Serum metal levels after minimally invasive repair of pectus excavatum.

PubMed

Cundy, Thomas P; Kirby, Christopher P

2012-08-01

Metal implants may wear and corrode, resulting in systemic dissemination of metallic debris that is measurable in serum. Concern exists regarding adverse health effects related to implant-derived debris. Minimally invasive repair of pectus excavatum (MIRPE) is a popular technique in which a stainless steel substernal bar is implanted to achieve deformity correction. Serum metal levels have not previously been investigated after MIRPE. Serum chromium, molybdenum, and nickel levels were measured in this cross-sectional study of 11 children implanted with pectus bars after MIRPE. Samples were analyzed using high-resolution inductively coupled plasma mass spectrometry. Median serum chromium and nickel values were elevated 3.3-fold (P = .0003) and 2.3-fold (P = .25), respectively, compared with age-matched controls. Serum chromium and nickel levels were abnormally elevated in 6 (55%) of 11 and 5 (45%) of 11, respectively. In patients whom postexplantation metal levels were measured, previously elevated levels were lowered. Serum chromium levels in children after MIRPE are comparable with adult cohorts with hip arthroplasty implants measured 1-year postoperatively. No acute metal toxicity was observed. Abnormally elevated levels of serum metal levels are measurable in children implanted with pectus bars. These findings warrant further investigation to assess the biocompatibility of this surgical implant in children. Copyright © 2012 Elsevier Inc. All rights reserved.

Incidence of Abnormal Liver Biochemical Tests in Hyperthyroidism

PubMed Central

Lin, Tiffany Y.; Shekar, Anshula O.; Li, Ning; Yeh, Michael W.; Saab, Sammy; Wilson, Mark; Leung, Angela M.

2017-01-01

Objective Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen their severity. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. Design Single-institution retrospective cohort study. Patients Patients ≥18 years old receiving medical care at a large, academic, urban U.S. medical center between 2002–2016. Measurements Inclusion criteria were a serum thyroid stimulating hormone [TSH] concentration < 0.3 mIU/L or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) and/or thyroxine (T4) concentration [total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. Results In this cohort of 1,514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0.02 mIU/L, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. Conclusions This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis. PMID:28199740

A community-based epidemiological study of elevated serum alanine aminotransferase levels in Kinmen, Taiwan

PubMed Central

Liu, Chi-Ming; Tung, Tao-Hsin; Liu, Jorn-Hon; Chen, Victor Tze-Kai; Lin, Ching-Heng; Hsu, Chung-Te; Chou, Pesus

2005-01-01

AIM: To explore any gender-related differences in prevalence of and condition-associated factors related to an elevated serum alanine aminotransferase (ALT) level amongst residents of Kinmen, Taiwan. METHODS: A total of 11 898 of a potential 20 112 regional residents aged 30 years or more completed a related questionnaire that was carried out by the Yang-Ming Crusade between 1991 and 1994 inclusively, with blood samples being collected by public nurses. The overall questionnaire response rate was 59.3% (52.4% for males and 66.0% for females). RESULTS: The prevalence of an elevated serum ALT level for this sub-population was found to be 7.2%, the prevalence revealing a statistically significant decrease with increasing population age (P<0.0001). Males exhibited a greater prevalence of elevated serum ALT level than did females (9.4% vs 5.3%, P<0.0001). Using multiple logistic regression analysis, in addition to male gender, a younger age, greater waist circumference, presence of type-2 diabetes and hyperuricemia were the significant factors associated with an elevated serum ALT level for both males and females. Gender-related differences as regards associated factors were also revealed. For males, obesity was significantly related to an elevated serum ALT level (OR = 1.28, 95%CI: 1.00-1.66) but this was not so for females (OR = 1.09, 95%CI: 0.84-1.42). Hypertriglyceridemia (OR = 1.80, 95%CI: 1.36-2.39) and hyperuricemia (OR = 1.61, 95%CI: 1.03-2.52) were significantly related to elevated serum ALT levels only for females. CONCLUSION: Several gender-related differences were noted pertaining to the prevalence of and relationship between obesity, hypertriglyceridemia and hyperuricemia and elevated serum ALT level in the present study. PMID:15786537

Cost-effectiveness of strategies used in the evaluation of pregnancies complicated by elevated maternal serum alpha-fetoprotein levels.

PubMed

Nadel, A S; Norton, M E; Wilkins-Haug, L

1997-05-01

To perform a cost-effectiveness analysis of various protocols used in the diagnostic evaluation of pregnancies complicated by elevated levels of maternal serum alpha-fetoprotein (MSAFP). The variables incorporated in this model were the prevalence of relevant fetal anomalies; the sensitivity and specificity of MSAFP at 2.0 or 2.5 multiples of the median (MoM); and the sensitivity, specificity, cost, and safety of targeted ultrasound and amniocentesis. We expressed the cost-effectiveness of each strategy as the total cost of the diagnostic evaluation divided by the number of anomalous fetuses identified, yielding the cost per identified anomalous fetus. In a hypothetical cohort of 100,000 singleton pregnancies, a strategy of targeted ultrasound for MSAFP of at least 2.0 MoM detected 90 of 110 structurally abnormal fetuses, without iatrogenic fetal loss, at a cost of $5700 per anomalous fetus. A strategy of amniocentesis with karyo-type determination for MSAFP of at least 2.5 MoM detected 15 additional abnormal fetuses (87 structural abnormalities, ten autosomal aneuploidies, and eight sex chromosomal aneuploidies), with nine iatrogenic fetal losses, at an incremental cost of $46,100 per anomalous fetus. The increased cost and iatrogenic fetal loss rate may not justify the increased diagnostic yield of amniocentesis as compared with ultrasound in the evaluation of pregnancies complicated by elevated MSAFP.

Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China.

PubMed

Chen, Shuang; Guo, Xiaofan; Chen, Yintao; Dong, Siyuan; Sun, Yingxian

2016-11-01

This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors. This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors. 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08-3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08-4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29-0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17-0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07-6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19-0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41-13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21-6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31-8.12, p = 0.011) were risk factors for elevated AST. A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients.

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

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

Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov; Ho, Wen-Chao; Caffrey, James L.

Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214more » had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues

T-Wave Abnormality as Electrocardiographic Signature of Myocardial Edema in Non-ST-Elevation Acute Coronary Syndromes.

PubMed

Cardona, Andrea; Zareba, Karolina M; Nagaraja, Haikady N; Schaal, Stephen F; Simonetti, Orlando P; Ambrosio, Giuseppe; Raman, Subha V

2018-01-26

T-wave abnormalities are common during the acute phase of non-ST-segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T-wave abnormalities in the presentation of non-ST-segment elevation acute coronary syndromes correspond to the presence of myocardial edema. Secondary analysis of a previously enrolled prospective cohort of patients presenting with non-ST-segment elevation acute coronary syndromes was conducted. Twelve-lead electrocardiography (ECG) and cardiac magnetic resonance with T2-weighted imaging were acquired before invasive coronary angiography. ECGs were classified dichotomously (ie, ischemic versus normal/nonischemic) and nominally according to patterns of presentation: no ST- or T-wave abnormalities, isolated T-wave abnormality, isolated ST depression, ST depression+T-wave abnormality. Myocardial edema was determined by expert review of T2-weighted images. Of 86 subjects (65% male, 59.4 years), 36 showed normal/nonischemic ECG, 25 isolated T-wave abnormalities, 11 isolated ST depression, and 14 ST depression+T-wave abnormality. Of 30 edema-negative subjects, 24 (80%) had normal/nonischemic ECGs. Isolated T-wave abnormality was significantly more prevalent in edema-positive versus edema-negative subjects (41.1% versus 6.7%, P =0.001). By multivariate analysis, an ischemic ECG showed a strong association with myocardial edema (odds ratio 12.23, 95% confidence interval 3.65-40.94, P <0.0001). Among individual ECG profiles, isolated T-wave abnormality was the single strongest predictor of myocardial edema (odds ratio 23.84, 95% confidence interval 4.30-132, P <0.0001). Isolated T-wave abnormality was highly specific (93%) but insensitive (43%) for detecting myocardial edema. T-wave abnormalities in the setting of non-ST-segment elevation acute coronary syndromes are related to the presence of myocardial edema. High specificity of this ECG alteration identifies a change in ischemic

Elevated serum RANTES chemokine levels in autoimmune Addison disease.

PubMed

Fichna, Marta; Żurawek, Magdalena; Budny, Bartłomiej; Komarowska, Hanna; Niechciał, Elżbieta; Fichna, Piotr; Ruchała, Marek

2018-04-30

INTRODUCTION    Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES    Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS    rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS    No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS    This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

Elevated Serum Pesticide Levels and Risk for Alzheimer Disease

PubMed Central

Richardson, Jason R.; Roy, Ananya; Shalat, Stuart L.; von Stein, Richard T.; Hossain, Muhammad M.; Buckley, Brian; Gearing, Marla; Levey, Allan I.; German, Dwight C.

2014-01-01

IMPORTANCE The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). OBJECTIVE To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. DESIGN, SETTING, AND PARTICIPANTS A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. MAIN OUTCOMES AND MEASURES Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. RESULTS Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54–5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. CONCLUSIONS

Elevated serum pesticide levels and risk for Alzheimer disease.

PubMed

Richardson, Jason R; Roy, Ananya; Shalat, Stuart L; von Stein, Richard T; Hossain, Muhammad M; Buckley, Brian; Gearing, Marla; Levey, Allan I; German, Dwight C

2014-03-01

The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20). To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association. A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer's Disease Research Center and the University of Texas Southwestern Medical School's Alzheimer's Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases. Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status. Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (-1.605; range, -3.095 to -0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were -1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein. Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may

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.

Kidney transplantation from deceased donors with elevated serum creatinine.

PubMed

Gallinat, Anja; Leerhoff, Sabine; Paul, Andreas; Molmenti, Ernesto P; Schulze, Maren; Witzke, Oliver; Sotiropoulos, Georgios C

2016-12-01

Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years.

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

PubMed Central

Evangelista, Andreia Silva; de Araújo, Thiago Ferreira; Abrantes-Lemos, Clarice Pires; Deguti, Marta Mitiko; Cançado, Eduardo Luiz Rachid

2015-01-01

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population. PMID:25654085

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism.

PubMed

Xiao, Fangsen; Lin, Mingzhu; Huang, Peiying; Zeng, Jinyang; Zeng, Xin; Zhang, Huijie; Li, Xiaoying; Yang, Shuyu; Li, Zhibin; Li, Xuejun

2015-10-01

Recent evidence from animal studies indicates that fibroblast growth factor 21 (FGF21), an endocrine hormone that regulates glucose, lipid metabolism, and energy homeostasis, is regulated by T3. However, the role of FGF21 in hyperthyroid patients is unknown. The objective was to study serum FGF21 levels in hyperthyroid patients and the association of serum FGF21 levels with hyperthyroidism. This was a case-control study. A total of 119 hyperthyroid patients and 108 healthy subjects were recruited. Of them, 41 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism was obtained. Serum FGF21 levels were determined using the ELISA method. Serum FGF21 levels were significantly elevated in hyperthyroid patients as compared with normal subjects [median 290.67 (interquartile range, 156.60-502.33) vs 228.10 (169.85.25-320.10) pg/mL; P < .001]. After thionamide treatment, serum FGF21 levels in hyperthyroid patients declined markedly from 249.10 (139.10-444.00) to 106.90 (38.70-196.15) pg/mL (P < .001). Logistic regression revealed that FGF21, basal metabolic rate, low-density lipoprotein cholesterol, and alanine transaminase were significantly associated with hyperthyroidism. With adjustment for potential confounders, serum FGF21 remained independently associated with hyperthyroidism, with an adjusted odds ratio of 3.123 (95% confidence interval, 1.306-7.468) (P = .010). Serum FGF21 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. And serum FGF21 level was independently associated with hyperthyroidism.

Hepatic lipidosis in anorectic, lactating holstein cattle: a retrospective study of serum biochemical abnormalities.

PubMed

Cebra, C K; Garry, F B; Getzy, D M; Fettman, M J

1997-01-01

The association between hepatic lipidosis (HL) and disease in 59 anorectic, ketotic, lactating Holstein heifers and cows was investigated. Severe HL, as determined by histologic evaluation of liver tissue, was present in 46 animals; only half of these animals required intensive treatment for ketosis, and only half had serum biochemical evidence of liver disease, as determined by the presence of a last value of 2-fold or greater than the upper limit of the reference ranges for at least 2 of the 4 serum tests: gamma-glutamyl transferase, aspartate aminotransferase, and sorbitol dehydrogenase activities and bile acid concentrations. Most cattle with biochemical evidence of liver disease and severe HL had been lactating for 14 or more days. Cows that required intensive treatment inconsistently had serum biochemical evidence of liver disease. Although cattle with severe HL had significantly higher serum bilirubin concentrations and aspartate aminotransferase and sorbitol dehydrogenase activities than cattle with less severe lipidosis, the specificity of abnormally high serum sorbitol dehydrogenase activity or bilirubin concentration for severe lipidosis was only 8%. Abnormally high serum aspartate aminotransferase activity was 83% sensitive and 62% specific for severe lipidosis. Serum glucose and total carbon dioxide concentrations were significantly lower in cattle with severe lipidosis than in those with mild or moderate lipidosis, and low serum glucose or total carbon dioxide concentrations were rare in cattle without severe lipidosis. From these data, we conclude that the use of a single biochemical or histopathologic criterion to define severity of disease or degree of liver compromise in anorectic, ketotic cows results in the misidentification of many animals.

Serum angiotensin-converting enzyme is elevated in association with underground coal mining

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

Thompson, A.B.; Cale, W.F.; Lapp, N.L.

1991-10-01

Serum angiotensin-converting enzyme activity (SACE) and lysozyme activity were measured in a group of 40 underground coal miners and two control groups, 20 subjects with sarcoidosis and 15 normal non-dust-exposed volunteers. The miners were grouped first according to whether they had recent exposure (still actively mining or retired three years or less prior to measurement) or temporally more distant exposure (retired more than three years prior to measurement). Secondly, they were grouped as to whether or not they had coal workers' pneumoconiosis (CWP). The subjects with sarcoidosis were grouped according to disease activity. As expected, the subjects with active sarcoidosismore » had elevated SACE activity compared with normal subjects. The coal miners as a group did not have elevation of their SACE activity. However, the coal miners with recent exposure had elevated SACE activity (57.1 {plus minus} 3.9 U/ml) compared with normal controls (43.8 {plus minus} 1.5 U/ml, p = 0.007). The SACE activity in miners without recent exposure was not elevated (39.8 {plus minus} 1.3 U/ml) compared with the normal controls. No increase in SACE activity was found when the miners were grouped according to the presence or absence of CWP. In contrast, the miners' serum lysozyme activity was not elevated. Since alveolar macrophages are a potential source of SACE, elevation of SACE activity in underground coal miners may reflect alveolar macrophage activation caused by increased pulmonary mixed coal mine dust burden. Furthermore, since both SACE and serum lysozyme are elevated in association with silicosis, these findings may confirm that the macrophage responses to inhaled silica and coal dust differ.« less

Elevation in serum troponin I predicts the benefit of tirofiban.

PubMed

Januzzi, J L; Chae, C U; Sabatine, M S; Jang, I K

2001-05-01

Elevations in serum troponins among patients with acute coronary syndromes have been shown to identify those patients who are at high risk for poor outcome and who accrue larger relative benefits from aggressive antiplatelet and antithrombotic therapies. We studied a group of patients from the PRISM-PLUS trial to explore whether simply using serum troponin I, a serum marker of cardiac injury, could predict benefit of GP IIb/IIIa receptor antagonism with tirofiban. For this study, the subjects consisted of 55 patients receiving the combination therapy of tirofiban/heparin, and 55 receiving heparin alone. The baseline characteristics were similar between the two treatment groups. Serial blood samples were obtained over the first 24-hour period following randomization to study drug, and were analyzed for troponin I (TnI) levels. Among those patients with elevated serum TnI (>0.5 ng/ml), the 30-day event rate for death or myocardial infarction (MI) was reduced from 20.6% among the heparin only group to 3.6% for those treated with the combination of tirofiban/heparin, an absolute risk reduction of 17% and relative risk reduction of 83% (p=0.06). Among the TnI negative patients, the rates of death/MI at 30 days were 9.5% and 11.1% among the combination and heparin treated groups respectively (p=NS). Irrespective of high-risk clinical factors, including ST segment depression, these data support the hypothesis that serum troponins identify those who benefit from aggressive antiplatelet therapy with tirofiban.

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.

High serum carotenoids are associated with lower risk for developing elevated serum alanine aminotransferase among Japanese subjects: the Mikkabi cohort study.

PubMed

Sugiura, Minoru; Nakamura, Mieko; Ogawa, Kazunori; Ikoma, Yoshinori; Yano, Masamichi

2016-04-01

Many recent studies have shown that antioxidant vitamins and/or carotenoids may reduce liver disease, but this association has not been well established with thorough longitudinal cohort studies. The objective of this study was to longitudinally investigate whether serum carotenoids at baseline are associated with the risk of developing elevated serum alanine aminotransferase (ALT) among Japanese subjects. We conducted a follow-up study of 1073 males and females aged between 30 and 79 years at baseline from the Mikkabi prospective cohort study. Those who participated in the baseline study and completed follow-up surveys were examined longitudinally. Exclusions included excessive alcohol consumption (≥60 g alcohol/d), hepatitis B and C and having a history of medication use for liver disease. A cohort of 213 males and 574 females free of elevated serum ALT (>30 IU/ml) at baseline was studied. Over a mean follow-up period of 7·4 (sd 3·1) years, thirty-one males and forty-nine females developed new elevated serum ALT. After adjustments for confounders, the hazard ratios for elevated serum ALT in the highest tertiles of basal serum β-carotene, β-cryptoxanthin and total provitamin A carotenoids against the lowest tertiles were 0·43 (95 % CI 0·22, 0·81), 0·51 (CI 0·27, 0·94) and 0·52 (CI 0·28, 0·97), respectively. For α-carotene and lycopene, borderline reduced risks were also observed; however, these were not significant. Our results further support the hypothesis that antioxidant carotenoids, especially provitamin A carotenoids, might help prevent earlier pathogenesis of non-alcoholic liver disease in Japanese subjects.

Cardiac hypertrophy elevates serum levels of fibroblast growth factor 23.

PubMed

Matsui, Isao; Oka, Tatsufumi; Kusunoki, Yasuo; Mori, Daisuke; Hashimoto, Nobuhiro; Matsumoto, Ayumi; Shimada, Karin; Yamaguchi, Satoshi; Kubota, Keiichi; Yonemoto, Sayoko; Higo, Tomoaki; Sakaguchi, Yusuke; Takabatake, Yoshitsugu; Hamano, Takayuki; Isaka, Yoshitaka

2018-05-08

Several experimental studies have shown that fibroblast growth factor 23 (FGF23) induces left ventricular hypertrophy (LVH). However, the opposite directional relationship, namely a potential effect of LVH on FGF23, remains uncertain. Here we evaluated the effects of LVH on FGF23 using cardiomyocyte-specific calcineurin A transgenic mice. At six weeks, these mice showed severe LVH, with elevated levels of serum intact FGF23. FGF23 levels were elevated in cardiomyocytes, but not osteocytes, of the transgenic animals. Moreover, transverse aortic constriction also upregulated myocardial FGF23 expression in wild type mice. The promoter region of the FGF23 gene contains two putative nuclear factors of activated T cells (NFAT)-binding sites, with NFAT1 activating the promoter in a proximal NFAT-binding site dependent manner. Neither serum, urinary, or fractional excretion values of calcium and phosphate nor serum levels of 1,25(OH) 2 vitamin D were different between wild type and transgenic mice. Moreover, the renal expression of FGF receptors and α-Klotho was comparable. However, plasma levels of antidiuretic hormone were significantly increased in the transgenic mice, and aquaporin-2 immunohistochemical staining was mainly positive in the apical membrane of the collecting duct, compared to a primarily cytoplasmic staining in wild type mice. Real-time PCR analyses of kidney CYP27B1 and CYP24A1 expression in wild type mice showed that exogenous antidiuretic hormone blocked FGF23's actions on these vitamin D activating or inactivating enzymes. Finally, the renal resistance of transgenic mice to FGF23 was partly overcome by tolvaptan. Thus, LVH in transgenic mice is associated with an increase in myocardial and serum intact FGF23, with the kidneys being protected against FGF23 excess by elevated antidiuretic hormone levels. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Approach to the patient with abnormal liver tests.

PubMed

Mahl, T C

1998-01-01

Patients with abnormal liver blood tests are frequently encountered by primary care practitioners. An understanding of the cellular implications of these abnormalities is helpful in determining the etiology of liver injury. Elevated serum aminotransferases suggest injury of hepatocytes. Elevations in alkaline phosphatase suggest injury to any part of the biliary tree. Neither of these enzymes measures liver function. Serum bilirubin and albumin levels, as well as prothrombin time, do measure function and can be used in conjunction with the physical examination and the specific etiology of the patient's disorder to determine a patient's prognosis. Many diverse disorders result in similar biochemical patterns of liver injury. The history, physical examination, and use of specific disease markers (hepatitis serology, autoimmune markers, and so forth) help to narrow the differential diagnosis. The definitive diagnosis of all liver diseases usually rests on histology: the liver biopsy is the gold standard. With the advent of treatments for liver disease, identifying and accurately diagnosing patients with liver disorders will result in improved quality of life and survival.

Adult Kawasaki's disease with myocarditis, splenomegaly, and highly elevated serum ferritin levels.

PubMed

Cunha, Burke A; Pherez, Francisco M; Alexiadis, Varvara; Gagos, Marios; Strollo, Stephanie

2010-01-01

Kawasaki's disease is a disease of unknown cause. The characteristic clinical features of Kawasaki's disease are fever> or =102 degrees F for> or =5 days accompanied by a bilateral bulbar conjunctivitis/conjunctival suffusion, erythematous rash, cervical adenopathy, pharyngeal erythema, and swelling of the dorsum of the hands/feet. Kawasaki's disease primarily affects children and is rare in adults. In children, Kawasaki's disease is more likely to be associated with aseptic meningitis, coronary artery aneurysms, and thrombocytosis. In adult Kawasaki's disease, unilateral cervical adenopathy, arthritis, conjunctival suffusion/conjunctivitis, and elevated serum transaminases (serum glutamic oxaloacetic transaminase [SGOT]/serum glutamate pyruvate transaminase [SGPT]) are more likely. Kawasaki's disease in adults may be mimicked by other acute infections with fever and rash, that is, group A streptococcal scarlet fever, toxic shock syndrome (TSS), and Rocky Mountain Spotted Fever (RMSF). Because there are no specific tests for Kawasaki's disease, diagnosis is based on clinical criteria and the syndromic approach. In addition to rash and fever, scarlet fever is characterized by circumoral pallor, oropharyngeal edema, Pastia's lines, and peripheral eosinophilia, but not conjunctival suffusion, splenomegaly, swelling of the dorsum of the hands/feet, thrombocytosis, or an elevated SGOT/SGPT. In TSS, in addition to rash and fever, there is conjunctival suffusion, oropharyngeal erythema, and edema of the dorsum of the hands/feet, an elevated SGOT/SGPT, and thrombocytopenia. Patients with TSS do not have cervical adenopathy or splenomegaly. RMSF presents with fever and a maculopapular rash that becomes petechial, first appearing on the wrists/ankles after 3 to 5 days. RMSF is accompanied by a prominent headache, periorbital edema, conjunctival suffusion, splenomegaly, thrombocytopenia, an elevated SGOT/SGPT, swelling of the dorsum of the hands/feet, but not oropharyngeal

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.

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.

Elevated Serum PSA is Associated With Human Herpesvirus 8 Infection and Increased Circulating Cytokine Levels in Men From Tobago.

PubMed

Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J

2017-05-01

Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acute Alcohol Consumption Elevates Serum Bilirubin, an Endogenous Antioxidant

PubMed Central

O’Malley, Stephanie S.; Gueorguieva, Ralitza; Wu, Ran; Jatlow, Peter I.

2015-01-01

Background Moderate alcohol consumption has been associated with both negative and favorable effects on health. The mechanisms responsible for reported favorable effects remain unclear. Higher (not necessarily elevated) concentrations of serum bilirubin, an antioxidant, have also been associated with reduced risk of cardiovascular disease and all-cause mortality. This study tests the hypothesis that single dose alcohol consumption elevates bilirubin providing a potential link between these observations. Methods 18 healthy individuals (8 cigarette smokers) were administered alcohol, calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL, in random order in 3 laboratory sessions separated by a week. Each session was preceded by and followed by 5–7 days of alcohol abstinence. Serum bilirubin was measured at 7:45 am prior to drinking, at 2 pm, and at 7:45 the next morning. Mixed effects regression models compared baseline and 24 hr. post-drinking bilirubin concentrations. Results Total serum bilirubin (sum of indirect and direct) concentration increased significantly after drinking from baseline to 24 hours in non-smokers (from Mean=0.38, SD=0.24 to Mean=0.51 SD=0.30, F(1, 32.2) =24.24, p<.0001) but not in smokers (from Mean=0.25, SD=0.12 to Mean=0.26, SD=0.15, F(1, 31.1) =0.04, p=0.84). In nonsmokers the indirect bilirubin concentration and the ratio of indirect (unconjugated) to direct (conjugated) bilirubin also increased significantly. Conclusions Alcohol consumption leads to increases in serum bilirubin in nonsmokers. Considering the antioxidant properties of bilirubin, our findings suggest one possible mechanism for the reported association between alcohol consumption and reduced risk of some disorders that could be tested in future longitudinal studies. PMID:25707709

Elevated serum gastrin is associated with a history of advanced neoplasia in Barrett's esophagus.

PubMed

Wang, Judy S; Varro, Andrea; Lightdale, Charles J; Lertkowit, Nantaporn; Slack, Kristen N; Fingerhood, Michael L; Tsai, Wei Yann; Wang, Timothy C; Abrams, Julian A

2010-05-01

Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett's esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. A total of 95 patients were enrolled. The mean age was 64.7 (+/-10.0) years, and 70.5% were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P=0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95% confidence interval (CI): 1.20-24.8). In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.

Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents.

PubMed

Ohlsson, Bodil; Roth, Bodil; Larsson, Ewa; Höglund, Peter

2017-04-01

Calprotectin is a marker of inflammation and zonulin is a marker of intestinal permeability. Diets with lower carbohydrate content and higher contents of fat, fiber and protein, e.g., Okinawan-based diet, are considered to reduce inflammation and intestinal permeability. The aim of the present study was to evaluate calprotectin and zonulin levels in serum and feces after intervention with an Okinawan-based Nordic diet. Thirty patients (17 women) with type 2 diabetes, mean age 57.5±8.2 years, BMI 29.9±4.1 kg/m 2 , were served the diet during 12 weeks, and were followed for another 16 weeks. Anthropometric and metabolic parameters were registered. Fasting levels of calprotectin and zonulin in serum and feces, and hormones in plasma, were measured by Luminex or ELISA before study start and after 12 and 28 weeks. Calprotectin in serum tended to be increased (P=0.074) after 12 weeks. Zonulin in serum and feces were elevated after 12 weeks (P=0.019 vs. P<0.001), and remained elevated in serum after 28 weeks (P=0.014). In contrast to baseline, there was a correlation between calprotectin and zonulin in serum and feces after dietary intervention (P=0.025 vs. P=0.079). Energy percentage of protein in breakfast correlated with serum calprotectin (P=0.008) and tended to correlate with serum zonulin (P=0.059). Calprotectin in serum tended to be elevated, and zonulin in serum and feces are elevated after introduction of an Okinawan-based Nordic diet. These biomarkers correlate with energy percentage of protein.

The elevated serum urea:creatinine ratio in canine babesiosis in South Africa is not of renal origin.

PubMed

de Scally, M P; Leisewitz, A L; Lobetti, R G; Thompson, P N

2006-12-01

Pigmented serum, usually due to free haemoglobin and/or bilirubin, is a common finding in dogs with babesiosis, resulting in interference with all biochemical tests that rely on photochemistry. This is particularly true of urea and creatinine determinations, complicating the diagnosis of acute renal failure, which is a serious complication of babesiosis. A disproportionately raised serum urea concentration of unknown origin occurs in severely anaemic canine babesiosis patients and gives rise to an increased serum urea:creatinine ratio. The assay for cystatin-C, an excellent measure of glomerular filtration rate, is unaffected by free serum haemoglobin, and due to its different intrinsic origins, is free of influence by the metabolic derangements and organ pathology, other than renal disease, encountered in canine babesiosis. Serum cystatin-C was used to compare the concentrations of serum urea and serum creatinine in dogs with the severely anaemic form of canine babesiosis as well as a canine babesiosis-free reference group. Mean serum urea and mean serum urea:creatinine ratio were significantly elevated in the babesia-infected group relative to the reference population in this study. Mean serum creatinine and mean serum cystatin-C were within the reference ranges. Therefore an elevated urea:creatinine ratio in canine babesiosis in the presence of a normal serum creatinine concentration is considered to be caused by an elevated serum urea concentration and is most likely of non-renal origin. Serum creatinine was therefore as specific a measure of renal function as serum cystatin-C in canine babesiosis in this study. The sensitivity of serum creatinine as a measure of renal function was not established by this study. Serum urea, however, proved to be of little use compared to serum cystatin-C and serum creatinine. Serum urea should therefore not be used to diagnose renal failure in canine babesiosis.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

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

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

Ciguatera fish poisoning with elevated muscle enzymes and abnormal spinal MRI.

PubMed

Wasay, Mohammad; Sarangzai, Amanullah; Siddiqi, Ather; Nizami, Qamaruddin

2008-03-01

We report three cases of ciguatera fish poisoning. One patient died secondary to respiratory failure. Two patients showed elevated muscle enzymes and one patients had an abnormal cervical spinal MRI. MRI findings have not been previously described. MRI findings explain the mechanism of the L'hermitte phenomenon (a common complaint) among these patients. Respiratory failure is rare in ciguatera fish poisoning. Our findings suggest this could be related to respiratory muscles involvement.

Abnormality of circadian rhythm of serum melatonin and other biochemical parameters in fibromyalgia syndrome.

PubMed

Mahdi, Abbas Ali; Fatima, Ghizal; Das, Siddhartha Kumar; Verma, Nar Singh

2011-04-01

Fibromyalgia syndrome (FMS) is a complex chronic condition causing widespread pain and variety of other symptoms. It produces pain in the soft tissues located around joints throughout the body. FMS has unknown etiology and its pathophysiology is not fully understood. However, abnormality in circadian rhythm of hormonal profiles and cytokines has been observed in this disorder. Moreover, there are reports of deficiency of serotonin, melatonin, cortisol and cytokines in FMS patients, which are fully regulated by circadian rhythm. Melatonin, the primary hormone of the pineal gland regulates the body's circadian rhythm and normally its levels begin to rise in the mid-to-late evening, remain high for most of the night, and then decrease in the early morning. FMS patients have lower melatonin secretion during the hours of darkness than the healthy subjects. This may contribute to impaired sleep at night, fatigue during the day and changed pain perception. Studies have shown blunting of normal diurnal cortisol rhythm, with elevated evening serum cortisol level in patients with FMS. Thus, due to perturbed level of cortisol secretion several symptoms of FMS may occur. Moreover, disturbed cytokine levels have also been reported in FMS patients. Therefore, circadian rhythm can be an important factor in the pathophysiology, diagnosis and treatment of FMS. This article explores the circadian pattern of abnormalities in FMS patients, as this may help in better understanding the role of variation in symptoms of FMS and its possible relationship with circadian variations of melatonin, cortisol, cytokines and serotonin levels.

Hashimoto's thyroiditis with elevated serum IgG4 concentrations is not equivalent to IgG4 Hashimoto's thyroiditis.

PubMed

Yu, Yang; Yu, Nan; Lu, Guizhi; Li, Ting; Zhang, Yang; Zhang, Jing; Gao, Ying; Gao, Yanming; Guo, Xiaohui

2018-06-01

Hashimoto's thyroiditis (HT) with serum IgG4 concentrations greater than 135 mg/dL can be diagnosed as elevated serum IgG4 HT. HT can also be classified into IgG4 HT and non-IgG4 HT based on an immunohistochemistry analysis of IgG4. The aim of our study was to determine the relationship between elevated serum IgG4 HT and IgG4 HT. Both thyroid tissues and serum samples stored before pathological examination from 93 patients with HT were collected. The serum levels of IgG, IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG and TPOAb IgG4 were measured by ELISAs. The expression levels of IgG4, IgG and TGF-β1 in thyroid tissues were detected by immunohistochemistry. Patients with HT were divided into two groups: elevated serum IgG4 HT (n = 12) and nonelevated serum IgG4 HT (n = 81). Hypothyroidism was found in 5 of 12 cases (41.7%) in the elevated serum IgG4 HT group and 10 of 81 cases (12.3%) in the nonelevated serum IgG4 HT group (P = .023). Serologically, there were no significant differences in the levels of TgAb IgG, TPOAb IgG, TgAb IgG4 and TPOAb IgG4 between the two groups, and the expression of TGF-β1 in thyroid tissues was not significantly different between the groups. Most importantly, the frequency of patients who satisfied the criteria for IgG4 HT diagnosis was comparable (25% vs 20.9%, P = .756). The measurement of serum IgG4 allows the identification of patients with HT closely associated with hypothyroidism. However, our study demonstrated that elevated serum IgG4 HT is not equivalent to IgG4 HT. © 2018 John Wiley & Sons Ltd.

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

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

PubMed Central

Toussirot, Éric; Gaugler, Béatrice; Bouhaddi, Malika; Nguyen, Nhu Uyen; Saas, Philippe; Dumoulin, Gilles

2010-01-01

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined. PMID:21234350

Postmenopausal pregnancy? Evaluation of elevated hCG in a 59-year-old woman.

PubMed

Basham, Mary Margaret; Bryan, Teresa

2017-06-05

Slightly elevated serum human chorionic gonadotropin (hCG) can be a normal finding in postmenopausal women. We report a case of a 59-year-old woman with a history of abnormal uterine bleeding who presented with a concern for pregnancy after developing nausea and vomiting a few weeks after unprotected intercourse. Although pregnancy was extremely unlikely, hCG was obtained in order to reassure the patient since she reported that her mother conceived at the age of 60. Serum hCG was positive, prompting concern for malignancy versus pregnancy. Stable serum hCG levels, elevated follicle-stimulating hormone and negative transvaginal ultrasound ruled out both malignancy and pregnancy. Positive serum pregnancy test and hCG elevation was attributed to normal postmenopausal state. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice.

