ming; Liu, Bing; Yang, Yiqiong; Cui, Wen; Ansong, Emmanuel; Dong, Huali; Macias, Virgilia; Yang, Wancai

2017-01-01

Esophagitis and Barrett's esophagus are linked to esophageal squamous cell carcinoma and adenocarcinoma, respectively. However, the underlying mechanisms are still unclear. This study analyzed the expression levels of and correlation between PLCE1 and PRKCA in human esophagitis, carcinogen NMBA-induced rat esophagus, PLCE1 genetic deficient mouse esophageal epithelial tissues and human esophageal cancer cell line, integrated with Online oncology data sets. We found that the expression levels of both PLCE1 and PRKCA were significantly elevated in human esophagitis, esophageal squamous cell carcinoma, Barrett's esophagus, esophageal adenocarcinoma and in NMBA-treated rat esophageal epithelia. However, PRKCA and cytokines were significantly downregulated in PLCE1-deficient mouse esophageal epithelia, and knockdown of PLCE1 in human esophageal cancer cells led to reduction of PRKCA and cytokines. Finally, high expression of both PLCE1 and PRKCA is significantly associated with poor outcomes of the patients with esophageal cancers. In conclusion, this study defined the initiation and progression of esophageal inflammation and malignant transformation, in which the positive correlation of PLCE1 and PRKCA exhibits critical clinical significance. PMID:28402280

Body Mass Index and Phenotype in Mild-to-Moderate Persistent Asthma

PubMed Central

Sutherland, E. Rand; Lehman, Erik B.; Teodorescu, Mihaela; Wechsler, Michael E.

2009-01-01

Background While obesity has been hypothesized to worsen asthma, data from studies of well-characterized asthmatics are lacking. Objective Evaluate the relationship between body mass index (BMI), asthma impairment and response to therapy. Methods BMI (kg/m2) and asthma phenotypic and treatment response data were extracted from Asthma Clinical Research Network (ACRN) studies. The cross-sectional relationship between BMI and asthma impairment was analyzed, as was the longitudinal relationship between BMI and response to asthma controller therapies. Results 1,265 subjects with mild-to-moderate persistent asthma were evaluated. Analyses of lean vs. overweight/obese asthmatics demonstrated small differences in FEV1 (3.05 vs. 2.91 L, p=0.001), FEV1/FVC (mean 83.5% vs. 82.4%, p=0.01), rescue albuterol use (1.1 vs. 1.2 puffs/day, p=0.03) and asthma-related quality of life (5.77 vs. 5.59, p=0.0004). Overweight/obese asthmatics demonstrated a smaller improvement in exhaled nitric oxide with inhaled corticosteroid (ICS) treatment than did lean asthmatics (3.6 vs. 6.5ppb, p=0.04). With ICS/long-acting beta agonist treatment, overweight/obese asthmatics demonstrated smaller improvements in lung function than lean asthmatics, with an 80mL (p=0.04) and 1.7% (p=0.02) lesser improvement in FEV1 and FEV1/FVC ratio, respectively. Significant differences in therapeutic response to leukotriene modifiers between BMI categories were not observed. Conclusions Elevated BMI is not associated with clinically-significant worsening of impairment in patients with mild-to-moderate persistent asthma. There is a modest association between elevated BMI and reduced therapeutic effect of ICS-containing regimens in this patient population. Prospective studies evaluating the impact of overweight and obesity on treatment response in asthma are warranted. Clinical Implications In individuals with mild to moderate persistent asthma, being overweight or obese does not appear to modify indices of asthma-related impairment. Elevated body mass index may reduce response to inhaled corticosteroid-containing treatment regimens. PMID:19501235

Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features

PubMed Central

Dumre, Shyam Prakash; Bhandari, Renu; Shakya, Geeta; Shrestha, Sanjaya Kumar; Cherif, Mahamoud Sama; Ghimire, Prakash; Klungthong, Chonticha; Yoon, In-Kyu; Hirayama, Kenji; Na-Bangchang, Kesara; Fernandez, Stefan

2017-01-01

Abstract. Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the 2010 outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably help in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond to any disastrous outbreaks. PMID:29031282

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

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

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Influence of elevated carbon dioxide and temperature on belowground carbon allocation and enzyme activities in tropical flooded soil planted with rice.

PubMed

Bhattacharyya, P; Roy, K S; Neogi, S; Manna, M C; Adhya, T K; Rao, K S; Nayak, A K

2013-10-01

Changes in the soil labile carbon fractions and soil biochemical properties to elevated carbon dioxide (CO2) and temperature reflect the changes in the functional capacity of soil ecosystems. The belowground root system and root-derived carbon products are the key factors for the rhizospheric carbon dynamics under elevated CO2 condition. However, the relationship between interactive effects of elevated CO2 and temperature on belowground soil carbon accrual is not very clear. To address this issue, a field experiment was laid out to study the changes of carbon allocation in tropical rice soil (Aeric Endoaquept) under elevated CO2 and elevated CO2 + elevated temperature conditions in open top chambers (OTCs). There were significant increase of root biomass by 39 and 44 % under elevated CO2 and elevated CO2 + temperature compared to ambient condition, respectively. A significant increase (55 %) of total organic carbon in the root exudates under elevated CO2 + temperature was noticed. Carbon dioxide enrichment associated with elevated temperature significantly increased soil labile carbon, microbial biomass carbon, and activities of carbon-transforming enzyme like β-glucosidase. Highly significant correlations were noticed among the different soil enzymes and soil labile carbon fractions.

Use of the Children's Communication Checklist-2 for classification of language impairment risk in young school-age children with attention-deficit/hyperactivity disorder.

PubMed

Timler, Geralyn R

2014-02-01

Children with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk for language impairment (LI). This study examined the feasibility of using the Children's Communication Checklist-2 (CCC-2; Bishop, 2006) to classify risk for LI in young children, ages 5-8 years, with ADHD. Parents of 32 children with ADHD and 12 typically developing peers completed the CCC-2. The Clinical Evaluation of Language Fundamentals, Fourth Edition (Semel, Wiig, & Secord, 2003) and the Test of Narrative Language (Gillam & Pearson, 2004) were administered to diagnose LI. Language samples were collected to examine clinical markers of LI. CCC-2 General Communication Composite scores ≤ 85 correctly classified 10 participants with ADHD diagnosed with LI as defined by composite scores ≤ 85 on the Clinical Evaluation of Language Fundamentals, Fourth Edition, or on the Test of Narrative Language. Five of these participants demonstrated 1 or more clinical markers of LI in language samples. Three additional participants, who received a General Communication Composite score ≤ 85 yet scored above 85 on the language tests, demonstrated CCC-2 profiles suggestive of pragmatic impairment. Sensitivity and specificity rates were 100% and 85.29%, respectively. CCC-2 scores and most measures were significantly correlated. The results support the feasibility of using the CCC-2 as a screener to identify children with ADHD who are at elevated risk for LI and need referral for comprehensive assessment.

Comparing the impact of supine and leg elevation positions during coronary artery bypass graft on deep vein thrombosis occurrence: a randomized clinical trial study.

PubMed

Ayatollahzade-Isfahani, Farah; Pashang, Mina; Omran, Abbas Salehi; Saadat, Soheil; Shirani, Shapour; Fathollahi, Mahmood Sheikh

2013-06-01

Deep vein thrombosis (DVT) is a common preoperative complication that occurs in patients who undergoing coronary artery bypass grafting surgery (CABG). Early ambulation, elastic stockings, intermittent pneumatic compression, and leg elevation, before and after surgery, are among preventative interventions. The goal of the study was to compare the effect of supine position with that of leg elevation on the occurrence of DVT during CABG and after, until ambulation. Between October, 2008, and May, 2011, a total of 185 eligible CABG patients admitted to the Cardiac Surgery Unit were randomly assigned to groups designated as the supine group (n = 92) or the leg-elevation group (n = 93). Of this total, 92 patients were assigned to the supine group and 93 to the leg-elevation group. Doppler ultrasonography of the superficial and deep veins in the lower extremities was performed for each patient before and after surgery. Logistic regression analysis was conducted to investigate the possible independent factors associated with DVT. DVT was detected in 25 (13.5%) patients: 17 (18.4%) patients in the supine position group and 8 (8.6%) in the leg-elevation group (P value = .065). After adjustment for confounding factors there was no effect of position on the presence of DVT (P = .126).Clots were often localized in legs ipsilateral to the saphenous vein harvest. The authors conclude that a positive, albeit not statistically significant, trend was evident toward higher incidence of silent DVT in supine position during and after CABG in comparison with leg elevation. Future studies with larger sample sizes are required to confirm this result. Copyright © 2013 Society for Vascular Nursing, Inc. Published by Mosby, Inc. All rights reserved.

The effect of standard care, ibuprofen, and music on pain relief and patient satisfaction in adults with musculoskeletal trauma.

PubMed

Tanabe, P; Thomas, R; Paice, J; Spiller, M; Marcantonio, R

2001-04-01

The purposes of this study were to determine the most effective nursing intervention to decrease pain for patients with minor musculoskeletal trauma and moderate pain at triage and to examine patient satisfaction. Patients were assigned to 1 of 3 intervention groups: (1) standard care (ice, elevation, and immobilization); (2) standard care and ibuprofen; or (3) standard care and music distraction. Patients were monitored for pain ratings for 60 minutes. Patients who sustained minor musculoskeletal trauma within the past 24 hours and presented with pain ratings of 4 or greater were included. Two patient satisfaction questions were asked upon discharge from the emergency department. Seventy-seven patients met the inclusion criteria. No differences in pain ratings between groups were demonstrated. A statistically significant reduction in pain for all patients occurred at 30 minutes (F = 16.18, P <.01) and was maintained at 60 minutes. However, 70% of patients continued to report pain ratings of 4 or greater (on a scale of 1 to 10) at 60 minutes. The reduction in pain was not found to be clinically significant.Eighty-four percent of patients stated that they were more satisfied with their overall care in the emergency department because of the immediate attention to pain relief they received at triage. No differences in satisfaction existed between treatment groups, although patients who reported higher pain ratings expressed statistically significant lower satisfaction with pain management scores (F = 9.375, P =.003). None of the therapies-standard care (ice, elevation, immobilization), standard care with ibuprofen, or standard care with music distraction-provided clinically significant pain relief to patients who had minor musculoskeletal trauma (ie, sprains and fractures) and moderate pain at triage. Interestingly, satisfaction scores were sometimes positive, even when pain was not relieved.

Elevated Levels of Dickkopf-1 Are Associated with β-Catenin Accumulation and Poor Prognosis in Patients with Chondrosarcoma

PubMed Central

Chen, Changbao; Zhou, Hua; Zhang, Xiaolin; Ma, Xinlong; Liu, Zhongjun; Liu, Xiaoguang

2014-01-01

Background Dickkopf-1 (DKK1) is an antagonist of Wnt/β-catenin signaling implicated in tumorigenesis. However, the biological role of DKK1 and β-catenin involved in chondrosarcoma has not been sufficiently investigated. This study was designed to investigate the expression profiles of DKK1 and β-catenin, and to clarify their clinical values in chondrosarcoma. Methods The mRNA and protein levels of DKK1 and β-catenin in fresh chondrosarcoma and the corresponding non-tumor tissues were analyzed by Real-time PCR and Western blot, respectively. The protein expression patterns of DKK1 and β-catenin were investigated by immunohistochemistry. The associations among DKK1 level, β-catenin accumulation, clinicopathological factors and the overall survival were separately evaluated. Results Both DKK1 and β-catenin levels were remarkably elevated in chondrosarcoma compared with the corresponding non-tumor tissues. High DKK1 level and positive β-catenin accumulation in chondrosarcoma specimens were 58.7% and 53.9%, respectively. Elevated DKK1 level significantly correlated with positive β-catenin accumulation, and they were remarkably associated with histological grade and Musculoskeletal Tumor Society stage. Furthermore, DKK1 level and β-catenin accumulation had significant impacts on the prognosis of chondrosarcoma patients. Multivariate analysis revealed that DKK1 level was an independent prognostic factor for overall survival. Conclusions Elevated DKK1 levels associated with β-catenin accumulation play a crucial role in chondrosarcoma. DKK1 can serve as a novel predictor of poor prognosis in patients with chondrosarcoma. PMID:25144498

Evidence-based practice: use of the ventilator bundle to prevent ventilator-associated pneumonia.

PubMed

Tolentino-DelosReyes, Arlene F; Ruppert, Susan D; Shiao, Shyang-Yun Pamela K

2007-01-01

To examine critical care nurses' knowledge about the use of the ventilator bundle to prevent ventilator-associated pneumonia. Published reports were reviewed for current evidence on the use of the ventilator bundle to prevent ventilator-associated pneumonia, and education sessions were held to present the findings to 61 nurses in coronary care and surgical intensive care units. Changes in the nurses' knowledge were evaluated by using a 10-item test, given both before and after the sessions. Changes in the nurses' practices related to ventilator-associated pneumonia, including elevation of the head of the bed to 30 degrees to 45 degrees , were observed in 99 intubated patients. After the education sessions, the nurses performed better on 8 of the 10 items tested (P from .03 to <.001). The areas of most significant improvement were elevation of the head of the bed (P < .001), charting of the elevation of the head of the bed (P= .009), oral care (P= .009), checking of the nasogastric tube for residual volume (P = .008), washing of hands before contact with patients (P < .001), and limiting the wearing of rings (P < .001) and nail polish (P = .04). Even after the education sessions, the nurses' compliance with hand-washing recommendations before contact with patients was low, though statistically some improvement was apparent. Contraindications to elevation of the head of the bed did not appear to affect the nurses' practices (P= .38). Education sessions designed to inform nurses about the ventilator bundle and its use to prevent ventilator-associated pneumonia have a significant effect on participants' knowledge and subsequent clinical practice.

Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles

NASA Astrophysics Data System (ADS)

Lu, Xuefeng; Chen, Qiuju; Fu, Yonglun; Ai, Ai; Lyu, Qifeng; Kuang, Yan Ping

2016-08-01

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

Sibling sex ratio and sexual orientation in men and women: new tests in two national probability samples.

PubMed

Bogaert, Anthony F

2005-02-01

One line of research on the etiology of sexual orientation has examined sibling sex ratio, the ratio of brothers to sisters collectively reported by a group of individuals, but this research has only used clinical and/or convenience samples. In the present study, homosexual men and women's sibling sex ratio was examined in two national probability samples. Results indicated that homosexual men had a sex ratio of 129.54 male live births to 100 female live births. This ratio was within the range of elevated sex ratios found in some previous studies of homosexual men, although it was only marginally significant (p = .09) relative to the known human sex ratio with regard to live births. Additional analyses indicated that this effect was likely the result of a high fraternal birth order (i.e., an elevated number of older brothers) in homosexual men. The sibling sex ratio for lesbians was 122.58 male live births to 100 female live births, which did not significantly differ from the known human sex ratio with regard to live births. The results for lesbians, however, should be interpreted with caution because the sample size (and resulting power) was low. The results in men add to research suggesting that homosexual men, unselected for gender identity or gender role behavior, do not have elevated sibling sex ratios. These results also suggest that research should concentrate on finding the cause(s) of the fraternal birth order effect, the consistent finding that homosexual men have an elevated number of older brothers.

Efficacy trial of a selective prevention program targeting both eating disorders and obesity among female college students: 1- and 2-year follow-up effects.

PubMed

Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C Nathan

2013-02-01

Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups. Female college students at risk for these outcomes because of body image concerns (N = 398) were randomized to the Healthy Weight 2 group-based 4-hr prevention program, which promotes lasting healthy improvements to dietary intake and physical activity and nutrition science health behavior change principles, or an educational brochure control condition. Intervention participants showed significantly less body dissatisfaction and eating disorder symptoms and lower eating disorder onset through 2-year follow-up versus controls, but the former 2 effects were small. There were no main effects for body mass index (BMI), depressive symptoms, dieting, caloric intake, physical activity, or obesity onset. Moderator analyses revealed stronger eating disorder symptom effects for youths with initially elevated symptoms and lower pressure to be thin, stronger BMI effects for youths with initially elevated symptoms and BMI scores, and weaker eating disorder symptom effects for youths with initially elevated pressure to be thin. The 60% reduction in eating disorder onset over the 2-year follow-up was clinically significant and a novel effect for a prevention program, but the main effects on continuous outcomes were small, suggesting that adding nutrition science principles weakened the intervention efficacy. Effects on both eating disorder symptoms and BMI were greater for those with elevated eating disorder symptoms and BMI at pretest, implying that it might be useful to target these individuals in future trials.

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

PubMed

Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

2000-01-01

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

False elevation of carboxyhemoglobin: case report.

PubMed

Mehrotra, Shruti; Edmonds, Marcia; Lim, Rodrick K

2011-02-01

Carbon monoxide toxicity in infants and children, like adults, produce nonspecific symptoms with normal vital signs necessitating the serum measurement of carboxyhemoglobin (COHb). In infants, the COHb may be falsely elevated. Our goal was to report a case of suspected carbon monoxide toxicity in an infant and the likely cause of the falsely elevated serum COHb. A previously healthy 3-month-old girl presented to the pediatric emergency department (ED) with smoke inhalation from a defective furnace. She was asymptomatic. On examination, she was alert, with Glasgow Coma Scale of 15 and normal vital signs. Cardiorespiratory and neurological examinations were completely normal. Because of concern regarding carbon monoxide poisoning, she was treated with normobaric oxygen therapy. Initial and subsequent serum COHb levels were persistently elevated, despite treatment and the infant appearing clinically well. As such, she had a prolonged stay in the ED. Further investigations found that fetal hemoglobin interferes with the spectrophotometric method used to analyze serum COHb levels. Carboxyhemoglobin serum level, in infants, may be falsely elevated due to the fetal hemoglobin interfering with standard methods of analysis. Knowledge of the false elevation using standard spectrophotometric methods of COHb in clinically well-appearing infants can decrease unnecessary oxygen therapy and monitoring time in the ED.

Knowledgeable Neighbors: a mobile clinic model for disease prevention and screening in underserved communities.

PubMed

Hill, Caterina; Zurakowski, David; Bennet, Jennifer; Walker-White, Rainelle; Osman, Jamie L; Quarles, Aaron; Oriol, Nancy

2012-03-01

The Family Van mobile health clinic uses a "Knowledgeable Neighbor" model to deliver cost-effective screening and prevention activities in underserved neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model and used operational data collected from 2006 to 2009 to evaluate the service. The Family Van successfully reached mainly minority low-income men and women. Of the clients screened, 60% had previously undetected elevated blood pressure, 14% had previously undetected elevated blood glucose, and 38% had previously undetected elevated total cholesterol. This represents an important model for reaching underserved communities to deliver proven cost-effective prevention activities, both to help control health care costs and to reduce health disparities.

Mixed dyslipidemias in primary care patients in France.

PubMed

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients.

Amyloid burden and incident depressive symptoms in cognitively normal older adults.

PubMed

Harrington, Karra D; Gould, Emma; Lim, Yen Ying; Ames, David; Pietrzak, Robert H; Rembach, Alan; Rainey-Smith, Stephanie; Martins, Ralph N; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

2017-04-01

Several studies have reported that non-demented older adults with clinical depression show changes in amyloid-β (Aβ) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that Aβ may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral Aβ and the presence of depression across a 54-month prospective observation period. Cognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high Aβ (n = 81) or low Aβ (n = 278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale - Short Form at 18-month intervals over 54 months. Whilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high Aβ group (9%) than the low Aβ group (2%) by the 54-month assessment. Results of this study suggest that elevated Aβ levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated Aβ. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Differential expression of IL-6/IL-6R and MAO-A regulates invasion/angiogenesis in breast cancer.