PubMed

Clinkenbeard, Erica L; Farrow, Emily G; Summers, Lelia J; Cass, Taryn A; Roberts, Jessica L; Bayt, Christine A; Lahm, Tim; Albrecht, Marjorie; Allen, Matthew R; Peacock, Munro; White, Kenneth E

2014-02-01

Fibroblast growth factor 23 (FGF23) gain of function mutations can lead to autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or delayed onset following puberty or pregnancy. We previously demonstrated that the combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice induced FGF23 expression and hypophosphatemia that paralleled the late-onset ADHR phenotype. Because anemia in pregnancy and in premature infants is common, the goal of this study was to test whether iron deficiency alters phosphate handling in neonatal life. Wild-type (WT) and ADHR female breeder mice were provided control or iron-deficient diets during pregnancy and nursing. Iron-deficient breeders were also made iron replete. Iron-deficient WT and ADHR pups were hypophosphatemic, with ADHR pups having significantly lower serum phosphate (p < 0.01) and widened growth plates. Both genotypes increased bone FGF23 mRNA (>50 fold; p < 0.01). WT and ADHR pups receiving low iron had elevated intact serum FGF23; ADHR mice were affected to a greater degree (p < 0.01). Iron-deficient mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25-dihydroxyvitamin D (1,25D). Iron repletion normalized most abnormalities. Because iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C-terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is modulated by iron status in young WT and ADHR mice and that hypoxia independently controls FGF23 expression in situations of normal iron. Therefore, disturbed iron and oxygen metabolism in neonatal life may have important effects on skeletal function and structure through FGF23 activity on phosphate regulation. © 2014 American Society for Bone and Mineral Research.

High serum serotonin in sudden infant death syndrome.

PubMed

Haynes, Robin L; Frelinger, Andrew L; Giles, Emma K; Goldstein, Richard D; Tran, Hoa; Kozakewich, Harry P; Haas, Elisabeth A; Gerrits, Anja J; Mena, Othon J; Trachtenberg, Felicia L; Paterson, David S; Berry, Gerard T; Adeli, Khosrow; Kinney, Hannah C; Michelson, Alan D

2017-07-18

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants ( n = 61) compared with autopsied controls ( n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] ( P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.

Serum interleukin-17 in Egyptian children with systemic lupus erythematosus: is it related to pulmonary affection?

PubMed

Hammad, A; Osman, E; Mosaad, Y; Wahba, M

2017-04-01

Objective Pulmonary involvement in paediatric systemic lupus erythematosus (pSLE) is not an uncommon finding; however, subclinical affection occurs more frequently. Many studies have reported that cytokine dysregulation as interleukin-17 (IL-17) over-expression plays a key role in the pathogenesis of systemic lupus erythematosus (SLE). We aim to assess serum levels of IL-17 A and their association with pulmonary involvement in children with SLE. Methods Serum IL-17A levels - determined by solid phase sandwich ELISA - were assessed in forty-two pSLE patients and compared to 45 age-matched healthy controls. All patients were subjected to pulmonary function tests to detect subclinical pulmonary affection. High-resolution CT (HRCT) chest scan was carried out in patients with abnormal pulmonary function tests (PFTs) and those with chronic respiratory symptoms. Results Abnormal PFTs were found in 73% of patients; of them, only 25% had abnormal findings in HRCT chest. Serum levels of IL-17 A were significantly elevated in pSLE patients as compared to healthy controls ( p < 0.001). The serum levels of IL-17 A had a highly significant positive correlation with SLEDAI ( r = 0.811 and p < 0.001) Strong negative correlation was found between serum levels of IL-17A with both FEV1 and FVC ( p < 0.05). Conclusions Serum IL-17A is elevated in pSLE patients, which correlates with disease activity. IL-17 seems to have a possible role in the pathogenesis of subclinical lung affection. Abnormal PFTS may be found in pSLE patients even with normal radiology.

A distinctive type of infantile inflammatory myopathy with abnormal myonuclei.

PubMed

Sripathi, N; Karpati, G; Carpenter, S

1996-03-01

Four infants developed progressive muscle weakness after a normal initial postnatal development. All patients had a moderate elevation of serum creatine kinase (CK) activity. Muscle biopsies revealed, in addition to myopathic features, endomysial and perivascular inflammation. Electron microscopy disclosed prominent myonuclear abnormalities. Corticosteroids in 3 patients were moderately beneficial. This appears to be a clinicopathologically distinct form of inflammatory myopathy of infants.

[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.

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-05-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome.

Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

PubMed

Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

2007-02-01

Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

Elevated Serum Gastrin Is Associated With a History of Advanced Neoplasia in Barrett’s Esophagus

PubMed Central

Wang, Judy S.; Varro, Andrea; Lightdale, Charles J.; Lertkowit, Nantaporn; Slack, Kristen N.; Fingerhood, Michael L.; Tsai, Wei Yann; Wang, Timothy C.; Abrams, Julian A.

2011-01-01

OBJECTIVES Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett’ s esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS A total of 95 patients were enrolled. The mean age was 64.7 (±10.0) years, and 70.5 % were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P = 0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95 % confidence interval (CI): 1.20–24.8). CONCLUSIONS In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression. PMID:19904251

Creatinine elevation associated with nitromethane exposure: a marker of potential methanol toxicity.

PubMed

Cook, Matthew D; Clark, Richard F

2007-10-01

Nitromethane, methanol, and oil are the common components of radio-controlled (R/C) vehicle fuels. Nitromethane can cause a false elevation of serum creatinine concentration as measured by the widely used Jaffe colorimetric method. We gathered data from our poison control system and from previously published case reports to see if a correlation exists between serum methanol concentrations and spuriously elevated serum creatinine concentrations after human exposures to R/C fuel. The California Poison Control System (CPCS) computerized database was queried for all cases of human exposure to R/C vehicle fuel reported between December 1, 2002 and December 1, 2004. Serum creatinine and methanol concentrations were recorded when available, as was the method used to determine serum creatinine. A MEDLINE search was used to obtain previously published cases of human nitromethane exposure associated with falsely elevated creatinine concentrations. During the 2-year period, serum creatinine concentrations were recorded in 7 of 26 R/C fuel exposures (all ingestions), and 6 of these were abnormal (range of 1.9-11.5 mg/dL). In this series, the higher the serum creatinine concentration measured by Jaffe method, the higher the serum methanol concentration. The MEDLINE search yielded data from six previously published case reports on this topic. The data from these case reports seem to follow the trend seen in our case series. These data suggest that a spuriously elevated serum creatinine (by Jaffe method) may have value as an early surrogate marker of methanol poisoning in those who ingest R/C fuel. Also, the degree to which the serum creatinine is elevated may indicate the severity of methanol poisoning.

Elevated serum erythropoietin in a patient with polycythaemia vera presenting with Budd-Chiari syndrome

PubMed Central

Jones, Catherine; Levy, Yair; Tong, Alex W

2014-01-01

Polycythaemia vera (PV) is a clonal disorder of bone marrow stem cells characterised by erythrocytosis. Diagnosis of PV requires exclusion of secondary causes of polycythaemia. It has been held that an elevated erythropoietin (Epo) level strongly indicates secondary erythrocytosis and excludes PV diagnosis, to the extent that the reduced serum Epo level is currently listed as a minor criterion in the WHO classification scheme for PV. However, patients with PV who co-present with Budd-Chiari syndrome have been documented with elevated serum Epo levels. For these patients, identification of the Janus kinase 2 (JAK2) V617F point mutation along with the transient nature of the Epo elevation provides certainty of PV diagnosis, as illustrated by the proband. In this case report, the patient's positive response to cytoreductive therapy (hydroxyurea 500 mg daily) and phlebotomy (750 mL over three phlebotomies) further supports validity of PV diagnosis with elevated Epo. The patient remains on rivaroxaban (Xarelto) for treatment of her portal vein thrombosis. PMID:25452296

[The relationship between the abnormal behavior and serum C-reactive protein in children with obstructive sleep apnea-hypopnea syndrome].

PubMed

Wang, Yan; Li, Yanzhong; Wang, Xin

2009-12-01

To explore the pathogenesis of abnormal behavior in children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The behavioral problems and C-reactive protein were measured in 40 children with OSAHS and 30 children with habitual snoring who underwent overnight Polysomnography, 40 cases of healthy children for the control group. The ratio of abnormal behavior in OSAHS and habitual snoring children was significantly higher than that of the healthy control group, while no significant difference between the two groups. The content of C-reactive protein in OSAHS children (4.24 mg/L) was significantly higher than habitual snoring (2.76 mg/L) and healthy control group (1.27 mg/L); in habitual snoring children C-reactive protein was higher than in healthy control group. The content of serum C-reactive protein in OSAHS children accompanied by abnormal behavior (4.63 mg/L) was significantly higher than that without abnormal behavior (3.23 mg/L). The content of serum C-reactive protein content in habitual snoring children accompanied by abnormal behavior (3.63 mg/L) was significantly higher than that without abnormal behavior (1.76 mg/L). OSAHS and habitual snoring children have more behavior problems. C-reactive protein levels are higher in children with OSAHS and habitual snoring, and the levels of C-reactive protein are related to the abnormal behavior in these children.

Testosterone replacement elevates the serum uric acid levels in patients with female to male gender identity disorder.

PubMed

Kurahashi, Hiroaki; Watanabe, Masami; Sugimoto, Morito; Ariyoshi, Yuichi; Mahmood, Sabina; Araki, Motoo; Ishii, Kazushi; Nasu, Yasutomo; Nagai, Atsushi; Kumon, Hiromi

2013-01-01

Gender identity disorder (GID) results from a disagreement between a person's biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual's muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

PubMed

Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

2010-02-01

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

[Interpretation of elevated serum troponin levels in end stage renal disease - case 2/2010].

PubMed

Artunc, Ferruh; Haap, Michael; Heyne, Nils; Weyrich, Peter; Wolf, Sabine

2010-02-01

We report on a female patient with rheumatoid arthritis and end-stage renal-disease following AA-amyloidosis who presented with chest pain to the emergency department. ECG showed no signs of ischemia, echocardiography revealed a concentric left ventricular hypertrophy with increased texture. Serum concentration of troponin I was mildly elevated whereas creatine kinase (CK)/ CK-MB were normal. The chief complaints resolved spontaneously and there was no change in the serum troponin-I and CK/CK-MB concentrations. Coronary heart disease was ruled out by angiography and cardiac involvement of the underlying AA-amyloidosis was diagnosed. After one month, the patient suffered from a syncope complicated by a pelvic ring fracture with hemorrhagic shock and declined chronic dialysis treatment. Patients with end-stage renal disease may exhibit a persisting elevation of serum troponin concentration reflecting the high burden of cardiovascular disease. Myocardial infarction can be distinguished by the lack of increase in serial tests. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Elevated serum α-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Moley, Kelle H

2011-10-01

To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. Prospective cohort. University hospital. Ninety-one women undergoing IVF. Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids. Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686). Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

PubMed

Marshall, Nicole E; Fraley, Gwen; Feist, Cori; Burns, Michael J; Pereira, Leonardo

2012-08-01

To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

PubMed

Coelho-Borges, Silvia; Cheinquer, Hugo; Wolff, Fernando Herz; Cheinquer, Nelson; Krug, Luciano; Ashton-Prolla, Patricia

2012-01-01

Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Abnormal serum IgG subclass pattern in children with Down's syndrome.

PubMed Central

Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

1992-01-01

Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome. PMID:1534650

/sup 67/Ga 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

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /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 less than .005). The frequency of abnormalmore » /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 indentification of inactive sacoidosis.« less

Early Elevation of Serum TNFα is Associated with Poor Outcome in Subarachnoid Hemorrhage

PubMed Central

Chou, Sherry HY.; Feske, Steven K.; Atherton, Juli; Konigsberg, Rachael G.; De Jager, Philip L.; Du, Rose; Lo, Eng H.; Ning, MingMing

2013-01-01

Objective Subarachnoid hemorrhage (SAH) is associated with inflammation which may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6) are associated with vasospasm and poor outcome in SAH. Methods In 52 consecutive SAH subjects, we compared TNFα and IL-6 levels on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to poor outcome at 3- and 6-months. Vasospasm was defined as >50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score >2. Results Elevated TNFα on post-SAH days 2–3 was associated with poor 3-month outcome (p=0.0004). Global elevation of TNFα over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (p=0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNFα nor IL-6 levels were associated with vasospasm. Conclusions Elevation in serum TNFα on post-SAH days 2–3 and global elevation of TNFα over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNFα in SAH-related brain injury and its potential as a SAH outcome biomarker. PMID:22918199

Elevated levels of serum nidogen-2 in esophageal squamous cell carcinoma.

PubMed

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Lee, Nikki Pui Yue; Chan, Kin Tak; Law, Simon Ying-Kit; Lung, Maria Li

2018-02-14

Nidogen-2 (NID2), a secretory basement membrane protein, has been implicated as a potential biomarker in ovarian cancer and hepatocellular carcinoma. In this study, we aimed to investigate the utility of detecting serum NID2 levels for identification of esophageal squamous cell carcinoma (ESCC) patients and prediction of poor survival outcome. Using an in-house NID2 enzyme-linked immunosorbent assay (ELISA), serum samples from 101 ESCC patients and 50 healthy controls were screened for their NID2 levels. The serum NID2 levels in ESCC patients (median 24.4 μg/L) are significantly higher (p= 4.3e-09) than that of the healthy controls (median 15.85 μg/L). The receiver operating characteristic (ROC) curve demonstrated an area under the curve of 0.756. At the threshold of 17.95 μg/L, the sensitivity and specificity achieved are 0.76 and 0.63, respectively. Kaplan-Meier survival analysis revealed that patients with high serum NID2 levels (⩾ 32.6 μg/L) have significantly higher risk of death (HR = 1.984, 95% CI: 1.175-3.349; log-rank p-value = 0.012) compared to those with low serum NID2 levels (< 20.0 μg/L). In conclusion, we show that detecting the elevation of serum NID2 levels has potential diagnostic and prognostic value for ESCC patients.

Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians.

PubMed

Haren, Matthew T; Li, Ming; Petkov, John; McDermott, Robyn A

2010-08-03

The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (>or=50 U/L) were analyzed using logistic regression. Overall, 26% of the population had GGT>or=50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT.

Alcohol, metabolic risk and elevated serum gamma-glutamyl transferase (GGT) in Indigenous Australians

PubMed Central

2010-01-01

Background The interaction between overweight/obesity and alcohol intake on liver enzyme concentrations have been demonstrated. No studies have yet examined the interaction between metabolic syndrome or multiple metabolic risk factors and alcohol intake on liver enzymes. The aim of this study was to examine if alcohol consumption modifies the effect of metabolic risk on elevated serum GGT in Indigenous Australians. Methods Data were from N = 2609 Indigenous Australians who participated in a health screening program in rural far north Queensland in 1999-2000 (44.5% response rate). The individual and interactive effects of metabolic risk and alcohol drinking on elevated serum GGT concentrations (≥50 U/L) were analyzed using logistic regression. Results Overall, 26% of the population had GGT≥50 U/L. Elevated GGT was associated with alcohol drinking (moderate drinking: OR 2.3 [95%CI 1.6 - 3.2]; risky drinking: OR 6.0 [4.4 - 8.2]), and with abdominal obesity (OR 3.7 [2.5 - 5.6]), adverse metabolic risk cluster profile (OR 3.4 [2.6 - 4.3]) and metabolic syndrome (OR 2.7 [2.1 - 3.5]) after adjustment for age, sex, ethnicity, smoking, physical activity and BMI. The associations of obesity and metabolic syndrome with elevated GGT were similar across alcohol drinking strata, but the association of an adverse metabolic risk cluster profile with elevated GGT was larger in risky drinkers (OR 4.9 [3.7 - 6.7]) than in moderate drinkers (OR 2.8 [1.6 - 4.9]) and abstainers (OR 1.6 [0.9 - 2.8]). Conclusions In this Indigenous population, an adverse metabolic profile conferred three times the risk of elevated GGT in risky drinkers compared with abstainers, independent of sex and ethnicity. Community interventions need to target both determinants of the population's metabolic status and alcohol consumption to reduce the risk of elevated GGT. PMID:20682033

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

PubMed

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

1984-03-01

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

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD).

PubMed

Bengtsson, A; Holm, L; Bäck, O; Fransson, J; Scheynius, A

1997-09-01

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.

Elevated serum homocysteine level is not associated with serum C-reactive protein in patients with probable Alzheimer's disease.

PubMed

Lepara, Orhan; Alajbegovic, Azra; Zaciragic, Asija; Nakas-Icindic, Emina; Valjevac, Amina; Lepara, Dzenana; Hadzovic-Dzuvo, Almira; Fajkic, Almir; Kulo, Aida; Sofic, Emin

2009-12-01

Elevated plasma homocysteine (Hcy) levels have been associated with Alzheimer's disease (AD) and cognitive impairment. Studies have shown that Hcy may have direct and indirect neurotoxicity effects. The aim of the study was to investigate serum Hcy concentration in patients with probable AD with age-matched controls and to determine whether there was an association between serum Hcy and C-reactive protein concentration in patients with probable AD. We also aimed to determine whether there was an association between serum tHcy concentration and cognitive impairment in patients with probable AD. Serum concentration of total Hcy was determined by the fluorescence polarization immunoassay on the AxSYM system, and serum C-reactive protein (CRP) concentration was determined by means of particle-enhanced immunonephelometry with the use of BN II analyzer. Cognitive impairment was tested by the MMSE score. Body mass index (BMI) was calculated for each subject included in the study. Age, systolic and diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 12.60 mumol/L, while in patients with probable AD the mean serum tHcy concentration was significantly higher than 16.15 mumol/L (p < 0.01). A significant negative association between serum tHcy concentration and cognitive impairment tested by the MMSE score in patients with probable AD was determined (r = -0.61634; p < 0.001). Positive, although not significant correlation between CRP and serum tHcy concentrations in patients with AD, was observed. Increased tHcy concentration in patients with probable AD, and the established negative correlation between serum tHcy concentration and cognitive damage tested by MMSE score in the same group of patients, suggests the possible independent role of Hcy in the pathogenesis of AD and cognitive impairment associated with this disease.

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

Sensitivity and specificity of western blot testing of cerebrospinal fluid and serum for diagnosis of equine protozoal myeloencephalitis in horses with and without neurologic abnormalities.

PubMed

Daft, Barbara M; Barr, Bradd C; Gardner, Ian A; Read, Deryck; Bell, William; Peyser, Karen G; Ardans, Alex; Kinde, Hailu; Morrow, Jennifer K

2002-10-01

To determine sensitivity and specificity of western blot testing (WBT) of CSF and serum for diagnosis of equine protozoal myeloencephalitis (EPM) in horses with and without neurologic abnormalities. Prospective investigation. 65 horses with and 169 horses without neurologic abnormalities. CSF and serum from horses submitted for necropsy were tested for Sarcocystis neurona-specific antibody with a WBT. Results of postmortem examination were used as the gold standard against which results of the WBT were compared. Sensitivity of WBT of CSF was 87% for horses with and 88% for horses without neurologic abnormalities. Specificity of WBT of CSF was 44% for horses with and 60% for horses without neurologic abnormalities. Regardless of whether horses did or did not have neurologic abnormalities, sensitivity and specificity of WBT of serum were not significantly different from values for WBT of CSF. Ninety-four horses without EPM had histologic evidence of slight CNS inflammation. The low specificity of WBT of CSF indicated that it is inappropriate to diagnose EPM on the basis of a positive test result alone because of the possibility of false-positive test results. The high sensitivity, however, means that a negative result is useful in ruling out EPM. There was no advantage in testing CSF versus serum in horses without neurologic abnormalities. Slight CNS inflammation was common in horses with and without S neurona-specific antibodies in the CSF and should not be considered an indication of CNS infection with S neurona.

Elevated serum galectin-9 levels in patients with atopic dermatitis.

PubMed

Nakajima, Rina; Miyagaki, Tomomitsu; Oka, Tomonori; Nakao, Momoko; Kawaguchi, Makiko; Suga, Hiraku; Morimura, Sohshi; Kai, Hiromichi; Asano, Yoshihide; Tada, Yayoi; Kadono, Takafumi; Sato, Shinichi; Sugaya, Makoto

2015-07-01

Galectin-9 is a member of the galectin family that has a wide spectrum of biological functions. Among them, galectin-9 has been known mainly as a potent chemoattractant for eosinophils. In addition, galectin-9 alters the T-cell balance by negatively regulating T-helper (Th)1 and Th17 cells, resulting in Th2 polarization. Atopic dermatitis (AD) is a skin allergic disease characterized by peripheral eosinophilia, mast cell activation and predominance of Th2 cells. To investigate possible roles of galectin-9 in AD, we measured serum galectin-9 levels in AD patients and investigated galectin-9 expression in lesional skin by immunohistochemistry. Serum galectin-9 levels in patients with AD were significantly higher than those in healthy controls and correlated with the Eczema Area and Severity Index. Serum galectin-9 levels were decreased after treatment, accompanied by improvement of skin lesions. Immunohistochemical study revealed that galectin-9 was expressed on epidermal keratinocytes and mast cells in lesional skin of AD. Our results suggest that elevated galectin-9 expression is associated with progression of AD and that galectin-9 could be a therapeutic target in AD. © 2015 Japanese Dermatological Association.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

PubMed

Vellinga, Namkje A R; Boerma, E Christiaan; Koopmans, Matty; Donati, Abele; Dubin, Arnaldo; Shapiro, Nathan I; Pearse, Rupert M; van der Voort, Peter H J; Dondorp, Arjen M; Bafi, Tony; Fries, Michael; Akarsu-Ayazoglu, Tulin; Pranskunas, Andrius; Hollenberg, Steven; Balestra, Gianmarco; van Iterson, Mat; Sadaka, Farid; Minto, Gary; Aypar, Ulku; Hurtado, F Javier; Martinelli, Giampaolo; Payen, Didier; van Haren, Frank; Holley, Anthony; Gomez, Hernando; Mehta, Ravindra L; Rodriguez, Alejandro H; Ruiz, Carolina; Canales, Héctor S; Duranteau, Jacques; Spronk, Peter E; Jhanji, Shaman; Hubble, Sheena; Chierego, Marialuisa; Jung, Christian; Martin, Daniel; Sorbara, Carlo; Bakker, Jan; Ince, Can

2017-10-18

Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

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

PubMed Central

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

2015-01-01

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

Racial and Ethnic Variation in Time to Prostate Biopsy After an Elevated Screening Level of Serum Prostate-specific Antigen.

PubMed

Reading, Stephanie R; Porter, Kimberly R; Hsu, Jin-Wen Y; Wallner, Lauren P; Loo, Ronald K; Jacobsen, Steven J

2016-10-01

To examine the racial and ethnic variation in time to prostate biopsy after an elevated screening level of serum prostate-specific antigen (PSA). Male members of the Kaiser Permanente of Southern California health plan, 45 years of age or older, with no history of prostate cancer or a prostate biopsy, and at least 1 elevated screening level of serum PSA between January 1, 1998 and December 31, 2007 were retrospectively identified (n = 59,506). All participants were passively followed via electronic health records until their time of prostate biopsy, death, membership disenrollment, or study conclusion (December 31, 2014), whichever was the initial event. Proportional hazard regression analyses were used to estimate the association between time from an elevated screening level of serum PSA to prostate biopsy, adjusting for age, benign prostatic hyperplasia, prostatitis, type 2 diabetes mellitus, hypertension, and Charlson Comorbidity Index score. Median time until biopsy was 0.6 years (214 days), with approximately 41% of participants receiving a prostate biopsy within the study period. Results from the fully adjusted analysis indicated that the non-Hispanic Asian or Pacific Islanders (hazard ratio: 1.10, 95% confidence interval: [1.04, 1.15]) and the non-Hispanic blacks (hazard ratio: 1.04, 95% confidence interval: [1.00, 1.08]) had a slightly shorter time to prostate biopsy after an elevated screening level of serum PSA compared to the non-Hispanic whites. These data suggest that, within an integrated healthcare organization, minimal differences exist between racial and ethnic subgroups in their time to prostate biopsy after an elevated screening level of serum PSA. Copyright © 2016. Published by Elsevier Inc.

Nonpalpable testicular pure seminoma with elevated serum alpha-fetoprotein presenting with retroperitoneal metastasis: a case report.

PubMed

Iwatsuki, Shoichiro; Naiki, Taku; Kawai, Noriyasu; Etani, Toshiki; Iida, Keitaro; Ando, Ryosuke; Nagai, Takashi; Okada, Atsushi; Tozawa, Keiichi; Sugiyama, Yosuke; Yasui, Takahiro

2016-05-05

Patients with a primary pure seminoma in the testis who have elevated serum alpha-fetoprotein are rare and should be treated as patients with nonseminomatous germ cell tumors. However, nonpalpable testicular tumors in this condition have never been reported. We describe a case of nonpalpable pure testicular seminoma with elevated serum alpha-fetoprotein presenting retroperitoneal metastasis. A 29-year-old Asian man was referred to our hospital with right flank pain. Computed tomography showed a mass located between his aorta and inferior vena cava, but a testicular tumor was not detected. His serum levels of lactate dehydrogenase, alpha-fetoprotein, and DUPAN-2 were high. Although no tumor or nodule was palpable in his testis, ultrasonography revealed multiple low echoic lesions in his right testicular parenchyma. He was diagnosed with right testicular cancer with retroperitoneal lymph node metastasis and underwent right high orchiectomy. A pathological examination revealed pure seminoma and no nonseminomatous components were found in the specimen. Three courses of induction systemic chemotherapy (cisplatin, etoposide, and bleomycin) normalized his serum alpha-fetoprotein and DUPAN-2 levels. Three additional courses of chemotherapy (etoposide and bleomycin) were performed, and treatment was completed with laparoscopic retroperitoneal lymph node dissection. Pathology of the dissected specimen showed fibrous and necrotic tissue with no viable cells. He is alive without recurrence 54 months after orchiectomy. We report a case of pure testicular seminoma with elevated serum alpha-fetoprotein and DUPAN-2 presenting retroperitoneal metastasis. We recommend an ultrasound examination of bilateral testes when large retroperitoneal tumors are detected in young men, even if a mass is not palpable in the scrotum.

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

PubMed Central

Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

2014-01-01

Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

PubMed

Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

2005-10-01

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

Elevated serum β₂-GPI-Lp(a) complexes levels in children with nephrotic syndrome.

PubMed

Zhang, Chunni; Luo, Yang; Huang, Zhongwei; Xia, Zhengkun; Cai, Xiaoyi; Yang, Yuhua; Niu, Dongmei; Wang, Junjun

2012-10-09

The complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a) [β₂-GPI-Lp(a)] exist in human circulation and are increased in serum from patients with some autoimmune diseases. This study aims to investigate the concentration of β₂-GPI-Lp(a) in serum of children with idiopathic nephrotic syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and renal function parameters to explore the potential of the complexes as an additional marker for evaluating pediatric NS. Serum concentrations of β₂-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by "Sandwich" ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The levels of serum lipids and kidney parameters were also determined. Multivariate logistic regression analysis was performed to identify correlate of β₂-GPI-Lp(a) and NS. The serum concentrations of β₂-GPI-Lp(a) complexes in children with NS were significantly higher than those in controls (median 0.95 U/ml vs 0.28 U/ml, P<0.0001). Ox-Lp(a) levels were also markedly elevated (median 14.55 mg/l vs 2.60 mg/l, P<0.0001] in NS children. The concentrations of β₂-GPI-Lp(a) were positively correlated with ox-Lp(a) (r=0.246, P=0.028), but not with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with Lp(a) (r=0.301, P=0.007) in NS children. Multivariate logistic regression analysis identified a positive association between NS and β₂-GPI-Lp(a) (OR=13.694, 95% CI 6.400-29.299, P<0.0001), after adjusting for kidney function parameters, serum lipids and ox-Lp(a). Elevated β₂-GPI-Lp(a) level was an independent and significant risk factor for pediatric NS and, enhanced Lp(a) oxidation partly contributes to the formation of β₂-GPI-Lp(a) complexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Serum Interleukin-34 Levels Are Elevated in Patients with Systemic Lupus Erythematosus.

PubMed

Wang, Hongxu; Cao, Ju; Lai, Xiaofei

2016-12-28

Interleukin-34 (IL-34) was initially identified as an alternative ligand for the colony-stimulating factor-1 receptor (CSF-1R) to mediate the biology of mononuclear phagocytic cells. Recently, IL-34 was found to be associated with chronic inflammation, such as in rheumatoid arthritis (RA). Both RA and systemic lupus erythematosus (SLE) are multifactorial autoimmune diseases and are characterized by excessive immune and inflammatory responses. Thus, we investigated whether IL-34 is involved in the pathogenesis of SLE. In all, 78 SLE patients and 53 healthy controls were enrolled in the research. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the concentrations of serological IL-34. Then serum IL-34 levels between the SLE group and healthy controls were analyzed by the Mann-Whitney U test. Meanwhile, the correlations between the serum IL-34 levels and disease activity indexes and other established serum markers were assessed. Furthermore, the serum IL-34 levels of 20 active SLE patients were reevaluated when diseases were in the remission stage from corticosteroids or immunosuppressive drugs. Serum IL-34 levels were significantly higher in SLE patients compared to healthy controls. Their levels were remarkably associated with accumulation of the clinical features of SLE. Additionally, IL-34 titers were positively correlated with the SLE disease activity indexes, anti-double-stranded DNA antibody (anti-dsDNA) titers and C-reactive protein (CRP) levels, and inversely with complement3 (C3) levels. Moreover, serum IL-34 levels were significantly decreased after successful treatment of SLE. Serum IL-34 could be a candidate biomarker for SLE as there are elevated serum levels in treatment-naive SLE patients and we saw a significant decrease after effective treatment.

Factors associated with serum thyroglobulin in a Ukrainian cohort exposed to iodine-131 from the accident at the Chernobyl Nuclear Plant.

PubMed

Peters, Kamau O; Tronko, Mykola; Hatch, Maureen; Oliynyk, Valeriy; Terekhova, Galyna; Pfeiffer, Ruth M; Shpak, Victor M; McConnell, Robert J; Drozdovitch, Vladimir; Little, Mark P; Zablotska, Lydia B; Mabuchi, Kiyohiko; Brenner, Alina V; Cahoon, Elizabeth K

2017-07-01

Serum thyroglobulin (Tg) is associated with the presence of thyroid disease and has been proposed as a biomarker of iodine status. Few studies have examined factors related to serum Tg in populations environmentally exposed to ionizing radiation and living in regions with endemic mild-to-moderate iodine deficiency. We screened 10,430 individuals who were living in Ukraine and under 18 years of age at the time of the 1986 Chernobyl Nuclear Power Plant accident for thyroid disease from 2001 to 2003. We estimated the percent change (PC) in serum Tg associated with demographic factors, iodine-131 thyroid dose, and indicators of thyroid structure and function using linear regression. We also examined these relationships for individuals with and without indications of thyroid abnormality. Mean and median serum Tg levels were higher among participants with abnormal thyroid structure/function. Percent change in serum Tg increased among females, smokers and with older age (p-values<0.001), and Tg increased with increasing thyroid volume, and serum thyrotropin (p-values for trend<0.001). We found no evidence of significant associations between iodine-131 thyroid dose and Tg. Serum Tg levels were inversely associated with iodized salt intake (PC=-7.90, 95% confidence interval: -12.08, -3.52), and over the range of urinary iodine concentration, the odds of having elevated serum Tg showed a U-shaped curve with elevated Tg at low and high urinary iodine concentrations. Serum Tg may be a useful indicator of population iodine status and a non-specific biomarker of structural and functional thyroid abnormalities in epidemiological studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum bicarbonate and structural and functional cardiac abnormalities in CKD - A report from the CRIC study

PubMed Central

Dobre, Mirela; Roy, Jason; Tao, Kaixiang (Kelvin); Anderson, Amanda; Bansal, Nisha; Chen, Jing; Deo, Raj; Drawz, Paul; Feldman, Harold; Hamm, LL; Hostetter, Thomas; Kusek, John W; Lora, Claudia; Ojo, Akinlolu; Sharma, Kumar; Rahman, Mahboob

2016-01-01

Background Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. Methods The association between serum bicarbonate and left ventricular hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction and diastolic dysfunction were assessed in 3483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. Results The mean eGFR was 42.5±17ml/min per 1.73m2. The overall prevalence of LVH was 51.2%, with 57.8%, 50.9% and 47.7% for bicarbonate categories <22, 22-26, and >26mmol/L, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95%CI 1.07–1.64, and 1.57; 95%CI 1.14–2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR1.07; 95%CI 0.66–1.72, and 1.27; 95%CI 0.64–2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up no significant changes in LV mass or EF were observed in any bicarbonate strata. Conclusions In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. PMID:27241893

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.

Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment.

PubMed

Iwasa, Motoh; Ishihara, Tomoaki; Mifuji-Moroka, Rumi; Fujita, Naoki; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Iwata, Kazuko; Kaito, Masahiko; Takei, Yoshiyuki

2015-01-01

Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT. Serum BCAA levels in subjects with DM were higher than non-DM and those in subjects with NAFL were also higher than non-NAFL. Treatment with pioglitazone and alogliptin (19 of 43 DM subjects) improved serum haemoglobin A1c and decreased BCAA levels. The decrease in BCAAs with improved glucose metabolism suggests that abnormal glucose metabolism is also a factor in elevated BCAA levels. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Body Fatness and Risk for Elevated Blood Pressure, Total Cholesterol, and Serum Lipoprotein Ratios in Children and Adolescents.

ERIC Educational Resources Information Center

Williams, Daniel P.; And Others

1992-01-01

Examines the relationship between body fat percent and risk for elevated blood pressure, serum total cholesterol, and serum lipoprotein ratios in 1,230 African-American and 2,090 white 5-18 year olds (1,667 males and 1,653 females). Results support body fatness standards in children and adolescents as cardiovascular risk factors. (SLD)

Elevated Serum Liver Enzymes in Patients with Obstructive Sleep Apnea-hypopnea Syndrome.

PubMed

Li, Jie; Zhang, Yan-Lin; Chen, Rui; Wang, Yi; Xiong, Kang-Ping; Huang, Jun-Ying; Han, Fei; Liu, Chun-Feng

2015-11-20

Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5-14 events/h, 15-29 events/h, and ≥30 events/h. A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO 2 ), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS.

Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.

PubMed

Robinson, Antwon D; Ramanathan, Kodangudi B; McGee, Jesse E; Newman, Kevin P; Weber, Karl T

2011-08-01

The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.

Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

PubMed

Kalkan, Çağdaş; Karakaya, Fatih; Soykan, İrfan

2016-11-01

Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (p<0.001). The presence of corpus atrophy (p=0.026, OR: 5.03, CI 95%: 1.21-20.88, β=1.61) and presence of enterochromaffin-like cell hyperplasia (p=0.017, OR: 6.59, CI 95%: 1.4-31.08, β=1.88) were found as risk factors associated with serum chromogranin A level. Factors influencing raised serum chromogranin A levels in autoimmune gastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

Serum titanium, niobium and aluminium levels two years following instrumented spinal fusion in children: does implant surface area predict serum metal ion levels?

PubMed

Cundy, Thomas P; Cundy, William J; Antoniou, Georgia; Sutherland, Leanne M; Freeman, Brian J C; Cundy, Peter J

2014-11-01

Measurement of serum metal ion levels is used to determine systemic exposure to implant-derived metal debris that may be generated by processes of wear and corrosion. The aim of this study is to investigate predictors of serum metal ion levels in children undergoing instrumented spinal arthrodesis using a titanium alloy, focusing on implant characteristics and instrumentation construct design variables. This prospective longitudinal cohort study involved 33 children. Serum samples were obtained preoperatively:and at five defined interval periods over the first:two post-operative years. Samples were analysed using high resolution:inductively coupled plasma mass spectrometry to measure titanium, niobium and aluminium concentrations. Instrumentation characteristics were catalogued and construct surface area (SA) measurements calculated using an implant-specific software algorithm tool. Significantly elevated levels of serum titanium and niobium were observed (p< 0.0001), with >95 % of post-operative levels abnormally elevated. Significant predictors of serum titanium and niobium levels included time since surgery, surgical procedure (posterior or anterior fusion), number of levels fused, number of pedicle screws inserted, total rod length, total metal SA, total exposed metal SA and total metal-on-metal SA. All significant instrumentation variables were highly correlated. There is a strong relationship between implant SA and both serum titanium and niobium levels. The direct clinical implications of these findings for patients are uncertain, but remain of concern. Surgeons should be aware of the strong correlation between implant surface area of the chosen construct and the subsequent serum metal ion levels.

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children.

PubMed

Watanabe, Kae; Karimpour-Fard, Anis; Michael, Alix; Miyamoto, Shelley D; Nakano, Stephanie J

2018-04-30

Cardiac allograft vasculopathy (CAV) is a leading cause of retransplantation and death in pediatric heart transplant recipients. Our aim was to evaluate the association between serum vascular endothelial growth factor-A (VEGF) and CAV development in the pediatric heart transplant population. In this retrospective study performed at a university hospital, VEGF concentrations were measured by enzyme-linked immunosorbent assay in banked serum from pediatric heart transplant recipients undergoing routine cardiac catheterization. In subjects with CAV (n = 29), samples were obtained at 2 time-points: before CAV diagnosis (pre-CAV) and at the time of initial CAV diagnosis (CAV). In subjects without CAV (no-CAV, n = 16), only 1 time-point was used. VEGF concentrations (n = 74) were assayed in duplicate. Serum VEGF is elevated in pediatric heart transplant recipients before catheter-based diagnosis of CAV (no-CAV mean: 144.0 ± 89.05 pg/ml; pre-CAV mean: 316.2 ± 118.3 pg/ml; p = 0.0002). Receiver-operating characteristic curve analysis of pre-CAV VEGF levels demonstrated an area under the curve of 87.7% (p = 0.0002), with a VEGF level of 226.3 pg/ml predicting CAV development with 77.8% sensitivity and 91.7% specificity. VEGF is similarly elevated in subjects with angiographically diagnosed CAV and in those with normal angiography but intravascular ultrasound (IVUS) evidence of CAV. The increase in serum VEGF before onset of detectable CAV is fundamental to its utility as a predictive biomarker and suggests further investigations of VEGF in the pathogenesis of CAV are warranted in the pediatric heart transplant population. Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Management of abnormal serum markers in the absence of aneuploidy or neural tube defects

PubMed Central

Schnettler, William T.; Hacker, Michele R.; Barber, Rachel E.; Rana, Sarosh

2013-01-01

Objective Few guidelines address the management of pregnancies complicated by abnormal maternal serum analytes (MSAs) in the absence of aneuploidy or neural tube defects (NTDs). Our objective was to gather preliminary data regarding current opinions and management strategies among perinatologists in the US. Methods This survey of Maternal Fetal Medicine (MFM) physicians and fellows used a secure electronic web-based data capture tool. Results A total of 545 potential participants were contacted, and 136 (25%) responded. The majority were experienced academic physicians with robust practices. Nearly all (97.7%) respondents reported a belief in an association between abnormal MSAs and adverse pregnancy outcomes other than aneuploidy or NTDs. Plasma protein A (PAPP-A) and α-fetoprotein (AFP) were most often chosen as markers demonstrating a strong association with adverse outcomes. Most (86.9%) respondents acknowledged that abnormal MSAs influenced their counseling approach, and the majority (80.1%) offered additional ultrasound examinations. Nearly half started at 28 weeks and almost one-third at 32 weeks. Respondents acknowledging a relevant protocol in their hospital or practice were more likely to offer additional antenatal testing (p = 0.01). Conclusions Although most perinatologists were in agreement regarding the association of MSAs with adverse pregnancy outcomes, a lack of consensus exists regarding management strategies. PMID:22372385

Brief oral stimulation, but especially oral fat exposure, elevates serum triglycerides in humans

PubMed Central

Mattes, Richard D.

2009-01-01

Oral exposure to dietary fat results in an early initial spike, followed by a prolonged elevation, of serum triglycerides in humans. The physiological and pathophysiological implications remain unknown. This study sought to determine the incidence of the effect, the required fat exposure duration, and its reliability. Thirty-four healthy adults participated in four to six response-driven trials held at least a week apart. They reported to the laboratory after an overnight fast, a catheter was placed in an antecubital vein, and a blood sample was obtained. Participants then ingested 50 g of safflower oil in capsules with 500 ml of water within 15 min to mimic a high fat meal but without oral fat exposure. Blood was collected 0, 10, 20, 30, 40, 50, 60, 120, 240, 360, and 480 min after capsule ingestion with different forms (full fat, nonfat, none) and durations of oral fat exposures (10 s, 5 min, 20 min, and/or 2 h). A triglyceride response (increase of triglyceride >10 mg/dl within 30 min) was observed in 88.2%, 70.5%, and 50% of participants with full-fat, nonfat, and no oral exposure, respectively. Test-retest reliability was 75% with full-fat exposure but only 45.4% with nonfat exposure. Full-fat and nonfat exposures led to comparable significant elevations of triglyceride over no oral stimulation with 10-s exposures, but full fat led to a greater rise than nonfat with 20 min of exposure. These data indicate that nutritionally relevant oral fat exposures reliably elevate serum triglyceride concentrations in most people. PMID:19074638

Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

PubMed Central

Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

2011-01-01

Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

Elevated Serum Liver Enzymes in Patients with Obstructive Sleep Apnea-hypopnea Syndrome

PubMed Central

Li, Jie; Zhang, Yan-Lin; Chen, Rui; Wang, Yi; Xiong, Kang-Ping; Huang, Jun-Ying; Han, Fei; Liu, Chun-Feng

2015-01-01

Background: Obstructive sleep apnea-hypopnea syndrome (OSAS) is associated with elevated liver enzymes and fatty liver. The purpose of this study was to measure serum liver enzyme levels in patients evaluated by polysomnography (PSG) and the factors associated with liver injury in OSAS patients. Methods: All patients referred to PSG for evaluation of sleep apnea symptoms between June 2011 and November 2014 were included in this study. Demographic data and PSG parameters were recorded. Serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase levels were systematically measured. OSAS patients were divided into mild, moderate, and severe groups according to the apnea-hypopnea index (AHI) values of 5–14 events/h, 15–29 events/h, and ≥30 events/h. Results: A total of 540 patients were enrolled in this study; among these patients, 386 were male. Elevated liver enzymes were present in 42.3% of OSAS patients (32.4% in mild/moderate group; 51.0% in severe group) and 28.1% patients without OSAS. Patients with OSAS had higher body mass index (BMI) (P < 0.01). In the bivariate correlation, the liver enzymes level was negatively correlated with age and the lowest arterial oxygen saturation (SaO2), and was positively correlated with BMI, oxygen desaturation index, percent of total time with oxygen saturation level <90% (TS90%), AHI, total cholesterol (TC), and triglyceride (TG). In logistic regression analysis, Age, BMI, TS90%, TC, and TG were included in the regression equation. Conclusions: Our data suggest that OSAS is a risk factor for elevated liver enzymes. The severity of OSAS is correlated with liver enzyme levels; we hypothesize that hypoxia is one of main causes of liver damage in patients with OSAS. PMID:26608975

Disease spectrum of abnormal serum free light chain ratio and its diagnostic significance

PubMed Central

Xu, Bin; Tang, Yi; Zhou, Jianfeng; Zhang, Peiling; Li, Huijun

2017-01-01

Objective To analyze the spectrum of abnormal serum free light chain ratio (sFLC κ/λ ratio), and to redefine the range of sFLC κ/λ ratio, so as to achieve hierarchical diagnosis of diseases with abnormal sFLC κ/λ ratio, resulting in the increased sensitivity and specificity in the diagnosis of monoclonal plasma diseases. Methods Enrolled 1,340 patients with abnormal sFLC κ/λ ratio (<0.26 or >1.65) were grouped: (1) group A: malignant plasma diseases; (2) group B: monoclonal gammopathies of undetermined significance (MGUS); (3) group C: reactive plasma diseases. These patients were further divided by renal function eGFR <60 or >60 ml/min/1.73m2 to eliminate renal diseases influencing the results. Statistical analyses was performed by using SPSS 22 software. Results When sFLC κ/λ ratio >3.49 and eGFR >60ml/min/1.73m2, the sensitivity and specificity of the diagnosis of malignant plasma diseases were 86.1% and 94.0%, respectively. When sFLC κ/λ ratio >2.89 and eGFR <60ml/min/1.73m2, the sensitivity and specificity of the diagnosis of malignant plasma diseases were 92.0% and 97.0%, respectively. Conclusion The sensitivity and specificity of the diagnosis of monoclonal plasma diseases can be significantly improved by redefining the cut-off value of sFLC κ/λ ratio and the renal function index of eGFR. PMID:29137262

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia

PubMed Central

Lim, Young H.; Ovejero, Diana; Sugarman, Jeffrey S.; DeKlotz, Cynthia M.C.; Maruri, Ann; Eichenfield, Lawrence F.; Kelley, Patrick K.; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J.; Gafni, Rachel I.; Boyce, Alison M.; Cowen, Edward W.; Bhattacharyya, Nisan; Guthrie, Lori C.; Gahl, William A.; Golas, Gretchen; Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.; Levy, Moise L.; Collins, Michael T.; Choate, Keith A.

2014-01-01

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23. PMID:24006476

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.

PubMed

Lim, Young H; Ovejero, Diana; Sugarman, Jeffrey S; Deklotz, Cynthia M C; Maruri, Ann; Eichenfield, Lawrence F; Kelley, Patrick K; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J; Gafni, Rachel I; Boyce, Alison M; Cowen, Edward W; Bhattacharyya, Nisan; Guthrie, Lori C; Gahl, William A; Golas, Gretchen; Loring, Erin C; Overton, John D; Mane, Shrikant M; Lifton, Richard P; Levy, Moise L; Collins, Michael T; Choate, Keith A

2014-01-15

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in Native American men.

PubMed

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O

2009-09-01

Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05-0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06-0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.

Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men

PubMed Central

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O.

2009-01-01

Background Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. Objective We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. Methods We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Results Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Conclusions Elevation in serum PCB levels is associated with a lower concentration of serum

HIV and antiretroviral therapy: lipid abnormalities and associated cardiovascular risk in HIV-infected patients.

PubMed

Kotler, Donald P

2008-09-01

It has been demonstrated that patients on highly active antiretroviral therapy are at increased risk for developing metabolic abnormalities that include elevated levels of serum triglycerides and low-density lipoprotein cholesterol and reduced levels of high-density lipoprotein cholesterol. This dyslipidemia is similar to that seen in the metabolic syndrome, raising the concern that highly active antiretroviral therapy also potentially increases the risk for cardiovascular complications. This paper reviews the contribution of both HIV infection and the different components of highly active antiretroviral therapy to dyslipidemia and the role of these abnormalities toward increasing the risk of cardiovascular disease in HIV-infected patients; therapeutic strategies to manage these risks are also considered.

Dietary exposure to brominated flame retardants and abnormal Pap test results.

PubMed

Jamieson, Denise J; Terrell, Metrecia L; Aguocha, Nnenna N; Small, Chanley M; Cameron, Lorraine L; Marcus, Michele

2011-09-01

This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests.

Dietary Exposure to Brominated Flame Retardants and Abnormal Pap Test Results

PubMed Central

Jamieson, Denise J.; Terrell, Metrecia L.; Aguocha, Nnenna N.; Small, Chanley M.; Cameron, Lorraine L.

2011-01-01

Abstract Objective This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Methods Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Results Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). Conclusions It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests. PMID:21797757

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.

Elevated levels of insulin-like growth factor (IGF)-I in serum rescue the severe growth retardation of IGF-I null mice.

PubMed

Wu, Yingjie; Sun, Hui; Yakar, Shoshana; LeRoith, Derek

2009-09-01

IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I.

Elevation of serum procalcitonin in patients after chemical pleurodesis with intrapleural injection of OK-432.

PubMed

Xu, Bing-ling; Yu, Jin-quan; Tang, Ke-jing; Liu, Da-yue; Kuang, Yu-kun

2014-01-01

In patients with refractory pleural effusion or pneumothorax, fever and elevated level of white blood cell count (WBC) are frequently observed after chemical pleurodesis with intrapleural injection of OK-432, which make it difficult to differentiate whether it was from the side effects of OK-432 or concurrent bacterial infection. Procalcitonin (PCT) levels were measured before and after pleurodesis so as to discuss whether PCT is useful for distinguishing between the side effects of OK-432 and concurrent bacterial infection. Twenty-six patients with refractory pleural effusion or pneumothorax who underwent chemical pleurodesis with intrapleural injection of OK-432 at the First Affiliated Hospital of Sun Yat-sen University between August 2010 and August 2012 were included in our study. Levels of PCT and WBC were measured before and after pleurodesis. Of all 26 patients, 22 patients were with refractory pleural effusion, and the other four were with pneumothorax. The median serum levels of PCT and WBC elevated from 0.155 to 1.470 ng/mL (P = 0.009) and from 5.920 to 10.475 × 10(9) /L (P = 0.000), respectively. No patient was given antibiotics and fever subsided. Intrapleural injection of OK-432 could increase the serum level of PCT and WBC with no bacterial infection. The serum PCT level may not be useful to distinguish whether fever was caused by the side effects of OK-432 or concurrent bacterial infection. © 2013 John Wiley & Sons Ltd.

Elevated serum tartrate-resistant acid phosphatase isoform 5a levels in metabolic syndrome.

PubMed

Huang, Yi-Jhih; Huang, Tsai-Wang; Chao, Tsu-Yi; Sun, Yu-Shan; Chen, Shyi-Jou; Chu, Der-Ming; Chen, Wei-Liang; Wu, Li-Wei

2017-09-29

Tartrate-resistant phosphatase isoform 5a is expressed in tumor-associated macrophages and is a biomarker of chronic inflammation. Herein, we correlated serum tartrate-resistant phosphatase isoform 5a levels with metabolic syndrome status and made comparisons with traditional markers of inflammation, including c-reactive protein and interleukin-6. One hundred healthy volunteers were randomly selected, and cut-off points for metabolic syndrome related inflammatory biomarkers were determined using receiver operating characteristic curves. Linear and logistic regression models were subsequently used to correlate inflammatory markers with the risk of metabolic syndrome. Twenty-two participants met the criteria for metabolic syndrome, and serum tartrate-resistant phosphatase isoform 5a levels of >5.8 μg/L were associated with metabolic syndrome (c-statistics, 0.730; p = 0.001; 95% confidence interval, 0.618-0.842). In addition, 1 μg/L increases in tartrate-resistant phosphatase isoform 5a levels were indicative of a 1.860 fold increase in the risk of metabolic syndrome (p = 0.012). Elevated serum tartrate-resistant phosphatase isoform 5a levels are associated with the risk of metabolic syndrome, with a cut-off level of 5.8 μg/L.

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea.

PubMed

Kheirandish-Gozal, Leila; Sans Capdevila, Oscar; Kheirandish, Ebrahim; Gozal, David

2008-01-01

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients.

PubMed

Bache, Matthias; Kappler, Matthias; Wichmann, Henri; Rot, Swetlana; Hahnel, Antje; Greither, Thomas; Said, Harun M; Kotzsch, Matthias; Würl, Peter; Taubert, Helge; Vordermark, Dirk

2010-04-08

Osteopontin (OPN) overexpression is correlated with a poor prognosis for tumor patients. However, only a few studies investigated the prognostic impact of expression of OPN in soft tissue sarcomas (STS) yet. This study is based on tumor and serum samples from 93 adult STS patients. We investigated OPN protein levels in serum (n = 86) and tumor tissue (n = 80) by ELISA and OPN mRNA levels in tumor tissue (n = 68) by quantitative real-time PCR. No correlation was found between OPN levels in serum and tumor tissue. Moreover, an elevated OPN protein level in the serum was significantly associated with clinical parameters such as higher stage (p = 0.004), higher grade (p = 0.003), subtype (p = 0.002) and larger tumor size (p = 0.03). OPN protein levels in the tumor tissue were associated with higher stage (p = 0.06), higher grade (p = 0.003), subtype (p = 0.07) and an increased rate of relapse (p = 0.02). In addition, using a Cox's proportional hazards regression model, we found that an elevated OPN protein level in the serum and tumor tissue extracts is a significant negative prognostic factor for patients with STS. The relative risks of tumor-related death were 2.2 (p < 0.05) and 3.7 (p = 0.01), respectively. Our data suggest OPN protein in serum as well as in tumor tissue extracts is an important prognostic factor for soft tissue sarcoma patients.

Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports.

PubMed

Tzamaloukas, Antonios H; Ing, Todd S; Elisaf, Moses S; Raj, Dominic S C; Siamopoulos, Kostas C; Rohrscheib, Mark; Murata, Glen H

2011-06-01

The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.

Management strategy in pregnancies with elevated second-trimester maternal serum alpha-fetoprotein based on a second assay.

PubMed

Spaggiari, Emmanuel; Ruas, Marie; Dreux, Sophie; Valat, Anne-Sylvie; Czerkiewicz, Isabelle; Guimiot, Fabien; Schmitz, Thomas; Delezoide, Anne-Lise; Muller, Françoise

2013-04-01

To assess maternal-fetal outcomes in pregnancies associated with persistently elevated second-trimester maternal serum alpha-fetoprotein. A retrospective cohort study in 658 patients with maternal serum alpha-fetoprotein ≥2.5 multiple of median, performed at routine Down syndrome screening. Maternal serum alpha-fetoprotein was assayed a second time in 341 of them. Outcomes were recorded in all cases. The group with unexplained maternal serum alpha-fetoprotein persistently ≥2.5 multiple of median was associated with more pregnancy complications 37 of 92 (40.2%) as fetal death, preeclampsia, intrauterine growth restriction, and congenital nephrotic syndrome, compared with the group with maternal serum alpha-fetoprotein that returned to a normal level 37 of 226 (16.4%) (P < .001). When maternal serum alpha-fetoprotein returns to a normal level on a second assay, the risk of adverse outcome significantly decreases, but these pregnancies are still at risk of complications and therefore need close surveillance. Repeat maternal serum alpha-fetoprotein assay allows identification of patients who should be offered amniocentesis to evaluate the risk of nephrotic syndrome and epidermolysis bullosa. Alpha-fetoprotein should be monitored in pregnancies associated with unexplained high maternal serum alpha-fetoprotein. A management strategy based on ultrasound examination, second maternal serum alpha-fetoprotein assay and amniocentesis is proposed to improve prenatal counseling and management of such pregnancies. However, a prospective study remains necessary to evaluate it. Copyright © 2013 Mosby, Inc. All rights reserved.

Frequency of abnormal hand and wrist radiographs at time of diagnosis of polyarticular juvenile rheumatoid arthritis.

PubMed

Mason, Tom; Reed, Ann M; Nelson, Audrey M; Thomas, Kristen B; Patton, Alice; Hoffman, Alan D; Achenbach, Sara; O'Fallon, William M

2002-10-01

To determine the frequency of radiographic abnormalities in hand/wrist radiographs of children with newly diagnosed polyarticular juvenile rheumatoid arthritis (polyJRA) because radiographs of small joints are an important tool in assessing outcomes in RA and there are clinical similarities between RA and polyJRA. A medical record review was performed to identify cases of polyJRA seen at Mayo Clinic from January 1, 1994, to December 31, 2001. Hand/wrist radiographs, obtained at the time of diagnosis, were reviewed by 3 radiologists with attention to periarticular osteopenia, joint space narrowing (JSN), or erosion. At least 2 radiologists had to independently identify abnormal findings on the same radiograph. The relative carpal length (RCL), judged by Poznanski's method, was also determined. From the review of 159 medical records, 60 cases of newly diagnosed polyJRA were identified. Twenty-five of these had hand/wrist radiographs at diagnosis; 18 sets were available for this study. Of those, 2/3 were female, 6% (1/18) had subcutaneous nodules, 7% (1/14) had elevated levels of serum rheumatoid factor, and 44% (7/16) had elevated serum levels of antinuclear antibodies. Median age at diagnosis was 10.2 years, median duration of hand/wrist symptoms at diagnosis was 10 months, and median number of joints with either swelling, pain on range of motion (ROM), or limited ROM was 14.5. Sixty-one percent of radiographs taken at the time of diagnosis of polyJRA were abnormal. While 44% had periarticular osteopenia, 28% had either erosions or JSN. Six (33%) had RCL > 2 SD below the mean for age. Five (83%) of those with RCL, > 2 SD below the mean for age, had periarticular osteopenia, JSN, or erosion. We conclude the frequency of abnormal hand/wrist radiographs is very high very early in the course of polyJRA. More studies are needed to determine to what extent these radiographic abnormalities correlate with clinical outcomes.

Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy.

PubMed

Saraswathula, Anirudh; Reap, Elizabeth A; Choi, Bryan D; Schmittling, Robert J; Norberg, Pamela K; Sayour, Elias J; Herndon, James E; Healy, Patrick; Congdon, Kendra L; Archer, Gerald E; Sanchez-Perez, Luis; Sampson, John H

2016-02-01

Regulatory B cells that secrete IL-10 (IL-10(+) Bregs) represent a suppressive subset of the B cell compartment with prominent anti-inflammatory capacity, capable of suppressing cellular and humoral responses to cancer and vaccines. B lymphocyte stimulator (BLyS) is a key regulatory molecule in IL-10(+) Breg biology with tightly controlled serum levels. However, BLyS levels can be drastically altered upon chemotherapeutic intervention. We have previously shown that serum BLyS levels are elevated, and directly associated, with increased antigen-specific antibody titers in patients with glioblastoma (GBM) undergoing lymphodepletive temozolomide chemotherapy and vaccination. In this study, we examined corresponding IL-10(+) Breg responses within this patient population and demonstrate that the IL-10(+) Breg compartment remains constant before and after administration of the vaccine, despite elevated BLyS levels in circulation. IL-10(+) Breg frequencies were not associated with serum BLyS levels, and ex vivo stimulation with a physiologically relevant concentration of BLyS did not increase IL-10(+) Breg frequency. However, BLyS stimulation did increase the frequency of the overall B cell compartment and promoted B cell proliferation upon B cell receptor engagement. Therefore, using BLyS as an adjuvant with therapeutic peptide vaccination could promote humoral immunity with no increase in immunosuppressive IL-10(+) Bregs. These results have implications for modulating humoral responses in human peptide vaccine trials in patients with GBM.

Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy.

PubMed

Tokumura, A; Kume, T; Taira, S; Yasuda, K; Kanzaki, H

2009-05-01

Altered lipid metabolism is associated with human abnormal pregnancy, such as pre-eclampsia and preterm labor, and potentially leads to fetus loss. A causative factor for the onset and progress of the systemic multifactorial syndromes associated with the pathological pregnancy is oxidized low-density lipoprotein, an active identity of which was postulated to be lysophosphatidic acid (LPA). We previously found that LPA is produced extracellularly by plasma lysophospholipase D (lysoPLD) activity of autotaxin, a tumor cell motility-stimulating protein. In this study, a convenient assay based on the choline released from endogenous substrate or exogenous lysophosphatidylcholine (LPC) was used for comparison of serum lysoPLD activity among patients with normal and abnormal pregnancy. The serum choline-producing activity was found to be mainly due to autotaxin, and dependent on its dilution rate. There was some association between low dilution dependency of serum lysoPLD activity toward an exogenous LPC and high lysoPLD activity toward endogenous substrates in cases of patients with preterm labor and pre-eclampsia. However, there was no difference in the serum level of LPC between women with normal pregnancy and those with pathological pregnancy. These results indicate that production of bioactive LPA by lysoPLD activity is elevated by an unknown mechanism that may be related to increased availability of endogenous substrates LPC, but not its concentration in human serum. If the level of LPA in blood circulation is elevated in the pathological pregnancies in vivo, it may play a role in induction and/or progression of systemic vascular dysfunction seen patients with preterm labor or pre-eclampsia.

High serum creatinine in acute pancreatitis: a marker for pancreatic necrosis?

PubMed

Lankisch, Paul Georg; Weber-Dany, Bettina; Maisonneuve, Patrick; Lowenfels, Albert B

2010-05-01

High serum creatinine is a well-known unfavorable prognostic parameter in acute pancreatitis. Elevated creatinine at 48 h after admission was recently described as a marker for pancreatic necrosis. As pancreatic necrosis is a serious complication of acute pancreatitis and its identification by a simple single laboratory test would be very helpful, the aim of this study was to test that statement. In a prospective multicenter study of 462 patients with a first attack of acute pancreatitis, serum creatinine was determined on admission, and at 24 and 48 h thereafter, and compared with the findings of contrast-enhanced computed tomography (CT) performed within 96 h of admission. Pancreatic necrosis was present in 62 (13%) of the patients. Serum creatinine levels (abnormal > or = 2 mg/dl) on admission and after 24 and 48 h were evaluated vs. the presence or absence of pancreatic necrosis. Sensitivity rates varied between 14 and 23%, specificity between 95 and 97%, positive predictive values between 41 and 50%, and negative predictive values between 87 and 89%. Receiver operating characteristic curves revealed an area under the curve of between 0.604 and 0.669. An elevated serum creatinine concentration at any time during the first 48 h of admission is not a marker for pancreatic necrosis in a first attack of acute pancreatitis. If serum creatinine is normal, necrotizing pancreatitis is unlikely, and contrast-enhanced CT need not be performed unless complications occur and/or the patient's condition deteriorates.

Effects of ocean acidification driven by elevated CO2 on larval shell growth and abnormal rates of the venerid clam, Mactra veneriformis

NASA Astrophysics Data System (ADS)

Kim, Jee-Hoon; Yu, Ok Hwan; Yang, Eun Jin; Kang, Sung-Ho; Kim, Won; Choy, Eun Jung

2016-11-01

The venerid clam ( Mactra veneriformis Reeve 1854) is one of the main cultured bivalve species in intertidal and shallow subtidal ecosystems along the west coast of Korea. To understand the effects of ocean acidification on the early life stages of Korean clams, we investigated shell growth and abnormality rates and types in the D-shaped, umbonate veliger, and pediveliger stages of the venerid clam M. veneriformis during exposure to elevated seawater pCO2. In particular, we examined abnormal types of larval shell morphology categorized as shell deformations, shell distortions, and shell fissures. Specimens were incubated in seawater equilibrated with bubbled CO2-enriched air at (400±25)×10-6 (ambient control), (800±25)×10-6 (high pCO2), or (1 200±28)×10-6 (extremely high pCO2), the atmospheric CO2 concentrations predicted for the years 2014, 2084, and 2154 (70-year intervals; two human generations), respectively, in the Representative Concentration Pathway (RCP) 8.5 scenario. The mean shell lengths of larvae were significantly decreased in the high and extremely high pCO2 groups compared with the ambient control groups. Furthermore, under high and extremely high pCO2 conditions, the cultures exhibited significantly increased abundances of abnormal larvae and increased severity of abnormalities compared with the ambient control. In the umbonate veliger stage of the experimental larvae, the most common abnormalities were shell deformations, distortions, and fissures; on the other hand, convex hinges and mantle protuberances were absent. These results suggest that elevated CO2 exerts an additional burden on the health of M. veneriformis larvae by impairing early development.

Carcinogenic Activities and Sperm Abnormalities of Methicillin Resistance Staphylococcus aureus and Inhibition of Their Virulence Potentials by Ayamycin.

PubMed

El-Gendy, Mervat Morsy Abbas Ahmed; Abdel-Wahhab, Khaled G; Mannaa, Fathia A; Farghaly, Ayman A; El-Bondkly, Ahmed M A

2017-11-01

This investigation aimed to study the in vivo harmful effects of the subcutaneous injection of different methicillin resistance Staphylococcus aureus extracts (MRSA2, MRSA4, MRSA10, MRSA69, MRSA70, MRSA76, and MRSA78). Such strains represented the highest minimum inhibition concentration toward methicillin with various multidrug-resistant patterns. The obtained results revealed that rats injected with the MRSA4 extract died immediately after the last dose indicating the high cytotoxicity of MRSA4 strain (100% mortality). While the mortalities in other groups injected by the other MRSA extracts ranged from 50 to 75%. In comparison with the normal animal group, all MRSA extracts induced a hepatotoxic effect which was indicated from the significant (p < 0.01) increases in the activities of the serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) enzymes. Moreover, alkaline phosphatase (ALP) combined with a partial nephrotoxicity that was monitored from the significant elevation of serum urea concentration. While serum creatinine levels did not affect. Similarly, a significant elevation was recorded in serum levels of tumor biomarkers (alpha fetoprotein; AFP, carcinoembryonic antigen; CEA, and lactate dehydrogenase; LDH) reflecting their carcinogenic potential. On the other hand, the percentage of micronuclei (MN) in polychromatic erythrocytes from bone marrow cells was statistically significant in all groups as compared to the control group. The percentage of sperm abnormalities was statistically significant compared to the control. Different types of head abnormalities and coiled tail were recorded. Consequently, the current study focused on fighting MRSA virulence factors by the new compound ayamycin, which proved to be potent anti-virulence factor against all MRSA strains under study by significant decreasing of their streptokinase activities, hemolysin synthesis, biofilm formation, and their cell surface hydrophobicity.

Elevated serum bilirubin levels are inversely associated with coronary artery atherosclerosis.

PubMed

Kang, Seung Joo; Kim, Donghee; Park, Hyo Eun; Chung, Goh Eun; Choi, Seung Ho; Choi, Su-Yeon; Lee, Whal; Kim, Joo Sung; Cho, Sang-Heon

2013-10-01

Inverse correlations of high serum bilirubin with metabolic and cardiovascular disease have been suggested. However, anti-atherogenic effects of bilirubin have not been well-established in terms of the presence of plaques and stenosis identified in coronary computed tomography (CT). A cross-sectional study was conducted on 2862 men who were free of cardiovascular disease and underwent coronary CT as part of a routine medical screening examination. Coronary stenotic lesions were considered to be incidences of coronary atherosclerosis, and stenosis was classified as stenosis <50% or ≥50%, according to degree of stenosis. The prevalences of coronary atherosclerosis and stenosis ≥50% in subjects with elevated bilirubin levels (>1.2 mg/dL) were lower than those in subjects with normal bilirubin levels (≤1.2 mg/dL) (19.9% vs. 27.9%, p < 0.001, 8.5% vs. 10.3%, p = 0.044). Bilirubin was inversely associated with total plaques (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48-0.73 in the 4th quartile vs. 1st quartile) and calcified plaques (OR 0.60, 95% CI 0.49-0.75) in univariate analysis. After adjusting for traditional risk factors, it was found that coronary atherosclerosis (OR 0.73, 95% CI 0.56-0.94 in the 4th quartile vs. 1st quartile) and calcified plaque (OR 0.66, 95% CI 0.53-0.84) were inversely associated with the bilirubin grade in a dose-dependent manner. The serum bilirubin level was inversely associated with coronary atherosclerosis and calcified plaques in a dose-dependent manner. These results suggested that serum bilirubin could be used as a protective biomarker of coronary artery disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Active CMV and EBV infections in renal transplant recipients with unexplained fever and elevated serum creatinine.

PubMed

Hasannia, Tahereh; Moosavi Movahed, Seyed Majid; Vakili, Rosita; Rafatpanah, Houshang; Hekmat, Reza; Valizadeh, Narges; Rezaee, Seyed Abdolrahim

2016-10-01

Proper identification of active cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are helpful for monitoring antiviral treatment in transplant recipients. Qualitative and quantitative CMV, EBV DNA PCR techniques in the context of serological tests are performed for early detection and differentiation of active and latent CMV and EBV infections in renal transplantation. Basically, 129 renal transplanted recipients monitored carefully and hospitalized for unexplained elevated creatinine levels or high fever and 21 of their donors were studied. CMV DNA was detected in 63.5% of the febrile episodes following transplantation and in 46.42% of readmitted patients using qualitative PCR method. In the first group, 15% of the patients and in the second group 42.85% of the patients had copy numbers more than cutoff point (900 copies/mL). Cutoff point had 100% sensitivity and 82.5% specificity for active and symptomatic CMV infection. Only 15.5% of the subjects were positive for EBV infection by qualitative PCR method. Among them 5% had >2000 copies/mL and were symptomatic. One subject with a history of three times hospitalization had higher EBV viral load and developed post-transplant lymphoproliferative disorder. CMV load was significantly correlated with elevated creatinine levels (OR = 3.1, p = 0.006), abnormal heart sounds (OR = 4.7; p = 0.02) and hypertension (OR = 3.6; p = 0.03). Only qRT-PCR could differentiate between latent and active infections and might be clinically useful for monitoring symptomatic CMV and EBV infections and initiation of the antiviral therapy. Elevated creatinine levels, hypertension, and abnormal heart sounds could be considered as main manifestations of HCMV infection in kidney recipients.

Marked elevation of serum macrophage migration inhibitory factor levels in patients with pemphigus vulgaris.

PubMed

Namazi, Mohammad Reza; Fallahzadeh, Mohammad Kazem; Shaghelani, Hassan; Kamali-Sarvestani, Eskandar

2010-02-01

There is ample evidence for involvement of macrophage migration inhibitory factor (MIF) in autoimmune and inflammatory diseases. The aim of this study was to determine whether MIF levels were raised in the sera of patients with pemphigus vulgaris (PV). Serum MIF levels were measured using ELISA method in 22 patients with active PV and 21 age- and sex-matched healthy controls and the results were compared with each other. The mean serum MIF levels was significantly higher in PV patients than in control subjects (11.99 +/- 1.63 pg/m vs. 1.83 +/- 0.22 pg/ml; P-value = 0.0001). Elevated MIF levels in the sera of PV patients could participate in disease induction by activation of T cells as well as induction of autoantibody production by B cells. Given that MIF counter-regulates the effects of steroids, MIF antagonists may prove to be very effective, novel steroid-sparing agents for this life-threatening conundrum.

Two Cases of Transiently Elevated Serum CEA Levels in Severe Hypothyroidism without Goiter.

PubMed

Sekizaki, Tomonori; Yamamoto, Chiho; Nomoto, Hiroshi

2018-04-27

Carcinoembryonic antigen (CEA), the level of which is known to increase in both patients with gastrointestinal cancers and those with non-neoplastic conditions, is one of the most widely-used tumor markers. Hypothyroidism is a common endocrinological disorder in which CEA levels can rise, and is sometimes overlooked as a diagnosis in the absence of typical symptoms or thyroid enlargement. We report the cases of two patients with non-goiterous severe hypothyroidism with markedly elevated CEA levels that effectively decreased with levothyroxine replacement therapy alone. Hypothyroidism should be considered as an important cause of unexplained high serum CEA levels in order to avoid unnecessary medical examination.

Clinical implications in the prevalence and associated cardiovascular factors of elevated serum alanine aminotransferase levels among elderly agricultural and fishing population in Taipei, Taiwan: experience at a teaching hospital.

PubMed

Chen, Yu-Fen; Hu, Yi-Chun; Shen, Hsi-Che; Chang, Hui-Te; Tung, Tao-Hsin

2014-01-01

To discuss the prevalence and associated factors related to an elevated serum alanine aminotransferase (ALT) level among the elderly agricultural and fishing population. A total of 6542 (3989 males and 2553 females) healthy adults voluntarily admitted to a teaching hospital for a physical checkup in 2010 in Taipei, Taiwan. Fasting blood samples were drawn via venipuncture, and clinical nurses interviewed the study participants using a structured questionnaire from. The overall prevalence of an elevated serum ALT level was 18.2% and revealed a statistically significant decrease with increasing age (P < 0.001). The men exhibited a higher prevalence than the women (19.7% vs 15.9%; P < 0.001). Male sex; younger age; and presence of obesity, hypertension, hyperuricemia, and hypoalbuminemia were significantly associated with an elevated serum ALT level. Sex-related differences were also revealed. For the men, type 2 diabetes (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.02-1.57), hypercholesterolemia (OR, 1.78; 95% CI, 1.22-2.83), hypertriglyceridemia (OR, 1.32; 95% CI, 1.04-1.73), and low high-density lipoprotein (OR, 1.26; 95% CI, 1.05-1.51) were significantly related to an elevated serum ALT level, but this was not so for the women. The disparity of ALT in age groups was revealed. Several sex-related differences were indicated pertaining to the prevalence of an elevated serum ALT level among elderly specific occupational population.

Retinal detachment in hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome: Color vision abnormality as the first and predominant manifestation.

PubMed

Morisawa, Hiroyuki; Makino, Shinji; Takahashi, Hironori; Sorita, Mari; Matsubara, Shigeki

2015-11-01

Serous retinal detachment is sometimes caused by hypertensive disorders in pregnancy and its associated conditions, in which the predominant eye symptoms are blurred vision, distorted vision, and reduced visual acuity. To our best knowledge, this is the first report of a puerperal woman with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome in whom color vision abnormality was the first and predominant manifestation of serous retinal detachment. At 32 weeks of gestation, the 34-year-old Japanese woman underwent cesarean section due to HELLP syndrome. She complained of color vision abnormality on day 1 post-partum and ophthalmological examination revealed serous retinal detachment of both eyes. The visual acuity was preserved. With supportive therapy, her color vision abnormality gradually ameliorated and retinal detachment completely resolved on day 34 post-partum without any sequelae. Obstetricians should be aware that color vision abnormality can be the first and predominant symptom of HELLP-related serous retinal detachment. © 2015 Japan Society of Obstetrics and Gynecology.

Serum Bicarbonate and Structural and Functional Cardiac Abnormalities in Chronic Kidney Disease - A Report from the Chronic Renal Insufficiency Cohort Study.

PubMed

Dobre, Mirela; Roy, Jason; Tao, Kaixiang; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; Deo, Rajat; Drawz, Paul; Feldman, Harold I; Hamm, L Lee; Hostetter, Thomas; Kusek, John W; Lora, Claudia; Ojo, Akinlolu O; Shrama, Kumar; Rahman, Mahboob

2016-01-01

Heart failure (HF) is a frequent occurrence in chronic kidney disease (CKD) patients and predicts poor survival. Serum bicarbonate is associated with increased rates of HF in CKD; however, the mechanisms leading to this association are incompletely understood. This study aims to assess whether serum bicarbonate is independently associated with structural and functional cardiac abnormalities in CKD. The association between serum bicarbonate and left ventricular (LV) hypertrophy (LVH), LV mass indexed to height2.7, LV geometry, ejection fraction (EF) and diastolic dysfunction was assessed in 3,483 participants without NYHA class III/IV HF, enrolled in the Chronic Renal Insufficiency Cohort study. The mean estimated glomerular filtration rate was 42.5 ± 17 ml/min/1.73 m2. The overall prevalence of LVH was 51.2%, with 57.8, 50.9 and 47.7% for bicarbonate categories <22, 22-26 and >26 mmol/l, respectively. Participants with low bicarbonate were more likely to have LVH and abnormal LV geometry (OR 1.32; 95% CI 1.07-1.64, and OR 1.57; 95% CI 1.14-2.16, respectively). However, the association was not statistically significant after adjustment for demographics, traditional cardiovascular risk factors, medications and kidney function (OR 1.07; 95% CI 0.66-1.72, and OR 1.27; 95% CI 0.64-2.51, respectively). No association was found between bicarbonate and systolic or diastolic dysfunction. During follow-up, no significant changes in LV mass or EF were observed in any bicarbonate strata. In a large CKD study, serum bicarbonate was associated with LV mass and concentric LVH; however, this association was attenuated after adjustment for clinical factors suggesting that the observed cardiac effects are mediated through yet unknown mechanisms. © 2016 Published by S. Karger AG, Basel.

Relation of metabolic syndrome with endometrial pathologies in patients with abnormal uterine bleeding.

PubMed

Özdemir, Suna; Batmaz, Gonca; Ates, Seda; Celik, Cetin; Incesu, Feyzanur; Peru, Celalettin

2015-01-01

We aimed to investigate the association of metabolic syndrome and metabolic risk factors with endometrial hyperplasia and carcinoma among women with abnormal uterine bleeding (AUB). This study included 199 patients who had undergone endometrial curettage due to abnormal uterine bleeding. We divided the patients into two groups according to whether they had an abnormal (n = 53) or normal endometrium (n = 146). Waist circumference, blood pressure, fasting glucose and serum lipid levels were measured and statistically analyzed. The women in each group were matched with regard to mean age, gravidity, parity and menopausal status. We found increased prevalence of metabolic syndrome, diabetes, general and abdominal obesity, hypertension, elevated levels of glucose, total cholesterol and LDL-cholesterol and reduced levels of HDL-cholesterol among women with endometrial carcinoma and hyperplasia. These results were detected particularly in postmenopausal (>50 years) women compared to pre-menopausal cases (<50 years). All metabolic parameters were similar between hyperplasia and cancer groups. Metabolic syndrome and its components have been shown to have profound impacts on initiation and progession of endometrial pathology, particularly during post-menopausal period.

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.

Elevated serum aluminum levels in hemodialysis patients associated with use of electric pumps--Wyoming, 2007.

PubMed

2008-06-27

Aluminum toxicity can cause osteomalacia, anemia, and dementia in hemodialysis patients and has historically been associated with exposure to contaminated water or dialysate preparations or ingestion of aluminum-containing phosphate binders. Since 2002, improvements in water treatment methods and use of non-aluminum-containing phosphate binders have resulted in low prevalence (<1%) of aluminum toxicity among hemodialysis patients. In the United States, reported cases of aluminum toxicosis are rare, and no outbreak has been reported since 1992. This report describes 10 patients treated at a hemodialysis unit in a Wyoming hospital (hospital A) in 2007 who had elevated serum aluminum levels that were detected through routine serum aluminum screening. An investigation was conducted by the Wyoming Department of Health, which determined that the source of exposure was dialysate acid concentrate that became contaminated with aluminum as it passed through two electric drum pumps. The drum pumps had been used to transfer dialysate acid concentrate from 55-gallon storage drums to 1-gallon jugs for use on individual hemodialysis machines. Removal of the pumps from service resulted in a rapid reduction in patient serum aluminum levels. The findings suggest that regular assessment of machine compatibility with dialysate fluid is needed.

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

PubMed Central

Draborg, Anette H.; Lydolph, Magnus C.; Westergaard, Marie; Olesen Larsen, Severin; Nielsen, Christoffer T.; Duus, Karen; Jacobsen, Søren; Houen, Gunnar

2015-01-01

Objective In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs’ association with Epstein-Barr virus (EBV) antibodies was examined. Methods Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance. Results Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001) also after adjusting for Ig levels (p<0.0001). The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI)) score of the SLE patients (r = 0.399, p = 0.007). Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009), and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA) concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation) whereas EBV-directed antibodies reflect the extent of previous infection/reactivations. Conclusion SLE patients have elevated concentrations of serum FLCs that

Frequency of metabolic abnormalities in urinary stones patients.

PubMed

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-11-01

To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis.

PubMed

Levin, Lynn I; Breen, Elizabeth C; Birmann, Brenda M; Batista, Julie L; Magpantay, Larry I; Li, Yuanzhang; Ambinder, Richard F; Mueller, Nancy E; Martínez-Maza, Otoniel

2017-07-01

Background: We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL). Methods: We measured serum levels of B-cell-stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository. Results: Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4-9.0; IL6 OR = 4.6; 95% CI, 2.9-7.5] and >1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6-6.7; IL6 OR = 2.9; 95% CI, 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases. Conclusion: In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis. Impact: The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Does elevation of serum creatinine in patients with chronic hepatitis C under therapy of telaprevir mean renal impairment?

PubMed

Matsui, Katsuomi; Kamijo-Ikemori, Atsuko; Sugaya, Takeshi; Ikeda, Hiroki; Okuse, Chiaki; Shibagaki, Yugo; Yasuda, Takashi; Kimura, Kenjiro

2015-11-01

Treatment with telaprevir (TVR) entails adverse side-effects including anaemia and elevation of serum creatinine (SCr) level. Our purpose was to evaluate the effects of treatment with TVR on renal function in adults with chronic hepatitis C. Thirteen adult patients with HCV genotype 1b who were scheduled to be treated with TVR, pegylated interferon (PEG IFN), and ribavirin (RBV) were prospectively followed. Patients were divided into two groups: (i) patients with an increase in SCr during the treatment (n = 8), and (ii) patients without an increase in SCr (n = 5). Urine and serum parameters were evaluated. Although there was no difference in SCr level between the two groups before HCV therapy, the SCr level was persistently high in the patients in the increase-in-SCr group during the triple therapy. The SCr level returned to the pre-treatment level after cessation of TVR. There were no differences in urinary L-FABP, NAG, serum cystatin C level and eGFRcys throughout the study between the two groups. The serum cystatin C level at pre-treatment tended to be higher in the increase-in-SCr group. Urinary L-FABP and NAG levels in these groups remained within normal limits during treatment. We found that the increase in SCr was not associated with the degree of renal impairment. The increase in SCr may have been induced as a result of a decrease in creatinine secretion from proximal tubules via inhibition of transporters of creatinine induced by TVR. Elevation of SCr levels with TVR therapy may not suggest renal impairment. © 2015 Asian Pacific Society of Nephrology.

Peritoneal tuberculosis with elevated serum Ca-125 level mimicking advanced stage ovarian cancer: a case report.

PubMed

Tan, Orkun; Luchansky, Edward; Rosenman, Stephen; Pua, Tarah; Azodi, Masoud

2009-08-01

Tuberculosis is still a common problem in immigrant population with peritoneal tuberculosis as the most common presentation of extrapulmonary disease. A 36-year-old woman presented with abdominal distention, night sweats and weight loss. Physical examination and radiologic studies revealed ascites, omental caking and bilateral enlarged ovaries with an elevated serum Ca-125 of 353 U/mL. Acid-fast stain and culture were negative for Mycobacterium tuberculosis. Diagnostic laparoscopy and biopsy revealed multiple granulomas with epithelioid cells and caseification necrosis confirming tuberculosis. Treatment with anti-tuberculin drugs resulted in resolution of symptoms with a reduction in Ca-125 to normal. Laparoscopic biopsy with frozen section evaluation would spare patients with peritoneal tuberculosis from unnecessary extensive surgery. Serum Ca-125 level may be useful in monitoring treatment response.

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

PubMed

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

2017-01-01

In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

Serum CEACAM1 Elevation Correlates with Melanoma Progression and Failure to Respond to Adoptive Cell Transfer Immunotherapy

PubMed Central

Ortenberg, R.; Sapoznik, S.; Zippel, D.; Shapira-Frommer, R.; Itzhaki, O.; Kubi, A.; Zikich, D.; Besser, M. J.; Schachter, J.; Markel, G.

2015-01-01

Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients for the first time in decades. However, the clinical management of melanoma is severely hampered by the absence of effective screening tools. The expression of the CEACAM1 adhesion molecule on melanoma cells is a strong predictor of poor prognosis. Interestingly, a melanoma-secreted form of CEACAM1 (sCEACAM1) has recently emerged as a potential tumor biomarker. Here we add novel evidences supporting the prognostic role of serum CEACAM1 by using a mice xenograft model of human melanoma and showing a correlation between serum CEACAM1 and tumor burden. Moreover, we demonstrate that serum CEACAM1 is elevated over time in progressive melanoma patients who fail to respond to immunotherapy as opposed to responders and stable disease patients, thus proving a correlation between sCEACAM1, response to treatment, and clinical deterioration. PMID:26688824

Falsely Elevated Serum Vitamin B12 Levels Were Associated with the Severity and Prognosis of Chronic Viral Liver Disease

PubMed Central

Sugihara, Takaaki; Koda, Masahiko; Okamoto, Toshiaki; Miyoshi, Kenichi; Matono, Tomomitsu; Oyama, Kenji; Hosho, Keiko; Okano, Jun-ichi; Isomoto, Hajime; Murawaki, Yoshikazu

2017-01-01

Background Vitamin B12 is stored primarily in the liver, and highly elevated serum vitamin B12 levels occur in acute hepatitis and severe alcoholic liver disease. We evaluated the relationship between vitamin B12 levels and liver disease severity and long term prognosis in patients with chronic viral hepatitis and cirrhosis. Methods We enrolled 90 patients (57 men, 33 women) with chronic viral hepatitis and cirrhosis who admitted to our hospital as a prospective cohort study. Overall, 37 patients had chronic hepatitis and 53 had cirrhosis (Child-Pugh A 33, B 13, and C 7); 57 patients had primary liver cancer. Serum vitamin B12 concentration and holotranscobalamin (holoTC) II (active form of vitamin B12) were determined and followed prospectively for at least 5 years. Results Mean total serum vitamin B12 concentration was significantly higher in Child-Pugh C (1308 ± 599 pg/mL) compared to those with chronic hepatitis (655 ± 551 pg/mL), Child-Pugh A (784 ± 559 pg/mL), and Child-Pugh B (660 ± 464 pg/mL) (P = 0.036) Presence of primary liver cancer also influenced serum vitamin B12 levels [657 (167–2956) vs. 432 (189–2956); P = 0.015]. Patients were divided into quartiles by vitamin B12 level. Patients without primary liver cancer in quartile 4 (≥ 880 pg/mL) demonstrated significantly poorer prognosis than those in quartiles 1–3 (< 880 pg/mL) (P = 0.023). The percentage of holohaptocorrin (holoHC) [(total vitamin B12 – holoTC II) × 100] was significantly higher in Child-Pugh B and C 86 (80–87)% than chronic hepatitis and Child-Pugh A 77 (31–89)% (P = 0.006) Multivariate analysis indicated serum vitamin B12 levels (HR = 1.001, P = 0.029) as a prognostic factor. Conclusion Falsely elevated serum vitamin B12 levels mainly composed of increased holoHC were associated with severity (Child-Pugh C and primary liver cancer) and prognosis in chronic viral liver disease. PMID:28331419

Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study.

PubMed

Ando, Yoshihito; Shimazaki, Haruo; Shiota, Katsutoshi; Tetsuka, Syuichi; Nakao, Koichi; Shimada, Tatsuhiro; Kurata, Kazumi; Kuroda, Jinichi; Yamashita, Akihiro; Sato, Hayato; Sato, Mamoru; Eto, Shinkichi; Onishi, Yasunori; Tanaka, Keiko; Kato, Satoshi

2016-07-08

Increasing numbers of patients with elevated anti-N-methyl-D-aspartate (NMDA) receptor antibody titers presenting exclusively with psychiatric symptoms have been reported. The aim of the present study was to clarify the prevalence of elevated serum anti-NMDA receptor antibody titers in patients with new-onset or acute exacerbations of psychiatric symptoms. In addition, the present study aimed to investigate the association between elevated anti-NMDA receptor titers and psychiatric symptoms. The present collaborative study included 59 inpatients (23 male, 36 female) presenting with new-onset or exacerbations of schizophrenia-like symptoms at involved institutions from June 2012 to March 2014. Patient information was collected using questionnaires. Anti-NMDA receptor antibody titers were measured using NMDAR NR1 and NR2B co-transfected human embryonic kidney (HEK) 293 cells as an antigen (cell-based assay). Statistical analyses were performed for each questionnaire item. The mean age of participants was 42.0 ± 13.7 years. Six cases had elevated serum anti-NMDA antibody titers (10.2 %), four cases were first onset, and two cases with disease duration >10 years presented with third and fifth recurrences. No statistically significant difference in vital signs or major symptoms was observed between antibody-positive and antibody-negative groups. However, a trend toward an increased frequency of schizophrenia-like symptoms was observed in the antibody-positive group. Serum anti-NMDA receptor antibody titers may be associated with psychiatric conditions. However, an association with specific psychiatric symptoms was not observed in the present study. Further studies are required to validate the utility of serum anti-NMDA receptor antibody titer measurements at the time of symptom onset.

Elevated serum alpha-fetoprotein in poorly differentiated adenocarcinoma with neuroendocrine differentiation of the ascending colon: a case report.

PubMed

Lin, Hung-Hsin; Chang, Chia-Chu; Yang, Shung-Haur; Chang, Shih-Ching; Chen, Wei-Shone; Liang, Wen-Yih; Lin, Jen-Kou; Jiang, Jeng-Kai

2016-03-15

Colorectal cancer (CRC) is the most common form of cancer and the third leading cause of death in Taiwan. Serum alpha-fetoprotein (AFP) has been extensively used as a biomarker for hepatocellular carcinoma (HCC) and yolk sac tumors. This case report presents a 90-year-old woman with right abdominal pain and poor appetite for 1 week. The computed tomography (CT) showed wall thickening in the proximal ascending colon with ruptured appendicitis. Preoperative serum AFP was high. There was no definite liver metastasis or other abnormal findings in the hepatobiliary systems. After initial empirical antibiotic treatment, we performed laparoscopic right hemicolectomy. The pathological assessment was poorly differentiated adenocarcinoma with neuroendocrine differentiation in the ascending colon. The tumor cells did not produce AFP. Amazingly, the follow-up serum AFP level 1 month after the surgery declined to normal range. The patient had an uneventful course after the surgery and was free of recurrence or metastasis within 5 months of follow-up. AFP may be a useful tumor marker in poorly differentiated colorectal cancer with neuroendocrine component patients and a prediction of early treatment response.

CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

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

Cheng, Jie; Krausz, Kristopher W.; Li, Feng

Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-typemore » mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.« less

Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation.

PubMed

Papillard-Marechal, Solesne; Sznajder, Marc; Hurtado-Nedelec, Margarita; Alibay, Yasmin; Martin-Schmitt, Caroline; Dehoux, Monique; Westerman, Mark; Beaumont, Carole; Chevallier, Bertrand; Puy, Herve; Stheneur, Chantal

2012-03-01

Only a few studies based on small cohorts have been carried out on iron status in anorexia nervosa (AN) patients. The aim of this study was to evaluate the role of hepcidin in hyperferritinemia in AN adolescents. Twenty-seven adolescents hospitalized for AN in the pediatric inpatient unit of Ambroise Paré Academic Hospital were enrolled in the study. The control group comprised 11 patients. Hematologic variables and markers of iron status, including serum hepcidin, were measured before and after nutritional rehabilitation. The mean age of patients was 14.4 y. Except for 2 AN patients and 1 control patient, all patients presented normal hemoglobin, vitamin B-12, and folate concentrations. Markers of inflammation and cytokines were normal throughout the study. None of the muscular lysis markers were elevated. Most AN patients had normal serum iron concentrations on admission. Serum ferritin concentrations were significantly higher in patients than in control subjects (198 compared with 49 μg/L, respectively; P < 0.001). The median hepcidin concentration was significantly higher in AN patients than in the control group (186.5 compared with 39.5 μg/L, respectively; P = 0.002). There was a highly significant correlation between ferritinemia and serum hepcidin concentrations (P < 0.0001). After nutritional rehabilitation, a significant reduction was observed (P = 0.004) in serum ferritin. Serum hepcidin analyzed in a smaller number of patients also returned to within the normal range. Hepcidin and ferritin concentrations were higher in the serum of AN patients, without any evidence of iron overload or inflammation. These concentrations returned to normal after nutritional rehabilitation. These results suggest that nutritional stress induced by malnourishment in the hepatocyte could be yet another mechanism that regulates hepcidin.

Molindone: higher doses needed to block pergolide-induced elevation of serum corticosterone than to elevate dopamine metabolites in brain.

PubMed

Fuller, R W; Snoddy, H D

1983-12-05

Molindone at a dose of 3 mg/kg i.p. in rats prevented pergolide-induced decreases in brain DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid), causing instead significant increases in these dopamine metabolites when given in combination with pergolide. Molindone alone at 3 mg/kg caused two-fold or greater increases in DOPAC and HVA and at doses as low as 0.3 mg/kg caused significant increases in these metabolites. However, molindone at 3 mg/kg and lower doses was without effect on pergolide-induced elevation of serum corticosterone, though a higher dose of molindone, 10 mg/kg, significantly antagonized this increase in corticosterone. These data support earlier findings with molindone, suggesting it has greater affinity for presynaptic dopamine autoreceptors than for postsynaptic dopamine receptors.

Positive Reinforcement Training for Blood Collection in Grizzly Bears (Ursus arctos horribilis) Results in Undetectable Elevations in Serum Cortisol Levels: A Preliminary Investigation.

PubMed

Joyce-Zuniga, Nicole M; Newberry, Ruth C; Robbins, Charles T; Ware, Jasmine V; Jansen, Heiko T; Nelson, O Lynne

2016-01-01

Training nonhuman animals in captivity for participation in routine husbandry procedures is believed to produce a lower stress environment compared with undergoing a general anesthetic event for the same procedure. This hypothesis rests largely on anecdotal evidence that the captive subjects appear more relaxed with the trained event. Blood markers of physiological stress responses were evaluated in 4 captive grizzly bears (Ursus arctos horribilis) who were clicker-trained for blood collection versus 4 bears who were chemically immobilized for blood collection. Serum cortisol and immunoglobulin A (IgA) and plasma β-endorphin were measured as indicators of responses to stress. Plasma β-endorphin was not different between the groups. Serum IgA was undetectable in all bears. Serum cortisol was undetectable in all trained bears, whereas chemically immobilized bears had marked cortisol elevations (p < .05). The highest cortisol elevations were found in 2 bears with extensive recent immobilization experience. These findings support the use of positive reinforcement training for routine health procedures to minimize anxiety.

Olive Leaf Extract Elevates Hepatic PPAR α mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.

PubMed

Yoon, Leena; Liu, Ya-Nan; Park, Hyunjin; Kim, Hyun-Sook

2015-07-01

We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400 mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR α) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR α and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats.

[A clinical evaluation of the increased serum myoglobin: creatine phosphokinase and lactic dehydrogenase in patients with thyroid disorders (author's transl)].

PubMed

Shimoda, S I; Kasai, K

1980-08-20

Since muscle dysfunction is frequently associated with a hypothyroid state, many clinical reports have indicated that serum enzyme activities derived from the muscle such as creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and glutamic-oxaloacetic transamynase (GOT) are elevated. These enzyme activities in the serum of hyperthyroidism, euthyroidism and hypothyrodism have been known to have a good inverse correlation with protein-bound iodine (PBI). Therefore, as part of a study of the relationship between thyroid states and muscle tissue, values of serum myoblobin (Mb) were measured by RIA. The values of Mb in untreated hyperthyroidism were significantly lower (P<0.01) and, in untreated hypothyroidism, Mb values were significantly higher (p<0.001) than in normal subjects. There was a significant inverse correlation (p<0.01) between T4 or T3 concentration and Mb levels in these subjects. The relationship found between either Mb and LDH or Mb and CPK was also studied in the present study, and it was found that Mb significantly correlated to both LDH and CPK (P<0.001). Abnormalities of these enzyme levels in serum returned to the normal range rapidly after the correction of the abnormal thyroid states in each patient.

Frequency of metabolic abnormalities in urinary stones patients

PubMed Central

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-01-01

Objective: To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Methods: Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Results: Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. Conclusion: This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients. PMID:24550954

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

PubMed Central

WENISCH, C; WENISCH, H; PARSCHALK, B; VANIJANONTA, S; BURGMANN, H; EXNER, M; ZEDWITZ-LIEBENSTEIN, K; THALHAMMER, F; GEORGOPOULOS, A; GRANINGER, W; LOOAREESUWAN, S

1996-01-01

Serum sCD14, tumour necrosis factor-alpha (TNF-α), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116+1440 μg/lversus 9453+1017 μg/lP<0.05) and both had higher levels than patients with septicaemia (6155+1635μg/l) and normal subjects (2776+747 μg/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria. PMID:8697639

An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value

PubMed Central

Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia

2017-01-01

Background In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). Patients and methods We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Results Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Conclusions Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value. PMID:28562682

Serial cytokine alterations and abnormal neuroimaging in newborn infants with encephalopathy.

PubMed

O'Hare, Fiona M; Watson, R William G; O'Neill, Amanda; Segurado, Ricardo; Sweetman, Deirdre; Downey, Paul; Mooney, Eoghan; Murphy, John; Donoghue, Veronica; Molloy, Eleanor J

2017-04-01

Inflammatory cytokines may play a role in the final common pathway in the pathogenesis of hypoxic-ischaemic injury in experimental models. We aimed to profile the systemic pro-and anti-inflammatory response over the first week of life in term infants at risk of neonatal encephalopathy. In a tertiary referral university neonatal intensive care unit, serial blood samples were analysed from 41 term infants (requiring resuscitation at birth) in this prospective observational pilot study. Serum levels of 10 pro-and anti-inflammatory cytokines were evaluated including interleukin(IL)-1α, IL-1β, IL-6, IL-8, IL-10, tumour necrosis factor(TNF)-α, interferon (IFN)-γ, vascular endothelial growth factor (VEGF), granulocyte/colony-stimulating factor (G-CSF) and granulocyte macrophage/colony-stimulating factor (GM-CSF). Infants with neonatal encephalopathy and abnormal neuroimaging (n = 15) had significantly elevated granulocyte macrophage/colony-stimulating factor at 0-24 h and interleukin-8, interleukin-6 and interleukin-10 at 24-48 hour. Tumour necrosis factor-α and vascular endothelial growth factor levels were lower at 72-96 hour (p < 0.05). Significantly elevated levels of interleukin-10 were associated with mortality. Serum cytokine changes and innate immune dysregulation in the first week of life may be indicators of outcome in neonatal encephalopathy but require validation in larger studies. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Waist circumference, body mass index, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal liver function tests in the Taiwanese population.

PubMed

Hsieh, Meng-Hsuan; Lin, Wen-Yi; Chien, Hsu-Han; Chien, Li-Ho; Huang, Chao-Kuan; Yang, Jeng-Fu; Chang, Ning-Chia; Huang, Chung-Feng; Wang, Chao-Ling; Chuang, Wan-Long; Yu, Ming-Lung; Dai, Chia-Yen; Ho, Chi-Kung

2012-09-01

Several studies have found that metabolic syndrome and uric acid level are related to abnormal liver function test results. The aim of this study was to explore the associations of risk factors [including blood pressure, blood sugar, total cholesterol, triglyceride, uric acid, waist circumference and body mass index (BMI) measurements] with abnormal liver function in the Taiwanese population.In total, 11,411 Taiwanese adults were enrolled in this study. Blood pressure was assessed according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, fasting blood sugar level according to the Bureau of Health Promotion, Department of Health, R.O.C., criteria, total cholesterol and triglyceride levels according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel III criteria, BMI according to the Asia-Pacific criteria, and waist circumference according to the Revised Diagnostic Criteria of Metabolic Syndrome in Taiwan. The prevalence of a past history of hypertension and diabetes mellitus was 17.7% and 6.5%, respectively, and the rates of abnormal measurements of blood pressure, BMI, waist circumference, fasting blood sugar, triglyceride, total cholesterol, uric acid (male/female), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were 76.2%, 67.6%, 40.0%, 28.6%, 30.6%, 57.3%, 37.9%/21.9%, 14.6% and 21.3%, respectively. Multivariate analysis showed that waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels were related to abnormal AST and ALT (p<0.05), but the odds ratio for waist circumference was larger than that for BMI. In conclusion, waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal AST and ALT readings in Taiwanese adults. Waist circumference might be a better indicator of risk of abnormal liver function than BMI. Copyright © 2012

Prevalence and Predictors of Abnormal Liver Enzymes in Young Women with Anorexia Nervosa

PubMed Central

Fong, Hiu-fai; DiVasta, Amy D.; DiFabio, Diane; Ringelheim, Julie; Jonas, Maureen M.; Gordon, Catherine M.

2008-01-01

Objective To determine the prevalence and predictors of abnormal liver enzyme levels in ambulatory young women with anorexia nervosa (AN). Study design In this cross-sectional study of 53 females with AN, serum concentrations of liver enzymes and hormones were measured. Anthropometric, dietary, and body composition information was collected. Correlational analyses were performed between liver enzyme concentrations and these variables. Results Elevated alanine aminotransferase (ALT) and gamma-glutamyltranspeptidase (GGT) levels were found in 14 subjects (26%) and 5 subjects (9%), respectively. ALT and GGT were inversely correlated with body mass index (r = −0.27 to −0.30, p ≤ 0.049) and percentage body fat (r = −0.36 to −0.47, p ≤ 0.007), but showed no relationship with lean body mass. Subjects with percentage body fat < 18% had higher ALT levels than those above this threshold (median 26.5 vs. 18.0 U/L, p = 0.01). Liver enzyme concentrations did not correlate with dietary variables, except for GGT and percentage of calories from protein (r = 0.28, p = 0.04). Conclusions Serum ALT and GGT concentrations are inversely related to adiposity in young women with AN. Future studies are needed to determine if these liver enzyme elevation signify unrecognized, clinically relevant liver disease. PMID:18534220

Oral iron acutely elevates bacterial growth in human serum.

PubMed

Cross, James H; Bradbury, Richard S; Fulford, Anthony J; Jallow, Amadou T; Wegmüller, Rita; Prentice, Andrew M; Cerami, Carla

2015-11-23

Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.

Elevated serum MDA and depleted non-enzymatic antioxidants, macro-minerals and trace elements are associated with bipolar disorder.

PubMed

Chowdhury, Manjurul Islam; Hasan, Maimuna; Islam, Mohammad Safiqul; Sarwar, Md Shahid; Amin, Mohammad Nurul; Uddin, S M Naim; Rahaman, Md Zahedur; Banik, Sujan; Hussain, Md Saddam; Yokota, Kazushige; Hasnat, Abul

2017-01-01

Genetic and neurobiological factors are considered to be the major causes of mood and mental disorders. However, over the past few years, increased levels of serum malondialdehyde and altered levels of various non-enzymatic antioxidants and essential minerals involved in abnormal functional activity have been identified as major contributing factors to the pathogenesis of several neurological disorders. The aim of this study was to determine the levels of the serum lipid peroxidation product malondialdehyde (MDA), antioxidants (vitamin A, E and C), macro-minerals (calcium, potassium and sodium) and trace elements (zinc, iron and selenium) in patients with bipolar disorder and to explore their role in disease progression. This is a prospective case-control study that evaluated 55 patients with bipolar disorder and 55 healthy volunteers matched by age and sex. Serum MDA levels were determined by UV spectrophotometry as a marker of lipid peroxidation. RP-HPLC was employed to investigate the serum vitamin A and E concentrations, whereas UV spectrophotometry was used to quantify levels of vitamin C. Serum macro-minerals and trace elements were analyzed by atomic absorption spectroscopy (AAS). Statistical analysis was performed with independent sample t-tests and Pearson's correlation test. We found significantly higher concentrations of MDA (p<0.05) and significantly lower concentrations of antioxidants (vitamin A, E and C) (p<0.05) in the patient group compared with control group. Regarding trace elements and macro-minerals, lower concentrations of zinc, calcium, iron, selenium, sodium and potassium were found in the patient group compared with control subjects (p<0.05). Our study suggests that high serum MDA concentrations and low serum concentrations of antioxidants, macro-minerals and trace elements are strongly associated with bipolar disorder. Copyright © 2016 Elsevier GmbH. All rights reserved.

Transient abnormal Q waves during exercise electrocardiography

PubMed Central

Alameddine, F F; Zafari, A M

2004-01-01

Myocardial ischaemia during exercise electrocardiography is usually manifested by ST segment depression or elevation. Transient abnormal Q waves are rare, as Q waves indicate an old myocardial infarction. The case of a patient with exercise induced transient abnormal Q waves is reported. The potential mechanisms involved in the development of such an abnormality and its clinical implications are discussed. PMID:14676264

Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

PubMed

Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P

2002-05-01

with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients with CAH may further enhance adrenal and ovarian androgen production, decrease the therapeutic efficacy of glucocorticoids, and contribute to later development of polycystic ovary syndrome and/or the metabolic syndrome and their complications.