PubMed

Bharti, Rashmi; Dey, Goutam; Das, Anjan Kumar; Mandal, Mahitosh

2018-04-26

Monoamine oxidases (MAO) are mitochondrial enzymes functioning in oxidative metabolism of monoamines. The action of MAO-A has been typically described in neuro-pharmacological domains. Here, we have established a co-relation between IL-6/IL-6R and MAO-A and their regulation in hypoxia induced invasion/angiogenesis. We employed various in-vitro and in-vivo techniques and clinical samples. We studied a co-relation among MAO-A and IL-6/IL-6R and tumour angiogenesis/invasion in hypoxic environment in breast cancer model. Activation of IL-6/IL-6R and its downstream was found in hypoxic cancer cells. This elevation of IL-6/IL-6R caused sustained inhibition of MAO-A in hypoxic environment. Inhibition of IL-6R signalling or IL-6R siRNA increased MAO-A activity and inhibited tumour angiogenesis and invasion significantly in different models. Further, elevation of MAO-A with 5-azacytidine (5-Aza) modulated IL-6 mediated angiogenesis and invasive signatures including VEGF, MMPs and EMT in hypoxic breast cancer. High grade invasive ductal carcinoma (IDC) clinical specimen displayed elevated level of IL-6R and depleted MAO-A expression. Expression of VEGF and HIF-1α was unregulated and loss of E-Cadherin was observed in high grade IDC tissue specimen. Suppression of MAO-A by IL-6/IL-6R activation promotes tumour angiogenesis and invasion in hypoxic breast cancer environment.

An Assessment of Psychological Need in Emergency Medical Staff in the Northern Health and Social Care Trust Area

PubMed Central

Aisling, Diamond; David, Curran

2016-01-01

Setting Psychological stress is increasingly recognised within emergency medicine, given the environmental and clinical stressors associated with the specialism. The current study assessed whether psychological distress is experienced by emergency medical staff and if so, what is the expressed need within this population? Participants Participants included ambulance personnel, nursing staff, doctors and ancillary support staff within two Accident and Emergency (A&E) departments and twelve ambulance bases within one Trust locality in NI (N = 107). Primary and secondary outcome measures The General Health Questionnaire (GHQ-12, Goldberg, 1972, 1978), Secondary Traumatic Stress Scale (STSS, Bride, 2004) and an assessment of need questionnaire were completed and explored using mixed method analysis. Results Results showed elevated levels of psychological distress within each profession except ambulance service clinical support officers (CSOs). Elevated levels of secondary trauma symptomatology were also found; the highest were within some nursing grades and junior doctors. Decreased enjoyment in job over time was significantly associated with higher scores. Analysis of qualitative data identified sources of stress to include low morale. A total of 65% of participants thought that work related stressors had negatively affected their mental health. Participants explored what they felt could decrease psychological distress including improved resources and psychoeducation. Conclusion There were elevated levels of distress and secondary traumatic stress within this population as well as an expressed level of need, on both systemic and support levels. PMID:27601762

The differing influence of several factors on the development of fatty liver with elevation of liver enzymes between genders with metabolic syndrome: A cross-sectional study.

PubMed

Sogabe, Masahiro; Okahisa, Toshiya; Nakasono, Masahiko; Fukuno, Hiroshi; Miyamoto, Yoshihiko; Okada, Yasuyuki; Okazaki, Jun; Miyoshi, Jinsei; Tomonari, Tetsu; Taniguchi, Tatsuya; Goji, Takahiro; Kitamura, Shinji; Miyamoto, Hiroshi; Muguruma, Naoki; Takayama, Tetsuji

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is known to be strongly associated with obesity, visceral fat, metabolic syndrome (MS), lifestyle, and lifestyle-related diseases in both males and females. However, the prevalence of NAFLD, MS, and clinical backgrounds is different between males and females. We conducted a cross-sectional study to examine the differing influence of lifestyle-related factors and visceral fat on fatty liver (FL) with elevation of liver enzymes between males and females with MS. We enrolled 42,134 persons who underwent a regular health check-up, and after excluding subjects who fulfilled excluding criteria, the remaining subjects were 2,110 persons with MS. We examined the differing influence of lifestyle-related factors and visceral fat on FL with elevation of alanine aminotransferase (ALT) (ALT elevation was defined as ALT level of ≥31 IU/l in the present study). The odds rations for FL with ALT elevation were as follows: WC, 1.83 (95% confidence interval (CI) 1.36-2.46); dyslipidemia, 1.89 (95% CI 1.34-2.68); hemoglobin A1c, 1.36 (95% CI 1.00-1.85); visceral fat type MS (V-type MS), 5.78 (95% CI 4.29-7.80); and light drinker, 0.56 (95% CI 0.41-0.78) in males with MS and BMI, 2.18 (95% CI 1.43-3.33); WC, 1.85 (95% CI 1.27-2.70); diastolic blood pressure, 1.69 (95% CI 1.16-2.45); triglyceride, 2.22 (95% CI 1.56-3.17); impaired glucose tolerance, 1.66 (95% CI 1.11-2.47); and V-type MS, 3.83 (95% CI 2.57-5.70) in females with MS. The prevalence of FL with ALT elevation and ALT was significantly higher in V-type MS than in the subcutaneous fat type MS in both males and females with MS (P < 0.001). Although V-type MS and WC is a common significant predictor of an increased prevalence of FL with ALT elevation in both males and females with MS, gender, lifestyle-related factors, and MS type in individuals with MS should be considered for the development of FL with ALT elevation.

A Developmental Decline in the Learning-Promoting Effects of Infant-Directed Speech for Infants of Mothers with Chronically Elevated Symptoms of Depression

PubMed Central

Kaplan, Peter S.; Danko, Christina M.; Kalinka, Christina J.; Cejka, Anna M.

2014-01-01

Infants of mothers who varied in symptoms of depression were tested at 4 and 12 months of age for their ability to associate a segment of an unfamiliar non-depressed mother’s infant-directed speech (IDS) with a face. At 4 months, all infants learned the voice-face association. At 12 months, despite the fact that none of the mothers were still clinically depressed, infants of mothers with chronically elevated self-reported depressive symptoms, and infants of mothers with elevated self-reported depressive symptoms at 4 months but not 12 months, on average did not learn the association. For infants of mothers diagnosed with depression in remission, learning at 12 months was negatively correlated with the postpartum duration of the mother’s depressive episode. At neither age did extent of pitch modulation in the IDS segments correlate with infant learning. However, learning scores at 12 months correlated significantly with concurrent maternal reports of infant receptive language development. The roles of the duration and timing of maternal depressive symptoms are discussed. PMID:22721737

Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans.

PubMed

Wiputra, Hadi; Lai, Chang Quan; Lim, Guat Ling; Heng, Joel Jia Wei; Guo, Lan; Soomar, Sanah Merchant; Leo, Hwa Liang; Biwas, Arijit; Mattar, Citra Nurfarah Zaini; Yap, Choon Hwai

2016-12-01

There are 0.6-1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2-0.9 mmHg during systole, and 0.1-0.2 mmHg during diastole. Diastolic wall shear stresses were found to be around 1 Pa, which could elevate to 2-4 Pa during systole in the outflow tract. Fetal right ventricles have complex flow patterns featuring two interacting diastolic vortex rings, formed during diastolic E wave and A wave. These rings persisted through the end of systole and elevated wall shear stresses in their proximity. They were observed to conserve ∼25.0% of peak diastolic kinetic energy to be carried over into the subsequent systole. However, this carried-over kinetic energy did not significantly alter the work done by the heart for ejection. Thus, while diastolic vortexes played a significant role in determining spatial patterns and magnitudes of diastolic wall shear stresses, they did not have significant influence on systolic ejection. Our results can serve as a baseline for future comparison with diseased hearts. Copyright © 2016 the American Physiological Society.

Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

PubMed

Forman, Mervyn B; Jackson, Edwin K

2007-11-01

High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

Differentiating immunoglobulin g4-related sclerosing cholangitis from hilar cholangiocarcinoma.

PubMed

Tabata, Taku; Kamisawa, Terumi; Hara, Seiichi; Kuruma, Sawako; Chiba, Kazuro; Kuwata, Go; Fujiwara, Takashi; Egashira, Hideto; Koizumi, Koichi; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Kurata, Masanao; Honda, Goro; Tsuruta, Koji; Itoi, Takao

2013-03-01

Few studies have differentiated immunoglobulin G (IgG) 4-related sclerosing cholangitis (IgG4-SC) from hilar cholangiocarcinoma (CC). Thus, we sought to investigate useful features for differentiating IgG4-SC from hilar CC. We retrospectively compared clinical, serological, imaging, and histological features of six patients with IgG4-SC and 42 patients with hilar CC. In patients with hilar CC, obstructive jaundice was more frequent (p<0.01), serum total bilirubin levels were significantly higher (p<0.05), serum CA19-9 levels were significantly higher (p<0.01), and serum duke pancreatic monoclonal antigen type 2 levels were frequently elevated (p<0.05). However, in patients with IgG4-SC, the serum IgG (p<0.05) and IgG4 (p<0.01) levels were significantly higher and frequently elevated. The pancreas was enlarged in all IgG4-SC patients but only in 17% of hilar CC patients (p<0.01). Salivary and/or lacrimal gland swelling was detected in only 50% of IgG4-SC patients (p<0.01). Endoscopic retrograde cholangiography revealed that the hilar or hepatic duct was completely obstructed in 83% of hilar CC patients (p<0.01). Lower bile duct stenosis, apart from hilar bile duct stenosis, was more frequent in IgG4-SC patients (p<0.01). Bile duct wall thickening in areas without stenosis was more frequent in IgG4-SC patients (p<0.01). An integrated diagnostic approach based on clinical, serological, imaging, and histological findings is necessary to differentiate IgG4-SC from hilar CC.

Cardiotoxic (Arrhythmogenic) Effects of 1,1-Difluoroethane Due to Electrolyte Imbalance and Cardiomyocyte Damage.

PubMed

Joshi, Kaushal; Barletta, Michael; Wurpel, John

2017-06-01

Inhalant abuse is the intentional inhalation of chemical vapors to attain euphoric effects. Many common household products are abused by inhalation and one is 1,1-difluoroethane (DFE), which is a halogenated hydrocarbon used in refrigeration, dust-off spray, and airbrush painting. Although many human DFE abuse cases have been studied, the etiology and mechanism of sudden death is still unknown. In this study, an animal model was used to simulate the human conditions of DFE inhalation abuse that results in sudden death.Current research targets mechanistic studies involving electrolyte changes and cardiomyocyte damage after DFE administration in vivo. To investigate these changes, Sprague Dawley rats (N = 6) were exposed to 30 seconds of 20 L/min of DFE in multiple doses. Isoflurane acted as a control. Two additional groups, epinephrine and epinephrine + DFE, were included to simulate the clinical condition of DFE abuse. Plasma sodium, potassium, calcium, and magnesium levels were measured, followed by lactate dehydrogenase, creatine kinase, and cardiac troponin I levels. In addition, oxidative stress markers were also evaluated in all animal groups. Electrolyte levels showed a significant rise in plasma potassium and magnesium levels for the treated groups. In addition, lactate dehydrogenase, creatine kinase, and cardiac troponin I levels in DFE and epinephrine + DFE administered rats were significantly elevated as compared with control. Some oxidative stress makers were also elevated significantly in treatment groups. Furthermore, histopathological analysis showed hyperemia/congestion in treated rats.These results support cardiotoxic effects indicating that DFE results in fatal arrhythmias, and the study can be important during clinical cases involving inhalant abuse.

Serum levels of vascular endothelial growth factor in preeclamptic and normotensive pregnancy.

PubMed

Hunter, A; Aitkenhead, M; Caldwell, C; McCracken, G; Wilson, D; McClure, N

2000-12-01

The purpose of these studies was first to determine if vascular endothelial growth factor (VEGF), a vascular permeability agent, is increased in the serum of women with preclinical and clinical preclampsia (PE), and second to determine how these levels change after delivery. Twenty preeclamptic and 25 normotensive women at term consented to have blood taken pre- and post-delivery. Ten preeclamptic, 10 gestational hypertensive, and 28 normotensive women had blood collected respectively at 12, 20, and 30 weeks gestation and predelivery. Serum was extracted from all samples, and VEGF concentrations were determined by radioimmunoassay. Predelivery, the median serum VEGF concentration in the preeclamptic group was 51.7 ng/mL, and in the control group the concentration was 13.9 ng/mL (P<0.0001). Serum VEGF concentrations fell within 24 hours of delivery in both groups, which resulted in median values of 3.8 ng/mL and 3.2 ng/mL respectively (P<0.3). At 12 and 20 weeks, there was no significant difference between the serum VEGF concentrations in the 3 groups (P<0.3, 0.052 respectively). At 30 weeks, prior to the onset of clinical PE, the serum VEGF levels in the eventual preeclamptic group were elevated significantly compared with the gestational hypertensive and normotensive groups (P<0.001). Predelivery serum VEGF concentrations were significantly elevated in the preeclamptic group and were similar to those in the first study (P<0.0001). These findings suggest that VEGF may be important in the pathophysiology of PE and has the potential to act as a preclinical marker for the condition.

Association between insulin resistance and plasma amino acid profile in non-diabetic Japanese subjects.

PubMed

Yamada, Chizumi; Kondo, Masumi; Kishimoto, Noriaki; Shibata, Takeo; Nagai, Yoko; Imanishi, Tadashi; Oroguchi, Takashige; Ishii, Naoaki; Nishizaki, Yasuhiro

2015-07-01

Elevation of the branched-chain amino acids (BCAAs), valine, leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine, has been observed in obesity-related insulin resistance. However, there have been few studies on Asians, who are generally less obese and less insulin-resistant than Caucasian or African-Americans. In the present study, we investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) and plasma amino acid concentration in non-diabetic Japanese participants. A total of 94 healthy men and women were enrolled, and plasma amino acid concentration was measured by liquid chromatography/mass spectrometry after overnight fasting. The associations between HOMA-IR and 20 amino acid concentrations, and anthropometric and clinical parameters of lifestyle-related diseases were evaluated. The mean age and body mass index were 40.1 ± 9.6 years and 22.7 ± 3.9, respectively. Significantly positive correlations were observed between HOMA-IR and valine, isoleucine, leucine, tyrosine, phenylalanine and total BCAA concentration. Compared with the HOMA-IR ≤ 1.6 group, the HOMA-IR > 1.6 group showed significantly exacerbated anthropometric and clinical parameters, and significantly elevated levels of valine, isoleucine, leucine, tyrosine, phenylalanine and BCAA. The present study shows that the insulin resistance-related change in amino acid profile is also observed in non-diabetic Japanese subjects. These amino acids include BCAAs (valine, isoleucine and leucine) and aromatic amino acids (tyrosine and phenylalanine), in agreement with previous studies carried out using different ethnic groups with different degrees of obesity and insulin resistance.

Swertiajaponin as an anti-browning and antioxidant flavonoid.

PubMed

Moon, Kyoung Mi; Lee, Bonggi; Cho, Won-Kyung; Lee, Bong-Seon; Kim, Choon Young; Ma, Jin Yeul

2018-06-30

Enzymatic browning is a major issue that needs to be solved in the food industry. Although swertiajaponin is a flavonoid rich in the whole herb of Swertia japonica that has been clinically used, its biological functions and applicat​ion in the foods have not been fully elucidated. Here, we showed that swertiajaponin efficiently blocked enzymatic browning in potatoes possibly by direct binding to and inactivating polyphenol oxidase. Furthermore, swertiajaponin showed potent antioxidant activity proven by markedly suppressed reactive oxygen species. Swertiajaponin significantly increased antioxidant properties of potato extract when it is added since it additively elevated total flavonoid content. Considering numerous beneficial effects of antioxidants, swertiajaponin may be used as a functional food additive to suppress enzymatic browning and elevate the antioxidant capacity of foods including beverages and soups by fortification of flavonoids. Copyright © 2018 Elsevier Ltd. All rights reserved.

Factors related to elevated vaginal pH in the first trimester of pregnancy.

PubMed

Zodzika, Jana; Rezeberga, Dace; Jermakova, Irina; Vasina, Olga; Vedmedovska, Natalija; Donders, Gilbert

2011-01-01

To assess different bacterial and epidemiological factors associations with increased vaginal pH in the pregnant women population during the first trimester. A cross-sectional, observational study. Three outpatient clinics in Riga. From July 2009 until January 2010, 139 unselected consecutive pregnant women at the first prenatal visit. Pregnant women were submitted to an interview, vaginal examination and vaginal specimen collection for pH measurement and native microscopy. Vaginal pH ≥4.5 was considered as elevated. Abnormal bacterial microflora was classified according to Donders. Elevated vaginal pH was significantly associated with bacterial vaginosis (p < 0.001), aerobic vaginitis (p < 0.001) and mixed aerobic vaginitis and bacterial vaginosis flora (p < 0.001) and presence of sperm cells in the smears (p= 0.024). Most cases with sperm were associated with abnormal vaginal flora. Normal lactobacillary morphotypes were more often found in the pH ≤4.4 group (p < 0.001), while leptosomic and short types were found more frequently with increased pH. Elevated vaginal pH is associated with different types of abnormal vaginal flora and the presence of sperm cells. © 2010 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2010 Nordic Federation of Societies of Obstetrics and Gynecology.

Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy.

PubMed Central

Beisswenger, P J; Moore, L L; Brinck-Johnsen, T; Curphey, T J

1993-01-01

RATIONALE: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs. OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86 +/- 5.66 vs 60.42 +/- 5.98 pmol/mg col) (P < 0.05). CONCLUSIONS: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase of diabetic nephropathy. Images PMID:8325987

Treatment of acute coronary syndrome: part 2: ST-segment elevation myocardial infarction.

PubMed

Trost, Jeffrey C; Lange, Richard A

2012-06-01

Familiarize clinicians with recent information regarding the diagnosis and treatment of ST-segment elevation myocardial infarction. PubMed search and review of relevant medical literature. Definition, pathophysiology, clinical presentation, diagnosis, and treatment of ST-segment elevation myocardial infarction are reviewed. Patients with ST-segment elevation myocardial infarction benefit from prompt reperfusion therapy. Adjunctive antianginal, antiplatelet, antithrombotic, beta blocker, angiotensin-converting enzyme inhibitor, and statin agents minimize ongoing cardiac ischemia, prevent thrombus propagation, and reduce the risk of recurrent cardiovascular events.

Elevated serum creatinine and hyponatraemia as prognostic factors in canine acute pancreatitis.

PubMed

Marchetti, V; Gori, E; Lippi, I; Luchetti, E; Manca, M L; Pierini, A

2017-11-01

To evaluate prognostic factors for canine acute pancreatitis (AP) based on clinical and laboratory data that can be easily assessed in veterinary practice. Retrospective study between January 2010 and December 2013. The diagnosis of AP was based on clinical signs and an abnormal SNAP® cPL™ test result, concurrently with an ultrasound pattern suggestive of pancreatitis. Dogs were divided into survivors and non-survivors. We evaluated 12 clinical and laboratory parameters: respiratory rate, rectal temperature, white blood cells, haematocrit, total serum proteins, albumin, creatinine, cholesterol, total and ionised calcium, sodium and potassium. Clinical and clinicopathological data were statistically compared between survivors and non-survivors. A value of P < 0.05 was considered significant and P < 0.01 as highly significant. The odds ratio (OR) was calculated. The study enrolled 50 client-owned dogs with a diagnosis of AP. Serum creatinine (P = 0.017) and sodium (P = 0.004) correlated significantly with the outcome. Serum sodium < 139.0 mmol/L (139.0 mEq/L) and serum creatinine > 212 μmol/L (2.4 mg/dL) were associated significantly with poor prognosis. Azotaemia (OR 12.5; 95% confidence interval (CI) 1.32-118.48) and hyponatraemia (OR 4.9; 95% CI 1.36-17.64) were associated with increased risk of death. In dogs with AP, hyponatraemia and azotaemia seem to be significantly associated with an increased risk of death. © 2017 Australian Veterinary Association.

Comparative observational study on the clinical presentation, intracranial volume measurements, and intracranial pressure scores in patients with either Chiari malformation Type I or idiopathic intracranial hypertension.