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

Elevated serum MFG-E8 level is possibly associated with the presence of high-intensity cerebral lesions on magnetic resonance imaging in patients with systemic lupus erythematosus.

PubMed

Kishi, Chikako; Motegi, Sei-Ichiro; Ishikawa, Osamu

2017-07-01

Human milk fat globule-EGF factor 8 (MFG-E8), also known as lactadherin, is a secreted glycoprotein that plays essential roles in the clearance of apoptotic cells and angiogenesis. It has been reported that serum MFG-E8 levels are higher in systemic lupus erythematosus (SLE) patients compared with in healthy controls; however, a previous study reported no correlation between serum MFG-E8 levels and SLE disease activity. The objective of this study was to assess serum MFG-E8 levels and their clinical associations in patients with SLE. Serum MFG-E8 levels in 49 Japanese patients with SLE, eight with cutaneous LE, and 28 healthy controls were examined. Serum MFG-E8 levels in SLE patients were significantly higher than those in cutaneous LE patients and healthy individuals. In addition, serum MFG-E8 levels were positively correlated with the SLE Disease Activity Index score, which reflects the disease activity of SLE. Notably, the frequency of the presence of high-intensity cerebral lesions on MRI in the SLE patients with elevated serum MFG-E8 levels was significantly higher than that in SLE patients with normal serum MFG-E8 levels. These findings suggest that elevated serum MFG-E8 levels may be associated with cerebrovascular diseases or neuropsychiatric SLE in patients with SLE, and that the measurement of serum MFG-E8 levels in SLE patients is useful for risk stratification of cerebrovascular disease or cerebrovascular disease-related neuropsychiatric SLE. © 2017 Japanese Dermatological Association.

Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes.

PubMed

Sims, Emily K; Chaudhry, Zunaira; Watkins, Renecia; Syed, Farooq; Blum, Janice; Ouyang, Fangqian; Perkins, Susan M; Mirmira, Raghavendra G; Sosenko, Jay; DiMeglio, Linda A; Evans-Molina, Carmella

2016-09-01

We tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. © 2016 by the American Diabetes Association.

Elevations in the Fasting Serum Proinsulin–to–C-Peptide Ratio Precede the Onset of Type 1 Diabetes

PubMed Central

Sims, Emily K.; Chaudhry, Zunaira; Watkins, Renecia; Syed, Farooq; Blum, Janice; Ouyang, Fangqian; Perkins, Susan M.; Mirmira, Raghavendra G.; Sosenko, Jay; DiMeglio, Linda A.

2016-01-01

OBJECTIVE We tested whether an elevation in the serum proinsulin–to–C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes. Samples were obtained ∼12 months before diabetes onset from PTP progressors in whom diabetes developed (n = 60), and were compared with age-, sex-, and BMI-matched nonprogressors who remained normoglycemic (n = 58). PI:C ratios were calculated as molar ratios and were multiplied by 100% to obtain PI levels as a percentage of C levels. RESULTS Although absolute PI levels did not differ between groups, PI:C ratios were significantly increased in antibody-positive subjects in whom there was progression to diabetes compared with nonprogressors (median 1.81% vs. 1.17%, P = 0.03). The difference between groups was most pronounced in subjects who were ≤10 years old, where the median progressor PI:C ratio was nearly triple that of nonprogressors; 90.0% of subjects in this age group within the upper PI:C quartile progressed to the development of diabetes. Logistic regression analysis, adjusted for age and BMI, demonstrated increased odds of progression for higher natural log PI:C ratio values (odds ratio 1.44, 95% CI 1.02, 2.05). CONCLUSIONS These data suggest that β-cell ER dysfunction precedes type 1 diabetes onset, especially in younger children. Elevations in the serum PI:C ratio may have utility in predicting the onset of type 1 diabetes in the presymptomatic phase. PMID:27385327

Impact of diabetic serum on endothelial cells: An in-vitro-analysis of endothelial dysfunction in diabetes mellitus type 2

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

Muenzel, Daniela; Lehle, Karla; Haubner, Frank

2007-10-19

Diabetic endothelial dysfunction was characterized by altered levels of adhesion molecules and cytokines. Aim of our study was to evaluate the effects of diabetic serum on cell-growth and proinflammatory markers in human saphenous vein endothelial cells (HSVEC) from diabetic and non-diabetic patients. Diabetic serum showed (1) complementary proliferative activity for non-diabetic and diabetic HSVEC, (2) unchanged surface expression of adhesion molecules, and (3) elevated levels of sICAM-1 in HSVEC of all donors. The concentration of sVCAM-1 was increased only in diabetic cells. The proinflammatory state of diabetic HSVEC characterized by increased levels of cytokines was compensated. We concluded that evenmore » under normoglycemic conditions the serum itself contains critical factors leading to abnormal regulation of inflammation in diabetics. We introduced an in vitro model of diabetes representing the endothelial situation at the beginning of diabetes (non-diabetic cells/diabetic serum) as well as the diabetic chronic state (diabetic cells/diabetic serum)« less

Freeze-Dried Strawberries Lower Serum Cholesterol and Lipid Peroxidation in Adults with Abdominal Adiposity and Elevated Serum Lipids123

PubMed Central

Basu, Arpita; Betts, Nancy M.; Nguyen, Angel; Newman, Emily D.; Fu, Dongxu; Lyons, Timothy J.

2014-01-01

Dietary flavonoid intake, especially berry flavonoids, has been associated with reduced risks of cardiovascular disease (CVD) in large prospective cohorts. Few clinical studies have examined the effects of dietary berries on CVD risk factors. We examined the hypothesis that freeze-dried strawberries (FDS) improve lipid and lipoprotein profiles and lower biomarkers of inflammation and lipid oxidation in adults with abdominal adiposity and elevated serum lipids. In a randomized dose-response controlled trial, 60 volunteers [5 men and 55 women; aged 49 ± 10 y; BMI: 36 ± 5 kg/m2 (means ± SDs)] were assigned to consume 1 of the following 4 beverages for 12 wk: 1) low-dose FDS (LD-FDS; 25 g/d); 2) low-dose control (LD-C); 3) high-dose FDS (HD-FDS; 50 g/d); and 4) high-dose control (HD-C). Control beverages were matched for calories and total fiber. Blood draws, anthropometrics, blood pressure, and dietary data were collected at screening (0 wk) and after 12-wk intervention. Dose-response analyses revealed significantly greater decreases in serum total and LDL cholesterol and nuclear magnetic resonance (NMR)–derived small LDL particle concentration in HD-FDS [33 ± 6 mg/dL, 28 ± 7 mg/dL, and 301 ± 78 nmol/L, respectively (means ± SEMs)] vs. LD-FDS (−3 ± 11 mg/dL, −3 ± 9 mg/dL, and −28 ± 124 nmol/L, respectively) over 12 wk (0–12 wk; all P < 0.05). Compared with controls, only the decreases in total and LDL cholesterol in HD-FDS remained significant vs. HD-C (0.7 ± 12 and 1.4 ± 9 mg/dL, respectively) over 12 wk (0–12 wk; all P < 0.05). Both doses of strawberries showed a similar decrease in serum malondialdehyde at 12 wk (LD-FDS: 1.3 ± 0.2 μmol/L; HD-FDS: 1.2 ± 0.1 μmol/L) vs. controls (LD-C: 2.1 ± 0.2 μmol/L; HD-C: 2.3 ± 0.2 μmol/L) (P < 0.05). In general, strawberry intervention did not affect any measures of adiposity, blood pressure, glycemia, and serum concentrations of HDL cholesterol and triglycerides, C-reactive protein, and adhesion

Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse

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

Sanchez-Jimenez, F.; Fielder, P.J.; Martinez, R.R.

1990-02-01

({sup 125}I)Iodomouse GH (({sup 125}I)iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operatedmore » pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse.« less

Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

PubMed

Sano, K; Asahina, M; Uehara, T; Matsumoto, K; Araki, N; Okuyama, R

2017-12-01

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. © 2017 European Academy of Dermatology and Venereology.

Elevated serum level of human alkaline phosphatase in obesity.

PubMed

Khan, Abdul Rehman; Awan, Fazli Rabbi; Najam, Syeda Sadia; Islam, Mehboob; Siddique, Tehmina; Zain, Maryam

2015-11-01

To investigate a correlation between serum alkaline phosphatase level and body mass index in human subjects. The comparative cross-sectional study was carried out at the National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan, from April 2012 to June 2013. Blood serum alkaline phosphatase levels were estimated and the subjects were divided into three sub-groups on the basis of their body mass. normal weight (<25kg/m2), overweight (25-27kg/m2) and obese (>27kg/m2) subjects. The serum samples were used for the estimation of clinically important biochemical parameters, using commercial kits on clinical chemistry analyser. Of the 197 subjects, 97(49%) were obese and 100(51%) were non-obese. The serum alkaline phosphatase level increased in obese (214±6.4 IU/L) compared to the non-obese subjects (184.5±5 IU/L). Furthermore, a significant linear relationship (r=0.3;p-0.0001) was found between serum alkaline phosphatase and body mass index. Other biochemical variables were not correlated to the body mass index. Over activity and higher amounts of alkaline phosphatase were linked to the development of obesity.

High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease.

PubMed

Lau, Wei Ling; Linnes, Michael; Chu, Emily Y; Foster, Brian L; Bartley, Bryan A; Somerman, Martha J; Giachelli, Cecilia M

2013-01-01

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear. We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice. In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high-turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification. HP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice.

Predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis.

PubMed

Rackham, Matthew D; Cundy, Thomas P; Antoniou, Georgia; Freeman, Brian J C; Sutherland, Leanne M; Cundy, Peter J

2010-04-20

Prospective cohort study. To determine the predictors of serum chromium levels after stainless steel posterior spinal instrumentation for adolescent idiopathic scoliosis. Abnormally elevated serum chromium levels have been detected in patients with adolescent idiopathic scoliosis after stainless steel instrumentation. To date, the relationship among serum chromium levels, time of implantation, and implant characteristics (including surface area, rod length, numbers of hooks, screws, and cross connectors) has not been studied. Thirty patients with adolescent idiopathic scoliosis undergoing posterior instrumented spinal arthrodesis using stainless steel implants between 1998 and 2002 were prospectively studied. Serum chromium levels were measured between October 2006 and June 2007. Postoperative radiographs were used to measure rod lengths, number of hooks, screws, cross-connectors, and cables. The surface area of each component and the total surface area for each patient were calculated. Possible associations between serum chromium levels, time of implantation, and implant characteristics were investigated. Implant exposure, whether expressed in the form of total metal implant surface area, rod length, or number of metal interfaces, was found to be positively associated with serum chromium levels. Specifically, chromium levels increased by a multiplicative factor of 1.0060 for every additional square centimeter of total metal implant surface area (P = 0.02). In addition, the chromium level was found to decrease by a multiplicative factor of 0.7766 for every additional year since surgery (P = 0.02). After adjusting for the number of years since surgery, metal implant exposure is positively associated with elevated serum chromium levels in adolescent idiopathic scoliosis patients with stainless steel posterior spinal implants. This is the first study to identify statistically significant positive associations between specific spinal implant characteristics (other than

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.

Brazilian female crack users show elevated serum aluminum levels.

PubMed

Pechansky, Flavio; Kessler, Felix Henrique Paim; Diemen, Lisia von; Bumaguin, Daniela Benzano; Surratt, Hilary L; Inciardi, James A

2007-03-01

There is no information in the literature on the impact of crack smoking using crushed aluminum cans as makeshift pipes, a common form of crack use in Brazil. Since aluminum intake is associated with neurological damage, we measured serum aluminum levels in crack smokers. The objective of this study was to ascertain the levels of aluminum in crack users who smoke on makeshift aluminum pipes. 71 female crack smokers, their mean age being 28.0 (+/- 7.7), provided information about their drug use, and had blood samples tested for serum aluminum level. 56 (79%) subjects smoked crack from crushed can pipes, while 15 (21%) smoked from other containers. Fifty-two (73.2%) out of the 71 subjects presented a serum aluminum level of 2 microg/l and 13 (18.3%) had a serum aluminum level of 6 microg/l cut-off point, which is above the reference value. When compared to non-drug users matched by their mean age and gender, they had similar median values and interquartile ranges for serum aluminum level [3 (2-4.6) for crack smokers; 2.9 (1.6-4.1) for controls], but with different means and standard deviations (4.7 +/- 4.9 and 2.9 +/- 1.7, respectively). Crack smokers have high serum aluminum level, but we are unsure of its complete association with aluminum cans. Further studies are needed. If such association is proven true in future research, further issues will be raised in dealing with this important disorder, including proper planning and evaluation of public health policies in this area.

Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome

PubMed Central

Lee, Hong Sub; Lee, Kwang Jae

2017-01-01

Background/Aims The role of dietary factors in the pathogenesis of irritable bowel syndrome (IBS) is still unclear. The aim of this study was to compare IgG4 levels to common food antigens between patients with IBS and healthy controls. Methods Thirty-two patients diagnosed as IBS according to the Rome III criteria (12 diarrhea subgroup; 20 non-diarrhea subgroup) and 32 sex and age-matched healthy controls participated in the study. Serum IgG4 titers to 90 common foods were measured in each subject. The number of subjects with positivity defined as the cut-off value ≥ 0.7 U/mL was compared. Results Patients with IBS had significantly higher IgG4 titers to wheat, leek and taro compared to those of controls. Serum IgG4 titers to ginger, cocoa, walnut, white radish, onion, and lettuce in IBS patients tended to be higher than controls. IgG4 titers to wheat, gluten and gliadin in the diarrhea subgroup, and lettuce, leek and taro in the non-diarrhea subgroup tended to be higher compared with controls. The number of subjects with positivity to apple, orange, lettuce, and leek was significantly higher in IBS patients than controls. The number of subjects with positivity to apple, orange, gluten, and gliadin in the diarrhea subgroup, and egg white, pineapple, soybean, lettuce, and leek in the non-diarrhea subgroup was significantly higher compared with controls. Conclusions Serum IgG4 antibody levels to some common foods are abnormally elevated in IBS patients. The type of foods with abnormally elevated serum IgG4 titers in the diarrhea subgroup may be different from that in the non-diarrhea subgroup. PMID:28992678

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

PubMed

Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

1991-10-01

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT

Hyperplastic thymus with increased angiogenesis is correlated with elevated serum thyroglobulin level in differentiated thyroid cancer patients with TENIS syndrome

PubMed Central

Zhang, Guangjian; Gao, Rui; Wang, Yuanbo; Liu, Yan; Li, Juan; Jia, Xi; Liang, Yiqian; Yang, Aimin

2018-01-01

Aims To investigate the association between angiogenetic activity of hyperplastic thymus and serum thyroglobulin (Tg) level in differentiated thyroid carcinoma patients with thyroglobulin (Tg)-elevated Negative Iodine Scintigraphy (TENIS) Syndrome. Methods A cohort of 30 consecutive patients who underwent total thyroidectomy followed by radioiodine ablation and had TENIS syndrome received integrin αvβ3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3PRGD2). The correlation of angiogenetic activity of the thymus and the serum Tg levels was evaluated in patients with enlarged thymus. Results Enlarged thymus was detected in 9 out of the 30 TENIS patients and all hyperplastic thymus showed an increased accumulation of the tracer (median tumor/background ratio: 2.8). Five of them had only mediastinal uptake and surgical removal of the mediastinal mass in one provided histopathologic evidence of thymic tissue. The other four were not assigned further treatment and were free of disease in the follow-up, though their stimulated Tg levels consistently increased. Four out of the 9 patients showed 99mTc-3PRGD2 uptake outside the mediastinum were assigned surgery followed by radioiodine treatment. Their stimulated Tg levels decreased after iodine ablation, but not drop back to normal. A significant linear correlation was observed between serum Tg levels and the degree of angiogenesis in the hyperplastic thymus. Conclusions The angiogenetic activity in hyperplastic thymus was related with the consistently elevated serum Tg levels in TENIS syndrome patients. Based on the existing literature and current data, we propose further intervention for patients with RGD uptake outside thymus, while close follow-up for patients with only mediastinal uptake. PMID:29423055

Elevated serum concentrations of HE4 as a novel biomarker of disease severity and renal fibrosis in kidney disease

PubMed Central

Liang, Jianbo; Yue, Caifeng; Wang, Fen; Song, Junli; Wang, Jianfeng; Liu, Min; Luo, Jinmei; Li, Laisheng

2016-01-01

Background Human epididymis protein 4 (HE4), has recently been reported as a mediator of renal fibrosis. However, serum HE4 levels appear in a large number of patient samples with chronic kidney disease (CKD), and the relationship of these levels to disease severity and renal fibrosis is unknown. Methods In 427 patients at different stages of CKD excluding gynecologic cancer and 173 healthy subjects, serum HE4 concentrations were tested by chemiluminescent microparticle immunoassay. Renal biopsy was performed on 259 of 427 subjects. Histological findings were evaluated using standard immunohistochemistry. Results The levels of serum HE4 were higher in CKD patients than in healthy subjects, and higher levels were associated with more severe CKD stages. Patients with more severe renal fibrosis tended to have higher HE4 levels, and correlation analysis showed a significant correlation between HE4 and degree of renal fibrosis (r = 0.938, P < 0.0001). HE4 can be a predictor of renal fibrosis in CKD patients; the area under the receiver-operating characteristic curve (AUC-ROC) was 0.99, higher than the AUC-ROC of serum creatinine (0.89). Conclusion Elevated levels of serum HE4 are associated with decreased kidney function, and also with an advanced stage of renal fibrosis, suggesting that HE4 may serve as a valuable clinical biomarker for renal fibrosis of CKD. PMID:27589683

Neural autoantibodies and neurophysiologic abnormalities in patients exposed to molds in water-damaged buildings.

PubMed

Campbell, Andrew W; Thrasher, Jack D; Madison, Roberta A; Vojdani, Aristo; Gray, Michael R; Johnson, Al

2003-08-01

Adverse health effects of fungal bioaerosols on occupants of water-damaged homes and other buildings have been reported. Recently, it has been suggested that mold exposure causes neurological injury. The authors investigated neurological antibodies and neurophysiological abnormalities in patients exposed to molds at home who developed symptoms of peripheral neuropathy (i.e., numbness, tingling, tremors, and muscle weakness in the extremities). Serum samples were collected and analyzed with the enzyme-linked immunosorbent assay (ELISA) technique for antibodies to myelin basic protein, myelin-associated glycoprotein, ganglioside GM1, sulfatide, myelin oligodendrocyte glycoprotein, alpha-B-crystallin, chondroitin sulfate, tubulin, and neurofilament. Antibodies to molds and mycotoxins were also determined with ELISA, as reported previously. Neurophysiologic evaluations for latency, amplitude, and velocity were performed on 4 motor nerves (median, ulnar, peroneal, and tibial), and for latency and amplitude on 3 sensory nerves (median, ulnar, and sural). Patients with documented, measured exposure to molds had elevated titers of antibodies (immunoglobulin [Ig]A, IgM, and IgG) to neural-specific antigens. Nerve conduction studies revealed 4 patient groupings: (1) mixed sensory-motor polyneuropathy (n = 55, abnormal), (2) motor neuropathy (n = 17, abnormal), (3) sensory neuropathy (n = 27, abnormal), and (4) those with symptoms but no neurophysiological abnormalities (n = 20, normal controls). All groups showed significantly increased autoantibody titers for all isotypes (IgA, IgM, and IgG) of antibodies to neural antigens when compared with 500 healthy controls. Groups 1 through 3 also exhibited abnormal neurophysiologic findings. The authors concluded that exposure to molds in water-damaged buildings increased the risk for development of neural autoantibodies, peripheral neuropathy, and neurophysiologic abnormalities in exposed individuals.

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

Serum HSP70

PubMed Central

Dutta, Sudhir K.; Girotra, Mohit; Singla, Montish; Dutta, Anand; Stephen, F. Otis; Nair, Padmanabhan P.; Merchant, Nipun B.

2014-01-01

Objectives Heat shock protein 70 (HSP70) is overexpressed in human pancreatic cancer cell lines. To determine if serum HSP70 levels are elevated in patients with pancreatic cancer and can function as a biomarker for early detection of pancreatic cancer. Methods Study subjects were divided into 3 groups: histologically proven pancreatic cancer (PC; n = 23), chronic pancreatitis (CP; n = 12), and matched normal control subjects (C; n = 10). Serum HSP70 levels were determined using a novel immunoelectrophoresis method developed and validated by the authors. Significance of difference between the groups was analyzed with analysis of variance (ANOVA). Receiver operating characteristic (ROC) curve analysis was performed to discriminate patients with pancreatic cancer from normal controls. Results The mean ± SE serum HSP70 levels in the PC, CP, and C groups were 1.68 ± 0.083 ng/mL, 0.40 ± 0.057 ng/mL, and 0.04 ng/mL, respectively. Serum HSP70 levels in the PC group were significantly higher compared with either the CP or C groups (P < 0.01). The sensitivity and specificity of elevated serum HSP70 in the PC group was 74% and 90%, respectively. Conclusions Serum HSP70 levels are significantly increased in patients with pancreatic cancer and may be useful as an additional biomarker for the detection of pancreatic cancer. PMID:22158074

Serum progranulin irrelated with Breg cell levels, but elevated in RA patients, reflecting high disease activity.

PubMed

Chen, Jiaxi; Li, Shuang; Shi, Jianfeng; Zhang, Lili; Li, Jun; Chen, Shiyong; Wu, Chunlong; Shen, Bo

2016-03-01

Soluble progranulin (PGRN) is known to directly regulate regulatory T cells; however, whether PGRN levels are elevated in patients with rheumatoid arthritis and affect the regulatory subsets of B cells remain unknown. In this study, a total of 80 RA patients and 60 healthy controls were studied. Serum progranulin levels were determined using enzyme-linked immune-sorbent assay. A receiver operating characteristic (ROC) curve was used to evaluate the feasibility of serum PGRN as a biomarker for distinguishing patients with RA. CD19(+)CD5(+)GrB(+) B cells were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). Serum progranulin levels in RA patients (median, 59.4 ng/mL) and in RA patients DAS28 > 5.1 (median, 71.98 ng/mL) were much higher than those in normal controls (median, 46.3 ng/mL; P < 0.001). The area under the ROC curve for progranulin levels was 0.705 for RA versus normal controls and the area under the ROC curve for progranulin levels in RA patients DAS28 > 5.1 was 0.977 versus normal controls (P < 0.001). Interestingly, serum progranulin and DAS28, CRP, ESR were all positively correlated in RA patients (P < 0.001). The number of CD19(+)CD5(+)GrB(+) B cells was significantly higher in RA patients (P < 0.05); however, the level of Breg cells was not related to PGRN (P > 0.05). Our findings indicated that induction of PGRN expression may play a role in RA immune reaction and PGRN levels could be a useful biomarker in RA inflammatory response, but irrelated with Breg cell levels.

Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review

PubMed Central

Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

2014-01-01

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker. PMID:25926909

Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review.

PubMed

Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

2014-11-01

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

Serum levels of endothelial and neural cell adhesion molecules in prostate cancer.

PubMed

Lynch, D F; Hassen, W; Clements, M A; Schellhammer, P F; Wright, G L

1997-08-01

Tumorigenesis and progression to metastatic disease are accompanied by changes in the expression of cell adhesion molecules (CAMs). Normally expressed CAMs, such as E-cadherin, are lost, while others, i.e., ICAM-1, VCAM-1, NCAM, and E-selectin, are altered and overexpressed in progressive disease and metastases. Abnormal levels of these latter CAMs have been observed in melanoma and carcinomas of the colon and breast, and NCAM is overexpressed in small-cell lung carcinoma (SCLC). The objective of this study was to determine if serum levels of ICAM-1, VCAM-1, NCAM, and E-selectin could differentiate patients with benign prostate hypertrophy (BPH) from those with prostate carcinoma (CaP) and identify prostate cancers with high potential for progression to metastatic disease. Serum levels of these CAMs were determined by ELISA in serum from normal males and females and from patients with BPH and CaP before and after treatment. Sera from patients with breast carcinoma, colon carcinoma, melanoma, and small-cell lung carcinoma were also evaluated, as soluble CAMs have been reported to be elevated in these cancer patients. ICAM-1 levels were elevated in sera from patients with breast carcinoma (P = 0.0004) and melanoma (P = 0.0001). VCAM-1 levels were elevated in sera from patients with colon carcinoma (P = 0.0001). NCAM levels were elevated in the sera of patients with SCLC (P = 0.0001). Normal levels of ICAM-1, E-selectin, and NCAM were found in both BPH and pretreatment CaP patients. Median NCAM levels in hormone-refractive CaP patients were significantly greater than in BPH (P = 0.0005) and CaP patients with pathologically determined organ-confined (P = 0.0014) or nonorgan-confined disease (P = 0.0385). VCAM-1 levels were significantly elevated in both BPH patients (P = 0.0002) and CaP patients (P = 0.0002) when compared with levels for normal age-matched donors. None of the CAMs were found to offer an advantage over prostatic-specific antigen (PSA) for monitoring Ca

Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study.

PubMed

Islam, Md Rabiul; Islam, Md Reazul; Ahmed, Imtiaz; Moktadir, Abdullah Al; Nahar, Zabun; Islam, Mohammad Safiqul; Shahid, Shelina Fatema Binte; Islam, Sheikh Nazrul; Islam, Md Saiful; Hasnat, Abul

2018-01-01

Major depressive disorder is diagnosed on the basis of patient's self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p  < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p  < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients ( r  =-0.170, p  = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder.

Elevated serum levels of malondialdehyde and cortisol are associated with major depressive disorder: A case-control study

PubMed Central

Islam, Md Reazul; Ahmed, Imtiaz; Moktadir, Abdullah Al; Nahar, Zabun; Islam, Mohammad Safiqul; Shahid, Shelina Fatema Binte; Islam, Sheikh Nazrul; Islam, Md Saiful; Hasnat, Abul

2018-01-01

Objectives: Major depressive disorder is diagnosed on the basis of patient’s self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. Methods: We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. Results: We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients (r =−0.170, p = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. Conclusion: The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder. PMID:29770218

Abnormal fatty acids in Canadian children with autism.

PubMed

Jory, Joan

2016-04-01

Fatty acids are critical for pediatric neurodevelopment and are abnormal in autism, although prior studies have demonstrated conflicting results and methodological differences. To our knowledge, there are no published data on fatty acid in Canadian children with autism. The aim of this study was to investigate red blood cell and serum fatty acid status to identify whether abnormalities exist in Canadian children with autism, and to enhance future cross-study comparison. Eleven Canadian children with autism (3 girls, 8 boys; age 3.05 ± 0.79 y) and 15 controls (9 girls, 6 boys; age 3.87 ± 1.06 y) met inclusion criteria, which included prior Diagnostic and Statistical Manual diagnosis of autism spectrum disorder, no recent medication or supplements, no specialty diets, and no recent illness. The children with autism demonstrated lower red blood cell docosahexaenoic acid (P < 0.0003), eicosapentaenoic acid (P < 0.03), arachidonic acid (P < 0.002), and ω-3/ω-6 ratios (P < 0.001). They also demonstrated lower serum docosahexaenoic acid (P < 0.02), arachidonic acid (P < 0.05), and linoleic acid (P < 0.02) levels. Fatty acids in both serum and red blood cells were abnormal in this small group of Canadian children with autism than in controls, underlining a need for larger age- and sex-matched investigations in this community. A potential role for fatty acid abnormalities within the complex epigenetic etiology of autism is proposed in relation to emerging understanding of relationships between cobalamin metabolism, gut microbiota, and propionic acid production. Copyright © 2016 Elsevier Inc. All rights reserved.

[Serum sclerostin levels and metabolic bone diseases].

PubMed

Yamauchi, Mika; Sugimoto, Toshitsugu

2013-06-01

Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

Approach to the hemodialysis patient with an abnormal serum bicarbonate concentration.

PubMed

Lisawat, Panupong; Gennari, F John

2014-07-01

We present a patient receiving hemodialysis with a persistently high serum bicarbonate concentration to illustrate the evaluation and management issues for patients with both high (>25 mEq/L) and low (<20 mEq/L) pretreatment values. Patients with high serum bicarbonate concentrations typically are malnourished and have low rates of endogenous acid production. Evaluation should begin with assessment of whether an acute and potentially reversible cause of metabolic alkalosis is present. If not, management should be directed at treating malnutrition. By contrast, patients with low predialysis serum bicarbonate concentrations, in the absence of an acute and reversible cause, may benefit from increasing the level by an adjustment in dialysate bicarbonate concentration. However, the level at which one should intervene and to what extent serum bicarbonate concentration should be increased are unresolved issues. Whether such an intervention will reduce mortality risk has not been determined. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Oral cancer screening: serum Raman spectroscopic approach

NASA Astrophysics Data System (ADS)

Sahu, Aditi K.; Dhoot, Suyash; Singh, Amandeep; Sawant, Sharada S.; Nandakumar, Nikhila; Talathi-Desai, Sneha; Garud, Mandavi; Pagare, Sandeep; Srivastava, Sanjeeva; Nair, Sudhir; Chaturvedi, Pankaj; Murali Krishna, C.

2015-11-01

Serum Raman spectroscopy (RS) has previously shown potential in oral cancer diagnosis and recurrence prediction. To evaluate the potential of serum RS in oral cancer screening, premalignant and cancer-specific detection was explored in the present study using 328 subjects belonging to healthy controls, premalignant, disease controls, and oral cancer groups. Spectra were acquired using a Raman microprobe. Spectral findings suggest changes in amino acids, lipids, protein, DNA, and β-carotene across the groups. A patient-wise approach was employed for data analysis using principal component linear discriminant analysis. In the first step, the classification among premalignant, disease control (nonoral cancer), oral cancer, and normal samples was evaluated in binary classification models. Thereafter, two screening-friendly classification approaches were explored to further evaluate the clinical utility of serum RS: a single four-group model and normal versus abnormal followed by determining the type of abnormality model. Results demonstrate the feasibility of premalignant and specific cancer detection. The normal versus abnormal model yields better sensitivity and specificity rates of 64 and 80% these rates are comparable to standard screening approaches. Prospectively, as the current screening procedure of visual inspection is useful mainly for high-risk populations, serum RS may serve as a useful adjunct for early and specific detection of oral precancers and cancer.

Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

PubMed

Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

2017-11-01

Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 < 37 U/mL (multivariate adjusted OR 2.10; 95% CI 1.21-3.65). Serum CA 19-9 is associated with an increased risk of prevalent metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

IgG abnormality in narcolepsy and idiopathic hypersomnia.

PubMed

Tanaka, Susumu; Honda, Makoto

2010-03-05

A close association between narcolepsy and the Human Leukocyte Antigen (HLA)-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects). The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml), healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43), narcolepsy patients (9.67+/-3.38), and idiopathic hypersomnia patients (13.81+/-3.80). None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

PubMed

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p < 0.001). Serum NO(x) were not found to be associated with lung fibrosis defined by lung function parameters or inflammation and fibrosis scores on HRCT. Twenty-two patients were found to have elevated serum NO(x) level defined as mean +/- 2 SD of normal controls. Logistic regression analysis revealed that age (OR 1.12, p = 0.02) and elevated pulmonary arterial pressure (PAP) (n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

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

Siegel, A.J.; Silverman, L.M.; Holman, B.L.

1985-10-01

Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runnersmore » tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise.« less

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PubMed

Rich, Tyvin; Innominato, Pasquale F; Boerner, Julie; Mormont, M Christine; Iacobelli, Stefano; Baron, Benoit; Jasmin, Claude; Lévi, Francis

2005-03-01

Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine

Elevated second-trimester maternal serum β-human chorionic gonadotropin and amniotic fluid alpha-fetoprotein as indicators of adverse obstetric outcomes in fetal Turner syndrome.

PubMed

Alvarez-Nava, Francisco; Soto, Marisol; Lanes, Roberto; Pons, Hector; Morales-Machin, Alisandra; Bracho, Ana

2015-12-01

The objective of this study was to determine the ability of biochemical analytes to identify adverse outcomes in pregnancies with Turner syndrome. Maternal serum and amniotic fluid (AF) marker concentrations were measured in 73 singleton pregnancies with Turner syndrome (10-22 weeks of gestation). Fetal Turner syndrome was definitively established by cytogenetic analysis. Two subgroups, fetuses with hydrops fetalis versus fetuses with cystic hygroma, were compared. Receiver operating characteristic curves and relative risk were established for a cut-off multiples of the median ≥3.5 for β-subunit of human chorionic gonadotropin (hCG) or AF alpha-fetoprotein (AFP). Forty-nine (67%) of 73 pregnant women had an abnormal maternal serum. While levels of pregnancy-associated plasma protein-A and free β-subunit (fβ)-hCG were not different to those of the control group, AFP, unconjugated estriol and β-hCG concentrations were significantly different in the study group (P < 0.05), when compared to those of unaffected pregnancies. Levels of β-hCG in pregnancies with hydrops fetalis were significantly higher than in those with cystic hygroma (P <0.0001), as were AF-AFP concentrations (P <0.0015). In addition, abnormalities in both maternal serum β-hCG and AF-AFP predicted fetal death. The relative risk of adverse obstetric outcome was 10.667 (P = 0.0004; 95% confidence interval [CI]: 1.554-73.203) for β-hCG and 2.19 (P = 0.0256; 95% CI: 1.001 to 4.779), for AF-AFP. Maternal serum β-hCG and AF-AFP levels may preferentially identify those Turner syndrome pregnancies with the highest risk of fetal death. © 2015 Japan Society of Obstetrics and Gynecology.

Elevated serum levels of ghrelin and TNF-α in patients with cyanotic and acyanotic congenital heart disease.

PubMed

Zhang, Sai; Guo, Gong-Liang; Yang, Li-Li; Sun, Li-Qun

2017-04-01

The levels of ghrelin and tumor necrosis factor alpha (TNF-α) are considered biological markers of congenital heart diseases (CHD). The present meta-analysis was conducted to investigate the clinical significance of serum levels of ghrelin and TNF-α in children with (CHD). Chinese and English scientific literature databases were searched to retrieve published studies relevant to ghrelin, TNF-α and CHD. Manual search was additionally employed to identify other relevant studies from cross-references. The retrieved studies were screened on the basis of our stringent inclusion and exclusion criteria to select high quality case-control studies for meta-analysis. We initially retrieved 108 published studies (20 in Chinese and 88 in English) from database searches. Finally, 6 case-control studies (5 in English and 1 in Chinese) were enrolled in our meta-analysis, and contained a total of 160 cyanotic congenital heart disease (CCHD) patients and 215 acyanotic congenital heart disease (ACHD) patients, along with 162 healthy controls. The results of meta-analysis showed that serum levels of ghrelin and TNF-α in CCHD or ACHD children were significantly higher than those in healthy controls. Our meta-analysis results showed that serum levels of ghrelin and TNF-α are elevated in children with CHD, and could be used as effective biologic markers in early diagnosis of CHD.