PubMed

Frič, Radek; Eide, Per Kristian

2017-04-01

OBJECTIVE Several lines of evidence suggest common pathophysiological mechanisms in Chiari malformation Type I (CMI) and idiopathic intracranial hypertension (IIH). It has been hypothesized that tonsillar ectopy, a typical finding in CMI, is the result of elevated intracranial pressure (ICP) combined with a developmentally small posterior cranial fossa (PCF). To explore this hypothesis, the authors specifically investigated whether ICP is comparable in CMI and IIH and whether intracranial volumes (ICVs) are different in patients with CMI and IIH, which could explain the tonsillar ectopy in CMI. The authors also examined whether the symptom profile is comparable in these 2 patient groups. METHODS The authors identified all CMI and IIH patients who had undergone overnight diagnostic ICP monitoring during the period from 2002 to 2014 and reviewed their clinical records and radiological examinations. Ventricular CSF volume (VV), PCF volume (PCFV), and total ICV were calculated from initial MRI studies by using volumetric software. The static and pulsatile ICP scores during overnight monitoring were analyzed. Furthermore, the authors included a reference (REF) group consisting of patients who had undergone ICP monitoring due to suspected idiopathic normal-pressure hydrocephalus or chronic daily headache and showed normal pressure values. RESULTS Sixty-six patients with CMI and 41 with IIH were identified, with comparable demographics noted in both groups. The occurrence of some symptoms (headache, nausea, and/or vomiting) was comparable between the cohorts. Dizziness and gait ataxia were significantly more common in patients with CMI, whereas visual symptoms, diplopia, and tinnitus were significantly more frequent in patients with IIH. The cranial volume measurements (VV, PCFV, and ICV) of the CMI and IIH patients were similar. Notably, 7.3% of the IIH patients had tonsillar descent qualifying for diagnosis of CMI (that is, > 5 mm). The extent of tonsillar ectopy was significantly different between the CMI and IIH cohorts (p < 0.001) but also between these 2 cohorts and the REF group. Pulsatile ICP was elevated in both cohorts without any significant between-group differences; however, static ICP was significantly higher (p < 0.001) in the IIH group. CONCLUSIONS This study showed comparable and elevated pulsatile ICP, indicative of impaired intracranial compliance, in both CMI and IIH cohorts, while static ICP was higher in the IIH cohort. The data did not support the hypothesis that reduced PCFV combined with increased ICP causes tonsillar ectopy in CMI. Even though impaired intracranial compliance seems to be a common pathophysiological mechanism behind both conditions, the mechanisms explaining the different clinical and radiological presentations of CMI and IIH remain undefined.

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants.

PubMed

Nadkarni, Girish N; Chauhan, Kinsuk; Verghese, Divya A; Parikh, Chirag R; Do, Ron; Horowitz, Carol R; Bottinger, Erwin P; Coca, Steven G

2018-04-20

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m 2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evaluation of reactive oxygen metabolites in patients with non-small cell lung cancer after chemotherapy.

PubMed

Wakabayashi, Toru; Kawashima, Tatsuo; Matsuzawa, Yasuo

2014-01-01

The aim of this study was to evaluate the level of reactive oxygen metabolites (ROMs) after chemotherapy in patients with non-small cell lung cancer (NSCLC) and its association with response to treatment. Fifty-eight untreated NSCLC patients and twenty-three healthy subjects were selected for the study. Patients received two courses of platinum-based chemotherapy and were evaluated for oxidative stress and treatment response. As a marker of reactive oxygen species, ROMs levels were measured using the d-ROMs test. ROMs level (mean ± standard deviation) before chemotherapy in NSCLC patients (416 ± 135 U.CARR) was significantly elevated (p = 0.016) compared to normal healthy subjects (320 ± 59 U.CARR). Patients who responded to chemotherapy showed significantly decreased (p = 0.014) ROMs levels after chemotherapy, whereas patients who had stable disease or progressive disease showed no change in ROMs level (p = 0.387). NSCLC patients had significantly elevated ROMs levels before chemotherapy compared with normal healthy subjects. Chemotherapy may suppress ROMs production in responders but not in non-responders. ROMs level may be a predictor of clinical outcome in patients receiving chemotherapy for NSCLC.

Dynamic magnetic resonance imaging of the behavior of the mid-urethra in healthy and stress incontinent women.

PubMed

Rinne, Kirsi Marja; Kainulainen, Sakari; Aukee, Sinikka; Heinonen, Seppo; Nilsson, Carl Gustaf

2010-03-01

Support of the mid-urethra is thought to be an essential element of urinary continence in the female. Our aim was to image the behavior of the mid-urethra in healthy volunteers and in stress urinary incontinence (SUI) patients by dynamic magnetic resonance imaging (MRI). Prospective study. Gynecology outpatient clinic association with Department of Radiology in University Hospital of Kuopio, Finland. Fifteen healthy volunteers and 40 SUI women underwent dynamic MRI at rest, during pelvic floor muscle contraction, coughing and voiding with a bladder volume of 200 ml. Our aim was to determine the precise location and movement of the mid-urethra during these activities. The co-ordinate location and movement of the mid-urethra. Continent volunteers can elevate their mid-urethra significantly higher than incontinent women. Moreover, the mid-urethra of incontinent women rotated significantly more dorsocaudally during straining and coughing than in continent women. Elevation of the mid-urethra was more marked in continent compared to urinary incontinent women on pelvic floor muscle contraction suggesting sufficient support of the urethra. Downward movement of the mid-urethra was more significant in stress incontinent women than in continent volunteers.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Improved Virologic Suppression With HIV Subspecialty Care in a Large Prison System Using Telemedicine: An Observational Study With Historical Controls

PubMed Central

Young, Jeremy D.; Patel, Mahesh; Badowski, Melissa; Mackesy-Amiti, Mary Ellen; Vaughn, Pyrai; Shicker, Louis; Puisis, Michael; Ouellet, Lawrence J.

2014-01-01

Correctional populations have an elevated human immunodeficiency virus (HIV) prevalence, yet many individuals lack access to subspecialty care. Our study showed that HIV-infected inmates had significantly greater virologic suppression and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of subspecialists conducting clinics via telemedicine. In other studies, these outcomes have been associated with reductions on HIV-related morbidity and mortality, as well as HIV transmission. PMID:24723283

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents.

PubMed

Giustino, Gennaro; Baber, Usman; Stefanini, Giulio Giuseppe; Aquino, Melissa; Stone, Gregg W; Sartori, Samantha; Steg, Philippe Gabriel; Wijns, William; Smits, Pieter C; Jeger, Raban V; Leon, Martin B; Windecker, Stephan; Serruys, Patrick W; Morice, Marie-Claude; Camenzind, Edoardo; Weisz, Giora; Kandzari, David; Dangas, George D; Mastoris, Ioannis; Von Birgelen, Clemens; Galatius, Soren; Kimura, Takeshi; Mikhail, Ghada; Itchhaporia, Dipti; Mehta, Laxmi; Ortega, Rebecca; Kim, Hyo-Soo; Valgimigli, Marco; Kastrati, Adnan; Chieffo, Alaide; Mehran, Roxana

2015-09-15

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women. Published by Elsevier Inc.

1. Statement of significance, site plan, plan, elevation, section, boxcar ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Statement of significance, site plan, plan, elevation, section, boxcar spring details, and outhouse plan and elevation. - Woods Landing Dance Hall, 2731 State Highway 230, Woods Landing, Albany County, WY

Modifiable clinical and lifestyle factors are associated with elevated alanine aminotransferase levels in newly diagnosed type 2 diabetes patients: results from the nationwide DD2 study.

PubMed

Mor, Anil; Svensson, Elisabeth; Rungby, Jørgen; Ulrichsen, Sinna Pilgaard; Berencsi, Klara; Nielsen, Jens Steen; Stidsen, Jacob Volmer; Friborg, Søren; Brandslund, Ivan; Christiansen, Jens Sandahl; Beck-Nielsen, Henning; Sørensen, Henrik Toft; Thomsen, Reimar Wernich

2014-11-01

Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients. Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11). Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels. Copyright © 2014 John Wiley & Sons, Ltd.

Characteristic of entire corneal topography and tomography for the detection of sub-clinical keratoconus with Zernike polynomials using Pentacam.

PubMed

Xu, Zhe; Li, Weibo; Jiang, Jun; Zhuang, Xiran; Chen, Wei; Peng, Mei; Wang, Jianhua; Lu, Fan; Shen, Meixiao; Wang, Yuanyuan

2017-11-28

The study aimed to characterize the entire corneal topography and tomography for the detection of sub-clinical keratoconus (KC) with a Zernike application method. Normal subjects (n = 147; 147 eyes), sub-clinical KC patients (n = 77; 77 eyes), and KC patients (n = 139; 139 eyes) were imaged with the Pentacam HR system. The entire corneal data of pachymetry and elevation of both the anterior and posterior surfaces were exported from the Pentacam HR software. Zernike polynomials fitting was used to quantify the 3D distribution of the corneal thickness and surface elevation. The root mean square (RMS) values for each order and the total high-order irregularity were calculated. Multimeric discriminant functions combined with individual indices were built using linear step discriminant analysis. Receiver operating characteristic curves determined the diagnostic accuracy (area under the curve, AUC). The 3rd-order RMS of the posterior surface (AUC: 0.928) obtained the highest discriminating capability in sub-clinical KC eyes. The multimeric function, which consisted of the Zernike fitting indices of corneal posterior elevation, showed the highest discriminant ability (AUC: 0.951). Indices generated from the elevation of posterior surface and thickness measurements over the entire cornea using the Zernike method based on the Pentacam HR system were able to identify very early KC.

Clinical performance of serum [-2]proPSA derivatives, %p2PSA and PHI, in the detection and management of prostate cancer.

PubMed

Huang, Ya-Qiang; Sun, Tong; Zhong, Wei-De; Wu, Chin-Lee

2014-01-01

Prostate-specific antigen (PSA) has been widely used as a serum marker for prostate cancer (PCa) screening or progression monitoring, which dramatically increased rate of early detection while significantly reduced PCa-specific mortality. However, a number of limitations of PSA have been noticed. Low specificity of PSA may lead to overtreatment in men who presenting with a total PSA (tPSA) level of < 10 ng/mL. As a type of free PSA (fPSA), [-2]proPSA is differentially expressed in peripheral zone of prostate gland and found to be elevated in serum of men with PCa. Two p2PSA-based derivatives, prostate health index (PHI) and %p2PSA, which were defined as [(p2PSA/fPSA) × √ tPSA] and [(p2PSA/fPSA) × 100] respectively, have been suggested to be increased in PCa and can better distinguish PCa from benign prostatic diseases than tPSA or fPSA. We performed a systematic review of the available scientific evidences to evaluate the potentials of %p2PSA and PHI in clinical application. Mounting evidences suggested that both %p2PSA and PHI possess higher area under the ROC curve (AUC) and better specificity at a high sensitivity for PCa detection when compare with tPSA and %fPSA. It indicated that measurements of %p2PSA and PHI significantly improved the accuracy of PCa detection and diminished unnecessary biopsies. Furthermore, elevations of %p2PSA and PHI are related to more aggressive diseases. %p2PSA and PHI might be helpful in reducing overtreatment on indolent cases or assessing the progression of PCa in men who undergo active surveillance. Further studies are needed before being applied in routine clinical practice.

Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India.

PubMed

Kaushal, H; Bras-Gonçalves, R; Avishek, K; Kumar Deep, D; Petitdidier, E; Lemesre, J-L; Papierok, G; Kumar, S; Ramesh, V; Salotra, P

2016-07-01

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic dermal complication that occurs usually after recovery from visceral leishmaniasis (VL). The disease manifests into macular, papular and/or nodular clinical types with mono- or polymorphic presentations. Here, we investigated differences in immunological response between these two distinct clinical forms in Indian PKDL patients. Peripheral blood mononuclear cells of PKDL and naive individuals were exposed in vitro to total soluble Leishmania antigen (TSLA). The proliferation index was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based lymphoproliferative assay. Cytokines and granzyme B levels were determined by cytometric bead array. Parasite load in tissue biopsy samples of PKDL was quantified by quantitative polymerase chain reaction (qPCR). The proportion of different lymphoid subsets in peripheral blood and the activated T cell population were estimated using flow cytometry. The study demonstrated heightened cellular immune responses in the polymorphic PKDL group compared to the naive group. The polymorphic group showed significantly higher lymphoproliferation, increased cytokines and granzyme B levels upon TSLA stimulation, and a raised proportion of circulating natural killer (NK) T cells against naive controls. Furthermore, the polymorphic group showed a significantly elevated proportion of activated CD4(+) and CD8(+) T cells upon in-vitro TSLA stimulation. Thus, the polymorphic variants showed pronounced cellular immunity while the monomorphic form demonstrated a comparatively lower cellular response. Additionally, the elevated level of both activated CD4(+) and CD8(+) T cells, coupled with high granzyme B secretion upon in-vitro TSLA stimulation, indicated the role of cytotoxic cells in resistance to L. donovani infection in polymorphic PKDL. © 2016 British Society for Immunology.

Hsp-27 levels and thrombus burden relate to clinical outcomes in patients with ST-segment elevation myocardial infarction

PubMed Central

Tian, Maozhou; Zhu, Lingmin; Lin, Hongyang; Lin, Qiaoyan; Huang, Peng; Yu, Xiao; Jing, Yanyan

2017-01-01

High thrombus burden, subsequent distal embolization, and myocardial no-reflow remain a large obstacle that may negate the benefits of urgent coronary revascularization in patients with ST-segment elevation myocardial infarction (STEMI). However, the biological function and clinical association of Hsp-27 with thrombus burden and clinical outcomes in patients with STEMI is not clear. Consecutive patients (n = 146) having STEMI undergoing primary percutaneous coronary intervention (pPCI) within 12 hours from the onset of symptoms were enrolled in this prospective study in the Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, P.R. China. Patients were divided into low thrombus burden and high thrombus burden groups. The present study demonstrated that patients with high-thrombus burden had higher plasma Hsp-27 levels ([32.0 ± 8.6 vs. 58.0 ± 12.3] ng/mL, P < 0.001). The median value of Hsp-27 levels in all patients with STEMI was 45 ng/mL. Using the receiver operating characteristic (ROC) curve analysis, plasma Hsp-27 levels were of significant diagnostic value for high thrombus burden (AUC, 0.847; 95% CI, 0.775–0.918; P < 0.01). The multivariate cox regression analysis demonstrated that Hsp-27 > 45 ng/mL (HR 2.801, 95% CI 1.296–4.789, P = 0.001), were positively correlated with the incidence of major adverse cardiovascular events (MACE). Kaplan-Meier survival analysis demonstrated that MACE-free survival at 180-day follow-up was significantly lower in patients with Hsp-27 > 45 ng/mL (log rank = 10.28, P < 0.001). Our data demonstrate that plasma Hsp-27 was positively correlated with high thrombus burden and the incidence of MACE in patients with STEMI who underwent pPCI. PMID:29088740

First-attack pediatric hypertensive crisis presenting to the pediatric emergency department.

PubMed

Yang, Wen-Chieh; Zhao, Lu-Lu; Chen, Chun-Yu; Wu, Yung-Kang; Chang, Yu-Jun; Wu, Han-Ping

2012-12-31

Hypertensive crisis in children is a relatively rare condition presenting with elevated blood pressure (BP) and related symptoms, and it is potentially life-threatening. The aim of this study was to survey children with first attacks of hypertensive crisis arriving at the emergency department (ED), and to determine the related parameters that predicted the severity of hypertensive crisis in children by age group. This was a retrospective study conducted from 2000 to 2007 in pediatric patients aged 18 years and younger with a diagnosis of hypertensive crisis at the ED. All patients were divided into four age groups (infants, preschool age, elementary school age, and adolescents), and two severity groups (hypertensive urgency and hypertensive emergency). BP levels, etiology, severity, and clinical manifestations were analyzed by age group and compared between the hypertensive emergency and hypertensive urgency groups. The mean systolic/diastolic BP in the hypertensive crisis patients was 161/102 mmHg. The major causes of hypertensive crisis were essential hypertension, renal disorders and endocrine/metabolic disorders. Half of all patients had a single underlying cause, and 8 had a combination of underlying causes. Headache was the most common symptom (54.5%), followed by dizziness (45.5%), nausea/vomiting (36.4%) and chest pain (29.1%). A family history of hypertension was a significant predictive factor for the older patients with hypertensive crisis. Clinical manifestations and severity showed a positive correlation with age. In contrast to diastolic BP, systolic BP showed a significant trend in the older children. Primary clinicians should pay attention to the pediatric patients who present with elevated blood pressure and related clinical hypertensive symptoms, especially headache, nausea/vomiting, and altered consciousness which may indicate that appropriate and immediate antihypertensive medications are necessary to prevent further damage.

First-attack pediatric hypertensive crisis presenting to the pediatric emergency department

PubMed Central

2012-01-01

Background Hypertensive crisis in children is a relatively rare condition presenting with elevated blood pressure (BP) and related symptoms, and it is potentially life-threatening. The aim of this study was to survey children with first attacks of hypertensive crisis arriving at the emergency department (ED), and to determine the related parameters that predicted the severity of hypertensive crisis in children by age group. Methods This was a retrospective study conducted from 2000 to 2007 in pediatric patients aged 18 years and younger with a diagnosis of hypertensive crisis at the ED. All patients were divided into four age groups (infants, preschool age, elementary school age, and adolescents), and two severity groups (hypertensive urgency and hypertensive emergency). BP levels, etiology, severity, and clinical manifestations were analyzed by age group and compared between the hypertensive emergency and hypertensive urgency groups. Results The mean systolic/diastolic BP in the hypertensive crisis patients was 161/102 mmHg. The major causes of hypertensive crisis were essential hypertension, renal disorders and endocrine/metabolic disorders. Half of all patients had a single underlying cause, and 8 had a combination of underlying causes. Headache was the most common symptom (54.5%), followed by dizziness (45.5%), nausea/vomiting (36.4%) and chest pain (29.1%). A family history of hypertension was a significant predictive factor for the older patients with hypertensive crisis. Clinical manifestations and severity showed a positive correlation with age. In contrast to diastolic BP, systolic BP showed a significant trend in the older children. Conclusions Primary clinicians should pay attention to the pediatric patients who present with elevated blood pressure and related clinical hypertensive symptoms, especially headache, nausea/vomiting, and altered consciousness which may indicate that appropriate and immediate antihypertensive medications are necessary to prevent further damage. PMID:23272766

Impact of mobile intensive care unit use on total ischemic time and clinical outcomes in ST-elevation myocardial infarction patients - real-world data from the Acute Coronary Syndrome Israeli Survey.

PubMed

Koifman, Edward; Beigel, Roy; Iakobishvili, Zaza; Shlomo, Nir; Biton, Yitschak; Sabbag, Avi; Asher, Elad; Atar, Shaul; Gottlieb, Shmuel; Alcalai, Ronny; Zahger, Doron; Segev, Amit; Goldenberg, Ilan; Strugo, Rafael; Matetzky, Shlomi

2017-01-01

Ischemic time has prognostic importance in ST-elevation myocardial infarction patients. Mobile intensive care unit use can reduce components of total ischemic time by appropriate triage of ST-elevation myocardial infarction patients. Data from the Acute Coronary Survey in Israel registry 2000-2010 were analyzed to evaluate factors associated with mobile intensive care unit use and its impact on total ischemic time and patient outcomes. The study comprised 5474 ST-elevation myocardial infarction patients enrolled in the Acute Coronary Survey in Israel registry, of whom 46% ( n=2538) arrived via mobile intensive care units. There was a significant increase in rates of mobile intensive care unit utilization from 36% in 2000 to over 50% in 2010 ( p<0.001). Independent predictors of mobile intensive care unit use were Killip>1 (odds ratio=1.32, p<0.001), the presence of cardiac arrest (odds ratio=1.44, p=0.02), and a systolic blood pressure <100 mm Hg (odds ratio=2.01, p<0.001) at presentation. Patients arriving via mobile intensive care units benefitted from increased rates of primary reperfusion therapy (odds ratio=1.58, p<0.001). Among ST-elevation myocardial infarction patients undergoing primary reperfusion, those arriving by mobile intensive care unit benefitted from shorter median total ischemic time compared with non-mobile intensive care unit patients (175 (interquartile range 120-262) vs 195 (interquartile range 130-333) min, respectively ( p<0.001)). Upon a multivariate analysis, mobile intensive care unit use was the most important predictor in achieving door-to-balloon time <90 min (odds ratio=2.56, p<0.001) and door-to-needle time <30 min (odds ratio=2.96, p<0.001). One-year mortality rates were 10.7% in both groups (log-rank p-value=0.98), however inverse propensity weight model, adjusted for significant differences between both groups, revealed a significant reduction in one-year mortality in favor of the mobile intensive care unit group (odds ratio=0.79, 95% confidence interval (0.66-0.94), p=0.01). Among patients with ST-elevation myocardial infarction, the utilization of mobile intensive care units is associated with increased rates of primary reperfusion, a reduction in the time interval to reperfusion, and a reduction in one-year adjusted mortality.

Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.

PubMed

He, Xiao-Tao; Zhou, Kai-Xiang; Zhao, Wen-Jun; Zhang, Chen; Deng, Jian-Ping; Chen, Fa-Ming; Gu, Ze-Xu; Li, Yun-Qing; Dong, Yu-Lin

2018-01-01

The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP.

[Anesthesia experiences on laparoscopic nephrectomy with da Vinci S robotics].

PubMed

Mou, Ling; Lan, Zhixun

2015-09-01

To summarize the clinical anesthesia experiences in 20 patients who underwent laparoscopic nephrectomy with da Vinci S robotics.
 Anesthesia data of 20 patients from Sichuan Provincial People's Hospital, who underwent laparoscopic nephrectomy with da Vinci S robotics from August 2014 to November 2014, were analyzed and summarized. The anesthesia time, operation time, CO(2) pneumoperitoneum time, PaCO(2) and PETCO(2) were recorded.
 All patients were anesthetized and underwent surgery with da Vinci S robotics. The anesthesia time was (220±14) min, the operation time was (187±11) min, and the CO(2) pneumoperitoneum time was (180±13) min. The PaCO(2) and PETCO(2) were significantly elevated at 1.5 h after operation compared with those at the baseline (before pneumoperitoneum) (P<0.05). The pH value was significantly decreased at 2.5 h after operation compared to that at the baseline (P<0.05). The peak airway pressure of inspiration was significantly elevated at 0.5 h after the beginning of pneumoperitoneum compared to that at the baseline (P<0.05).
 The hemodynamics is stable during the laparoscopic nephrectomy with da vinci S robotics. However, the duration of CO(2) pneumoperitoneum is significantly increased compared to that of other surgical procedures, resulting in high airway resistance and acid-base disturbance.

Effects of atorvastatin treatment on left ventricular diastolic function in peritoneal dialysis patients-The ALEVENT clinical trial.

PubMed

Wu, Cho-Kai; Yeh, Chih-Fan; Chiang, Jiun-Yang; Lin, Ting-Tse; Wu, Yi-Fan; Chiang, Chih-Kang; Kao, Tze-Wah; Hung, Kuan-Yu; Huang, Jenq-Wen

Left ventricular diastolic dysfunction (LVDD) is common among patients undergoing peritoneal dialysis (PD). Increased levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein, predict the development of LVDD. We hypothesized that PD patients with elevated high-sensitivity C-reactive protein levels might benefit from statin treatment for LVDD and designed a randomized clinical trial to prove the hypothesis. We screened 213 PD patients and randomly assigned 32 men and women with low-density lipoprotein cholesterol levels <130 mg/dL, high-sensitivity C-reactive protein levels of ≥1.5 mg/L, and LVDD, diagnosed by conventional and tissue Doppler imaging (TDI) echocardiography, to treatment with atorvastatin, 40 mg daily, or without. The primary end points were changes in TDI diastolic parameters or global strain imaging diastolic parameters. Atorvastatin reduced low-density lipoprotein cholesterol levels by 43% and high-sensitivity C-reactive protein levels by 45% (both P < .001). Follow-up TDI showed significant improvement of early mitral flow velocities divided by early diastolic peak velocities of the mitral annulus at the medial and lateral site (Nominal change for E/E medial : -5.01 ± 6.36 vs 1.80 ± 6.59 for atorvastatin and control, respectively, P = .02). There was also a significant improvement in global strain imaging after atorvastatin treatment (global strain rate, -17.12 ± 1.42 vs -14.61 ± 1.78 for atorvastatin and control, respectively, P = .002 and E/SR IVR , 462.35 ± 110.54 vs 634.09 ± 116.81, P = .003). In this trial of PD patients without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels and LVDD, atorvastatin significantly improved cardiac diastolic function (ClinicalTrials.gov number, NCT01503671). Copyright © 2017. Published by Elsevier Inc.

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

[Distribution characteristics of heavy metals along an elevation gradient of montane forest].

PubMed

Wan, Jia-rong; Nie, Ming; Zou, Qin; Hu, Shao-chang; Chen, Jia-kuan

2011-12-01

In the present paper, the concentrations of fourteen heavy metals (Fe, Al, Ti, Cu, Cr, Mn, V, Zn, Ni, Co, Pb, Se, Cd and As) were determined by ICP-AES and atomic absorption spectroscopy along an elevation gradient of montane forest. The results show that the elevation gradient had significant effects on the concentrations of Fe, Al, Ti, V, Pb and As. And the concentrations of Cu, Cr, Mn, Zn, Ni, Co, Se and Cd were not significantly affected by the elevation gradient. Because the studying area is red soil, the elevation gradient had significant effects on the concentrations of Fe, Al and Ti which are characteristic heavy metals of red soil, suggesting that the red soil at different elevations has different intensities of weathering desilication and bioaccumulation. Other heavy metals have different relationships with the elevation gradient, such as the concentrations of Cr, Zn and Cd were high at relatively high elevation and Pb and As were high at relatively low elevation. These results suggest that the different elevations of montane forest soils were polluted by differently types of heavy metals.

Utility of routine psychological screening in the childhood cancer survivor clinic.

PubMed

Recklitis, Christopher; O'Leary, Tara; Diller, Lisa

2003-03-01

This study examined the utility of routine psychologic screening in a childhood cancer survivor clinic by evaluating patient acceptance, comparing subjects' symptoms to normative data, examining the utility of specific tests, and identifying risk factors associated with psychological distress. During their annual clinic visit, 101 adult survivors of childhood cancer (median age, 25 years) completed the Symptom Checklist 90 Revised (SCL-90), as well as the Short Form 36 (SF-36), Beck Depression Inventory (BDI), and one additional suicide question. Psychological distress was operationally defined according to the published SCL-90 clinical case rule, classifying subjects with a consistent pattern of symptom elevations as clinical cases. The majority of subjects (80%) completed the screening in less than 30 minutes and reported little (15%) or no (84%) distress. Sixty-four percent believed it would help "very much" or "moderately" in getting to know them, and 35% thought it would help "slightly." On the SCL-90, 32 subjects (31.7%) had a positive screen, indicating significant psychological distress. All subjects with clinically significant symptoms on the BDI and SF-36 Mental Health Scale were cases on the SCL-90 (case-positive). Suicidal symptoms were reported in 13.9% of the sample, all of whom were SCL-90 cases. In a logistic regression model, subjects' dissatisfaction with physical appearance, poor physical health, and treatment with cranial radiation were associated with psychological distress. Results demonstrate that routine psychological screening can be successfully integrated into the cancer survivor clinic and may be effective in identifying those survivors with significant distress who require further evaluation.

A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.

PubMed

Elmunzer, B Joseph; Scheiman, James M; Lehman, Glen A; Chak, Amitabh; Mosler, Patrick; Higgins, Peter D R; Hayward, Rodney A; Romagnuolo, Joseph; Elta, Grace H; Sherman, Stuart; Waljee, Akbar K; Repaka, Aparna; Atkinson, Matthew R; Cote, Gregory A; Kwon, Richard S; McHenry, Lee; Piraka, Cyrus R; Wamsteker, Erik J; Watkins, James L; Korsnes, Sheryl J; Schmidt, Suzette E; Turner, Sarah M; Nicholson, Sylvia; Fogel, Evan L

2012-04-12

Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

Diagnosis of glutathione synthetase deficiency in newborn screening.

PubMed

Simon, E; Vogel, M; Fingerhut, R; Ristoff, E; Mayatepek, E; Spiekerkötter, U

2009-12-01

Glutathione synthetase (GSS) deficiency is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with haemolytic anaemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low GSS activity in erythrocytes or cultured skin fibroblasts. Diagnosis can be confirmed by mutational analysis. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. The most important determinants for outcome and survival in patients with GSS deficiency are early diagnosis and early initiation of treatment. The case of a newborn with GSS deficiency diagnosed by tandem mass spectrometry (MS/MS)-based newborn screening is described. After onset of clinical symptoms on the 2nd day of life, expanded newborn screening revealed normal results for all disorders included in the German screening programme; however, selective MS/MS screening revealed a >10-fold elevation of 5-oxoproline in dried blood, leading to the presumptive diagnosis of GSS deficiency by the 5th day of life. Diagnosis was later confirmed by detection of markedly reduced glutathione concentration in erythrocytes and mutational analysis of the GSS gene. Presently, GSS deficiency is not included in newborn screening programmes in Europe. As outcome depends significantly on early start of treatment, routine inclusion of this disorder in newborn screening panels should be considered.

Impact of the Metabolic Syndrome on the Clinical Outcome of Patients with Acute ST-Elevation Myocardial Infarction

PubMed Central

Lee, Min Goo; Ahn, Youngkeun; Chae, Shung Chull; Hur, Seung Ho; Hong, Taek Jong; Kim, Young Jo; Seong, In Whan; Chae, Jei Keon; Rhew, Jay Young; Chae, In Ho; Cho, Myeong Chan; Bae, Jang Ho; Rha, Seung Woon; Kim, Chong Jin; Choi, Donghoon; Jang, Yang Soo; Yoon, Junghan; Chung, Wook Sung; Cho, Jeong Gwan; Seung, Ki Bae; Park, Seung Jung

2010-01-01

We sought to determine the prevalence of metabolic syndrome (MS) in patients with acute myocardial infarction and its effect on clinical outcomes. Employing data from the Korea Acute Myocardial Infarction Registry, a total of 1,990 patients suffered from acute ST-elevation myocardial infarction (STEMI) between November 2005 and December 2006 were categorized according to the National Cholesterol Education Program-Adult Treatment Panel III criteria of MS. Primary study outcomes included major adverse cardiac events (MACE) during one-year follow-up. Patients were grouped based on existence of MS: group I: MS (n=1,182, 777 men, 62.8±12.3 yr); group II: Non-MS (n=808, 675 men, 64.2±13.1 yr). Group I showed lower left ventricular ejection fraction (LVEF) (P=0.005). There were no differences between two groups in the coronary angiographic findings except for multivessel involvement (P=0.01). The incidence of in-hospital death was higher in group I than in group II (P=0.047), but the rates of composite MACE during one-year clinical follow-up showed no significant differences. Multivariate analysis showed that low LVEF, old age, MS, low high density lipoprotein cholesterol and multivessel involvement were associated with high in-hospital death rate. In conclusion, MS is an important predictor for in-hospital death in patients with STEMI. PMID:20890426

Pediatric idiopathic intracranial hypertension - Is the fixed threshold value of elevated LP opening pressure set too high?

PubMed

Gerstl, Lucia; Schoppe, Nikola; Albers, Lucia; Ertl-Wagner, Birgit; Alperin, Noam; Ehrt, Oliver; Pomschar, Andreas; Landgraf, Mirjam N; Heinen, Florian

2017-11-01

Idiopathic intracranial hypertension (IIH) in children is a rare condition of unknown etiology and various clinical presentations. The primary aim of this study was to evaluate if our pediatric IIH study group fulfilled the revised diagnostic criteria for IIH published in 2013, particularly with regard to clinical presentation and threshold value of an elevated lumbar puncture opening pressure. Additionally we investigated the potential utilization of MR-based and fundoscopic methods of estimating intracranial pressure for improved diagnosis. Clinical data were collected retrospectively from twelve pediatric patients diagnosed with IIH between 2008 and 2012 and revised diagnostic criteria were applied. Comparison with non-invasive methods for measuring intracranial pressure, MRI-based measurement (MR-ICP) and venous ophthalmodynamometry was performed. Only four of the twelve children (33%) fulfilled the revised diagnostic criteria for a definite diagnosis of IIH. Regarding noninvasive methods, MR-ICP (n = 6) showed a significantly higher mean of intracranial pressure compared to a healthy age- and sex-matched control group (p = 0.0043). Venous ophthalmodynamometry (n = 4) showed comparable results to invasive lumbar puncture. The revised diagnostic criteria for IIH may be too strict especially in children without papilledema. MR-ICP and venous ophthalmodynamometry are promising complementary procedures for monitoring disease progression and response to treatment. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Impact of playing American professional football on long-term brain function.

PubMed

Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

2011-01-01

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.

PubMed

Boor, Peter; Eitner, Frank; Cohen, Clemens D; Lindenmeyer, Maja T; Mertens, Peter R; Ostendorf, Tammo; Floege, Jürgen

2009-09-01

Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold. We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR. PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN. Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.

Evaluation of Chitotriosidase as a Marker of Inflammatory Status in Critical Limb Ischemia.

PubMed

Ciocan, Răzvan A; Drugan, Cristina; Gherman, Claudia D; Cătană, Cristina-Sorina; Ciocan, Andra; Drugan, Tudor C; Bolboacă, Sorana D

2017-11-01

Chitotriosidase is an enzyme secreted by activated macrophages. This study aims to investigate the usefulness of circulating chitotriosidase activity as a marker of inflammatory status in patients with critical limb ischemia (CLI). An observational gender-matched case-control study was conducted on patients hospitalized with the primary diagnosis of CLI, as well as a control group. The control group consisted of healthy volunteers. Forty-three patients were included in each group. Similar demographic characteristics (median age of 60-62 years and overweight) were observed in both groups. Chitotriosidase activity ranged from 110 nmol/ml/hr to 1530 nmol/ml/hr in the CLI group and from 30 nmol/ml/hr to 440 nmol/ml/hr in the control group; demonstrating significantly elevated values in the CLI group ( p <0.001). Median plasma chitotriosidase activity was significantly elevated in smokers compared with non-smokers in both groups ( p <0.05). However, this activity had higher values in CLI than in control subjects. Receiver operating characteristic (ROC) analysis was then performed in order to verify the diagnostic accuracy of chitotriosidase as an inflammatory biomarker in CLI. Circulating chitotriosidase is a test which can potentially be used for the monitoring of CLI patients without other inflammatory conditions. However, the interpretation of elevated values must take into account the inflammatory response induced by tobacco exposure. © 2017 by the Association of Clinical Scientists, Inc.

Systems responses of rats to aflatoxin B1 exposure revealed with metabonomic changes in multiple biological matrices.

PubMed

Zhang, Limin; Ye, Yangfang; An, Yanpeng; Tian, Yuan; Wang, Yulan; Tang, Huiru

2011-02-04

Exposure to aflatoxins causes liver fibrosis and hepatocellular carcinoma posing a significant health risk for human populations and livestock. To understand the mammalian systems responses to aflatoxin-B1 (AFB1) exposure, we analyzed the AFB1-induced metabonomic changes in multiple biological matrices (plasma, urine, and liver) of rats using (1)H NMR spectroscopy together with clinical biochemistry and histopathologic assessments. We found that AFB1 exposure caused significant elevation of glucose, amino acids, and choline metabolites (choline, phosphocholine, and glycerophosphocholine) in plasma but reduction of plasma lipids. AFB1 also induced elevation of liver lipids, amino acids (tyrosine, histidine, phenylalanine, leucine, isoleucine, and valine), choline, and nucleic acid metabolites (inosine, adenosine, and uridine) together with reduction of hepatic glycogen and glucose. AFB1 further caused decreases in urinary TCA cycle intermediates (2-oxoglutarate and citrate) and elevation of gut microbiota cometabolites (phenylacetylglycine and hippurate). These indicated that AFB1 exposure caused hepatic steatosis accompanied with widespread metabolic changes including lipid and cell membrane metabolisms, protein biosynthesis, glycolysis, TCA cycle, and gut microbiota functions. This implied that AFB1 exposure probably caused oxidative-stress-mediated impairments of mitochondria functions. These findings provide an overview of biochemical consequences of AFB1 exposure and comprehensive insights into the metabolic aspects of AFB1-induced hepatotoxicity in rats.

Left ventricular ejection fraction to predict early mortality in patients with non-ST-segment elevation acute coronary syndromes.

PubMed

Bosch, Xavier; Théroux, Pierre

2005-08-01

Improvement in risk stratification of patients with non-ST-segment elevation acute coronary syndrome (ACS) is a gateway to a more judicious treatment. This study examines whether the routine determination of left ventricular ejection fraction (EF) adds significant prognostic information to currently recommended stratifiers. Several predictors of inhospital mortality were prospectively characterized in a registry study of 1104 consecutive patients, for whom an EF was determined, who were admitted for an ACS. Multiple regression models were constructed using currently recommended clinical, electrocardiographic, and blood marker stratifiers, and values of EF were incorporated into the models. Age, ST-segment shifts, elevation of cardiac markers, and the Thrombolysis in Myocardial Infarction (TIMI) risk score all predicted mortality (P < .0001). Adding EF into the model improved the prediction of mortality (C statistic 0.73 vs 0.67). The odds of death increased by a factor of 1.042 for each 1% decrement in EF. By receiver operating curves, an EF cutoff of 48% provided the best predictive value. Mortality rates were 3.3 times higher within each TIMI risk score stratum in patients with an EF of 48% or lower as compared with those with higher. The TIMI risk score predicts inhospital mortality in a broad population of patients with ACS. The further consideration of EF adds significant prognostic information.

Serum Amylase in Bulimia Nervosa and Purging Disorder: Differentiating the Association with Binge Eating versus Purging Behavior

PubMed Central

Wolfe, Barbara E.; Jimerson, David C.; Smith, Adrian; Keel, Pamela K.

2011-01-01

Objective Elevated serum amylase levels in bulimia nervosa (BN), associated with increased salivary gland size and self-induced vomiting in some patients, provide a possible marker of symptom severity. The goal of this study was to assess whether serum hyperamylasemia in BN is more closely associated with binge eating episodes involving consumption of large amounts of food or with purging behavior. Method Participants included women with BN (n=26); women with “purging disorder” (PD), a subtype of EDNOS characterized by recurrent purging in the absence of objectively large binge eating episodes (n=14); and healthy non-eating disorder female controls (n=32). There were no significant differences in age or body mass index (BMI) across groups. The clinical groups reported similar frequency of self-induced vomiting behavior and were free of psychotropic medications. Serum samples were obtained after overnight fast and were assayed for alpha-amylase by enzymatic method. Results Serum amylase levels were significantly elevated in BN (60.7 ± 25.4 international units [IU]/liter, mean ± sd) in comparison to PD (44.7 ± 17.1 IU/L, p < 02) and to Controls (49.3 ± 15.8, p < .05). Conclusion These findings provide evidence to suggest that it is recurrent binge eating involving large amounts of food, rather than self-induced vomiting, which contributes to elevated serum amylase values in BN. PMID:21781981

Macro- and microadenoma of thyrotropin secreting pituitary tumors--two clinical cases.