Osmolar relation between cerebrospinal fluid and serum in hyperosmolar hypernatraemic dehydration.

PubMed Central

Habel, A H; Simpson, H

1976-01-01

The relation between cerebrospinal fluid (CSF) and serum osmolality was studied in 16 patients with hyperosmolar hypernatraemic dehydration before treatment. After correcting shock and acidosis, 0-45% saline in 2-5 or 5% dextrose was infused in each patient over a 48- to 72-hour period. During rehydration, serum osmolality, electrolyte concentrations, urea nitrogen, and blood pH were measured sequentially. Five patients developed severe neurological abnormalities within 48 hours of addmission (convulsions 2, convulsions with hemiplegia 2, hemiplegia 1). Of these, 3 had residual defects on follow-up at least one year later. This group was indistinguishable from the 11 without significant neurological abnormality, both on clinical grounds before rehydration, and after analysis of admission and subsequent serum biochemical variables. A significant osmolar gap (greater than 4 mmol/kg H2O) between serum and CSF was found in 13 patients. Severe neurological disturbance only occurred when CSF osmolality exceeded that of serum by 7 or more mmol/kg H2O. Discriminant analysis of the paired osmolar data showed that D = -117+1-74 X(CSF osmolality) -1-41 X (serum osmolality), and that severe neurological abnormality was predicted when D was positive. PMID:11753

Serum concentrations of polychlorinated dibenzo-p-dioxins among ceramicists.

PubMed

Demond, Avery; Jiang, Xiaohui; Broadwater, Kendra; Meeker, John; Luksemburg, William; Maier, Martha; Garabrant, David; Franzblau, Alfred

2015-01-01

Polychlorinated dibenzo-p-dioxins (PCDDs) occur naturally in ball clay at elevated concentrations. Thus, persons who habitually work with clay may be at risk for exposure to PCDDs. An earlier case report provided some evidence of elevated PCDD levels in serum for long-term hobby ceramicists; however, no previous study has measured serum dioxin concentrations among ceramicists. This study measured PCDD serum levels for 27 individuals involved in ceramics making. The average residual, defined as the average of the [log measured serum lipid concentration – log background serum lipid concentration], was calculated and then tested to determine whether it was significantly different from zero. The p-values for the average residuals indicated that the serum lipid concentrations for several PCDD congeners were elevated relative to background. The number of significant residuals increased dramatically if the background concentrations were adjusted to account for the fact that they were not contemporaneous with the measurements for the ceramicists. The ratio of the 1,2,3,6,7,8-HxCDD concentration to the 1,2,3,7,8,9-HxCDD concentration was greater than 1.0, unlike in ball clay, suggesting that although long-term working with ball clay elevates the PCDD levels in serum somewhat, it is not the predominant source of the PCDD body burden for ceramicists.

Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS.

PubMed

Irani, Mohamad; Minkoff, Howard; Seifer, David B; Merhi, Zaher

2014-05-01

Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis. The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS. DESIGN, SETTINGS, PARTICIPANTS, AND INTERVENTION: Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group. Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured. In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = -0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P < .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01). In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.

Serum lipoprotein concentrations in cystic fibrosis

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

Vaughan, W.J.; Lindgren, F.T.; Whalen, J.B.

1978-02-17

Two major classes of lipoproteins, low density and high density, are decreased in the serum of patients with cystic fibrosis; major apoproteins are also decreased. Since essential fatty acids and certain fat-soluble vitamins depend on lipoproteins for transport in the serum, knowledge of lipoprotein levels in cystic fibrosis patients could prove valuable in understanding (i) the basis for the abnormally low serum levels of these fatty acids and vitamins and (ii) the effects of therapies involving these molecules.

Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

PubMed

Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

2015-10-01

Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

PubMed Central

Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

2015-01-01

Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

Elevated Serum Beta-D-Glucan with Pseudomonas, Aspergillus, and a Partially Acid-Fast Organism in Respiratory Cultures: A Case of Hickam's Dictum Over Occam's Razor.

PubMed

Khan, Salman; Hamula, Camille; Rana, Meenakshi; Sullivan, Timothy; Dunn, Dallas; Patel, Pinki; Mishkin, Aaron; Huprikar, Shirish

2017-10-01

We describe a case of a man with ectopic Cushing's syndrome, elevated serum beta-D-glucan, and respiratory cultures with Pseudomonas, Aspergillus, and a partially acid-fast organism. Our case highlights challenges in diagnosis and management of coinfection in an immunocompromised host.

Prenatal diagnosis and molecular cytogenetic characterization of de novo pure partial trisomy 6p associated with microcephaly, craniosynostosis and abnormal maternal serum biochemistry.

PubMed

Chen, Chih-Ping; Chen, Ming; Chen, Chen-Yu; Chern, Schu-Rern; Wu, Peih-Shan; Chang, Shun-Ping; Kuo, Yu-Ling; Chen, Wen-Lin; Pan, Chen-Wen; Wang, Wayseen

2014-02-25

We present prenatal diagnosis and molecular cytogenetic characterization of de novo pure trisomy 6p22.3 → p25.3 encompassing BMP6 in a fetus associated with microcephaly and craniosynostosis on prenatal ultrasound, abnormal maternal serum biochemistry of a low PAPP-A level in the first-trimester combined test, and a karyotype of 46,XX,der(22)t(6;22)(p22.3;p13)dn. The present case demonstrates the usefulness of rapid prenatal identification of the origin of the extra chromosome material on the short arm of an acrocentric chromosome by spectral karyotyping, fluorescence in situ hybridization and array comparative genomic hybridization. We review the phenotypic abnormality of craniosynostosis in previously reported patients with partial trisomy 6p. We discuss the genotype-phenotype correlation of the involved gene of BMP6 in this case. Copyright © 2013 Elsevier B.V. All rights reserved.

Is the coexistence of sustained ST-segment elevation and abnormal Q waves a risk factor for electrical storm in implanted cardioverter defibrillator patients with structural heart diseases?

PubMed

Furushima, Hiroshi; Chinushi, Masaomi; Iijima, Kenichi; Hasegawa, Kanae; Sato, Akinori; Izumi, Daisuke; Watanabe, Hiroshi; Aizawa, Yoshifusa

2012-05-01

The aim of this study was to determine whether or not the coexistence of sustained ST-segment elevation and abnormal Q waves (STe-Q) could be a risk factor for electrical storm (ES) in implanted cardioverter defibrillator (ICD) patients with structural heart diseases. In all, 156 consecutive patients received ICD therapy for secondary prevention of sudden cardiac death and/or sustained ventricular tachyarrhythmias were included. Electrical storm was defined as ≥3 separate episodes of ventricular tachycardia (VT) and/or ventricular fibrillation (VF) terminated by ICD therapies within 24 h. During a mean follow-up of 1825 ± 1188 days, 42 (26.9%) patients experienced ES, of whom 12 had coronary artery disease, 15 had idiopathic dilated cardiomyopathy, 6 had hypertrophic cardiomyopathy, 4 had arrhythmogenic right ventricular cardiomyopathy, 4 had cardiac sarcoidosis, and 1 had valvular heart disease. Sustained ST-segment elevation and abnormal Q waves in ≥2 leads on the 12-lead electrocardiography was observed in 33 (21%) patients. On the Kaplan-Meier analysis, patients with STe-Q had a markedly higher risk of ES than those without STe-Q (P< 0.0001). The multivariate Cox proportional hazards regression model indicated that STe-Q and left ventricular ejection fraction (LVEF) (<30%) were independent risk factors associated with the recurrence of VT/VF (STe-Q: HR 1.962, 95% CI 1.24-3.12, P= 0.004; LVEF: HR 1.860, 95% CI 1.20-2.89, P= 0.006), and STe-Q was an independent risk factor associated with ES (HR 4.955, 95% CI 2.69-9.13, P< 0.0001). Sustained ST-segment elevation and abnormal Q waves could be a risk factor of not only recurrent VT/VF but also ES in patients with structural heart diseases.

Elevated androstenedione in young adult but not early adolescent prenatally androgenized female rats.

PubMed

Shah, Ami B; Nivar, Isaac; Speelman, Diana L

2018-01-01

Elevated testosterone (T) is routinely reported as a marker of hyperandrogenemia in rodent models for polycystic ovary syndrome (PCOS). In women with PCOS, elevated serum androstenedione (A4) is associated with more severe phenotypes, including a positive correlation with serum T, DHEAS, free androgen index (FAI), LH, and LH/FSH ratio. Furthermore, A4, along with calculated free T and FAI, was identified as one of the best predictors of PCOS in adult women of all ages (18 to > 50 y). The objective of this study was to investigate serum A4 levels in early adolescent and young adult prenatally androgenized (PNA) female rats, a model for PCOS. Pregnant rats were injected with 5 mg T daily during gestational days 16-19 (PNA rats, experimental group) or an equal volume of vehicle (control group). Female offspring of both groups had tail vein blood drawn for serum analysis at 8 and 16 weeks of age. ELISAs were used to quantify serum A4 and T levels. Serum A4 and T were elevated in 16-week-old PNA rats compared to controls. There was no significant difference in either hormone at 8 weeks of age. The PNA rats demonstrated elevated serum A4 and T in young adulthood, as has been observed in women with PCOS, further validating this as a model for PCOS and underscoring the importance of serum A4 elevation as a parameter inherent to PCOS and a rodent model for the disorder. Significant A4 elevation develops between early adolescence and early adulthood in this PNA rat model.

Intrathoracic administration of OK-432 elevates the serum procalcitonin levels.

PubMed

Ogasawara, Takashi; Umezawa, Hiroki; Kato, Shinpei; Yano, Toshiaki; Kasamatsu, Norio; Hashizume, Ikko

2012-01-01

The intrathoracic administration of OK-432, a lyophilized preparation of the heat- and penicillin-treated Su-strain of type 3, group A Streptococcus pyogenes, is performed in Japan for pleurodesis of malignant pleural effusion or pneumothorax. Persistent fever is often observed after pleurodesis. To elucidate whether procalcitonin (PCT) is useful for distinguishing between the side effects of OK-432 and infection, we measured the serum PCT levels before and after pleurodesis. We performed a prospective study of 12 patients with refractory pleural effusion or pneumothorax who required pleurodesis using OK-432 between August 2011 and February 2012. The serum PCT and C-reactive protein (CRP) levels were measured on days 1 and 3. Of the 12 patients, five had pneumothorax and seven had uncontrolled pleural effusion with carcinomatous pleurisy. The median serum levels of PCT and CRP increased from 0.055 to 1.59 ng/mL (p=0.0022) and from 1.52 to 16.82 mg/dL (p=0.0022), respectively. The fevers subsided without antibiotic administration. The serum PCT level may not be useful for distinguishing fever caused by side effects of OK-432 from that caused by bacterial infection. The intrathoracic administration of OK-432 increased the serum levels of both PCT and CRP in the absence of any bacterial infection.

Increased Serum Sodium and Serum Osmolarity Are Independent Risk Factors for Developing Chronic Kidney Disease; 5 Year Cohort Study.

PubMed

Kuwabara, Masanari; Hisatome, Ichiro; Roncal-Jimenez, Carlos A; Niwa, Koichiro; Andres-Hernando, Ana; Jensen, Thomas; Bjornstad, Petter; Milagres, Tamara; Cicerchi, Christina; Song, Zhilin; Garcia, Gabriela; Sánchez-Lozada, Laura G; Ohno, Minoru; Lanaspa, Miguel A; Johnson, Richard J

2017-01-01

Epidemics of chronic kidney disease (CKD) not due to diabetes mellitus (DM) or hypertension have been observed among individuals working in hot environments in several areas of the world. Experimental models have documented that recurrent heat stress and water restriction can lead to CKD, and the mechanism may be mediated by hyperosmolarity that activates pathways (vasopressin, aldose reductase-fructokinase) that induce renal injury. Here we tested the hypothesis that elevated serum sodium, which reflects serum osmolality, may be an independent risk factor for the development of CKD. This study was a large-scale, single-center, retrospective 5-year cohort study at Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We analyzed 13,201 subjects who underwent annual medical examination of which 12,041 subjects (age 35 to 85) without DM and/or CKD were enrolled. This analysis evaluated age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, hyperuricemia, fasting glucose, BUN, serum sodium, potassium, chloride and calculated serum osmolarity. Elevated serum sodium was an independent risk factor for development of CKD (OR: 1.03, 95% CI, 1.00-1.07) after adjusted regression analysis with an 18 percent increased risk for every 5 mmol/L change in serum sodium. Calculated serum osmolarity was also an independent risk factor for CKD (OR: 1.04; 95% CI, 1.03-1.05) as was BUN (OR: 1.08; 95% CI, 1.06-1.10) (independent of serum creatinine). Elevated serum sodium and calculated serum osmolarity are independent risk factors for developing CKD. This finding supports the role of limiting salt intake and preventing dehydration to reduce risk of CKD.

Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor.

PubMed

Andrews, Tory J; Cox, Robert D; Parker, Christina; Kolb, James

2017-02-01

Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications. We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose > 500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. Acetone is one of the three main ketone bodies formed during DKA and it may be present at considerable concentrations, contributing to the serum osmolality. Copyright © 2016 Elsevier Inc. All rights reserved.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core

PubMed Central

Corban, Michel T; Hung, Olivia Y; Mekonnen, Girum; Eshtehardi, Parham; Eapen, Danny J; Rasoul-Arzrumly, Emad; Kassem, Hatem Al; Manocha, Pankaj; Ko, Yi-An; Sperling, Laurence S; Quyyumi, Arshed A; Samady, Habib

2016-01-01

Background Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. Methods and Results Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47–63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. Conclusions In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC. PMID:26911453

Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core.

PubMed

Corban, Michel T; Hung, Olivia Y; Mekonnen, Girum; Eshtehardi, Parham; Eapen, Danny J; Rasoul-Arzrumly, Emad; Al Kassem, Hatem; Manocha, Pankaj; Ko, Yi-An; Sperling, Laurence S; Quyyumi, Arshed A; Samady, Habib

2016-01-01

Co-existence of vulnerable plaque and pro-thrombotic state may provoke acute coronary events. It was hypothesized that elevated serum levels of fibrin and fibrinogen degradation products (FDP) are associated with larger total plaque and necrotic core (NC) areas. Seventy-five patients presenting with stable anginal symptoms (69%) or stabilized acute coronary syndrome (ACS; 31%), and found to have non-obstructive coronary artery disease (CAD) with a fractional flow reserve >0.8, were studied. Invasive virtual histology intravascular ultrasound (VH-IVUS) was performed in 68 LAD arteries, 6 circumflex arteries, and 1 right coronary artery. Serum FDP levels were measured using ELISA technique. Plaque volumetrics and composition were assessed in each VH-IVUS frame and averaged. The median age of patients was 56 (47-63) years; 52% were men and 23% had diabetes. The average length of coronary artery studied was 62 mm. After adjustment for systemic risk factors, medications, CRP levels and ACS, male gender (P<0.001) and serum FDP levels (P=0.02) were independent predictors of a larger NC area. Older age (P<0.001), male gender (P<0.0001) and increased serum FDP level (P=0.03) were associated with a larger plaque area. In patients with CAD, a higher serum level of FDP is independently associated with larger plaques and greater plaque NC.

Elevated serum levels of free triiodothyronine in adolescent boys with gynaecomastia compared with controls.

PubMed

Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Hagen, Casper P; Hilsted, Linda; Andersson, Anna-Maria; Juul, Anders

2014-08-01

Pubertal gynaecomastia is a frequent phenomenon occurring in 20-40% of otherwise healthy adolescent boys. Little is known about the aetiology of pubertal gynaecomastia. Markedly elevated thyroid hormone levels in adults with hyperthyroidism are associated with gynaecomastia. A cross-sectional examination of 444 healthy boys with and without pubertal gynaecomastia. We evaluated TSH, triiodothyronine (T3), thyroxine (T4), free T4 and free T3 in a cohort of healthy boys with and without pubertal gynaecomastia. Boys with gynaecomastia had significantly higher serum free T3, even after correction for age, BMI and pubertal stage. After inclusion of IGF1 in the model the differences disappeared. TSH, T4, free T4 and T3 did not differ between the groups. We speculate that the GH/IGF1 axis and thyroid hormones interact and influence the development of pubertal gynaecomastia. © 2014 European Society of Endocrinology.

A phase II, randomized, controlled trial of S-adenosylmethionine in reducing serum alpha-fetoprotein (AFP) in patients with hepatitis C cirrhosis and elevated AFP

PubMed Central

Morgan, Timothy R.; Osann, Kathryn; Bottiglieri, Teodoro; Pimstone, Neville; Hoefs, John C.; Hu, Ke-Qin; Hassanein, Tarek; Boyer, Thomas D.; Kong, Lorene; Chen, Wen-Pin; Richmond, Ellen; Gonzalez, Rachel; Rodriguez, Luz M.; Meyskens, Frank L.

2015-01-01

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC while administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum AFP level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 grams/day, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. 110 subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury, or markers of oxidative stress or antioxidant potential. PMID:26130251

Elevated serum uric acid level predicts rapid decline in kidney function

PubMed Central

Kuwabara, Masanari; Bjornstad, Petter; Hisatome, Ichiro; Niwa, Koichiro; Roncal-Jimenez, Carlos A; Andres-Hernando, Ana; Jensen, Thomas; Milagres, Tamara; Sato, Yuka; Garcia, Gabriela; Ohno, Minoru; Lanaspa, Miguel A; Johnson, Richard J

2018-01-01

Background While elevated serum uric acid level (SUA) is a recognized risk factor for chronic kidney disease (CKD), it remains unclear whether change in SUA is independently associated with change in estimated glomerular filtration rate (eGFR) over time. Accordingly, we examined the longitudinal associations between change in SUA and change in eGFR over 5-years in a general Japanese population. Methods This was a large, single-center, retrospective 5-year cohort study at St. Luke's International Hospital, Tokyo, Japan, between 2004 and 2009. We included 13,070 subjects (30–85 years) in our analyses whose data were available at 2004 and 2009. Of those, we excluded 492 subjects with eGFR <60 mL/min/1.73m2 at baseline. In addition to examining the entire cohort (n=12,578), we stratified our analyses by baseline eGFR groups; 60–90 mL/min/1.73m2, 90–120 mL/min/1.73m2, and ≥120 mL/min/1.73m2. Linear and logistic regressions models were applied to examine the relationships between baseline and change in SUA, change in eGFR and rapid eGFR decline (defined as the highest quantile of change in eGFR), adjusted for age, sex, body mass index, abdominal circumference, hypertension, dyslipidemia, and diabetes mellitus. Results After multivariable adjustments including baseline eGFR, 1 mg/dL increase in baseline SUA was associated with greater odds of developing rapid eGFR decline (OR: 1.27, 95% CI: 1.17–1.38), and 1 mg/dL increase in SUA over 5-years was associated with 3.77-fold greater odds of rapid eGFR decline (OR: 3.77, 95% CI: 3.35–4.26). Conclusions Elevated baseline SUA and increasing SUA over time were independent risk factors for rapid eGFR decline over 5-years. PMID:28285309

Bone mineral density, serum albumin and serum magnesium.

PubMed

Saito, Noboru; Tabata, Naoto; Saito, Saburou; Andou, Yoshihisa; Onaga, Yukiko; Iwamitsu, Akihiro; Sakamoto, Morihide; Hori, Tuyoshi; Sayama, Harumi; Kawakita, Toshiko

2004-12-01

This study explores clinical and laboratory abnormalities that contribute to the prevalence of bone fractures in frail and control elderly patients, to ascertain factors that relate to bone strength and fragility. Patients were selected as free from renal failure and not taking supplements or medications that affect their magnesium status, and categorized according to their underlying diseases, sex and age, and evaluated by tests of bone strength. Findings, differentiating elderly patients on the basis of their magnesium, calcium, serum albumin, body mass, bone mineral density and their fracture occurrence were tabulated. Evidence is presented of low magnesium and albumin serum levels, especially in women with low bone density, as well as of low calcium and trace minerals.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

PubMed

Kim, Ha-Na; Kang, Sung-Goo; Roh, Yong Kyun; Choi, Min-Kyu; Song, Sang-Wook

2017-08-01

Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

Elevated serum magnesium associated with SGLT2 inhibitor use in type 2 diabetes patients: a meta-analysis of randomised controlled trials.

PubMed

Tang, Huilin; Zhang, Xi; Zhang, Jingjing; Li, Yufeng; Del Gobbo, Liana C; Zhai, Suodi; Song, Yiqing

2016-12-01

By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels. Weighted mean differences (WMD) between each SGLT2 inhibitor and placebo were calculated using a random-effects model. Dose-dependent relationships for each SGLT2 inhibitor were evaluated using meta-regression analysis. Eighteen eligible RCTs, including 15,309 patients and four SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin and ipragliflozin) were evaluated. In patients without chronic kidney disease, each SGLT2 inhibitor significantly increased serum magnesium levels compared with placebo (canagliflozin: WMD 0.06 mmol/l for 100 mg and 0.09 mmol/l for 300 mg; dapagliflozin: WMD 0.1 mmol/l for 10 mg; empagliflozin: WMD 0.04 mmol/l for 10 mg and 0.07 mmol/l for 25 mg; and ipragliflozin: WMD 0.05 mmol/l for 50 mg). Canagliflozin increased serum magnesium in a linear dose-dependent manner (p = 0.10). Serum phosphate was significantly increased by dapagliflozin. Serum sodium appeared to significantly differ by SGLT2 inhibitor type. No significant changes in serum calcium and potassium were observed. Findings were robust after including trials involving patients with chronic kidney disease. SGLT2 inhibitors marginally increased serum magnesium levels in type 2 diabetes patients indicating a drug class effect. Further investigations are required to examine the clinical significance of elevated magnesium levels in individuals with type 2 diabetes.

Factors determining extreme brain natriuretic peptide elevation.

PubMed

Guglin, Maya; Hourani, Rayan; Pitta, Sridevi

2007-01-01

Brain natriuretic peptide (BNP) level is elevated in heart failure and reflects its severity. It is unknown why some patients have extremely high BNP levels. The authors retrospectively reviewed data on 179 consecutive patients whose BNP levels fell within one of several predetermined ranges: mild elevation, 500 to 1000 pg/mL (n=82); moderate elevation, 2000 to 3000 pg/mL (n=48); and high elevation, 4000 to 20,000 pg/mL (n=49). The statistical analysis was conducted with the unpaired t test and Pearson's correlation coefficient. Adjustments were made for age, sex, and serum creatinine level. Patients with moderate BNP elevation were more symptomatic and had more advanced structural and hemodynamic changes than did patients with lower BNP elevation. Characteristics of the high BNP level group did not differ from those of the moderate BNP level group. Serum creatinine level correlated with BNP level, but neither age nor sex did. High BNP level (4000-20,000 pg/mL) is determined more by renal dysfunction than by the severity of heart failure.

Soluble B7-H4 blood serum levels are elevated in women at high risk for preeclampsia in the first trimester, as well as in patients with confirmed preeclampsia.

PubMed

Mach, Pawel; Nolte-Boenigk, Luisa; Droste, Leonie; Fox, Laura; Frank, Mirjam; Schmidt, Boerge; Herse, Florian; Verlohren, Stefan; Wicherek, Lukasz; Iannaccone, Antonella; Birdir, Cahit; Andrikos, Dimitrios; Kimmig, Rainer; Gellhaus, Alexandra; Köninger, Angela

2018-05-24

B7-H4 negatively regulates T-cell-mediated immunity and might play an important role in preeclampsia (PE). Here, we have investigated the association between PE and maternal soluble B7-H4 (sB7-H4) serum levels and B7-H4 mRNA expression in the placenta. Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in women between 11 and 13 weeks' gestation with elevated risk for PE (n = 48) and women without elevated risk for PE (n = 47). In the third trimester, sB7-H4 serum levels (n = 166) and B7-H4 mRNA expression in the placenta (n = 54) were determined in women with early-onset PE, late-onset PE, fetal growth restriction (FGR), and in healthy controls. In the first trimester, significant higher levels of sB7-H4 were detected in women at elevated risk for PE compared to women without risk for PE (P < .0001). sB7-H4 has some predictive ability to identify cases with an elevated risk of developing PE with area under the curve (AUC) value of 0.88 (95% CI 0.8-0.94). Using a specificity of 90.0% led to a sensitivity of 47.9% and a threshold of 3.63 ng/mL. In the third trimester, the highest serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in early-onset PE. Significant higher serum levels of sB7-H4 and B7-H4 mRNA expression in the placenta were observed in women with early-onset PE (P = .01 and P = .006, respectively) and late-onset PE (P = .03 and P = .004, respectively) compared to healthy controls, but not compared to FGR. sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester of pregnancy, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hereditary fructose intolerance mimicking a biochemical phenotype of mucolipidosis: A review of the literature of secondary causes of lysosomal enzyme activity elevation in serum.

PubMed

Ferreira, Carlos R; Devaney, Joseph M; Hofherr, Sean E; Pollard, Laura M; Cusmano-Ozog, Kristina

2017-02-01

We describe a patient with failure to thrive, hepatomegaly, liver dysfunction, and elevation of multiple plasma lysosomal enzyme activities mimicking mucolipidosis II or III, in whom a diagnosis of hereditary fructose intolerance (HFI) was ultimately obtained. She presented before introduction of solid foods, given her consumption of a fructose-containing infant formula. We present the most extensive panel of lysosomal enzyme activities reported to date in a patient with HFI, and propose that multiple enzyme elevations in plasma, especially when in conjunction with a normal plasma α-mannosidase activity, should elicit a differential diagnosis of HFI. We also performed a review of the literature on the different etiologies of elevated lysosomal enzyme activities in serum or plasma. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Serum trace metal levels in Alzheimer's disease and normal control groups.

PubMed

Park, Jun-Hyun; Lee, Dong-Woo; Park, Kyung Su; Joung, Hyojee

2014-02-01

To determine whether serum trace metals are related to abnormal cognition in Alzheimer's disease (AD). We studied serum lead (Pb), cadmium (Cd), mercury (Hg), and arsenic(As) in 89 patients with AD and in 118 cognitively normal individuals. We analyzed the results of the blood tests and the food intake. Serum Pb levels correlated with word list recall (P = .039) and word list recognition (P = .037). Without age adjustment, serum Cd levels (P = .044) were significantly higher in the AD group. After stratified age adjustment, the levels of selected trace metals did not differ significantly between AD and normal individuals. Food intakes regarding selected trace metals were not significantly different between the 2 groups. In this study, serum Pb, Cd, Hg, and As levels were not directly related to abnormal cognition in AD. Serum Pb levels were significantly negatively correlated with verbal memory scores.

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

PubMed Central

2014-01-01

Introduction We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Methods Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables. Results In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Conclusion Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose

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.

Elevated serum progastrin-releasing peptide (31-98) level is a predictor of short response duration after hormonal therapy in metastatic prostate cancer.

PubMed

Yashi, Masahiro; Nukui, Akinori; Kurokawa, Shinsuke; Ochi, Masanori; Ishikawa, Shinya; Goto, Kentaro; Kobayashi, Yutaka; Muraishi, Osamu; Tokue, Akihiko

2003-09-01

The neuroendocrine (NE) pathway has been attracting attention as a mechanism for the androgen-independent progression because the neuropeptide provokes tumor growth and inhibits apoptosis under androgen-deprived milieu in prostate cancer cells. On the basis that serum progastrin-releasing peptide (ProGRP) is elevated in patients with advanced disease stage, we examined the prognostic value of the neuropeptide. Serum ProGRP status was determined with an enzyme-linked immunosorbent assay (ELISA) in 460 men with benign and malignant prostatic diseases, chronic renal failure, and healthy controls. Seventy patients with metastatic prostate cancer including four patients (5.7%) with NE carcinoma who underwent hormonal therapy were enrolled in the prognostic analyses by Cox proportional hazards model. The serum status steadily shifted toward predominant expression of ProGRP with the progression of prostate cancer into metastatic and androgen-independent stages. Univariate analysis revealed that the deteriorated performance status (PS) and extent of bony disease (EOD), and high serum alkaline phosphatase (ALP), serum ProGRP, and nadir prostate-specific antigen (PSA) levels were associated with a lower progression-free survival (PFS) rate (P < 0.005). Multivariate analysis demonstrated that PS, serum ProGRP, and nadir PSA held an independent predictive value for PFS (P < 0.05), and all correlated with bone-related factors. Serum ProGRP was the most significant predictor among pre-treatment factors in this model (P = 0.0094). The neuropeptide precursor ProGRP is a distinct serum marker that is useful to know the NE milieu and provides prognostic information in patients with advanced prostate cancer. Standard therapy for metastatic prostate cancer may make progress when further studies will clarify the causative link between serum ProGRP level and androgen-independent disease progression. Copyright 2003 Wiley-Liss, Inc.

Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

PubMed

Rooney, Mary R; Pankow, James S; Sibley, Shalamar D; Selvin, Elizabeth; Reis, Jared P; Michos, Erin D; Lutsey, Pamela L

2016-10-01

Elevated serum calcium has been associated with a variety of metabolic abnormalities and may be associated with a greater risk of diabetes. The purpose of this study was to test the hypothesis that serum calcium concentration is positively and independently associated with the incidence of diabetes and to evaluate the association of calcium-sensing receptor (CaSR) gene single nucleotide polymorphism (SNP) rs1801725 with incident diabetes. Atherosclerosis Risk in Communities study participants free of diabetes at baseline (n = 12,800; mean age: 53.9 y; 22.6% black) were studied for incident diabetes. Serum calcium was measured at baseline and corrected for serum albumin. Diabetes was defined by use of glucose concentrations, self-report, or medication use. Cox proportional hazards regression was used. During a mean 8.8 y of follow-up, 1516 cases of diabetes were reported. Participants in the highest compared with lowest calcium quintile were at greater risk of incident diabetes after adjustment for demographic and lifestyle factors [HR (95% CI): 1.34 (1.14, 1.57); P-trend across quintiles <0.0001] and with further adjustment for waist circumference and body mass index [1.26 (1.07, 1.48); P-trend = 0.004]. Additional adjustment for biomarkers on the metabolic pathway (e.g., 25-hydroxyvitamin D, parathyroid hormone, phosphorus) had little impact. The calcium-diabetes association was statistically significant in blacks [1.48 (1.11, 1.98); P-trend = 0.002] but not whites [1.17 (0.96, 1.43); P-trend = 0.17] after adjustment for adiposity. In whites, CaSR gene SNP rs1801725 was associated with serum calcium but not with risk of diabetes. Consistent with 3 previous cohort studies, elevated serum calcium was found to be associated with a greater risk of type 2 diabetes. Further research is needed to understand the role, if any, that calcium plays in the pathogenesis of diabetes. © 2016 American Society for Nutrition.

Evaluation of serum lipid profile, body mass index, and waistline in Chinese patients with type 2 diabetes mellitus.

PubMed

Cui, Rongtao; Qi, Zhiming; Zhou, Lin; Li, Zuohong; Li, Qing; Zhang, Junyong

2016-01-01

People with type 2 diabetes are at an increased risk of hypertension, arteriosclerosis, heart disease, and stroke. Glucose intolerance (insulin resistance) is the main feature of type 2 diabetes. Obesity leads to insulin resistance, dyslipidemia, etc. The aim of this study was to assess the biochemical parameters and measures of obesity in type 2 diabetes mellitus (T2DM). A total of 2,273 males and 6,547 females previously healthy volunteers (aged 41-95 years old) were recruited by open invitation. The basic information, including age, sex, height, weight, body mass index (BMI), waistline, hipline, menstrual cycle, and medical history, was collected by questionnaire survey and physical examination. Serum lipid profile, liver transaminase, blood glucose, postprandial blood glucose, and hemoglobin A1c were obtained after 12 hours of fasting. According to our results, diabetic patients presented serum lipid abnormality. Elevated triglyceride (TG) levels (≥1.7 mmol/L) were noted in 19.69% of males and 20.40% of females, and reduced high-density lipoprotein cholesterol (HDL-C) levels (≤1.15 mmol/L) were noted in 21.96% of males and 15.74% of females. The combination of elevated TG and reduced HDL-C was the most prevalent of the combined lipid abnormalities. In contrast, no differences were observed in the levels of low-density lipoprotein cholesterol and total cholesterol. Moreover, there were statistically significant differences in the levels of BMI and waistline between T2DM and non-T2DM participants. After adjustment for BMI, logistic regression analysis revealed that the subjects with BMI ≤20 kg/m(2) and >30 kg/m(2) had a significantly elevated hazard ratio of T2DM compared with participants having a BMI range of 20-30 kg/m(2) in both males and females. However, there was a significant difference between T2DM patients and non-T2DM patients in waistline (χ (2)=8.57, P<0.001) than in BMI parameter (χ (2)=6.29, P<0.001). The present study shows for the first

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners

PubMed Central

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-01-01

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT (p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW (p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW (p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron. PMID:28335426

Elevated Serum Hepcidin Levels during an Intensified Training Period in Well-Trained Female Long-Distance Runners.

PubMed

Ishibashi, Aya; Maeda, Naho; Sumi, Daichi; Goto, Kazushige

2017-03-14

Iron is essential for providing oxygen to working muscles during exercise, and iron deficiency leads to decreased exercise capacity during endurance events. However, the mechanism of iron deficiency among endurance athletes remains unclear. In this study, we compared iron status between two periods involving different training regimens. Sixteen female long-distance runners participated. Over a seven-month period, fasting blood samples were collected during their regular training period (LOW; middle of February) and during an intensified training period (INT; late of August) to determine blood hematological, iron, and inflammatory parameters. Three-day food diaries were also assessed. Body weight and lean body mass did not differ significantly between LOW and INT, while body fat and body fat percentage were significantly lower in INT ( p < 0.05). Blood hemoglobin, serum ferritin, total protein, and iron levels, total iron-binding capacity, and transferrin saturation did not differ significantly between the two periods. Serum hepcidin levels were significantly higher during INT than LOW ( p < 0.05). Carbohydrate and iron intakes from the daily diet were significantly higher during INT than LOW ( p < 0.05). In conclusion, an elevated hepcidin level was observed during an intensified training period in long-distance runners, despite an apparently adequate daily intake of iron.

A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels.