PubMed

Hubalewska-Hola, Alicja; Fröss, Katarzyna; Kostecka-Matyja, Marta; Sowa-Staszczak, Anna; Szybiński, Zbigniew; Huszno, Bohdan; Ptak, Marzena

2003-01-01

Thyrotropin secreting adenoma, thyrotropinoma (TSH-oma), is a rare cause of hyperthyroidism--called secondary hyperthyroidism. The hormonal profile in pituitary hyperthyroidism is characterized by a nonsuppressed TSH in the presence of high levels of free thyroid hormones (fT4, fT3) reflecting an abnormal feedback. The diagnosis of TSH-oma is often made at the stage of macroadenoma because of the aggressive nature of the tumor and due to the fact that patients are mistakenly treated for more common primary hyperthyroidism for a long time. Two cases of TSH-secreting adenoma were detected in Chair and Department of Endocrinology, Collegium Medicum of the Jagiellonian University in Krakow for the last twenty years. Case 1: 49 year old woman was admitted to the Clinic of Endocrinology in 1999 with recurring hyperthyroidism treated with surgical thyroid ablation in 1992 and thyreostatics for the previous nine years. On admission to the Clinic her thyroid panel presented with elevated free hormone levels (mainly fT3-14.8 pmol/l) and not suppressed TSH-0.7 mIU/l suggesting central hyperthyroidism. MRI scan of the pituitary gland revealed microadenoma of 5 mm in diameter. She was qualified to transsphenoidal resection of the tumor. Histopathology revealed acidophilic adenoma with positive TSH staining. Thyroid hormones 8 days after the operation suggested full effectiveness of the surgery. Case 2: 65 year old man treated for one year with L-Thyroxin because of elevated TSH (60 mIU/l) and then with thyreostatics for elevated fT3 and fT4 was admitted to the Clinic of Endocrinology in 2000 with suspected thyrotropinoma. On admission to the Clinic thyroid panel suggested hyperthyroidism with fT4-40 pmol/l, FT3-11.2 pmol/l without suppression of TSH 2.2 mIU/l. MRI scan revealed a pituitary tumor 20 x 18 x 20 mm, compressing the optic chiasm. He was administered octreotide as a preparation for the operation. The patient underwent trans-sphenoidal resection of the adenoma (histopathologically a chromophobic adenoma). The example of presented patients suggests that clinical course of the pituitary tumor producing TSH and the rate of the tumor growth may differ significantly. Surgical resection of TSH producing adenoma is the most effective therapy. It should be proceeded by octreotide administration in patients with macroadenoma.

Sarcopenia is a risk factor for elevated aminotransferase in men independently of body mass index, dietary habits, and physical activity.

PubMed

Yoo, Ki Deok; Jun, Dae Won; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Yoon, Byung Chul; Choi, Ho Soon

2015-04-01

Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice. To examine the relationship between sarcopenia and aminotransferase activity in a large population-based cohort. Data from the Korean National Health and Nutrition Examinations were used. A total of 13,431 subjects were included. A whole-body dual X-ray absorptiometry scan was performed on each patient to measure total and regional muscle mass. Appendicular skeletal muscle mass indices were also obtained. The prevalence of sarcopenia was significantly higher in the group with elevated aminotransferase levels than in the normal liver enzyme group (males: 26.5% vs. 16.9%; females: 38.3% vs. 22.1%, p<0.05). The skeletal muscle index was negatively correlated with most cardiometabolic risk factors, including fasting glucose and cholesterol levels. The frequency of elevated aminotransferase increased in male patients with sarcopenia after adjusting for potential confounding factors including age, body mass index, fasting glucose level, dietary, and exercise habits. However, the correlation was no longer observed in women after adjusting for body mass index. Sarcopenia is a risk factor for elevated aminotransferase in men, independently of body mass index, dietary habits, and physical activity. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Spontaneous normalization of anti-tissue transglutaminase antibody levels is common in children with type 1 diabetes mellitus.

PubMed

Waisbourd-Zinman, Orith; Hojsak, Iva; Rosenbach, Yoram; Mozer-Glassberg, Yael; Shalitin, Shlomit; Phillip, Moshe; Shamir, Raanan

2012-05-01

The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5-10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up. This study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors. The files of all children diagnosed with type 1 diabetes mellitus from 2003-2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized. Forty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements. Physicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Cardiac troponin increases among marathon runners in the Perth Marathon: the Troponin in Marathons (TRIM) study.

PubMed

Hubble, Kelley M; Fatovich, Daniel M; Grasko, Jonathon M; Vasikaran, Samuel D

2009-01-19

To determine the prevalence of elevated troponin levels after a marathon, and test for an association with reduced renal clearance. Prospective observational study of entrants running the full (42 km) 2007 Perth Marathon, Western Australia. Elevated troponin levels (> or = 0.1 microg/L) after the race; pre- and post-race survey data, and biochemical parameters. 27% of runners (92/346) enrolled in the study, of whom 88 (96%) completed it. Most were men (71%; 65/92); mean age was 43.1 years (SD, 9.8 years; range, 25-64 years) and mean body mass index (BMI) was 24.1 kg/m(2). Raised troponin levels were seen in 32% of participants (28/88), the highest being 1.4 microg/L. The strongest predictor for developing elevated troponin levels was a decrease in weight (odds ratio [OR], 2.15; 95% CI, 1.27-3.65). Creatinine increase was also associated with elevated troponin levels (OR, 1.03; 95% CI, 1.01-1.06), but pre-race estimated glomerular filtration rate, age, sex, BMI, training factors, marathon experience and race time were not. Most runners (99%; 87/88) had elevated levels of ischaemia-modified albumin after the race. Troponin level increases were common among marathon finishers. The strongest predictors were weight loss and an increase in creatinine levels, suggesting that reduced renal clearance is an associated factor. Further study is needed to determine the clinical significance of these findings, and to understand the mechanism.

Association between systemic inflammatory markers and serum prostate-specific antigen in men without prostatic disease - the 2001-2008 National Health and Nutrition Examination Survey.

PubMed

McDonald, Alicia C; Vira, Manish A; Vidal, Adriana C; Gan, Wenqi; Freedland, Stephen J; Taioli, Emanuela

2014-05-01

Serum prostate specific antigen (PSA) may be elevated in otherwise healthy men; systemic inflammation has been associated with cancer. The study of systemic inflammatory markers in men without clinical prostate disease, but with elevated PSA may characterize the subgroup of men at higher risk for subsequent prostate cancer. We investigated the associations between systemic inflammatory markers and serum PSA in 3,164 healthy men without prostatic disease, aged >40 years, from the 2001 to 2008 U.S. National Health and Nutrition Examination Survey (NHANES). Serum total PSA levels and concentrations of serum C-reactive protein (CRP) and plasma fibrinogen, neutrophil count, lymphocyte count, and platelet count were recorded. Neutrophil-lymphocyte ratio (NLR) ratio and platelet-lymphocyte (PLR) ratio were calculated. PSA elevation was defined as levels equal or greater than 4 ng/ml. Elevated serum PSA (194 men, 6.1% of the total), was significantly associated with plasma fibrinogen (ORmultiv  = 1.88; 95% CI, 1.09-3.25), and NLR (ORmultiv  = 1.14; 95% CI, 1.03-1.26), after adjustment for age, smoking, body mass index, education, race, co-morbidities, and use of medications. Markers of systemic inflammation were associated with elevated PSA in men without known prostatic disease. Future studies are needed to examine these markers' relationship with prostate cancer occurrence and progression. © 2014 Wiley Periodicals, Inc.

Longitudinal study of bone loss in chronic spinal cord injury patients

PubMed Central

Karapolat, Inanc; Karapolat, Hale Uzumcugil; Kirazli, Yesim; Capaci, Kazim; Akkoc, Yesim; Kumanlioglu, Kamil

2015-01-01

[Purpose] This prospective longitudinal study evaluated the changes in bone metabolism markers and bone mineral density of spinal cord injury patients over 3 years. We also assessed the relationships among the bone mineral density, bone metabolism, and clinical data of spinal cord injury patients. [Subjects and Methods] We assessed the clinical data (i.e., immobilization due to surgery, neurological status, neurological level, and extent of lesion) in 20 spinal cord injury patients. Bone mineral density, and hormonal and biochemical markers of the patients were measured at 0, 6, 12, and 36 months. [Results] Femoral neck T score decreased significantly at 36 months (p < 0.05). Among the hormonal markers, parathyroid hormone and vitamin D were significantly elevated, while bone turnover markers (i.e., deoxypyridinoline and osteocalcin) were significantly decreased at 12 and 36 months (p < 0.05). [Conclusion] Bone mineral density of the femoral neck decreases significantly during the long-term follow-up of patients with spinal cord injury due to osteoporosis. This could be due to changes in hormonal and bone turnover markers. PMID:26157234

Serum Procalcitonin for Predicting Significant Infections and Mortality in Pediatric Oncology.

PubMed

Gunasekaran, Vinod; Radhakrishnan, Nita; Dinand, Veronique; Sachdeva, Anupam

2016-12-15

To evaluate the role of serum procalcitonin (PCT) level at admission in predicting significant infections and deaths among children on chemotherapy presenting with fever. Children with clinically significant (CSI) and microbiologically documented (MDI) infections were identified using standard definitions. Association of PCT with CSI, MDI and mortality was analyzed. We evaluated 821 febrile episodes in 316 children. CSI, MDI and deaths were seen in 40.9%, 20.1% and 2.9%, respectively. PCT levels ranged from 0.05-560ng/mL. Median PCT was higher in episodes with CSI (0.80 vs. 0.28) and MDI (0.71 vs. 0.34) (P<0.001). PCT ≥0.7ng/mL optimally predicted CSI (AUC-0.740) and MDI (AUC-0.636). Relative risk of mortality for PCT ≥5ng/mL was 7.1. PCT ≥0.7ng/mL had poor sensitivity (45-55%) but good specificity and NPV (70-90%). PCT was elevated in nearly half of documented viral and fungal infections. PCT predicts significant infections and mortality in pediatric oncology but it has poor sensitivity to guide clinical decisions.

Assessment of ground transportation stress in juvenile Kemp's ridley sea turtles (Lepidochelys kempii).

PubMed

Hunt, Kathleen E; Innis, Charles J; Kennedy, Adam E; McNally, Kerry L; Davis, Deborah G; Burgess, Elizabeth A; Merigo, Constance

2016-01-01

Sea turtle rehabilitation centres frequently transport sea turtles for long distances to move animals between centres or to release them at beaches, yet there is little information on the possible effects of transportation-related stress ('transport stress') on sea turtles. To assess whether transport stress is a clinically relevant concern for endangered Kemp's ridley sea turtles (Lepidochelys kempii), we obtained pre-transport and post-transport plasma samples from 26 juvenile Kemp's ridley sea turtles that were transported for 13 h (n = 15 turtles) or 26 h (n = 11 turtles) by truck for release at beaches. To control for effects of handling, food restriction and time of day, the same turtles were also studied on 'control days' 2 weeks prior to transport, i.e. with two samples taken to mimic pre-transport and post-transport timing, but without transportation. Blood samples were analysed for nine clinical health measures (pH, pCO2, pO2, HCO3, sodium, potassium, ionized calcium, lactate and haematocrit) and four 'stress-associated' parameters (corticosterone, glucose, white blood cell count and heterophil-to-lymphocyte ratio). Vital signs (heart rate, respiratory rate and cloacal temperature) were also monitored. Corticosterone and glucose showed pronounced elevations due specifically to transportation; for corticosterone, this elevation was significant only for the longer transport duration, whereas glucose increased significantly after both transport durations. However, clinical health measures and vital signs showed minimal or no changes in response to any sampling event (with or without transport), and all turtles appeared to be in good clinical health after both transport durations. Thus, transportation elicits a mild, but detectable, adrenal stress response that is more pronounced during longer durations of transport; nonetheless, Kemp's ridley sea turtles can tolerate ground transportation of up to 26 h in good health. These results are likely to depend on specific transportation and handling protocols.

Cinacalcet: AMG 073, Calcimimetics--Amgen/NPS Pharmaceuticals, KRN 1493, NPS 1493.

PubMed

2003-01-01

Cinacalcet [AMG 073, KRN 1493, NPS 1493] is an orally active, second-generation calcimimetic compound licensed by NPS Pharmaceuticals to Amgen in the US for potential treatment of hyperparathyroidism (HPT). Cinacalcet modulates (increases the sensitivity of) calcium receptors on the surface of parathyroid cells thereby inhibiting the oversecretion of parathyroid hormone, which characterises HPT. It also represents a potentially significant advance for chronic kidney disease patients diagnosed with secondary HPT, a common yet serious metabolic disorder where parathyroid hormone levels are elevated. Patients with this disease can suffer from bone disease, bone pain and fractures, soft tissue calcification, vascular calcification and cardiovascular complications. Amgen has rights to develop and sell cinacalcet throughout the world except in Japan, Taiwan and China, where the compound was licensed to Kirin Brewery. Kirin is developing it as KRN 1493 in phase II clinical studies in Japan. In December 2001, commencement of a phase III clinical trial with cinacalcet for the treatment of secondary HPT, triggered a 3 million US dollars milestone payment to NPS Pharmaceuticals. In September 2003, submission of an NDA to the US FDA for cinacalcet for secondary HPT will be followed by a milestone payment of 6 million US dollars to NPS. NPS, Kirin and Amgen were also developing another compound, tecalcet, for HPT, but that project has been discontinued in favour of cinacalcet. In September 2003, Amgen submitted an NDA to the US FDA for secondary HPT in patients with chronic kidney disease. In April 2003, Amgen announced positive results from a phase III clinical trial with cinacalcet in patients with secondary HPT. In a clinical study in patients on dialysis suffering from the effects of chronically elevated levels parathyroid hormone, cinacalcet appeared to be safe and well tolerated and was significantly more effective than placebo. Two more additional efficacy studies with cinacalcet have also been completed. Phase II trials of cinacalcet in dialysis patients with secondary HPT and in patients with primary HPT were successfully completed.

Assessment of ground transportation stress in juvenile Kemp’s ridley sea turtles (Lepidochelys kempii)

PubMed Central

Hunt, Kathleen E.; Innis, Charles J.; Kennedy, Adam E.; McNally, Kerry L.; Davis, Deborah G.; Burgess, Elizabeth A.; Merigo, Constance

2016-01-01

Sea turtle rehabilitation centres frequently transport sea turtles for long distances to move animals between centres or to release them at beaches, yet there is little information on the possible effects of transportation-related stress (‘transport stress’) on sea turtles. To assess whether transport stress is a clinically relevant concern for endangered Kemp’s ridley sea turtles (Lepidochelys kempii), we obtained pre-transport and post-transport plasma samples from 26 juvenile Kemp’s ridley sea turtles that were transported for 13 h (n = 15 turtles) or 26 h (n = 11 turtles) by truck for release at beaches. To control for effects of handling, food restriction and time of day, the same turtles were also studied on ‘control days’ 2 weeks prior to transport, i.e. with two samples taken to mimic pre-transport and post-transport timing, but without transportation. Blood samples were analysed for nine clinical health measures (pH, pCO2, pO2, HCO3, sodium, potassium, ionized calcium, lactate and haematocrit) and four ‘stress-associated’ parameters (corticosterone, glucose, white blood cell count and heterophil-to-lymphocyte ratio). Vital signs (heart rate, respiratory rate and cloacal temperature) were also monitored. Corticosterone and glucose showed pronounced elevations due specifically to transportation; for corticosterone, this elevation was significant only for the longer transport duration, whereas glucose increased significantly after both transport durations. However, clinical health measures and vital signs showed minimal or no changes in response to any sampling event (with or without transport), and all turtles appeared to be in good clinical health after both transport durations. Thus, transportation elicits a mild, but detectable, adrenal stress response that is more pronounced during longer durations of transport; nonetheless, Kemp’s ridley sea turtles can tolerate ground transportation of up to 26 h in good health. These results are likely to depend on specific transportation and handling protocols. PMID:27293750

The MMP-9 -1562 C/T Polymorphism in the Presence of Metabolic Syndrome Increases the Risk of Clinical Events in Patients with Coronary Artery Disease

PubMed Central

Opstad, Trine B.; Arnesen, Harald; Pettersen, Alf Å.; Seljeflot, Ingebjørg

2014-01-01

Background and Objectives Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 −1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 −1562 C/T polymorphism in subjects with CAD and MetS. Methods Patients (n = 1000) with verified CAD stratified in Mets +/− (n = 244/756), were analyzed for the MMP-9 −1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients. Results Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001). Conclusion In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation. PMID:25191702

The MMP-9 -1562 C/T polymorphism in the presence of metabolic syndrome increases the risk of clinical events in patients with coronary artery disease.

PubMed

Opstad, Trine B; Arnesen, Harald; Pettersen, Alf Å; Seljeflot, Ingebjørg

2014-01-01

Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS. Patients (n = 1000) with verified CAD stratified in Mets +/- (n = 244/756), were analyzed for the MMP-9 -1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients. Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001). In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.

Effect of Group Positive Psychotherapy on Improvement of Life Satisfaction and The Quality of Life in Infertile Woman.

PubMed

Seyedi Asl, Seyed Teymur; Sadeghi, Kheirollah; Bakhtiari, Mitra; Ahmadi, Seyed Mojtaba; Nazari Anamagh, Alireza; Khayatan, Tayebeh

2016-01-01

Positive psychotherapy is one of the new approaches in psychology which is innovated for treating psychological disorders and enhancing positive emotions. The aim of this study is to investigate the effectiveness of the group positive psychotherapy on elevation of life satisfaction and quality of life in infertile women. In a randomized trial study, Beck Depression Inventory II (BDI-II) and clinical interview were used in a pre-test post-test control group design. After analyzing the result of the questionnaire, 36 infertile women who showed signs of mild to moderate depression were randomly placed into two following groups: control (n=18) and intervention (n=18). Before the treatment, the members of both groups answered BDI-II, Satisfaction With Life Scale (SWLS) and 12 item Short Form Health Survey (SF-12). The intervention group received six sessions of group positive psychotherapy, but the treatment of the control group began six weeks after the intervention group. The results showed that the life satisfaction scores of the intervention group were significantly elevated from 22.66 in pre-test to 26.13 in post-test (P<0.001), while this improvement was not significant in the control group (P=0.405). The difference between life satisfaction scores of the intervention and the control groups was also significant (F=8.92, P=0.006). However, no significant change in the quality of life level of the intervention and control groups was observed (P=0.136). Thus it can be deduced from the findings that this treatment method could be introduced as solution to increase the life satisfaction in infertile women, but not as a treatment for elevating their quality of life (Registration Number: IRCT2013042810063N3).

Prognostic significance of smoking in addition to established risk factors in patients with Dukes B and C colorectal cancer: a retrospective analysis.

PubMed

Diamantis, N; Xynos, I D; Amptulah, S; Karadima, M; Skopelitis, H; Tsavaris, N

2013-01-01

To investigate the prognostic significance of smoking in addition to established risk factors in patients with Dukes stage B and C colorectal cancer (CRC). 291 consecutive non-selected CRC patients were studied retrospectively. Twenty-three variables were examined using a regression statistical model to identify relevant prognostic factors related to disease free survival (DFS) and overall survival (OS). On multivariate analysis DFS was found to be negatively affected in patients with a smoking history of ≤10 pack-years vs. non-smokers (p<0.016). Additionally, performance status (PS)<90 (p<0.001), Dukes stage C (p<0.001) and elevated tumor markers (p<0.001) at the time of diagnosis were found to adversely affect DFS. Smoking also had a significant association with relapse. Patients with a smoking history of ≤10 pack-years had 2.45 (p<0.018) higher risk of recurrence compared to patients with no smoking history. OS was influenced by Karnofsky performance status (PS), Dukes stage, and elevated tumor markers. In particular patients with PS< 90 had a 4.69-fold higher risk of death (p<0.001) than patients with better PS. Stage C disease was associated with 2.27-fold higher risk of death (p<0.001) than stage B disease, and patients with elevated tumor markers at the time of diagnosis had 2.74-fold higher risk of death (p<0.014) when compared to those whose tumor markers were normal at presentation. Our study associates smoking and relapse incidence in non-clinical- trial CRC patients and reiterates the prognostic significance of PS, stage and tumor markers at the time of diagnosis.

The Effect of Cisplatin on Blood Ammonia Elevation by Alanyl-Glutamine Supplementation.

PubMed

Obayashi, Yoko; Kajiwara, Kenta; Nakamura, Eiji

2018-01-01

Although there are many clinical studies in which the beneficial effect of glutamine formulation on mucositis induced by chemo/radiotherapy was evaluated, the results are sometimes conflicting with the report of clinical deterioration. Then, we hypothesized that chemotherapy may increase the incidence of hyperammonemia without comparable change of major parameters of hepatic/renal disorder. To verify our hypothesis, we examined the increase in blood ammonia level with 1-h intravenous infusion of alanyl-glutamine on day 1-4 after cisplatin (CDDP) administration in rats and assessed the correlation with hepatic/renal parameters. Hepatic parameters (glutamate-oxaloacetic transaminase [GOT] and glutamic-pyruvic transaminase [GPT]) with CDDP did not change until day 3 and only GOT increased on day 4. Renal parameters (plasma creatinine, blood urea nitrogen) with CDDP continuously increased up to day 4. Alanyl-glutamine infusion significantly elevated blood ammonia level of CDDP rats with the peak on day 3, although the same dose did not change that of control rats. These results indicates that CDDP enhances the increase in blood ammonia level by glutamine supplementation without correlating with primary parameters for hepatic/renal dysfunction. © 2018 S. Karger AG, Basel.

Clinical significance of increased serum levels of FGF-23 in fibrous dysplasia.

PubMed

Florez, Helena; Mandelikova, Stanislava; Filella, Xavier; Monegal, Ana; Guañabens, Núria; Peris, Pilar

2017-12-30

Fibrous dysplasia (FD) can be associated with the development of hypophosphatemic osteomalacia, caused by the production of FGF-23 by dysplastic bone tissue. This study analysed FGF-23 levels in patients with FD, and their association with disease activity and serum phosphate values. Twelve adult patients with FD were included in the study. Clinical history, disease extension and activity and treatments received were reviewed, and the relationship of those values with FGF-23 and serum P levels was analysed. FGF-23 was elevated in 6/12 patients (50%). Patients with high FGF-23 levels had similar age and disease activity and extension than those who did not. No differences were observed in serum phosphate values between both groups (increased FGF-23: 3.9±0.9 mg/dl vs. decreased FGF-23: 3.5±0.6 mg/dl). In fact, none of the patients with increased FGF-23 had low serum phosphate values. Adult FD patients frequently present elevated FGF-23 values with no serum phosphate level repercussion, suggesting an alteration in the processing of this protein in the dysplastic bone tissue for this pathology. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Clinical, demographic, and laboratory characteristics of children with nephrolithiasis.

PubMed

Sas, David J; Becton, Lauren J; Tutman, Jeffrey; Lindsay, Laura A; Wahlquist, Amy H

2016-06-01

While the incidence of pediatric kidney stones appears to be increasing, little is known about the demographic, clinical, laboratory, imaging, and management variables in this patient population. We sought to describe various characteristics of our stone-forming pediatric population. To that end, we retrospectively reviewed the charts of pediatric patients with nephrolithiasis confirmed by imaging. Data were collected on multiple variables from each patient and analyzed for trends. For body mass index (BMI) controls, data from the general pediatrics population similar to our nephrolithiasis population were used. Data on 155 pediatric nephrolithiasis patients were analyzed. Of the 54 calculi available for analysis, 98 % were calcium based. Low urine volume, elevated supersaturation of calcium phosphate, elevated supersaturation of calcium oxalate, and hypercalciuria were the most commonly identified abnormalities on analysis of 24-h urine collections. Our stone-forming population did not have a higher BMI than our general pediatrics population, making it unlikely that obesity is a risk factor for nephrolithiasis in children. More girls presented with their first stone during adolescence, suggesting a role for reproductive hormones contributing to stone risk, while boys tended to present more commonly at a younger age, though this did not reach statistical significance. These intriguing findings warrant further investigation.

Thrombocytosis and thrombosis.

PubMed

Vannucchi, Alessandro M; Barbui, Tiziano

2007-01-01

The aim of this review is to discuss current diagnostic approaches to, and classification of, patients presenting with thrombocytosis, in light of novel information derived from the discovery of specific molecular abnormalities in chronic myeloproliferative disorders (CMPD), which represent the most common cause of primary thrombocytosis. The JAK2V617F and the MPLW515L/K mutations have been found in patients with essential thrombocythemia, polycythemia vera, and primary myelofibrosis, and less frequently in other myeloproliferative disorders complicated by thrombocytosis. However, neither mutation is disease specific nor is it universally present in patients with elevated platelet counts due to a CMPD; therefore, distinguishing between reactive and primary forms of thrombocytosis, as well as among the different clinical entities that constitute the CMPD, still requires a multifaceted diagnostic approach that includes as a key step the accurate evaluation of bone marrow histology. The role of elevated platelet counts in thrombosis, which represent the predominant complication of CMPD,significantly affecting prognosis and quality of life as well as, paradoxically, in the pathogenesis of the hemorrhagic manifestations, will be discussed. Established and novel potential risk factors for thrombosis, including the clinical relevance of the JAK2V617F mutation, and current management strategies for thrombocytosis are also briefly discussed.

Depleted uranium exposure and health effects in Gulf War veterans

PubMed Central

Squibb, Katherine S; McDiarmid, Melissa A

2006-01-01

Health effects stemming from depleted uranium (DU) exposure in a cohort of Gulf War veterans who were in or on US Army vehicles hit by friendly fire involving DU munitions are being carefully monitored through the Baltimore Veterans Affairs (VA) DU Follow-Up Program initiated in 1993. DU exposure in this cohort has been directly measured using inductively coupled plasma-mass spectrometer (ICP-MS) isotopic analysis for DU in urine specimens. Soldiers with embedded DU fragments continue to excrete elevated concentrations of U in their urine, documenting ongoing systemic exposure to U released from their fragments. Biennial surveillance visits provide a detailed health assessment that includes basic clinical measures and surveillance for early changes in kidney function, an expected target organ for U. Tests also include measurements of genotoxicity and neuroendocrine, neurocognitive and reproductive function. With the exception of the elevated urine U excretion, no clinically significant expected U-related health effects have been identified to date. Subtle changes in renal function and genotoxicity markers in veterans with urine U concentrations greater than 0.1 μg−1 creatinine, however, indicate the need for continued surveillance of these DU-exposed veterans. PMID:16687268

Parenting stress in pediatric IBD: relations with child psychopathology, family functioning, and disease severity.

PubMed

Gray, Wendy N; Graef, Danielle M; Schuman, Shana S; Janicke, David M; Hommel, Kevin A

2013-05-01

Parenting stress in pediatric inflammatory bowel disease (IBD) has been under-examined. Data validating use of the Pediatric Inventory for Parents (PIP), a measure of parenting stress associated with caring for a chronically ill child, in chronic diseases with intermittent, unpredictable disease courses, such as IBD, are needed. This study presents validity data in support of the PIP in pediatric IBD and examines relations between parenting stress and important psychosocial and medical outcomes. Adolescents (N = 130) with IBD and their caregivers across 3 sites completed measures of parenting stress, family functioning, and emotional/behavioral functioning. Disease severity was also assessed for each participant. The PIP demonstrates excellent internal consistency. Parenting stress was significantly higher among those with unhealthy general family functioning and those with children with borderline or clinically elevated internalizing symptoms. Caregiving stress was greater among parents of youth with more active Crohn's disease. Results supported the reliability and validity of the PIP for assessing caregiving stress in pediatric IBD. Routine assessment of parenting stress is recommended, particularly among parents reporting unhealthy family functioning and parents of youth with borderline or clinically elevated internalizing symptoms and more active disease.

Infectious mononucleosis in university students in the United kingdom: evaluation of the clinical features and consequences of the disease.

PubMed

Macsween, Karen F; Higgins, Craig D; McAulay, Karen A; Williams, Hilary; Harrison, Nadine; Swerdlow, Anthony J; Crawford, Dorothy H

2010-03-01

Infectious mononucleosis (IM) is common among university students. We undertook to analyze the clinical features and sequelae of the disease in a cohort of students at Edinburgh University. Consecutive IM case patients were recruited from 2000 through 2002 at the University Health Service after diagnosis of IM. IM resulted in marked reductions in student study time, physical exercise, and non-exercise-related social activities, and sustained increases in reported number of hours of sleep. The disease profile differed between the sexes, with significantly more females reporting fatigue, which was more likely to be prolonged (P = .003) and to lead to loss of study time (P = .013). Female case patients were more likely to discontinue their studies following IM (16% vs 0%; P = .056). Within the typically elevated lymphocyte counts in IM, we identified an elevated gammadelta T cell component that may contribute to the disease pathogenesis. IM results in substantial morbidity among university students, reported as more profound in females, and affecting academic studies, physical exercise, and social activities. Immunization to prevent IM and strategies to reduce post-IM disability would be beneficial in this population.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

PubMed

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-07-14

Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

PubMed

Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

2010-06-01

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

PubMed

Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B; Zorumski, Charles F; Conway, Charles; Nagele, Peter

2017-04-01

While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new cardiac troponin elevation after electroconvulsive therapy, the clinical relevance of which is unclear in the absence of signs of myocardial ischemia.

Cardioprotective effect of sulphonated formononetin on acute myocardial infarction in rats.

PubMed

Zhang, Shumin; Tang, Xuexi; Tian, Jingwei; Li, Chunmei; Zhang, Guanbo; Jiang, Wanglin; Zhang, Zunting

2011-06-01

This study was designed to investigate the therapeutic effect of sodium formononetin-3'-sulphonate (Sul-F), a water-soluble derivate of formononetin, on acute myocardial infarction in rats. The results showed that treatment with Sul-F significantly prevented the elevation of ST-segment level, decreased the contents of creatine kinase-MB, lactate dehydrogenase, alanine aminotransferase and cardiac troponin T in serum and reduced the myocardium necrosis scores. The number of apoptosis cardiocytes is well accordance with the up-regulated expression of Bcl-2 and the down-regulated expression of Bax. Meanwhile, Sul-F significantly increased the cardiac mitochondrial ATP content, improved ATP synthase activity, decreased thiobarbituric acid-reactive substances content and attenuated the decrease in superoxide dismutase and glutathione peroxidase activities. These findings indicate that Sul-F has a protective potential against myocardial infarction injury. A possible mechanism for the protective effect is the elevated expression of endogenous antioxidant defence enzymes degraded lipid peroxidation products and improved energy metholism of cardiac mitochondrial, thus attenuating cardiocyte apoptosis. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Knowledgeable Neighbors:A Mobile Clinic Model for Disease Prevention and Screening in Underserved Communities

PubMed Central

Zurakowski, David; Bennet, Jennifer; Walker-White, Rainelle; Osman, Jamie L.; Quarles, Aaron; Oriol, Nancy

2012-01-01

The Family Van mobile health clinic uses a “Knowledgeable Neighbor” model to deliver cost-effective screening and prevention activities in underserved neighborhoods in Boston, MA. We have described the Knowledgeable Neighbor model and used operational data collected from 2006 to 2009 to evaluate the service. The Family Van successfully reached mainly minority low-income men and women. Of the clients screened, 60% had previously undetected elevated blood pressure, 14% had previously undetected elevated blood glucose, and 38% had previously undetected elevated total cholesterol. This represents an important model for reaching underserved communities to deliver proven cost-effective prevention activities, both to help control health care costs and to reduce health disparities. PMID:22390503

Rostral anterior cingulate cortex activity and early symptom improvement during treatment for major depressive disorder

PubMed Central

Korb, Alexander S.; Hunter, Aimee M.; Cook, Ian A.; Leuchter, Andrew F.

2011-01-01

In treatment trials for Major Depressive Disorder (MDD), early symptom improvement is predictive of eventual clinical response. Clinical response may also be predicted by elevated pretreatment theta (4-7 Hz) current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC). We investigated the relationship between pretreatment EEG and early improvement in predicting clinical outcome in 72 MDD subjects across three placebo-controlled treatment trials. Subjects were randomized to receive fluoxetine, venlafaxine, or placebo. Theta current density in the rACC and mOFC was computed with Low-Resolution Brain Electromagnetic Tomography (LORETA). An ANCOVA, examining week 8 Hamilton Depression Rating Scale (HamD) percent change, showed a significant effect of week-2-HamD-percent-change, and a significant three-way interaction of week-2-HamD-percent-change × Treatment × rACC. Medication subjects with robust early improvement showed almost no relationship between rACC theta current density and final clinical outcome. However, in subjects with little early improvement, rACC activity showed a strong relationship with clinical outcome. The model examining mOFC showed a trend in the three-way interaction. A combination of pretreatment rACC activity and early symptom improvement may be useful for predicting treatment response. PMID:21546222

[MMPI-2 profiles in groups of systemic autoimmune disease - rheumatoid arthritis and systemic lupus erythematosus - patients].

PubMed

Csókási, Krisztina; Hargitai, Rita; Járai, Róbert; Nagy, László; Czirják, László; Kiss, Enikö Csilla

2015-01-01

Systemic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are characterized by the alteration of immunological response, which can damage many organs and systems and result in a wide variety of clinical presentations. In addition to physical symptoms, psychiatric disorders are also common to many autoimmune diseases. Anxiety, depression, psychosis and cognitive deficits have the highest prevalence. The aim of this study was to display the degree of psychopathological symptoms in patients with RA and SLE. Female inpatients with RA (N=68) and SLE (N=78) were recruited from the Rheumatology and Immunology Clinic of the University of Pecs and were asked to complete the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a short demografical form. The clinical personality profiles of the patient groups were explored and compared with each other. High scores (above 64T) were detected on the Hypochondriasis (Hs), Depression (D) and Hysteria (Hy) scales in both groups. Besides, the participants performed elevated scores on the Masculinity-Feminity (Mf), Psychasthenia (Pt) and Social Introversion (Si) clinical scales. They scored in the elevated range on the Physical Malfunctioning, Subjective Depression, Lassitude-Malaise and Somatic Complaints subscales of the neurotic triad. No significant difference was found on the ten clinical scales between the SLE and RA patients. Characteristics of MMPI-2 profiles in SLE and RA patients seem to be the consequence of the disease and a common feature of chronic conditions. High scores on the neurotic triad scales may reflect the comorbid psychiatric disorders and the somatic symptoms alike, so further investigations with the revised Hungarian MMPI-2 are needed.

Evaluation of liver function tests in scleroderma patients.

PubMed

Salem, Gehan Ibrahim Abdelrazek; Abdulrahman, Awni Ali

2012-08-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs, and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This study was done to evaluate the frequency of liver disease in patients with scleroderma and, secondarily, to study the frequency of infection of hepatitis B and C virus in these patients and determine frequency of serum auto-antibodies in this disease. We studied patients with scleroderma, localized or systemic, in the outpatient clinic of rheumatology and dermatology departments, at King Khalid University Hospital. As for a comparison, healthy persons coming to the clinic with the same mean age were considered as control group. Forty patients with the diagnosis of scleroderma included in this work, 35% had elevated gamma-glutamyl-transferase (γ-GT), 30% had elevated alkaline phosphatase (AP) and in 17.5%, the alanine-amino-transferase (ALT) was above the reference values. The ALT had changed to be more in scleroderma patients than in controls. Twenty percent (20%) of the patients tested positive for anti-smooth muscle antibodies (anti-SMA) and only one patient had anti-mitochondrial antibodies (AMA). There was no statistical difference between the two groups regarding antibody testing. Anti-HCV antibodies were observed in one patient, and HBsAg was detected in another scleroderma patient. There was no patient with clinically significant hepatic disease. In this study, although changes in liver enzymes in patients with scleroderma were not uncommon, there was no scleroderma patient with clinical manifestations of liver disease.

Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices

PubMed Central

Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K.; Parker, Anita; Bergeron, Angela L.; Pradhan, Subhashree; Vijayan, K. Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R.; Delgado, Reynolds M.; Dong, Jing Fei; Frazier, O.H.

2014-01-01

BACKGROUND Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. METHODS We enrolled 20 patients undergoing implantation of the HeartMate II LVAD and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. RESULTS During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm (n=1), non–ST-elevation myocardial infarction (n=2), arterial thrombosis (n=2), gastrointestinal bleeding (n=2), and stroke (n=3). Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11%±1.26 vs 0.69±0.46, P=0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39%±1.22 at discharge and then leveled to 1.97%±1.25 at 3-month follow-up. Importantly, patients who developed an adverse event had significantly higher levels of PS+ microparticles than did patients with no events (3.82%±1.17 vs 1.57%±0.59, P<0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters. CONCLUSIONS Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. PMID:24656391

CO 2 elevation improves photosynthetic performance in progressive warming environment in white birch seedlings.

PubMed

Zhang, Shouren; Dang, Qing-Lai

2013-01-01

White birch (Betula paperifera Mash) seedlings were exposed to progressively warming in greenhouses under ambient and elevated CO 2 concentrations for 5 months to explore boreal tree species' potential capacity to acclimate to global climate warming and CO 2 elevation. In situ foliar gas exchange, in vivo carboxylation characteristics and chlorophyll fluorescence were measured at temperatures of 26 (o)C and 37 (o)C. Elevated CO 2 significantly increased net photosynthetic rate (Pn) at both measurement temperatures, and Pn at 37 (o)C was higher than that at 26 (o)C under elevated CO 2. Stomatal conductance (gs) was lower at 37 (o)C than at 26 (o)C, while transpiration rate (E) was higher at 37 (o)C than that at 26 (o)C. Elevated CO 2 significantly increased instantaneous water-use efficiency (WUE) at both 26 (o)C and 37 (o)C, but WUE was markedly enhanced at 37 (o)C under elevated CO 2. The effect of temperature on maximal carboxylation rate (Vcmax), PAR-saturated electron transport rate (Jmax) and triose phosphate utilization (TPU) varied with CO 2, and the Vcmax and Jmax were significantly higher at 37 (o)C than at 26 (o)C under elevated CO 2. However, there were no significant interactive effects of CO 2 and temperature on TPU. The actual photochemical efficiency of PSII (DF/ Fm'), total photosynthetic linear electron transport rate through PSII (JT) and the partitioning of JT to carboxylation (Jc) were higher at 37 (o)C than at 26 (o)C under elevated CO 2. Elevated CO 2 significantly suppressed the partitioning of JT to oxygenation (Jo/JT). The data suggest that the CO 2 elevation and progressive warming greatly enhanced photosynthesis in white birch seedlings in an interactive fashion.

Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

PubMed

Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

2015-11-01

Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P < 0.001). Patients with significant fibrosis had higher levels of IL-8 (P = 0.027), transforming growth factor alpha (TGF-α) (P = 0.011), IL-2R (P = 0.002), and CXCL-11 (P = 0.032) than the group without significant fibrosis. In addition, 31.8% and 29.1% of 151 patients with ALT < 2 × ULN had at least moderate inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT < 2 × ULN. Based on certain cytokines and clinical parameters, an inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis of significant fibrosis in patients with normal or mildly elevated ALT.

IL-17A and Serum Amyloid A Are Elevated in a Cigarette Smoke Cessation Model Associated with the Persistence of Pigmented Macrophages, Neutrophils and Activated NK Cells

PubMed Central

Hansen, Michelle J.; Chan, Sheau Pyng J.; Langenbach, Shenna Y.; Dousha, Lovisa F.; Jones, Jessica E.; Yatmaz, Selcuk; Seow, Huei Jiunn; Vlahos, Ross; Anderson, Gary P.; Bozinovski, Steven

2014-01-01

While global success in cessation advocacy has seen smoking rates fall in many developed countries, persistent lung inflammation in ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed in mice exposed to cigarette smoke (CS) for 4 months following cessation from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells and lung innate NK cells remained significantly elevated following smoking cessation. Analysis of neutrophil mobilization markers showed a transition from acute mediators (MIP-2α, KC and G-CSF) to sustained drivers of neutrophil and macrophage recruitment and activation (IL-17A and Serum Amyoid A (SAA)). Follicle-like lymphoid aggregates formed with CS exposure and persisted with cessation, where they were in close anatomical proximity to pigmented macrophages, whose number actually increased 3-fold following CS cessation. This was associated with the elastolytic protease, MMP-12 (macrophage metallo-elastase) which remained significantly elevated post-cessation. Both GM-CSF and CSF-1 were significantly increased in the CS cessation group relative to the control group. In conclusion, we show that smoking cessation mediates a transition to accumulation of pigmented macrophages, which may contribute to the expanded macrophage population observed in COPD. These macrophages together with IL-17A, SAA and innate NK cells are identified here as candidate persistence determinants and, we suggest, may represent specific targets for therapies directed towards the amelioration of chronic airway inflammation. PMID:25405776

Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes.

PubMed

Beisswenger, P J; Makita, Z; Curphey, T J; Moore, L L; Jean, S; Brinck-Johnsen, T; Bucala, R; Vlassara, H

1995-07-01

Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23], microalbuminuria [12], or macroalbuminuria [12]) and retinopathy (none [13], background [20], or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (< or = 28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P < 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult Sickle Cell Anaemia Patients in Bone Pain Crisis have Elevated Pro-Inflammatory Cytokines

PubMed Central

Alagbe, Adekunle Emmanuel; Aworanti, Oladapo Wale

2018-01-01

Background and Objectives Inflammatory markers that influence bone pain crisis (BPC) and other complications of sickle cell anaemia (SCA) are numerous and play various roles. This study determined the plasma levels of tumour necrosis factor (TNF) - α, interleukin - 8 (IL-8), and endothelin - 1 (ET-1) in adult SCA patients during BPC and in steady state. In addition, the plasma levels of these cytokines were correlated with the severity of BPC of the patients. Methods and Materials Sixty adult SCA patients (30 during BPC and 30 during steady state) and 30 haemoglobin A controls were enrolled for this cross-sectional study. The severity of BPC was assessed clinically, and questionnaires were filled. Plasma levels of TNF- α, IL-8 and ET-1 were quantified by ELISA, and haematological parameters were determined using a 5-part auto-analyzer. Plasma levels were correlated with the severity of bone pain crisis. Results were considered statistically significant if p<0.05. Results Plasma TNF-α, IL-8, and ET-1 were significantly elevated in the BPC group than in the steady state group and the controls. Plasma TNF-α, IL-8 and ET-1 were markedly higher in the severe BPC groups than the steady state and control groups, There was a positive correlation between TNF-α and ET-1 in the bone pain crisis group. Conclusion Elevated levels of plasma TNF-α, IL-8, and ET-1 further establish the chronic inflammatory state in SCA and equally affirm their significant contribution, not only to pathogenesis but also to the severity of pain in SCA. PMID:29531654

Association between hepatitis B co-infection and elevated liver stiffness among HIV-infected adults in Lusaka, Zambia.

PubMed

Vinikoor, Michael J; Mulenga, Lloyd; Siyunda, Alice; Musukuma, Kalo; Chilengi, Roma; Moore, Carolyn Bolton; Chi, Benjamin H; Davies, Mary-Ann; Egger, Matthias; Wandeler, Gilles

2016-11-01

To describe liver disease epidemiology among HIV-infected individuals in Zambia. We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography, we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardised screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co-infection as well as male sex, increased age and WHO clinical stage 3 or 4 were independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimise treatment outcomes. © 2016 John Wiley & Sons Ltd.

Recognized Obstructive Sleep Apnea is Associated With Improved In-Hospital Outcomes After ST Elevation Myocardial Infarction.

PubMed

Mohananey, Divyanshu; Villablanca, Pedro A; Gupta, Tanush; Agrawal, Sahil; Faulx, Michael; Menon, Venugopal; Kapadia, Samir R; Griffin, Brian P; Ellis, Stephen G; Desai, Milind Y

2017-07-20

Obstructive sleep apnea (OSA) is an independent risk factor for many cardiovascular conditions such as coronary artery disease, myocardial infarction, systemic hypertension, pulmonary hypertension, and stroke. However, the association of OSA with outcomes in patients hospitalized for ST-elevation myocardial infarction remains controversial. We used the nation-wide inpatient sample between 2003 and 2011 to identify patients with a primary discharge diagnosis of ST-elevation myocardial infarction and then used the International Classification of Diseases, Clinical Modification code 327.23 to identify a group of patients with OSA. The primary outcome of interest was in-hospital mortality, and secondary outcomes were in-hospital cardiac arrest, length of stay and hospital charges. Our cohort included 1 850 625 patients with ST-elevation myocardial infarction, of which 1.3% (24 623) had documented OSA. OSA patients were younger and more likely to be male, smokers, and have chronic pulmonary disease, depression, hypertension, known history of coronary artery disease, dyslipidemia, obesity, and renal failure ( P <0.001 for all). Patients with OSA had significantly decreased in-hospital mortality (adjusted odds ratio, 0.78 [95% CI, 0.73-0.84]), longer hospital stay (5.00±4.68 versus 4.85±5.96 days), and incurred greater hospital charges ($79 460.12±70 621.91 versus $62 889.91±69 124.15). There was no difference in incidence of in-hospital cardiac arrest (adjusted odds ratio, 0.93 [95% CI, 0.84-1.03]) between these 2 groups. ST-elevation myocardial infarction patients with recognized OSA had significantly decreased mortality compared with patients without OSA. Although patients with OSA had longer hospital stays and incurred greater hospital charges, there was no difference in incidence of in-hospital cardiac arrest. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

High-Sensitivity C-Reactive Protein as a Predictor of Cardiovascular Events after ST-Elevation Myocardial Infarction

PubMed Central

Ribeiro, Daniel Rios Pinto; Ramos, Adriane Monserrat; Vieira, Pedro Lima; Menti, Eduardo; Bordin, Odemir Luiz; de Souza, Priscilla Azambuja Lopes; de Quadros, Alexandre Schaan; Portal, Vera Lúcia

2014-01-01

Background The association between high-sensitivity C-reactive protein and recurrent major adverse cardiovascular events (MACE) in patients with ST-elevation myocardial infarction who undergo primary percutaneous coronary intervention remains controversial. Objective To investigate the potential association between high-sensitivity C-reactive protein and an increased risk of MACE such as death, heart failure, reinfarction, and new revascularization in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods This prospective cohort study included 300 individuals aged >18 years who were diagnosed with ST-elevation myocardial infarction and underwent primary percutaneous coronary intervention at a tertiary health center. An instrument evaluating clinical variables and the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) risk scores was used. High-sensitivity C-reactive protein was determined by nephelometry. The patients were followed-up during hospitalization and up to 30 days after infarction for the occurrence of MACE. Student's t, Mann-Whitney, chi-square, and logistic regression tests were used for statistical analyses. P values of ≤0.05 were considered statistically significant. Results The mean age was 59.76 years, and 69.3% of patients were male. No statistically significant association was observed between high-sensitivity C-reactive protein and recurrent MACE (p = 0.11). However, high-sensitivity C-reactive protein was independently associated with 30-day mortality when adjusted for TIMI [odds ratio (OR), 1.27; 95% confidence interval (CI), 1.07-1.51; p = 0.005] and GRACE (OR, 1.26; 95% CI, 1.06-1.49; p = 0.007) risk scores. Conclusion Although high-sensitivity C-reactive protein was not predictive of combined major cardiovascular events within 30 days after ST-elevation myocardial infarction in patients who underwent primary angioplasty and stent implantation, it was an independent predictor of 30-day mortality. PMID:25120085

[Significance of PSMA imaging in prostate cancer].

PubMed

Gasch, C; Düwel, C; Kopka, K; Kratochwil, C; Vinsensia, M; Eiber, M; Maurer, T; Haberkorn, U; Hadaschik, B; Giesel, F L

2017-01-01

Prostate cancer (PCa) is one of the most common malignancies of men in developed countries. To improve clinical diagnostics of PCa, 68 Ga-PSMA-11 was recently introduced as a new PET tracer. 68 Ga-PSMA-11 is able to specifically bind to the prostate-specific membrane antigen (PSMA), which is upregulated on the surface of prostate cancer cells in most patients. To analyse the current significance of 68 Ga-PSMA-11 PET imaging in prostate cancer in relation to staging of men with initial diagnosis, biochemical recurrence and metastatic disease. Retrospective analysis of current literature (PubMed search) regarding 68 Ga-PSMA-11 PET diagnostics in primary staging, in biochemical recurrence and in metastasized disease. Compared to conventional imaging, 68 Ga-PSMA-11 PET/CT reaches a higher sensitivity with an excellent specificity in the clinical diagnosis of primary staging as well as staging for recurrence and advanced, metastasized disease. In biochemical recurrence, 68 Ga-PSMA-11 PET/CT shows significantly higher detection rates in comparison to choline PET/CT, especially in patients with low PSA values. In the clinical diagnosis of recurrent disease, therapy concepts were changed in more than a quarter of the patients due to the use of 68 Ga-PSMA-11 PET/CT. The significance of staging with 68 Ga-PSMA-11 PET/CT in advanced metastasized patients remains uncertain. Due to the excellent results of 68 Ga-PSMA-11 PET imaging, even in patients with slightly elevated PSA levels, it will continue to play an important role in clinical diagnostics of prostate cancer and, thus, its clinical utilization will become more widely spread.

Cytokines as a predictor of clinical response following hip arthroscopy: minimum 2-year follow-up.

PubMed

Shapiro, Lauren M; Safran, Marc R; Maloney, William J; Goodman, Stuart B; Huddleston, James I; Bellino, Michael J; Scuderi, Gaetano J; Abrams, Geoffrey D

2016-08-01

Hip arthroscopy in patients with osteoarthritis has been shown to have suboptimal outcomes. Elevated cytokine concentrations in hip synovial fluid have previously been shown to be associated with cartilage pathology. The purpose of this study was to determine whether a relationship exists between hip synovial fluid cytokine concentration and clinical outcomes at a minimum of 2 years following hip arthroscopy. Seventeen patients without radiographic evidence of osteoarthritis had synovial fluid aspirated at time of portal establishment during hip arthroscopy. Analytes included fibronectin-aggrecan complex as well as a multiplex cytokine array. Patients completed the modified Harris Hip Score, Western Ontario and McMaster Universities Arthritis Index and the International Hip Outcomes Tool pre-operatively and at a minimum of 2 years following surgery. Pre and post-operative scores were compared with a paired t-test, and the association between cytokine values and clinical outcome scores was performed with Pearson's correlation coefficient with an alpha value of 0.05 set as significant. Sixteen of seventeen patients completed 2-year follow-up questionnaires (94%). There was a significant increase in pre-operative to post-operative score for each clinical outcome measure. No statistically significant correlation was seen between any of the intra-operative cytokine values and either the 2-year follow-up scores or the change from pre-operative to final follow-up outcome values. No statistically significant associations were seen between hip synovial fluid cytokine concentrations and 2-year follow-up clinical outcome assessment scores for those undergoing hip arthroscopy.

The role of technology and telemetry medicine in the initial management of a ST-segment elevated myocardial infarction in a rural emergency department.

PubMed

Hood, Michael L

2018-05-01

The 12-lead electrocardiogram (ECG) is an integral part of the diagnostic tools available for recognising a patient who is experiencing an ST-segment elevated myocardial infarction (STEMI). Consequently, a great emphasis is placed on the rapid acquisition and expert interpretation of the 12-lead ECG so that the appropriate reperfusion management might be commenced to optimise patient outcomes by preventing further damage to the myocardium. With the advancement of telemetric and diagnostic abilities of the modern ECG machine, the role of frontline rural emergency clinicians is as important as ever. This clinical case report describes the presentation and management of a person experiencing a STEMI in a rural Australian hospital emergency department setting. The emanating point of interest from this case report is the early clinician recognition of significant ST-segment elevation in multiple leads of the initial ECG trace, indicating a STEMI. Despite the presence of significant acute ST-segment changes throughout the trace, the ECG's diagnostic analysis of the 12-lead ECG did not identify it as meeting STEMI criteria. Subsequently, the ECG was not recommended by the ECG machine for telemetric transmission to the remote on-call cardiologist for immediate STEMI management guidance. This article focuses on the telemetric technology utilised in the management of STEMIs in the rural emergency department, the diagnostic ability of the modern ECG and the role of the frontline rural emergency clinician in the utilisation of such technology. Competent utilisation of key technologies applied to the ECG machine require the clinician to be well trained in the technical use of the equipment, have a thorough understanding of how the technology interacts within the established clinical pathway and be ready to apply its use in a timely manner in order to prevent delays in treatment. Furthermore, an over-reliance on the diagnostic ability of the modern ECG machine in the rural or remote context may potentially lead to poor patient outcomes.

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.

Rapid health assessment in Aceh Jaya District, Indonesia, following the December 26 tsunami.

PubMed

Brennan, Richard J; Rimba, Kamaruddin

2005-08-01

To rapidly determine the public health impact of the Asian tsunami on the population of three communities in Aceh Jaya District, Indonesia, and to prioritize health interventions. Rapid health assessment, utilizing direct observations, interviews with key informants, a single focus group discussion, town mapping, a review of medical records and a systematic random sample of the entire town of Calang, capital of Aceh Jaya District, Indonesia. Almost 100% of dwellings were destroyed in all three communities. For the town of Calang: only 18.2% of the pre-tsunami population remained 2 weeks following the disaster, with an estimated 70% of the population having died at the time of impact; government estimates of the remaining population were inflated by approximately 250%; mortality rates were not elevated post-tsunami; 100% of the population lacked access to sanitation and clean water; 85% of children under 5 years reported diarrhoea over the preceding 2 week period; 95% of individuals with a medical complaint reported satisfactory access to clinical care; acute malnutrition was not a significant problem; and over one-fifth of households were hosting an orphan. For the villages of Rigah and Sayeung: approximately 46.2 and 86.0% of the population survived the tsunami impact, respectively; mortality rates were not elevated post tsunami; 100% of the population lacked access to sanitation and clean water; diarrhoea was the main cause of morbidity; primary care services were available only in Rigah; and only Rigah had received external assistance. Almost two-thirds of the population of the three communities died as a result of the tsunami's impact. Although mortality rates were not elevated post tsunami, significant threats to public health persisted, especially water-borne diseases. Priority activities included emergent environmental health interventions, mobile clinics to the two villages and a more detailed assessment of the needs of orphans. Data were shared with agencies better placed to address needs in the areas of shelter and food aid.

Current concepts about chromium supplementation in type 2 diabetes and insulin resistance.

PubMed

Wang, Zhong Q; Cefalu, William T

2010-04-01

Chromium has been established to be an essential trace element in mammals in regard to maintenance of normal carbohydrate metabolism. Studies that provided chromium to human subjects in documented deficiency states noted improved glucose levels. However, controversy exists as to whether dietary supplementation with chromium should be routinely recommended in subjects without documented deficiencies. Over the recent past, several well-designed clinical trials have provided evidence in favor of and against a beneficial effect of chromium. It appears that across all subject phenotypes (eg, lean and obese, insulin sensitive and insulin resistant), a consistent significant and beneficial effect of chromium may not be observed. Specifically, recent data fail to demonstrate significant improvement in carbohydrate metabolism in individuals with metabolic syndrome, impaired glucose tolerance, or consistently in individuals with type 2 diabetes. However, patient selection may be an important factor in determining clinical response, as it was concluded that a clinical response to chromium (ie, decreased glucose and improved insulin sensitivity) may be more likely in insulin-resistant individuals with type 2 diabetes who have more elevated fasting glucose and hemoglobin A(1c) levels.

Methoxyflurane revisited: tale of an anesthetic from cradle to grave.

PubMed

Mazze, Richard I

2006-10-01

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.

Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria

PubMed Central

Kuzmina, Zoya; Gounden, Verena; Curtis, Lauren; Avila, Daniele; Taylor, Tiffani; Baruffaldi, Judy; Cowen, Edward W.; Naik, Haley B.; Hasni, Sarfaraz A.; Mays, Jacqueline W.; Mitchell, Sandra; Baird, Kristin; Steinberg, Seth M.; Pavletic, Steven Z.

2017-01-01

There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P < 0.0001), IgG (P < 0.0001), and IgA (P = 0.001), elevated uric acid (P = 0.008) and total protein (P = 0.0004), and higher numbers of CD31 (P = 0.002), CD41 (P = 0.001), CD81 (P = 0.023) T cells, and CD191 B cells (P < 0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n = 66) was associated with reduced presence of autoantibodies (48 vs. 66% P = 0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P = 0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD. PMID:25363867

Effect of Elevated Reperfusion Pressure on "No Reflow" Area and Infarct Size in a Porcine Model of Ischemia-Reperfusion.

PubMed

Pantsios, Chris; Kapelios, Chris; Vakrou, Styliani; Diakos, Nikolaos; Pozios, Iraklis; Kontogiannis, Chris; Nanas, John; Malliaras, Konstantinos

2016-07-01

The "no reflow" phenomenon (microvascular obstruction despite restoration of epicardial blood flow) develops postreperfusion in acute myocardial infarction and is associated with poor prognosis. We hypothesized that increased reperfusion pressure may attenuate the no reflow phenomenon, as it could provide adequate flow to overcome the high resistance of the microvasculature within the no reflow zone. Thus, we investigated the effect of modestly elevated blood pressure during reperfusion on the extent of no reflow area and infarct size in a porcine model of ischemia-reperfusion. Eighteen farm pigs underwent acute myocardial infarction by occlusion of the anterior descending coronary artery for 1 hour, followed by 2 hours of reperfusion. Just prior to reperfusion, animals were randomized into 2 groups: in group 1 (control group, n = 9), no intervention was performed. In group 2 (n = 9), aortic pressure was increased by ∼20% (compared to ischemia) by partial clamping of the ascending aorta during reperfusion. Following 2 hours of reperfusion, animals were euthanized to measure area at risk, infarct size, and area of no reflow. Partial clamping of the ascending aorta resulted in modest elevation of blood pressure during reperfusion. The area at risk did not differ between the 2 groups. The no reflow area was significantly increased in group 2 compared to control animals (50% ± 13% vs 37% ± 9% of the area at risk; P = .04). The infarcted area was significantly increased in group 2 compared to control animals (75% ± 17% vs 52% ± 23% of the area at risk; P = .03). Significant positive correlations were observed between systolic aortic pressure and no reflow area, between systolic aortic pressure and infarcted area and between infarcted area and no reflow area during reperfusion. Modestly elevated blood pressure during reperfusion is associated with an increase in no reflow area and in infarct size in a clinically relevant porcine model of ischemia-reperfusion. © The Author(s) 2015.

Effects of elevation and seed source on tracheid length in young ponderosa pine

Treesearch

R. M. Echols

1973-01-01

Tracheid lengths in 30-year-old ponderosa pine progeny test plantations in the central Sierra Nevada of California were analyzed for effects of (a) elevation of seed parents and (b) elevation and location of test sites. The influence of elevation of seed parents on progeny tracheid length was not significant. Plantation location was significant, but interaction between...

Clinical utility of transperineal template-guided mapping biopsy of the prostate after negative magnetic resonance imaging-guided transrectal biopsy.

PubMed

Sivaraman, Arjun; Sanchez-Salas, Rafael; Ahmed, Hashim U; Barret, Eric; Cathala, Nathalie; Mombet, Annick; Uriburu Pizarro, Facundo; Carneiro, Arie; Doizi, Steeve; Galiano, Marc; Rozet, Francois; Prapotnich, Dominique; Cathelineau, Xavier

2015-07-01

We evaluated the prostate cancer detection with transperineal template-guided mapping biopsy in patients with elevated prostate-specific antigen and negative magnetic resonance imaging (MRI)-guided biopsy. Totally 75 patients underwent transperineal template-guided mapping biopsy for prior negative MRI-guided (cognitive registration) biopsy during April 2013 to August 2014. Primary objective was to report clinically significant cancer detection in this cohort of patients. Significant cancer was defined using varying thresholds of MCL or Gleason grade 3+4 or greater or both. Cancers with more than 80% of positive core length anterior to the level of urethra were termed anterior zone cancer. Secondary objective was to evaluate the potential clinical and radiological predictors for significant cancer detection. The mean age was 61.6 ± 6.5 years and median prostate-specific antigen was 10.4 ng/dl (7.9-18) with a mean MRI target size of 7.2mm (4-11). Transperineal template-guided mapping biopsy identified cancer in 36% (27/75) patients and 66.6% (18/27) of them were anterior zone cancers. The rates of detection of clinically significant and insignificant cancer according to the several definitions used range from 22.7% to 30.7% and 5.3% to 13.3%, respectively. Multivariate analysis did not identify any predictors for finding clinically significant and anterior cancers in this group of patients. Transperineal template-guided mapping biopsy appears to be an excellent biopsy protocol for downstream management following negative MRI-guided biopsy. Most of the cancers detected were predominantly anterior tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

MicroRNA-126 deficiency enhanced the activation and function of CD4+ T cells by elevating IRS-1 pathway.

PubMed

Chu, F; Hu, Y; Zhou, Y; Guo, M; Lu, J; Zheng, W; Xu, H; Zhao, J; Xu, L

2018-02-01

Recent evidence has shown that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4 + T cells remains largely unknown. Here we first found that the activation and proliferation, as well as the expression of interferon (IFN)-γ, of CD4 + T cells from miR-126 knock-down (KD) mice using the miRNA-sponge technique were enhanced significantly in vitro, compared with those in CD4 + T cells from wild-type (WT) mice. To monitor further the possible effect of miR-126 deficiency on the function of CD4 + T cells in vivo, we used dextran sulphate sodium (DSS)-induced murine model of acute autoimmune colitis and found that miR-126 deficiency could elevate the pathology of colitis. Importantly, the proportion of CD4 + T cells in splenocytes increased significantly in miR-126KD mice. Moreover, the expression levels of CD69 and CD44 on CD4 + T cells increased significantly and the expression level of CD62L decreased significantly. Of note, adoptive cell transfer assay showed that the pathology of colitis was more serious in carboxyfluorescein succinimidyl ester (CFSE)-labelled miR-126KD CD4 + T cell-transferred group, compared with that in the CFSE-labelled WT CD4 + T cells transferred group. Consistently, the expression levels of CD69 and CD44 on CFSE + cells increased significantly. Furthermore, both the proliferation and IFN-γ secretion of CFSE + cells also increased significantly in the CFSE-labelled miR-126KD CD4 + T cell-transferred group. Mechanistic evidence showed that the expression of insulin receptor substrate 1 (IRS-1), as a functional target of miR-126, was elevated in CD4 + T cells from miR-126KD mice, accompanied by altered transduction of the extracellular regulated kinase, protein B (AKT) and nuclear factor kappa B (NF-κB) pathway. Our data revealed a novel role in which miR-126 was an intrinsic regulator in the function of CD4 + T cells, which provided preliminary basis for exploring further the role of miR-126 in the development, function of CD4 + T cells and related clinical diseases. © 2017 British Society for Immunology.

Evaluation of a novel supplement to reduce blood glucose through the use of a modified oral glucose tolerance test

PubMed Central

Smith, Adam J; Giunta, Brian; Shytle, R Douglas; Blum, James M

2011-01-01

Elevated blood glucose is a major component in metabolic syndrome and pre-diabetes, sometimes leading to type 2 diabetes mellitus (DM II). Additionally, it may lead to adipose deposits when left elevated for long periods. The epidemiology of DM II clearly shows that uncontrolled blood glucose levels leads to many adverse conditions including heart disease, retinal damage, renal failure, erectile dysfunction, and other significant medical conditions. Here we conducted a single-center, prospective, randomized, double-blinded, placebo-controlled, parallel-group- clinical trial of a nutraceutical supplement vs. placebo to measure its glucose lowering effect in generally healthy adults before and after a simple sugars meal. Subjects reported to the test clinic on multiple days to receive placebo or treatment, a simple sugars meal, as well as pre-and postprandial blood glucose measurement (modified oral glucose tolerance test). Each subject served as his or her own control and thirty-one subjects completed the trial with at least one oral glucose tolerance test (OGTT) with the nutraceutical supplement and placebo. Statistical analysis revealed the nutraceutical supplement significantly lowered postprandial glucose levels by 36% and 59% at 45 and 60 minutes, respectively (***P<.001). The study was limited by its composition of primarily overweight females. Future studies will be required over longer periods in more heterogeneous and larger groups to determine the long-term effect of this supplement on blood glucose levels in terms of prophylaxis or treatment for DM II. PMID:21416063

The biological basis of autism spectrum disorders: Understanding causation and treatment by clinical geneticists.

PubMed

Geier, David A; Kern, Janet K; Geier, Mark R

2010-01-01

Autism spectrum disorders (ASDs) also known as pervasive developmental disorders (PDD) are a behaviorally defined group of neurodevelopmental disorders that are usually diagnosed in early childhood. ASDs disproportionately affect male children. Mercury (Hg) a heavy metal, is widespread and persistent in the environment. Mercury is a ubiquitous source of danger in fish, drugs, fungicides/herbicides, dental fillings, thermometers, and many other products. Elevated Hg concentrations may remain in the brain from several years to decades following exposure. This is important because investigators have long recognized that Hg is a neurodevelopmental poison; it can cause problems in neuronal cell migration and division, and can ultimately cause cell degeneration and death. Case-reports of patients have described developmental regressions with ASD symptoms following fetal and/or early childhood Hg exposure, and epidemiological studies have linked exposure to Hg with an elevated risk of a patient being diagnosed with an ASD. Immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with ASDs were reported following Hg intoxication with similarities extending to neuroanatomy, neurotransmitters, and biochemistry. The sexual dimorphism of ASDs may result from synergistic neurotoxicity caused by the interaction of testosterone and Hg; in contrast, estrogen is protective, mitigating the toxicity of Hg. Mercury exposure may significantly increase androgen levels, and as a result, patients diagnosed with an ASD may significantly benefit from anti-androgen therapy. Finally, the clinical geneticist has a wealth of biomarkers to evaluate and treat patients diagnosed with an ASD.

The efficacy of an elevated concentration of lidocaine HCl in impacted lower third molar surgery.

PubMed

Ping, Bushara; Kiattavorncharoen, Sirichai; Saengsirinavin, Chavengkiat; Im, Puthavy; Durward, Callum; Wongsirichat, Natthamet

2015-06-01

There have been few studies on the effect of an elevated concentration of lidocaine hydrochloride in the surgical removal of an impacted lower third molar. This study aimed to examine the efficacy of 4% lidocaine along with 1:100,000 epinephrine compared to 2% lidocaine along with 1:100,000 epinephrine as inferior alveolar nerve block for the removal of an impacted lower third molar. This single-blind study involved 31 healthy patients (mean age: 23 y; range: 19-33 y) with symmetrically impacted lower third molars as observed on panoramic radiographs. Volunteers required 2 surgical interventions by the same surgeon with a 3-week washout period. The volunteers were assigned either 4% lidocaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine as local anesthetic during each operation. We recorded the time of administration, need for additional anesthetic administration, total volume of anesthetic used. We found that the patient's preference for either of the 2 types of local anesthetic were significantly different (P < 0.05). However, the extent of pulpal anesthesia, surgical duration, and duration of soft tissue anesthesia were not significantly different. Our study suggested that inferior alveolar nerve block using 4% lidocaine HCl with 1:100,000 epinephrine as a local anesthetic was clinically more effective than that using 2% lidocaine HCl with 1:100,000 epinephrine; the surgical duration was not affected, and no clinically adverse effects were encountered.

SLC34A3 Intronic Deletion in an Iranian Kindred with Hereditary Hypophosphatemic Rickets with Hypercalciuria and Review of Reported Cases.

PubMed

Hasani-Ranjbar, Shirin; Ejtahed, Hanieh Sadat; Amoli, Mahsa M; Bitarafan, Fatemeh; Qorbani, Mostafa; Soltani, Akbar; Yarjoo, Bahareh

2018-05-29

Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) is a very rare inheritable hypophosphatemic rickets/osteomalacia characterized by decreased renal phosphate reabsorption, hypophosphatemia, vitamin D refractory rickets, hyperphosphaturia, hypercalciuria, elevated circulating 1, 25-dihydroxy vitamin D levels and low serum parathyroid hormone (PTH) levels, leading to growth retardation, limb deformities, bone pain, muscle weakness, rickets and osteomalacia. Biallelic mutations in SLC34A3/NPT2c gene are responsible for the occurrence of the disease. In this paper we describe the clinical examination, biochemical profile and gene analysis of Iranian kindred with a 101bp deletion in SLC34A3 gene. 12 members of a family of previously reported patient with HHRH (3 homozygote and 7 heterozygote) and 10 healthy controls were evaluated. All patients had significantly increased risk of kidney stone formation, bone deformities and short stature compared with unrelated healthy controls. The heterozygous patients displayed milder clinical symptoms compared with homozygous patients. These patients displayed mild or no hypophosphatemia and they did not develop skeletal deformities. Recurrent renal stones and hypercalciuria were the main presentations of heterozygous patients which could be confused with familial hypercalciuria. In addition, biochemical analysis showed significantly low serum sodium level and elevated alkaline phosphatase in patients. Genetic counseling and screening for SLC34A3 mutations can be helpful in adult onset phenotype with unexplained osteoporosis, bone deformities and especial recurrent renal stones. In subjects with vitamin D deficiency the results should be interpreted cautiously.

Acute risk factors for suicide attempts and death: prospective findings from the STEP-BD study

PubMed Central

Ballard, Elizabeth D; Vande Voort, Jennifer L; Luckenbaugh, David A; Machado-Vieira, Rodrigo; Tohen, Mauricio; Zarate, Carlos A

2016-01-01

Objectives Suicide is unfortunately common in psychiatric practice, but difficult to predict. This study sought to assess which clinical symptoms increase in the months before suicidal behavior in a sample of psychiatric outpatients with bipolar disorder. Methods Data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial were used. A total pf 103 participants who attempted suicide or died by suicide during the trial were included; a 15% random sample of the remaining participants (n = 427) was used as a comparison sample. Linear mixed models in the six months before suicidal behavior were conducted for each of five proposed acute risk factors for suicidal behavior. Participants were assessed using the Clinical Monitoring Form (CMF) at each visit for the following potential acute risk factors for suicidal behavior: suicidal ideation, loss of interest, anxiety, psychomotor agitation, and high-risk behavior. Results Each of the five symptoms was elevated overall in individuals who engaged in suicidal behavior (p < 0.05). The severity of both suicidal ideation and loss of interest significantly increased in the months before suicidal behavior (p < 0.001). Anxiety demonstrated comparable effect sizes across multiple models. Psychomotor agitation and high-risk behavior were not significantly elevated before suicidal behavior. Conclusions Suicidal ideation, loss of interest and, to a lesser extent, anxiety may represent acute suicide risk factors up to four months before suicidal behavior in outpatients with bipolar disorder. Further investigation of these potential acute risk factors in prospective analyses is warranted. PMID:27233466

Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection.

PubMed

Kawano, Yoshihiko; Iwata, Seiko; Kawada, Jun-ichi; Gotoh, Kensei; Suzuki, Michio; Torii, Yuka; Kojima, Seiji; Kimura, Hiroshi; Ito, Yoshinori

2013-09-01

Chronic active Epstein-Barr virus (CAEBV) infection has high mortality and morbidity, and biomarkers for disease severity and prognosis are required. MicroRNAs (miRNAs) are small noncoding RNAs, and EBV encodes multiple miRNAs. Because plasma contains sufficiently stable miRNAs, circulating EBV-associated miRNA profiles were investigated as novel biomarkers in CAEBV infection. Plasma miRNA expression was assessed for 12 miRNAs encoded within 2 EBV open reading frames (BART and BHRF). Expression levels were investigated in 19 patients with CAEBV infection, 14 patients with infectious mononucleosis, and 11 healthy controls. Relative expression levels of plasma miRNAs were determined by TaqMan probe-based quantitative assay. Plasma miR-BART1-5p, 2-5p, 5, and 22 levels in patients with CAEBV infection were significantly greater than those in patients with infectious mononucleosis and in controls. Plasma miR-BART2-5p, 4, 7, 13, 15, and 22 levels were significantly elevated in patients with CAEBV infection with systemic symptoms, compared with levels in patients with no systemic symptoms. The levels of miR-BART2-5p, 13, and 15 showed clinical cutoff values associated with specific clinical conditions, in contrast to plasma EBV loads. Levels of specific plasma EBV miRNAs were elevated differentially in patients with CAEBV infection. Several EBV miRNAs, particularly miR-BART2-5p, 13, and 15, are potentially biomarkers of disease severity or prognosis.

A Schiff base-derived copper (II) complex is a potent inducer of apoptosis in colon cancer cells by activating the intrinsic pathway.

PubMed

Hajrezaie, Maryam; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Hassandarvish, Pouya; Gwaram, Nura Suleiman; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Looi, Chung Yeng; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood Ameen

2014-01-01

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87  μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25  μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.

A Schiff Base-Derived Copper (II) Complex Is a Potent Inducer of Apoptosis in Colon Cancer Cells by Activating the Intrinsic Pathway

PubMed Central

Hajrezaie, Maryam; Paydar, Mohammadjavad; Zorofchian Moghadamtousi, Soheil; Hassandarvish, Pouya; Gwaram, Nura Suleiman; Zahedifard, Maryam; Rouhollahi, Elham; Karimian, Hamed; Looi, Chung Yeng; Ali, Hapipah Mohd; Abdul Majid, Nazia; Abdulla, Mahmood Ameen

2014-01-01

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents. PMID:24737979

Effectiveness of a multidisciplinary critical pathway based on a computerised physician order entry system for ST-segment elevation myocardial infarction management in the emergency department: a retrospective observational study.

PubMed

Park, Yoo Seok; Chung, Sung Phil; You, Je Sung; Kim, Min Joung; Chung, Hyun Soo; Hong, Jung Hwa; Lee, Hye Sun; Wang, Jinwon; Park, Incheol

2016-08-16

The purpose of this study was to investigate whether a multidisciplinary organised critical pathway (CP) for ST-segment elevation myocardial infarction (STEMI) management can significantly attenuate differences in the duration from emergency department (ED) arrival to evaluation and treatment, regardless of the arrival time, by eliminating off-hour and weekend effects. Retrospective observational cohort study. 2 tertiary academic hospitals. Consecutive patients in the Fast Interrogation Rule for STEMI (FIRST) program. A study was conducted on patients in the FIRST program, which uses a computerised physician order entry (CPOE) system. The patient demographics, time intervals and clinical outcomes were analysed based on the arrival time at the ED: group 1, normal working hours on weekdays; group 2, off-hours on weekdays; group 3, normal working hours on weekends; and group 4, off-hours on weekends. Clinical outcomes categorised according to 30-day mortality, in-hospital mortality and the length of stay. The duration from door-to-data or FIRST activation did not differ significantly among the 4 groups. The median duration between arrival and balloon placement during percutaneous coronary intervention did not significantly exceed 90 min, and the proportions (89.6-95.1%) of patients with door-to-balloon times within 90 min did not significantly differ among the 4 groups, regardless of the ED arrival time (p=0.147). Moreover, no differences in the 30-day (p=0.8173) and in-hospital mortality (p=0.9107) were observed in patients with STEMI. A multidisciplinary CP for STEMI based on a CPOE system can effectively decrease disparities in the door-to-data duration and proportions of patients with door-to-balloon times within 90 min, regardless of the ED arrival time. The application of a multidisciplinary CP may also help attenuate off-hour and weekend effects in STEMI clinical outcomes. 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/

Comparison of the technique of anterior cervical distraction and screw elevating-pulling reduction and conventional anterior cervical reduction technique for traumatic cervical spine fractures and dislocations.

PubMed

Li, Haoxi; Huang, Yufeng; Cheng, Changzhi; Lin, Zhoudan; Wu, Desheng

2017-04-01

To analyze and confirm the advantages of anterior cervical distraction and screw elevating-pulling reduction which are absent in conventional anterior cervical reduction for traumatic cervical spine fractures and dislocations. A retrospective study was conducted on 86 patients with traumatic cervical spine fractures and dislocations who received one-stage anterior approach treatment for a distraction-flexion injury with bilateral locked facet joints between January 2010 and June 2015. They were 54 males and 32 females with an age ranging from 20 to 73 years (average age, 40.1 ± 5.6 years). These patients were distributed into group A and group B in the sequence of visits, with 44 cases of conventional anterior cervical reduction (group A) and 42 cases of anterior cervical distraction and screw elevating-pulling reduction (group B). Comparison of intraoperative blood loss, operation duration and vertebral reduction rate was made between the two groups. The follow-up time was 12-18 months, and the clinical outcomes of surgery were evaluated according to ASIA score, VAS score and JOA score. Statistically significant difference was revealed between group A and group B in the surgical time and the correction rate of cervical spine dislocation (p < 0.05), with the results of group B better than those of group A. For the two groups, statistically significant difference was shown between the ASIA score, VAS score and JOA score before and after operation (p < 0.05), with the results better after operation, while no statistically significant difference was revealed in such scores between the two groups (p > 0.05), with the therapeutic effect of group A the same with that of group B. Anterior cervical distraction and screw elevating-pulling reduction is simple with low risk, short operation duration, good effect of intraoperative vertebral reduction and well-recovered function after the operation. Meanwhile, as a safe and effective operation method for cervical spine fractures and dislocations, it can reduce postoperative complications and the risk of the iatrogenic cervical spinal cord injury caused by prying or facet joint springing during conventional reduction, having more obvious advantages compared to the conventional surgical reduction adopted by group A, with good cervical spine stability as shown in long-term follow-up. Therefore, it is suitable for clinical promotion and application. Copyright © 2017. Published by Elsevier Ltd.

Prevalence and predictors of anxiety and depression after completion of chemotherapy for childhood acute lymphoblastic leukemia: A prospective longitudinal study

PubMed Central

Kunin-Batson, Alicia S.; Lu, Xiaomin; Balsamo, Lyn; Graber, Kelsey; Devidas, Meenakshi; Hunger, Stephen P.; Carroll, William L.; Winick, Naomi J.; Mattano, Leonard A.; Maloney, Kelly W.; Kadan-Lottick, Nina S.

2016-01-01

Background The months immediately following completion of treatment for childhood acute lymphoblastic leukemia (ALL) are often regarded as a stressful time for children and families. In this prospective, longitudinal study, the prevalence and predictors of anxiety and depressive symptoms after completion of treatment were examined. Methods Participants included 160 children (ages 2-9 years) with standard-risk ALL enrolled on Children's Oncology Group protocol AALL0331. Parents completed standardized rating scales of children's emotional-behavioral functioning, and measures of coping and family functioning at ∼1, 6, and 12 months after diagnosis, and again 3 months following completion of chemotherapy. Results Three months off-therapy, 24% of survivors had at-risk/clinically elevated anxiety scores and 28% had elevated depression scores, significantly higher than the expected 15% in the general population (p=0.028 and 0.001, respectively). Patients with elevated anxiety one-month post-diagnosis were at greater risk for off–therapy anxiety (OR=4.1; 95% CI, 1.31-12.73, p=0.022), and those with elevated depressive symptoms 6-months post-diagnosis were at greater risk for off-therapy depression (OR=7.88, 95% CI, 2.61-23.81, p=0.0002). In adjusted longitudinal analyses, unhealthy family functioning (p=0.008), and less reliance on social support coping (p=0.009) were associated with risk for emotional distress. Children from Spanish-speaking families (p=0.05) were also at greater risk for distress. Conclusions A significant proportion of children experience emotional distress during and after therapy for ALL. These data provide a compelling rationale for targeted early screening, and psychosocial interventions to support family functioning and coping skills. PMID:27028090

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay.

PubMed

Gersch, Robert P; Fourman, Mitchell S; Phillips, Brett T; Nasser, Ahmed; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T

2015-08-01

Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm(2), P < 0.01 and 12.4 ± 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm(2)). AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

PubMed Central

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

2015-01-01

Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207