PubMed

Hallaq, Haifa; Pinter, Emese; Enciso, Josephine; McGrath, James; Zeiss, Caroline; Brueckner, Martina; Madri, Joseph; Jacobs, Harris C; Wilson, Christine M; Vasavada, Hemaxi; Jiang, Xiaobing; Bogue, Clifford W

2004-10-01

The homeobox gene Hhex has recently been shown to be essential for normal liver, thyroid and forebrain development. Hhex(-/-) mice die by mid-gestation (E14.5) and the cause of their early demise remains unclear. Because Hhex is expressed in the developing blood islands at E7.0 in the endothelium of the developing vasculature and heart at E9.0-9.5, and in the ventral foregut endoderm at E8.5-9.0, it has been postulated to play a critical role in heart and vascular development. We show here, for the first time, that a null mutation of Hhex results in striking abnormalities of cardiac and vascular development which include: (1) defective vasculogenesis, (2) hypoplasia of the right ventricle, (3) overabundant endocardial cushions accompanied by ventricular septal defects, outflow tract abnormalities and atrio-ventricular (AV) valve dysplasia and (4) aberrant development of the compact myocardium. The dramatic enlargement of the endocardial cushions in the absence of Hhex is due to decreased apoptosis and dysregulated epithelial-mesenchymal transformation (EMT). Interestingly, vascular endothelial growth factor A (Vegfa) levels in the hearts of Hhex(-/-) mice were elevated as much as three-fold between E9.5 and E11.5, and treatment of cultured Hhex(-/-) AV explants with truncated soluble Vegfa receptor 1, sFlt-1, an inhibitor of Vegf signaling, completely abolished the excessive epithelial-mesenchymal transformation seen in the absence of Hhex. Therefore, Hhex expression in the ventral foregut endoderm and/or the endothelium is necessary for normal cardiovascular development in vivo, and one function of Hhex is to repress Vegfa levels during development.

Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus.

PubMed

Schober, Karsten E; Cornand, Corinna; Kirbach, Babett; Aupperle, Heike; Oechtering, Gerhard

2002-08-01

To determine whether serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are increased in dogs with gastric dilatationvolvulus (GDV) and whether concentrations correlate with severity of ECG abnormalities or outcome. Prospective case series. 85 dogs with GDV. Serum cTnl and cTnT concentrations were measured 12 to 24, 48, 72, and 96 hours after surgery. Dogs were grouped on the basis of severity of ECG abnormalities and outcome. cTnl and cTnT were detected in serum from 74 (87%) and 43 (51%) dogs, respectively. Concentrations were significantly different among groups when dogs were grouped on the basis of severity of ECG abnormalities (none or mild vs moderate vs severe). Dogs that died (n = 16) had significantly higher serum cTnI (24.9 ng/ml) and cTnT (0.18 ng/ml) concentrations than did dogs that survived (2.05 and < 0.01 ng/ml, respectively). Myocardial cell injury was confirmed at necropsy in 4 dogs with high serum cardiac troponin concentrations. Results indicate that concentrations of cTnI and cTnT suggestive of myocardial cell injury can commonly be found in serum from dogs with GDV and that serum cardiac troponin concentrations are associated with severity of ECG abnormalities and outcome.

CXCL13 levels in serum but not in saliva are elevated in Asian Indian patients with primary Sjögren's syndrome.

PubMed

Mandal, Santosh Kumar; Sandhya, Pulukool; Kabeerdoss, Jayakanthan; Ramya, Janardana; Mahasampath, Gowri; Danda, Debashish

2018-05-01

Human and animal model studies suggest CXCL13 is a potential biomarker in primary Sjögren's syndrome (pSS). CXCL13 has not been studied in Indian patients with pSS. pSS cases classified by American European Consensus Group (AECG) or American college of Rheumatology(ACR) 2012 criteria, attending rheumatology clinic between July 2014 and July 2015 were included. Hospital staff and healthy, non-blood related family members of patients constituted the control group. pSS cases underwent clinical evaluation, laboratory investigations, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary and serum CXCL13 were quantified by indirect ELISA. CXCL13 positivity was determined using Receiver Operator Characteristic (ROC) curve. STATA13.1 (StataCorpLP,Texas,USA) software was used for statistical analysis. In this study, 45 pSS cases and 42 healthy controls were recruited. In pSS, median levels of serum CXCL13, but not salivary CXCL13 was significantly higher as compared to the corresponding levels in healthy controls (p < 0.001). Using cutoff of 43.03 pg/ml obtained by ROC, serum CXCL13 positivity was seen in 31/43(72.1%) cases and 10/34 (29.4%) controls, respectively. Serum CXCL13 levels among pSS patients on treatment, treatment naïve patients and healthy controls were statistically different. Serum CXCL13 positivity was associated with oral symptoms (p = 0.02), ocular signs (p = 0.03) and hyperglobulinemia (p = 0.01). There was no association of salivary CXCL13 level with any of the clinical variables. While serum CXCL13 was elevated in pSS, salivary CXCL13 was not. In conclusion, serum CXCL13 positivity was found to be associated with oral symptoms, ocular signs and hyperglobulinemia in pSS.

Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

PubMed Central

Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

2015-01-01

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

Leptin Elevation as a Risk Factor for Slipped Capital Femoral Epiphysis Independent of Obesity Status.

PubMed

Halverson, Schuyler J; Warhoover, Tracy; Mencio, Gregory A; Lovejoy, Steven A; Martus, Jeffrey E; Schoenecker, Jonathan G

2017-05-17

Slipped capital femoral epiphysis (SCFE) is strongly associated with childhood obesity, yet the prevalence of obesity is orders of magnitude greater than the prevalence of SCFE. Therefore, it is hypothesized that obesity is not, by itself, a sufficient condition for SCFE, but rather one component of a multifactorial process requiring preexisting physeal pathology. Leptin elevation is seen to varying degrees in patients with obesity, and as leptin has been shown to cause physeal pathology similar to the changes seen in SCFE, we propose that leptin may be a factor distinguishing between patients with SCFE and equally obese children without hip abnormalities. Serum leptin levels were obtained from 40 patients with SCFE and 30 control patients with approximate body mass index (BMI) matching. BMI percentiles were calculated according to Centers for Disease Control and Prevention population data by patient age and sex. Patients were compared by demographic characteristics, leptin levels, odds of leptin elevation, and odds of SCFE. The odds of developing SCFE was increased by an odds ratio of 4.9 (95% confidence interval [CI], 1.31 to 18.48; p < 0.02) in patients with elevated leptin levels, regardless of obesity status, sex, and race. When grouping patients by their obesity status, non-obese patients with SCFE showed elevated median leptin levels at 5.8 ng/mL compared with non-obese controls at 1.7 ng/mL (p = 0.006). Similarly, obese patients with SCFE showed elevated median leptin levels at 17.9 ng/mL compared with equally obese controls at 10.5 ng/mL (p = 0.039). Serum leptin levels increased in association with obesity (p < 0.001), with an increase in leptin of 0.17 ng/mL (95% CI, 0.07 to 0.27 ng/mL) per BMI percentile point. To our knowledge, this study is the first to clinically demonstrate an association between elevated serum leptin levels and SCFE, regardless of BMI. This adds to existing literature suggesting that SCFE is a multifactorial process and that leptin

Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease.

PubMed

Bchir, Sarra; Nasr, Hela Ben; Bouchet, Sandrine; Benzarti, Mohamed; Garrouch, Abdelhamid; Tabka, Zouhair; Susin, Santos; Chahed, Karim; Bauvois, Brigitte

2017-07-01

A growing body of evidence points towards smoking-related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase-9 (pro- and active MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and the proMMP-9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable-phase COPD patients (82 smokers, 18 never-smokers) and 28 healthy adults (21 smokers, 7 never-smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP-9, NGAL and proMMP-9/NGAL in COPD smokers. While the triad discriminated between smokers and non-smokers in the COPD group, MMP-9 and proMMP-9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack-years did not alter the findings. Serum MMP-9, NGAL and proMMP-9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP-3 (but not of IL-6 and MMP-12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack-years. Among COPD smokers, levels of MMP-9, NGAL and proMMP-9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP-9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP-9, NGAL, proMMP-9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Correlation between ovarian chocolate cyst and serum carbohydrate antigen 125 level and the effect of ultrasound-guided interventional sclerotherapy on serum carbohydrate antigen 125 level.

PubMed

Wang, Si-Ming; Cai, Huai-Qiu; Dong, Xiao-Qiu; Fan, Qiu-Lan; Wang, Lu-Lu; Shao, Xiao-Hui; Zhang, Li-Wei

2015-01-01

This study was to investigate the correlation between ovarian chocolate cysts and serum carbohydrate antigen (CA)-125 levels and to demonstrate the effect of ultrasound-guided interventional sclerotherapy (UGIS) on serum CA-125 levels. Based on the serum CA-125 level, as determined by chemiluminescence detection prior to UGIS, 105 patients with ovarian chocolate cysts were divided into the normal group (CA-125 ≤ 35 U/mL, 45 patients) and the abnormal group (35 U/mL < CA-125 ≤ 200 U/mL, 60 patients). There were six clinical indicators including age, disease duration, dysmenorrhea history, child-bearing history, abortion history and surgical history. The ultrasonography characteristics were cyst diameter, cyst wall thickness and the side on which the cyst occurred. The correlations between serum CA-125 levels pretreatment and the clinical indicators and ultrasonography characteristics was analyzed. The serum CA-125 levels pretreatment, 3 months post-treatment and 6 months post-treatment were compared. The pretreatment serum CA-125 levels of the 105 patients positively correlated with disease duration (r = 0.3932, P = 0.0040), dysmenorrhea history (r = 0.2351, P = 0.0111), cyst diameter (r = 0.3415, P < 0.0001) and cyst wall thickness (r = 0.4263, P < 0.0001). Compared with the pretreatment level, the mean serum CA-125 level in the abnormal group at 3 months post-treatment was significantly lower (P < 0.01), and at 6 months post-treatment, the mean serum CA-125 level had decreased to a normal level (P < 0.01). UGIS significantly decreased abnormal serum CA-125 levels in patients with ovarian chocolate cysts. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Fatty acyltranferases in serum in cystic fibrosis (CF) patients

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

Zielenski, J.; Newman, L.J.; Slomiany, B.L.

1987-05-01

Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15 l of serum was mixed with 0.85 nmol ( UC)palmitoyl CoA, 200 g of serine and threonine and incubated at 37C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation ofmore » ( UC)palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of ( UC)palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids.« less

Surgical outcomes in patients with primary mediastinal non-seminomatous germ cell tumours and elevated post-chemotherapy serum tumour markers.

PubMed

De Latour, Bertrand; Fadel, Elie; Mercier, Olaf; Mussot, Sacha; Fabre, Dominique; Fizazi, Karim; Dartevelle, Philippe

2012-07-01

Platinum-based chemotherapy followed by surgical resection of residual masses has become the standard treatment of patients with primary mediastinal non-seminomatous germ cell tumours (NSGCTs). Persistent serum tumour marker (STM) elevation after chemotherapy usually indicates a poor prognosis. We retrospectively assessed surgical outcomes in patients with high STM levels after chemotherapy for primary mediastinal NSGCT. Between 1983 and 2010, residual tumour excision was performed in 21 patients, 20 men and one woman with a median age of 30 years (range: 19-49 years), with primary mediastinal NSGCTs and high STM levels after platinum-based chemotherapy, followed by second-line chemotherapy in 11 patients. Alpha-fetoprotein was elevated in all 21 patients and β-human chorionic gonadotropin in three patients. Permanent histology demonstrated viable germ cell tumour (n=13), teratoma (n=3) or necrosis (n=5). After surgery, the STM levels returned to normal in 11 patients. Eight patients are alive with a median follow-up of 98 months. The 5-year survival rate was 36% and was not significantly affected by the use of preoperative second-line chemotherapy. At univariate analysis, only postoperative STM elevation and residual viable tumour, indicating incomplete resection, were significantly associated with lower survival (P=0.018 and P=0.04, respectively). In patients with primary mediastinal NSGCTs and elevated post-chemotherapy STMs, surgery is warranted when complete resection is deemed feasible. In specialized oncology centres, this aggressive approach can provide a cure in some patients.

Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia

PubMed Central

Howard, M; Ashwell, S; Bond, L; Holbrook, I

2000-01-01

Aim—To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. Methods—24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 109/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. Results—At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. Conclusions—Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia. Key Words: thrombocythaemia • hypercalcaemia • hyperkalaemia PMID:10767824

Primary human immunodeficiency virus infection presenting as elevated aminotransferases.

PubMed

Chen, Yi-Jan; Tsai, Hung-Chin; Cheng, Ming-Fang; Lee, Susan Shin-Jung; Chen, Yao-Shen

2010-06-01

Primary human immunodeficiency virus type 1 (HIV-1) infection is often under-diagnosed because of its nonspecific presentations. Elevated aminotransferase levels is one of its clinical manifestations, but is infrequently reported in the literature. The objective of this study was to investigate cases of elevated aminotransferases as a manifestation of primary HIV-1 infection. A retrospective chart review from October 1990 to May 2009 of HIV-1 infected patients in a registered database at a tertiary hospital was conducted to identify patients diagnosed with primary HIV-1 infection. An elevated aminotransferase level was broadly defined as above-normal values of alanine or aspartate aminotransferases. Acute hepatitis markers were determined using stored serum samples. Twenty-three of the 827 (2.8%) patients were identified as having a primary HIV-1 infection. All were male, with a median age of 26 years (range, 19-77 years), and the majority were men who had sex with men (19/23, 82.6%). The most common clinical manifestations were fever (95.7%), elevated aminotransferases (65.2%), fatigue (47.8%), and pharyngitis (47.8%). The median CD4 lymphocyte count was 374/μL (range, 109-674/μL) and the median log HIV viral load was 5.0 (range, 4.3-5.9). For the 15 patients with abnormal liver function tests, the median aspartate aminotransferase level was 112 U/L (range, 62-969 U/L) and the median alanine aminotransferase level was 146 U/L (range, 42-1,110 U/L). Elevated aminotransferases may be an initial manifestation of primary HIV infection and is more common than expected. Primary HIV-1 infection should be one of the differential diagnoses considered in young men presenting with unexplained, new-onset liver function impairment. Copyright © 2010 Taiwan Society of Microbiology. Published by Elsevier B.V. All rights reserved.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

PubMed

Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

2005-01-01

To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications.

PubMed

Gentry, Chris A; Nguyen, Ann T

2013-12-01

Adverse events associated with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) for outpatient infections, particularly those likely caused by community-acquired methicillin-resistant Staphylococcus aureus, have not been adequately characterized. Describe hyperkalemia and acute renal injury associated with high-dose TMP-SMX. An electronic medical record database retrospective study was conducted of outpatients receiving high-dose or low-dose TMP-SMX, comparing the incidences of hyperkalemia and acute renal injury. Of 6162 patients, more developed hyperkalemia (3.06% vs 1.05%, P < .0001) or acute renal injury (1.99% vs 0.700%, P = .0001) in the high-dose TMP-SMX group. Variables independently associated with hyperkalemia included age >58 years (odds ratio [OR] = 3.44; 95% CI = 1.86-7.0; P < .0001), concomitant receipt of an NSAID (OR = 1.71; 95% CI = 1.02-2.79; P = .044) or an ACE inhibitor (OR = 3.27; 95% CI = 2.06-5.14; P < .0001), high-dose TMP-SMX prescribed (OR = 2.92; 95% CI = 1.85-4.60; P < .0001), and baseline elevated serum creatinine (OR = 45.1; 95% CI = 21.7-93.2; P < .0001). Variables independently associated with acute renal injury included concomitant receipt of an ACE inhibitor (OR = 2.36; 95% CI = 1.01-5.24; P = .048) or a potassium supplement (OR = 4.10; 95% CI = 1.45-10.1; P = .010), high-dose TMP-SMX prescribed (OR = 3.70; 95% CI = 1.70-8.12; P = .0012), and baseline elevated serum creatinine (OR = 2110; 95% CI = 724-7980; P < .0001). Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose TMP-SMX.

[Changes of serum aminotransferase in children with obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Zhenjiang; Duo, Likun

2013-08-01

Obstructive sleep apnea hypopnea syndrome (OSAHS) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSAHS is an independent risk factor for liver injury or not is uncertain. To assess the hypothesis that OSAHS is associated with liver injury independent of obesity. One hundred and thirty children with OSAHS and 77 children with primary snoring(PS) were enrolled. Polysomnography was performed. Body mass index (BMI), liver function tests, serum lipids, fasting plasma glucose (FPG), and insulin (INS) were measured. Seventeen children of OSAHS had elevated serum aminotransferase levels,while only 2 children of non-OSAHS had elevated serum aminotransferase in healthy control group (chi2 = 5.18, P < 0.05; OR = 5.64 CI 1.27-24.97). Fifteen children of obese had elevated serum aminotransferase levels, while only 4 children had elevated serum aminotransferase in non-obese group (chi2 = 4.58, P < 0.05; (OR = 1.97 CI 1.06-3.67). Seventy cases of obese children, 15 cases of elevated aminotransferase levels (21.4%), namely fatty liver patients, of these children, 14 had OSAHS (93.3%). In contrast, OSAHS was present in only 67.3% of obese children without elevated aminotransferase. OSAHS may be a risk factor for liver injury independent of obesity; Increased liver enzyme levels are frequently found in obese snoring children, particularly among those with OSAHS.

Equation-derived body fat percentage indicates metabolic abnormalities among normal-weight adults in a rural Chinese population.

PubMed

Liu, Xin; Zhao, Yaling; Li, Qiang; Dang, Shaonong; Yan, Hong

2017-07-08

Obesity classification using body mass index (BMI) may miss subjects with elevated body fat percentage (BF%) and related metabolic risk factors. We aimed to evaluate whether BF% calculated by equations could provide more information about metabolic risks, in addition to BMI classification, in a cross-sectional rural Chinese population. A total of 2,990 men and women aged 18-80 years were included in this study. BF% was calculated using previously validated Chinese-specific equations. Metabolic syndrome was defined according to the updated National Cholesterol Education Program Panel III criteria for Asian Americans. In total, 33.6% men and 32.9% women were overweight/obese according to BMI classification. Among those within the normal BMI range, 25.4% men and 54.7% women were indicated as overweight or obese given their elevated BF% (men: BF% ≥ 20%; women: BF% ≥ 30%). In both men and women, compared with those with normal BMI and BF% (NBB), subjects with normal BMI but elevated BF% (NBOB) were more likely to carry abnormal serum lipid profile and to have higher risks of metabolic syndrome. The multivariable adjusted odds ratios (95% confidence intervals) for metabolic syndrome were 5.45 (2.37-9.53, P < 0.001) and 5.65 (3.36-9.52, P < 0.001) for men and women, respectively. Moreover, the women with NBOB also showed higher blood pressure and serum uric acid than women with NBB. Our study suggested that high BF% based on equations may indicate adverse metabolic profiles among rural Chinese adults with a normal BMI. © 2017 Wiley Periodicals, Inc.

Abnormal Liver Biochemistry Is Common in Pediatric Inflammatory Bowel Disease: Prevalence and Associations.

PubMed

Valentino, Pamela L; Feldman, Brian M; Walters, Thomas D; Griffiths, Anne M; Ling, Simon C; Pullenayegum, Eleanor M; Kamath, Binita M

2015-12-01

Liver enzymes (LEs) abnormalities associated with pediatric inflammatory bowel diseases (IBD) are understudied. We undertook to describe the development and associations of abnormal LEs in pediatric IBD. We ascertained a cohort of 300 children with IBD and collected retrospective data. A Kaplan-Meier analysis determined the time to development of different thresholds of abnormal LEs. Associations between clinical variables and the development of abnormal LEs were determined. The probability of developing the first episode of abnormal LEs above the upper limit of normal (ULN) within 150 months was 58.1% (16.3% by 1 mo post-IBD diagnosis). There was a 6% prevalence of primary sclerosing cholangitis (PSC) or autoimmune sclerosing cholangitis (ASC) in this cohort. Of those diagnosed with PSC/ASC, 93% had persistent LE elevations at a threshold of >2× ULN, while those without PSC/ASC had a 4% probability of this abnormality. Elevated gamma glutamyltranspeptidase levels of 252 U/L had a 99% sensitivity and 71% specificity for PSC/ASC in IBD. After exclusion of patients with PSC/ASC, corticosteroids, antibiotics, and exclusive enteral nutrition demonstrated strongly positive associations with the first development of abnormal LEs >ULN (hazard ratio 2.1 [95% confidence interval, 1.3-3.3], hazard ratio 5.6 [95% confidence interval, 3.6-8.9], hazard ratio 4.2 [95% confidence interval, 1.6-11.3], respectively). Abnormal LEs are common in pediatric IBD and occur early. PSC/ASC is associated with persistently high LEs and gamma glutamyltranspeptidase levels >252 U/L. Children with IBD are at risk of elevated LEs if they require medications other than 5-ASA to induce IBD remission.

Biochemical abnormalities in workers exposed to molybdenum dust.

PubMed

Walravens, P A; Moure-Eraso, R; Solomons, C C; Chappell, W R; Bentley, G

1979-01-01

Exposure to molybdenum in dust was measured in a molybdenite roasting plant. This exposure was accompanied by large elevations of serum ceruloplasmin and smaller increases in mean serum uric acid levels in the workers. Absorption of molybdenum from the dust was demonstrated by increases in plasma and urinary molybdenum levels. It remains necessary to demonstrate whether such exposure results in long-term health effects.

Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy.

PubMed

Jenkins, Dorothea D; Rollins, Laura Grace; Perkel, Jessica K; Wagner, Carol L; Katikaneni, Lakshmi P; Bass, W Thomas; Kaufman, David A; Horgan, Michael J; Languani, Sheela; Givelichian, Lawrence; Sankaran, Koravangattu; Yager, Jerome Y; Martin, Renee H

2012-10-01

Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. Monocyte chemotactic protein-1 (MCP-1) and interleukins (IL)-6, IL-8, and IL-10 were significantly higher in the H group. Elevated IL-6 and MCP-1 within 9 hours after birth and low macrophage inflammatory protein 1a (MIP-1a) at 60 to 70 hours of age were associated with death or severely abnormal neurodevelopment at 12 months of age. However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.

Occult abnormal pregnancies after first post-embryo transfer serum beta-human chorionic gonadotropin levels of 1.0-5.0 mIU/mL.

PubMed

Maslow, Bat-Sheva L; Bartolucci, Alison; Sueldo, Carolina; Engmann, Lawrence; Benadiva, Claudio; Nulsen, John C

2016-04-01

To assess the occult pregnancy rate after "negative" first post-embryo transfer (ET) serum β-hCG results. Two-part retrospective cohort study and nested case series. University-based fertility center. A total of 1,571 negative first post-ET serum β-hCG results were included in the study; 1,326 results (primary cohort, June 2009-December 2013) were initially reported as <5 mIU/mL and 245 results (secondary cohort, January 2014-March 2015) were reported as discrete values from 1.0 to 5.0 mIU/mL. None. Rates of occult pregnancy, ectopic pregnancy, and complications after negative first post-ET serum β-hCG results. A total of 88.8% (1,178/1,326) of the negative first post-ET results reported as <5 were actually <1.0 mIU/mL. Occult pregnancy was incidentally identified in 1.2% (12/1,041) of subjects with follow-up. Six had ectopic pregnancies, and seven experienced serious complications; 11 (91.7%) of the 12 occult pregnancies had a first post-ET serum β-hCG level of 1.0-5.0 mIU/mL and 1 (8.3%) <1.0 mIU/mL. All pregnancies with serious complications had initial β-hCG levels of 1.0-5.0 mIU/mL. Of the 245 results reported as discreet values, occult pregnancies were diagnosed in 5.5% (9/163) of subjects with follow-up. One had an ectopic pregnancy, which was treated with methotrexate. There were no serious complications in the secondary cohort. The majority of negative first post-ET serum β-hCG levels are <1.0 mIU/mL. Results from 1.0 to 5.0 mIU/mL may fail to exclude abnormal pregnancy and are associated with poor outcomes compared with β-hCG levels <1.0 mIU/mL. Serial serum β-hCG may be warranted in this population. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

PubMed Central

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients.

PubMed

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

Elevated Serum Cyclophilin B Levels Are Associated with the Prevalence and Severity of Metabolic Syndrome.

PubMed

Zhang, Hang; Fan, Qin; Xie, Hongyang; Lu, Lin; Tao, Rong; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-01-01

Inflammation plays a central role in the pathogenesis of metabolic syndrome (MetS). Cyclophilin B (CypB) can be constitutively secreted in response to inflammatory stimuli and oxidative stress, participating in tissue or systemic inflammation. We investigated the relationship between CypB and MetS in both humans and mice. Serum CypB levels were determined in 211 subjects with MetS and 292 subjects without MetS (non-MetS) (133 healthy controls and 159 high-risk subjects with one to two MetS components). Additionally, CypB expression in metabolic organs was examined in mice fed with high-fat diet (HFD) and genetically obese (ob/ob) mice. Serum CypB level was significantly higher in MetS subjects compared with both groups of non-MetS subjects (193.80 ± 83.22 vs. 168.38 ± 65.01 vs. 124.26 ± 47.83 ng/mL, P  < 0.001). Particularly, serum CypB level was significantly higher in subjects with hypertension, central obesity, diabetes mellitus or hyperglycemia, elevated levels of triglycerides, or reduced levels of high-density lipoprotein than in those without. Moreover, CypB was positively associated with the number of MetS components ( r  = 0.404, P  < 0.001), indicating that a higher serum CypB level reflected more severe MetS. Multivariate regression revealed that a one SD increase in CypB was associated with an odds ratio of 1.506 (1.080-2.101, P  = 0.016) for MetS prevalence after adjusting for age, gender, conventional risk factors, and medication. Stratified analyses by age and gender demonstrated that subjects >60 years old with higher CypB levels were more likely to have MetS, and the risk for MetS was higher and more significant in women compared with men. Additionally, CypB expression levels were lower at baseline and dramatically enhanced in metabolic organs (such as the liver) and visceral and subcutaneous adipose tissue from HFD-induced obese mice and ob/ob mice. Increased CypB levels were significantly and independently

Elevation of cardiac troponin T in patients with amyotrophic lateral sclerosis.

PubMed

Mach, Lukas; Konecny, Tomas; Helanova, Katerina; Jaffe, Allan S; Sorenson, Eric J; Somers, Virend K; Reeder, Guy S

2016-12-01

Limited evidence suggests that specificity of cardiac troponin T (cTnT), a highly sensitive biomarker of myocardial injury, is reduced in patients with skeletal myopathies. Whether amyotrophic lateral sclerosis (ALS)-the most common motor neuron disease-could be also associated with abnormal plasma or serum cTnT levels remains unclear. Our objective was to assess cTnT levels in patients with ALS without known cTnT elevating conditions. Among ALS patients seen at our institution until 2012 we identified those who had their cTnT measured. Patients who suffered from conditions known to elevate cTnT were excluded. A case-control analysis comparing cTnT levels of these ALS patients to matched non-ALS controls fulfilling the same inclusion criteria was performed. We included 40 ALS patients of whom 27 (68 %) patients had a positive cTnT. In the control group (n = 40), 2 (5 %) tested as cTnT positive (p < 0.001). Among the ALS patients who underwent cTnT evaluation on more occasions (n = 7; median follow-up = 1.08 years), 2 (29 %) patients tested positive during the initial measurement while 6 (86 %) of them had positive cTnT at the subsequent evaluations. ALS patients with increased cTnT had been diagnosed with ALS significantly earlier than those without the elevation. Our findings raise the possibility that ALS may cause cTnT elevations. Further studies are needed to confirm these findings, clarify the pathophysiological mechanism, and establish the significance of cTnT elevations in patients with ALS.

[Serum creatine kinase activity in dogs and cats with metabolic diseases].

PubMed

Neumann, S

2005-09-01

Elevated Creatine kinase-activitiy (CK) indicates disturbances of the muscle cell integrity. In addition to primary muscle disease, like trauma, inflammation or dystrophy, diseases of other organs can lead to secondary muscle involvement, which will be indicated by increased serum activities of the CK. The mechanisms of muscle cell disturbance are still unknown. An elevated protein catabolism in the muscle cell is suspected. In the present study we investigated, if dogs and cats with metabolic diseases have increased CK-activity in the serum. From 34 dogs and cats in a group with different metabolic diseases without metabolic acidosis 19% of the dogs and 50% of the cats had increased CK-activity in the serum. From 33 dogs and cats with different metabolic diseases connected with metabolic acidosis 86% of the dogs and 95% of the cats had simultaneously increased CK-activity in the serum. In comparison to healthy dogs and cats animals with metabolic diseases have significant and in cases of metabolic di-seases with metabolic acidosis cats have high significant elevation (dogs significant) of CK-activity in the serum. There was no significant correlation between the groups of patients. In conclusion we think that our results show that metabolic diseases often induce secondary myopathy, measured by CK-activity in the serum, but metabolic acidosis has no direct influence on elevated CK activity in dogs and cats.

Effect of kisspeptin-10, LH and hCG on serum testosterone concentrations in stallions, donkeys and mules.

PubMed

Akhtar, Rana Waseem; Shah, Syed Aftab Hussain; Qureshi, Irfan Zia

2017-10-15

This study was conducted to determine the response of serum testosterone (T) in male equines (stallions, donkeys and mules) after administering intravenous doses of kisspeptin-10 (KP-10), human chorionic gonadotropin (hCG) and luteinizing hormone (LH) and saline as a control. The animals were divided into four groups of three each: Group I, 3 ml of 0.95% saline; Group II, 50 μg KP-10; Group III, 2500 IU hCG and group IV, 400 μg LH. The administration of KP-10 and hCG to stallions resulted in a significant increase in serum T concentration at 240 min; whereas it was significantly higher at 30, 60, 120, and 240 min with LH treatment as compared to pre-dose concentrations. Both KP-10 and hCG significantly elevated the T concentrations in donkeys at 120 and 240 min, respectively; whereas it was significantly higher at 60, 120, and 240 min with LH treatment as compared to pre-dose concentration. Both KP-10 and LH elevated T in donkeys at 240 min as compared to the control and hCG concentrations. After 120 and 240 min, T concentrations in mules were higher (p < 0.05) with administration of KP-10, hCG and LH as compared to the control. In conclusion, the administration of KP-10, hCG and LH elevate the serum T concentration in normal male equines. It is suggested that KP-10 may be useful in situations where an increase in T is desired. Further work is required to determine the effect of KP-10 on T in male equids with reproductive abnormalities before it can be used in clinical situations. Copyright © 2017 Elsevier Inc. All rights reserved.

Fasting serum CGRP levels are related to calcium concentrations, but cannot be elevated by short-term calcium/vitamin D supplementation.

PubMed

Hu, Fudong; Chen, Lianglong; Che, Hailan; Fang, Jun; Lv, Fenghua; Li, Hongjun; Zhang, Surong; Guo, Changlei; Yin, Honglei; Zhang, Shaoli; Zuo, Yulan

2015-02-01

Calcitonin gene-related peptide (CGRP) is an important cardioprotective neuropeptide. Few studies have shown that calcium supplementation may increase CGRP levels transiently. However, the relationship between CGRP and calcium is poorly known. This study was to explore the correlation between serum calcium and CGRP in coronary artery disease (CAD), and observe whether short-term calcium/vitamin D supplementation would increase fasting serum CGRP. A randomized, placebo-controlled and double-blind clinical trial, and a supplementary study for further analysis of the correlations were conducted. The results showed that the correlation between serum calcium and CGRP was positive in CAD without myocardial infarction (MI) (r = 0.487, P = 0.029), but negative in acute and healing MI (r = -0.382, P = 0.003). Moreover, we found a positive correlation between lg (amino-terminal pro-B-type natriuretic peptide, NT-proBNP) and CGRP (r = 0.312, P = 0.027), but a negative correlation between lg (NT-proBNP) and serum calcium (r = -0.316, P = 0.025) in acute and healing MI. As to the clinical trial, participants subjected to CAD but without evolving or acute MI, together with blood calcium ≤ 2.4 mmol/L, were randomized into three groups. Among the groups of placebo, caltrate (600 mg elemental calcium; 125 IU vitamin D3, per tablet) 1 tablet/d and caltrate 2 tablets/d, there were no significant differences in baseline characteristics. After short-term (5 days) treatments, the results indicated that the effect of grouping was not statistically significant (P = 0.915). In conclusion, the correlations between serum calcium and CGRP in different types of CAD are inconsistent, and the main reason may be associated with elevated natriuretic peptides after acute MI. Further, our study shows that short-term calcium/vitamin D supplementation cannot significantly increase fasting serum CGRP levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Serum TK levels in CLL identify Binet stage A patients within biologically defined prognostic subgroups most likely to undergo disease progression.

PubMed

Matthews, Christine; Catherwood, Mark A; Morris, T C M; Kettle, Paul J; Drake, Mary B; Gilmore, William S; Alexander, H Denis

2006-10-01

Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients. Furthermore, the use of serum TK measurement to identify subcategories of disease within those defined by IgV(H) mutational status, gene usage and chromosomal aberrations was investigated. Ninety-one CLL patients were enrolled. Serum TK levels were measured using a radioenzyme assay. IgV(H) mutational status and V(H) gene usage were determined using BIOMED-2 primers and protocol. Recurring chromosomal abnormalities were detected by interphase fluorescent in situ hybridisation (FISH). Flow cytometry and reverse transcriptase polymerase chain reaction (RT-PCR) determined CD38 and Zap-70 expression, respectively. Significantly higher serum TK levels were found in IgV(H) unmutated, compared with IgV(H) mutated, patients (P < 0.001). Elevated TK levels were also found in patients with CD38 and Zap-70 positivity (P = 0.004, P < 0.001, respectively), short lymphocyte doubling time (LDT) (P = 0.044) and poor or intermediate prognosis chromosomal aberrations (P < 0.001). A TK level of >8.5 U/L best identified patients with progressive disease. Elevated TK levels could identify patients categorised, at diagnosis, into good prognosis subgroups by the various biological markers (mutated IgV(H), good prognosis chromosomal aberrations, Zap-70(-) and CD38(-)) who subsequently showed disease progression. Additionally, patients with V(H)3-21 gene usage showed high TK levels, irrespective of mutational status, and serum TK measurement retained predictive power as disease progressed in all subcategories studied.

Association of abnormal plasma bilirubin with aggressive HCC phenotype

PubMed Central

Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

2014-01-01

Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

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.

Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder

PubMed Central

Brady, Roscoe O; McCarthy, Julie M; Prescot, Andrew P; Jensen, J Eric; Cooper, Alissa J; Cohen, Bruce M; Renshaw, Perry F; Ongür, Dost

2017-01-01

Objectives Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls. Methods Fourteen stably medicated euthymic outpatients with bipolar disorder type I (mean age 32.6 years, eight male) and 14 healthy control participants (mean age 36.9 years, 10 male) completed a proton magnetic resonance spectroscopy scan at 4-Tesla after providing informed consent. We collected data from two 16.7-mL voxels using MEGAPRESS, and they were analyzed using LCModel. Results GABA/creatine ratios were elevated in bipolar disorder participants compared to healthy controls [F(1,21) = 4.4, p = 0.048] in the anterior cingulate cortex (25.1% elevation) and the parieto-occipital cortex (14.6% elevation). Bipolar disorder participants not taking GABA-modulating medications demonstrated greater GABA/creatine elevations than patients taking GABA-modulating medications. Conclusions We found higher GABA/creatine levels in euthymic bipolar disorder outpatients compared to healthy controls, and the extent of this elevation may be affected by the use of GABA-modulating medications. Our findings suggest that elevated brain GABA levels in bipolar disorder may be associated with GABAergic dysfunction and that GABA-modulating medications reduce GABA levels in this condition. PMID:23634979

Elevated serum antiphospholipid antibodies in adults with celiac disease.

PubMed

Laine, Outi; Pitkänen, Katariina; Lindfors, Katri; Huhtala, Heini; Niemelä, Onni; Collin, Pekka; Kurppa, Kalle; Kaukinen, Katri

2018-05-01

An increased incidence of thrombosis is suggested in celiac disease. We explored serum levels of antiphospholipid antibodies in untreated and treated adult celiac disease patients. A cohort of 179 biopsy-proven celiac disease patients (89 untreated, 90 on long-term gluten-free diet) and 91 non-celiac controls underwent clinical examination, assessment of celiac serology and enzyme immunoassay testing for anticardiolipin IgG and IgM, prothrombin IgG, and phosphatidylserine-prothrombin IgG and IgM. The level of antiphospholipid antibodies was higher in celiac disease patients compared with controls: anticardiolipin IgG 4.9 (0.7-33.8) vs 2.2 (0.4-9.6) U/ml, antiprothrombin IgG 2.9 (0.3-87.8) vs 2.1 (0.5-187.0) U/ml, antiphosphatidylserine-prothrombin IgG 6.9 (0.0-54.1) vs 2.3 (0.5-15.1) U/ml; p < 0.05 for all. Anticardiolipin IgG, antiprothrombin IgG and antiphosphatidylserine-prothrombin IgG were higher in treated compared with untreated patients. The phenotype of celiac disease at presentation (gastrointestinal symptoms, malabsorption or anemia, and extraintestinal symptoms or screen-detected disease) had no effect on the level of serum antiphospholipid antibodies. The serum level of antiphospholipid antibodies is increased in adults with celiac disease. The higher level of antibodies in treated patients suggests that the increase is not gluten-dependent. The prothrombotic role of antiphospholipid antibodies in celiac disease warrants further studies. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS).

PubMed

Diamanti-Kandarakis, Evanthia; Katsikis, Ilias; Piperi, Christina; Kandaraki, Eleni; Piouka, Athanasia; Papavassiliou, Athanasios G; Panidis, Dimitrios

2008-10-01

Nonenzymatic advanced glycation and oxidation end-products, advanced glycation end-products (AGEs), impart a potent impact on vessels and other tissues in diabetic state and in euglycaemic conditions with increased oxidative stress. Insulin resistant (IR) polycystic ovary syndrome (PCOS) women, have elevated serum AGEs, increased receptor (RAGE) expression, and increased deposition with differential localization in the polycystic ovarian tissue (theca and granulosa) compared to normal. To determine whether the raised AGE levels in noninsulin resistant women with PCOS is a distinct finding compared with those presenting the isolated components of the syndrome and among PCOS subphenotypes. Noninsulin resistant women were selected in order to show that serum AGEs are elevated in PCOS independently of the presence of IR. Clinical trial. One hundred and ninety-three age- and BMI-matched young lean noninsulin resistant women were studied. Among them, 100 women were diagnosed with PCOS according to Rotterdam criteria, and divided to subphenotypes (hyperandrogenaemia with or without PCO morphology and with or without anovulation). Sixty-eight women with the isolated components of the PCOS phenotype were also studied along with 25 healthy women. Serum AGE levels, metabolic, hormonal profiles and intravaginal ultrasound were determined in all subjects. The studied population did not differ in BMI, fasting insulin concentration, waist : hip and glucose : insulin ratios. PCOS women exhibited statistically higher AGEs levels (7.96 +/- 1.87 U/ml, P < 0.001) compared with those with isolated hyperandrogenaemia (5.61 +/- 0.61 U/ml), anovulation (5.53 +/- 1.06 U/ml), US-PCO morphology (5.26 +/- 0.25 U/ml) and controls (5.86 +/- 0.89 U/ml). In PCOS, serum AGEs are distinctly elevated compared with women having the isolated characteristics of the syndrome. No difference was observed between PCOS subphenotypes. As chronic inflammation and increased oxidant stress have been

Elevated serum uric acid levels are associated with endothelial dysfunction in HIV patients receiving highly-active antiretroviral therapy.

PubMed

Pirro, Matteo; Bianconi, Vanessa; Schiaroli, Elisabetta; Francisci, Daniela; Mannarino, Massimo R; Bagaglia, Francesco; Sahebkar, Amirhossein; Merriman, Tony; Baldelli, Franco

2018-05-01

Elevated serum uric acid (SUA) levels may be associated with endothelial dysfunction. Increased rates of metabolic syndrome (MS) and elevated SUA levels were described in human immunodeficiency virus (HIV) infected patients. We investigated whether SUA levels are associated with endothelial dysfunction in HIV positive patients receiving highly-active antiretroviral therapy (HAART) irrespective of MS. In this cross-sectional study of 250 HIV positive patients receiving stable HAART, we evaluated the relationship between MS, SUA levels and endothelial function. SUA levels and brachial artery flow-mediated dilation (bFMD) were measured. The relationship between logarithmic (LG)-transformed SUA levels and bFMD was evaluated after correction for MS. MS was detected in 28.4% of patients and elevated SUA levels (≥6 mg/dL) in 25.2%. MS was associated with higher LG-SUA levels (age-, gender- and glomerular filtration rate-adjusted beta = 0.204, p = 0.001). The crude linear association between LG-SUA levels and LG-bFMD (beta = -0.166, p = 0.008) was abolished after correction for MS (beta = -0.089, p = 0.172). When SUA levels were used as a categorical variable (≥6 mg/dL or <6 mg/dL and SUA quartiles, respectively), the association between LG-SUA levels and LG-bFMD remained significant after adjustment for MS (beta = -0.142, p = 0.022 and beta = -0.163, p = 0.010, respectively). MS significantly affects SUA levels in HAART-treated HIV infected patients. The negative association between SUA and bFMD is independent of MS only for elevated SUA levels. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum glycerophosphate levels are increased in Japanese men with type 2 diabetes.

PubMed

Daimon, Makoto; Soga, Tomoyoshi; Hozawa, Atsushi; Oizumi, Toshihide; Kaino, Wataru; Takase, Kaoru; Karasawa, Shigeru; Jimbu, Yumi; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kayama, Takamasa; Saito, Kaori; Tomita, Masaru; Kato, Takeo

2012-01-01

To identify metabolites showing changes in serum levels among Japanese male with diabetes. We performed metabolite profiling by coupling capillary electrophoresis with electrospray ionization time-of-flight mass spectrometry using fasting serum samples from Japanese male subjects with diabetes (n=17), impaired glucose tolerance (IGT; n=5) and normal glucose tolerance (NGT; n=14). Other than the expected differences in characteristics related to abnormal glucose metabolism, the percent body fat was significantly different among subjects with diabetes, IGT and NGT (27.3±6.2, 22.2±4.5 and 19.2±6.0%, respectively, p=0.0022). Therefore, percent body fat was considered as a possible confounding factor in subsequent analyses. Of 560 metabolites detected using our platform, the levels of 74 metabolites were quantified in all of the serum samples. Significant differences between diabetes and NGT were observed for 24 metabolites. The top-ranked metabolite was glycerol-3-phophate (glycerophosphate), which was significantly higher in subjects with diabetes than in those with NGT, even after Bonferroni correction for multiple testing (11.7±3.6 vs. 6.4±1.9 µM, respectively; corrected p=0.0222). Stepwise multiple regression analyses revealed that serum glycerophosphate levels were significantly correlated with 2-h plasma glucose after a 75-g oral glucose tolerance test (r=0.553, p=0.0005), independently of other characteristics, including FPG and HbA1c. Serum glycerophosphate levels were found to be elevated in Japanese men with diabetes, and correlated with 2-h PG, independent of FPG and HbA1c. Namely, serum glycerophosphate level at fasting condition can be a marker for predicting glucose intolerance. These results warrant further studies to evaluate the relevance of glycerophosphate in the pathophysiology of diabetes.

The Effect of Serum 25-Hydroxyvitamin D Concentrations on Elevated Serum C-Reactive Protein Concentrations in Normal Weight, Overweight and Obese Participants of a Preventive Health Program.

PubMed

Mastroeni, Silmara S B S; Munasinghe, Lalani L; Pham, Truong-Minh; Loehr, Sarah A; Ekwaru, John Paul; Mastroeni, Marco F; Veugelers, Paul J

2016-11-04

The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP concentrations, and trials and meta analyses have been inconsistent in their conclusions regarding the effect of vitamin D supplementation on CRP concentrations. These supplementation trials were mostly conducted among patients with more or less inflammatory complications and did not consider potential distinctive effects by weight status. To further our understanding of the potential influences of vitamin D on CRP, we analyzed longitudinal observations of 6755 participants of a preventative health program. On average, serum 25(OH)D concentrations increased from 88.3 to 121.0 nmol/L and those of CRP decreased from 1.7 to 1.6 mg/L between baseline and follow up. Relative to obese participants without temporal increases in 25(OH)D, those who showed improvements of <25, 25-50, 50-75, and more than 75 nmol/L at follow up were 0.57 (95% confidence interval: 0.37-0.88), 0.54 (0.34-0.85), 0.49 (0.30-0.80), and 0.48 (0.29-0.78) times as likely to have elevated CRP concentrations (≥1 mg/L), respectively. These associations were less pronounced and not statistically significant for normal weight and overweight participants. Herewith, the findings suggest that promotion of adequate serum 25(OH)D concentrations among obese individuals along with healthy lifestyles may alleviate the public health burden associated with cardiovascular disease.

The Effect of Serum 25-Hydroxyvitamin D Concentrations on Elevated Serum C-Reactive Protein Concentrations in Normal Weight, Overweight and Obese Participants of a Preventive Health Program

PubMed Central

Mastroeni, Silmara S. B. S.; Munasinghe, Lalani L.; Pham, Truong-Minh; Loehr, Sarah A.; Ekwaru, John Paul; Mastroeni, Marco F.; Veugelers, Paul J.

2016-01-01

The hypothesized effect of vitamin D on C-reactive protein (CRP) has received substantial attention as a potential means to alleviate the risk for cardiovascular disease. However, observational studies have been inconsistent in their reporting of associations between serum 25-hydroxyvitamin D (25(OH)D) and CRP concentrations, and trials and meta analyses have been inconsistent in their conclusions regarding the effect of vitamin D supplementation on CRP concentrations. These supplementation trials were mostly conducted among patients with more or less inflammatory complications and did not consider potential distinctive effects by weight status. To further our understanding of the potential influences of vitamin D on CRP, we analyzed longitudinal observations of 6755 participants of a preventative health program. On average, serum 25(OH)D concentrations increased from 88.3 to 121.0 nmol/L and those of CRP decreased from 1.7 to 1.6 mg/L between baseline and follow up. Relative to obese participants without temporal increases in 25(OH)D, those who showed improvements of <25, 25–50, 50–75, and more than 75 nmol/L at follow up were 0.57 (95% confidence interval: 0.37–0.88), 0.54 (0.34–0.85), 0.49 (0.30–0.80), and 0.48 (0.29–0.78) times as likely to have elevated CRP concentrations (≥1 mg/L), respectively. These associations were less pronounced and not statistically significant for normal weight and overweight participants. Herewith, the findings suggest that promotion of adequate serum 25(OH)D concentrations among obese individuals along with healthy lifestyles may alleviate the public health burden associated with cardiovascular disease. PMID:27827910

Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation.

PubMed

Bowers, T K; Craddock, P R; Jacob, H S

1977-01-01

A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

PubMed

Zhai, Linzhu; Zhao, Yuanyuan; Peng, Songguo; Zhu, Ke; Yu, Rongjian; Chen, Hailong; Lin, Tongyu; Lin, Lizhu

2016-12-01

There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

Combined effects of admission serum creatinine concentration with age and gender on the prognostic significance of subjects with acute ST-elevation myocardial infarction in China.

PubMed

Li, Zhao-Yang; Pu-Liu; Chen, Zhao-Hong; An, Feng-Hui; Li, Li-Hua; Li-Li; Guo, Chang-Yan; Gu, Yan; Liu, Zhe; Zhu, Tie-Bing; Wang, Lian-Sheng; Li, Chun-Jian; Kong, Xiang-Qing; Ma, Wen-Zhu; Yang, Zhi-Jian; Jia, En-Zhi

2014-01-01

to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China. 1424 acute STEMI patients were enrolled in the study. Anthropometric and laboratory measurements were collected from every patient. A Cox proportional hazards regression model was used to determine the relationships between the admission serum creatinine level (Cr level), age, sex and the in-hospital mortality. A crossover analysis and a stratified analysis were used to determine the combined impact of Cr levels with age and gender. Female (HR 1.687, 95%CI 1.051 ∼ 2.708), elevated Cr level (HR 5.922, 95%CI 3.780 ∼ 9,279) and old age (1.692, 95%CI 1.402 ∼ 2.403) were associated with a high risk of death respectively. After adjusting for other confounders, the renal dysfunction was still independently associated with a higher risk of death (HR 2.48, 95% CI 1.32 ∼ 4.63), while female gender (HR 1.19, 95%CI 0.62 ∼ 2.29) and old age (HR 1.77, 95%CI 0.92 ∼ 3.37) was not. In addition, crossover analysis revealed synergistic effects between elevated Cr level and female gender (SI = 3.01, SIM = 2.10, AP = 0.55). Stratified analysis showed that the impact of renal dysfunction on in-hospital mortality was more pronounced in patients <60 years old (odds ratios 11.10, 95% CI 3.72 to 33.14) compared with patients 60 to 74 years old (odds ratios 5.18, 95% CI 2.48 ∼ 10.83) and patients ≥ 75 years old (odds ratios 3.99, 95% CI 1.89 to 8.42). Serum Cr concentration on admission was a strong predictor for in-hospital mortality among Chinese acute STEMI patients especially in the young and the female.

Elevated serum tumor necrosis factor-alpha and soluble tumor necrosis factor receptors correlate with aberrant energy metabolism in liver cirrhosis.

PubMed

Shiraki, Makoto; Terakura, Yoichi; Iwasa, Junpei; Shimizu, Masahito; Miwa, Yoshiyuki; Murakami, Nobuo; Nagaki, Masahito; Moriwaki, Hisataka

2010-03-01

Protein-energy malnutrition is frequently observed in patients with liver cirrhosis and is associated with their poor prognosis. Tumor necrosis factor-alpha (TNF-alpha) is elevated in those patients and may contribute to the alterations of energy metabolism. Our aim was to characterize the aberrant energy metabolism in cirrhotic patients with regard to TNF-alpha. Twenty-four patients (mean age 65 +/- 6 y) with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twelve healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls (59 +/- 8 y). Serum levels of TNF-alpha, soluble 55-kDa TNF receptor (sTNF-R55), soluble 75-kDa TNF receptor (sTNF-R75), and leptin were determined by immunoassay. Substrate oxidation rates of carbohydrate and fat were estimated by indirect calorimetry after overnight bedrest and fasting. In cirrhotic patients, serum levels of TNF-alpha, sTNF-R55, and sTNF-R75 were significantly higher than those in the controls and correlated with the increasing grade of disease severity as defined by Child-Pugh classification. Serum leptin concentration was not different between cirrhotics and controls but correlated with their body mass index. The decrease in substrate oxidation rate of carbohydrate and the increase in substrate oxidation rate of fat significantly correlated with serum TNF-alpha, sTNF-R55, and sTNF-R75 concentrations. Tumor necrosis factor-alpha might be associated with the aberrant energy metabolism in patients with liver cirrhosis. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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.

Association of serum prostate-specific antigen levels with the results of the prostate needle biopsy.

PubMed

Janbaziroudsari, Hamid; Mirzaei, Arezoo; Maleki, Nasrollah

2016-09-01

To investigate the relationship of serum prostate-specific antigen (PSA) levels with outcomes of prostate needle biopsy in men 50 or more years old. We measured serum PSA levels in 1472 healthy men 50 or more years old. Men who had serum PSA values 4.0ng/mL or higher underwent digital rectal examination. If there were either an elevated PSA level (≥4ng/mL) or abnormal digital rectal examination, a transrectal ultrasound-guided prostate biopsy was performed. The mean serum total PSA level was 13.73±11.44ng/mL, and the mean serum free PSA level was 4.99±0.97ng/mL. Of the 260 men who had serum total PSA levels of≥4ng/mL, 139 underwent biopsy. Of these 139 men, 45 (32.4%) had prostate cancer. Benign prostatic hyperplasia with or without prostatitis was diagnosed in 94 patients (67.6%). There was no significant correlation between age and histologic results of prostate needle biopsy (P-value=0.469). The serum free PSA showed no significant correlation with histologic results of prostate needle biopsy, whereas the serum total PSA level had a significant correlation in patients with adenocarcinoma compared with other diagnosis. The overall frequency of detection of prostate adenocarcinoma was 32.4%. This study revealed that no level of PSA was associated with a 100% positive predictive value and negative biopsy can occur virtually at any PSA level. There is a need to create awareness among the general population and health professionals for an early diagnosis of this common form of cancer. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats.

PubMed

Shao, Shan-shan; Zhao, Yuan-fei; Song, Yong-feng; Xu, Chao; Yang, Jian-mei; Xuan, Shi-meng; Yan, Hui-li; Yu, Chun-xiao; Zhao, Meng; Xu, Jin; Zhao, Jia-jun

2014-11-01

Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.

Expanding the spectrum of phenotypes associated with germline PIGA mutations: a child with developmental delay, accelerated linear growth, facial dysmorphisms, elevated alkaline phosphatase, and progressive CNS abnormalities.

PubMed

van der Crabben, Saskia N; Harakalova, Magdalena; Brilstra, Eva H; van Berkestijn, Frédérique M C; Hofstede, Floris C; van Vught, Adrianus J; Cuppen, Edwin; Kloosterman, Wigard; Ploos van Amstel, Hans Kristian; van Haaften, Gijs; van Haelst, Mieke M

2014-01-01

Phosphatidyl inositol glycan (PIG) enzyme subclasses are involved in distinct steps of glycosyl phosphatidyl inositol anchor protein biosynthesis. Glycolsyl phosphatidyl inositol-anchored proteins have heterogeneous functions; they can function as enzymes, adhesion molecules, complement regulators and co-receptors in signal transduction pathways. Germline mutations in genes encoding different members of the PIG family result in diverse conditions with (severe) developmental delay, (neonatal) seizures, hypotonia, CNS abnormalities, growth abnormalities, and congenital abnormalities as hallmark features. The variability of clinical features resembles the typical diversity of other glycosylation pathway deficiencies such as the congenital disorders of glycosylation. Here, we report the first germline missense mutation in the PIGA gene associated with accelerated linear growth, obesity, central hypotonia, severe refractory epilepsy, cardiac anomalies, mild facial dysmorphic features, mildly elevated alkaline phosphatase levels, and CNS anomalies consisting of progressive cerebral atrophy, insufficient myelinization, and cortical MRI signal abnormalities. X-exome sequencing in the proband identified a c.278C>T (p.Pro93Leu) mutation in the PIGA gene. The mother and maternal grandmother were unaffected carriers and the mother showed 100% skewing of the X-chromosome harboring the mutation. These results together with the clinical similarity of the patient reported here and the previously reported patients with a germline nonsense mutation in PIGA support the determination that this mutation caused the phenotype in this family. © 2013 Wiley Periodicals, Inc.

Pregnant serum induces neuroinflammation and seizure activity via TNFα.

PubMed

Cipolla, Marilyn J; Pusic, Aya D; Grinberg, Yelena Y; Chapman, Abbie C; Poynter, Matthew E; Kraig, Richard P

2012-04-01

Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective

Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*

PubMed Central

Jones, John W.; Ways, Peter

1967-01-01

Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states. The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess. Images PMID:6027078

Abnormal aldosterone physiology and cardiometabolic risk factors.

PubMed

Vaidya, Anand; Underwood, Patricia C; Hopkins, Paul N; Jeunemaitre, Xavier; Ferri, Claudio; Williams, Gordon H; Adler, Gail K

2013-04-01

Abnormal aldosterone physiology has been implicated in the pathogenesis of cardiometabolic diseases. Single aldosterone measurements capture only a limited range of aldosterone physiology. New methods of characterizing aldosterone physiology may provide a more comprehensive understanding of its relationship with cardiometabolic disease. We evaluated whether novel indices of aldosterone responses to dietary sodium modulation, the sodium-modulated aldosterone suppression-stimulation index (SASSI for serum and SAUSSI for urine), could predict cardiometabolic risk factors. We performed cross-sectional analyses on 539 subjects studied on liberal and restricted sodium diets with serum and urinary aldosterone measurements. SASSI and SAUSSI were calculated as the ratio of aldosterone on liberal (maximally suppressed aldosterone) to the aldosterone on restricted (stimulated aldosterone) diets and associated with risk factors using adjusted regression models. Cardiometabolic risk factors associated with either impaired suppression of aldosterone on liberal diet, or impaired stimulation on restricted diet, or both; in all of these individual cases, these risk factors associated with higher SASSI or SAUSSI. In the context of abnormalities that constitute the metabolic syndrome, there was a strong positive association between the number of metabolic syndrome components (0-4) and both SASSI and SAUSSI (P<0.0001) that was independent of known aldosterone secretagogues (angiotensin II, corticotropin, potassium). SASSI and SAUSSI exhibited a high sensitivity in detecting normal individuals with zero metabolic syndrome components (86% for SASSI and 83% for SAUSSI). Assessing the physiological range of aldosterone responses may provide greater insights into adrenal pathophysiology. Dysregulated aldosterone physiology may contribute to, or result from, early cardiometabolic abnormalities.

Glutamatergic system abnormalities in posttraumatic stress disorder.

PubMed

Nishi, Daisuke; Hashimoto, Kenji; Noguchi, Hiroko; Hamazaki, Kei; Hamazaki, Tomohito; Matsuoka, Yutaka

2015-12-01

Accumulating evidence suggests involvement of the glutamatergic system in the biological mechanisms of posttraumatic stress disorder (PTSD), but few studies have demonstrated an association between glutamatergic system abnormalities and PTSD diagnosis or severity. We aimed to examine whether abnormalities in serum glutamate and in the glutamine/glutamate ratio were associated with PTSD diagnosis and severity in severely injured patients at risk for PTSD and major depressive disorder (MDD). This is a nested case-control study in TPOP (Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid) trial. Diagnosis and severity of PTSD were assessed 3 months after the accidents using the Clinician-Administered PTSD Scale. The associations of glutamate levels and the glutamine/glutamate ratio with diagnosis and severity of PTSD and MDD were investigated by univariate and multiple linear regression analyses. Ninety-seven of 110 participants (88 %) completed assessments at 3 months. Serum glutamate levels were significantly higher for participants with full or partial PTSD than for participants without PTSD (p = 0.049) and for participants with MDD than for participants without MDD (p = 0.048). Multiple linear regression analyses showed serum glutamate levels were significantly positively associated with PTSD severity (p = 0.02) and MDD severity (p = 0.03). The glutamine/glutamate ratio was also significantly inversely associated with PTSD severity (p = 0.03), but not with MDD severity (p = 0.07). These findings suggest that the glutamatergic system may play a major role in the pathogenesis of PTSD and the need for new treatments targeting the glutamatergic system to be developed for PTSD.

Serum calprotectin levels correlate with biochemical and histological markers of disease activity in TNBS colitis

PubMed Central

Cury, Didia Bismara; Mizsputen, Sender Jankiel; Versolato, Clara; Miiji, Luciana Odashiro; Pereira, Edson; Delboni, Maria Aparecida; Schor, Nestor; Moss, Alan C.

2014-01-01

Background and aim Serum calprotectin is elevated in patients with inflammatory bowel disease (IBD). Whether it correlates other markers of disease activity is unknown. The aim of this study was to correlate serum calprotectin with biochemical and histological measures of intestinal inflammation. Materials and methods TNBS colitis was induced in wistar rats, and serial blood samples were collected at 0, 3, and 12 days. Animals were subsequently sacrificed for pathological evaluation at day 12. Serum calprotectin and cytokines were measured by ELISA. Pathologic changes were classified at the macroscopic and microscopic levels. Results TNBS colitis induced elevated serum calprotectin, TNF and IL-6 within 24 h. Levels of serum calprotectin remained elevated in parallel to persistence of loose stool and weight loss to day 12. Serum calprotectin levels correlated with serum levels of TNF-α and IL6 (p < 0.001), but not CRP. Animals with liquid stool had significantly higher levels of serum calprotectin than control animals. There was a correlation between macroscopic colitis scores, and levels of serum calprotectin. Conclusion Serum calprotectin levels correlate with biochemical and histological markers of inflammation in TNBS colitis. This biomarker may have potential for diagnostic use in patients with IBD. PMID:23685388

Elevated red blood cell 2,3-diphosphoglycerate levels in black blood donors.

PubMed

Wallas, C H

1978-01-01

Mean levels of 2,3-diphosphoglycerate (DPG) were significantly increased in erythrocytes (RBC) from 43 nonanemic black blood donors (4.80 +/- 0.06 micromoles/l RBC) compared with 22 white donors 4.47 +/- 0.08 micromoles/l RBCs from eight of the 12 black donors with DPG levels greater than 5 micromoles/l RBC. Although a potentially hemolytic disorder could be defined in four (AS hemoglobin, beta-Thalassemia minor, G6PD deficiency), reticulocyte counts were normal. However, when RBCs from the subgroup were compared to RBCs from an additional 25 unselected white donors, the following suggested an abnormally large population of young RBCs in the subgroup: 1) normal or elevated RBC-ATP with normal serum phosphate level; 2) significantly increased activities of RBC age-dependent enzymes hexokinase (p less than 0.02), pyruvate kinase (p less than 0.05), and glutamicoxaloacetic transaminase (p less than 0.01), with normal activity of phosphoglycerate kinase, an age-independent enzyme; 3) decreased dense (older) RBCs as determined by sedimentation in phthalate esters. Since DPG is increased in young RBCs and falls as the RBC ages, loss of older relatively DPG depleted RBCs due to shortened survival could account for the elevated DPG levels seen in the subgroup.

High provitamin A carotenoid serum concentrations, elevated retinyl esters, and saturated retinol-binding protein in Zambian preschool children are consistent with the presence of high liver vitamin A stores.

PubMed

Mondloch, Stephanie; Gannon, Bryan M; Davis, Christopher R; Chileshe, Justin; Kaliwile, Chisela; Masi, Cassim; Rios-Avila, Luisa; Gregory, Jesse F; Tanumihardjo, Sherry A

2015-08-01

Biomarkers of micronutrient status are needed to best define deficiencies and excesses of essential nutrients. We evaluated several supporting biomarkers of vitamin A status in Zambian children to determine whether any of the biomarkers were consistent with high liver retinol stores determined by using retinol isotope dilution (RID). A randomized, placebo-controlled, biofortified maize efficacy trial was conducted in 140 rural Zambian children from 4 villages. A series of biomarkers were investigated to better define the vitamin A status of these children. In addition to the assessment of total-body retinol stores (TBSs) by using RID, tests included analyses of serum carotenoids, retinyl esters, and pyridoxal-5'-phosphate (PLP) by using high-pressure liquid chromatography, retinol-binding protein by using ELISA, and alanine aminotransferase (ALT) activity by using a colorimetric assay. Children (n = 133) were analyzed quantitatively for TBSs by using RID. TBSs, retinyl esters, some carotenoids, and PLP differed by village site. Serum carotenoids were elevated above most nonintervened reference values for children. α-Carotene, β-carotene, and lutein values were >95th percentile from children in the US NHANES III, and 13% of children had hypercarotenemia (defined as total carotenoid concentration >3.7 μmol/L). Although only 2% of children had serum retinyl esters >10% of total retinol plus retinyl esters, 16% of children had >5% as esters, which was consistent with high liver retinol stores. Ratios of serum retinol to retinol-binding protein did not deviate from 1.0, which indicated full saturation. ALT activity was low, which was likely due to underlying vitamin B-6 deficiency, which was confirmed by very low serum PLP concentrations. The finding of hypervitaminosis A in Zambian children was supported by high circulating concentrations of carotenoids and mildly elevated serum retinyl esters. ALT-activity assays may be compromised with co-existing vitamin B-6

Prospective evaluation of 68 Ga-DOTATATE PET/CT in limited disease neuroendocrine tumors and/or elevated serum neuroendocrine biomarkers.

PubMed

Gabriel, Sophie; Garrigue, Philippe; Dahan, Laetitia; Castinetti, Frédéric; Sebag, Frédéric; Baumstark, Karine; Archange, Cendrine; Abhishek, Jha; Pacak, Karel; Guillet, Benjamin; Taïeb, David

2018-05-22

The 68 Ga-labelled somatostatin analogues ( 68 Ga-DOTA-SSAs) is becoming popular as an important diagnostic tool in neuroendocrine tumors as evidenced by a growing number of reports detailing institutional experience with various DOTA peptides. However, only few prospective studies have compared 68 Ga-DOTA-SSAs and somatostatin receptor scintigraphy (SRS) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and pulmonary neuroendocrine tumors. The aim of our prospective study was to perform head-to-head comparison between 68 Ga-DOTATATE PET/CT and standard imaging work-up (SI) that included multiphasic CT, liver MRI, and SRS using single photon emission computed tomography. In this prospective study, the patients were enrolled only if they met any of the following inclusion criteria were: i- initial staging of a NETs without distant metastases on SI or neuroendocrine tumor with unknown primary on SI; ii-restaging of NETs that could be treated by focused therapeutic interventions; iii- elevated serum neuroendocrine hormones or peptides. The exclusion criteria was grade 3 GEP-NETs. Thirty-two patients were enrolled in the study. Eleven patients (6 pancreas, 4 ileum, 1 duodenal) were included for initial evaluation and staging of NETs, 8 patients (5 pancreas, 1 ileal, 1 lung, 1 duodenal gastrinoma) for restaging, and 13 patients for elevated serum neuroendocrine biomarkers (5 ectopic Cushing's syndrome, 5 organic hypoglycemia, 1 patient each with elevated vasoactive inhibitory peptide, chromogranin A, and neuron-specific enolase). 68 Ga-DOTATATE PET/CT detected more primary tumors than SRS (15/18 vs 10/18: p=0.074). The missed tumors on 68 Ga-DOTATATE PET/CT were located in the lung in 2 cases and duodenum in 1 case. For other anatomical regions (nodal and distant metastasis), no statistical difference was observed between imaging modalities using 68 Ga-DOTATATE PET/CT and SRS. Overall, 68 Ga-DOTATATE PET/CT+CT+MRI detected 31/33 of the involved regions

Serum VEGFR-3 as a potential biomarker in psoriasis.

PubMed

Hong, Xia; Jiang, Shan; Marmolejo, Nancy; Vangipuram, Ramya; Ramos-Rojas, Elmira; Yuan, Yulin; Lin, Zuan-Tao; Li, Yaxi; Qiu, Jingyi; Xing, Yikun; Haley, Christopher; Tyring, Stephen K; Wu, Tianfu

2018-06-29

To discover novel biomarkers of psoriasis, a target-specific antibody array screening of serum samples from psoriasis patients was initially performed. The results revealed that Vascular endothelial growth factor receptor 3 (VEGFR-3) was significantly elevated in the sera of psoriasis patients, compared to healthy controls. Next, ELISA validation studies in a larger cohort of psoriasis patients (N=73) were conducted which confirmed that serum VEGFR-3 was indeed significantly increased in patients with psoriasis compared to healthy controls (P < 0.001). Furthermore, Receiver operating characteristic (ROC) curve analysis demonstrated that serum VEGFR-3 exhibited potential in distinguishing healthy controls from psoriasis patients: Area Under the Curve (AUC) = 0.85, P < 0.001. In addition, serum levels of VEGFR-3 were correlated with Psoriasis Area Severity Index (PASI) scores (R = 0.32, P = 0.008) in psoriasis patients. Interestingly, serum VEGFR-3 levels were significantly elevated in psoriatic arthritis compared to non-psoriatic arthritis (P = 0.026). A pilot longitudinal study demonstrated that serum levels of VEGFR-3 could reflect disease progression in psoriasis. Collectively, serum VEGFR-3 may have a clinical value in monitoring disease activity of psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Occupational exposure levels of bioaerosol components are associated with serum levels of the acute phase protein Serum Amyloid A in greenhouse workers.

PubMed

Madsen, Anne Mette; Thilsing, Trine; Bælum, Jesper; Garde, Anne Helene; Vogel, Ulla

2016-01-20

Occupational exposure to particles may be associated with increased inflammation of the airways. Animal experiments suggest that inhaled particles also induce a pulmonary acute phase response, leading to systemic circulation of acute phase proteins. Greenhouse workers are exposed to elevated levels of bioaerosols. The objective of this study is to assess whether greenhouse workers personal exposure to bioaerosol components was associated with serum levels of the acute phase proteins Serum Amyloid A (SAA) and C-reactive protein (CRP). SAA and CRP levels were determined in serum sampled repeatedly from 33 greenhouse workers. Blood was drawn repeatedly on Mondays and Thursdays during work weeks. Acute phase protein levels were compared to levels in a comparison group of 42 people and related to individual exposure levels to endotoxin, dust, bacteria, fungi and β-glucan. Serum levels of SAA and CRP were not significantly different in greenhouse workers and a reference group, or on the two work days. In a mixed model, SAA levels were positively associated with endotoxin exposure levels (p = 0.0007). Results for fungi were not clear. CRP levels were positively associated with endotoxin exposures (p = 0.022). Furthermore, when workers were categorized into three groups based on SAA and CRP serum levels endotoxin exposure was highest in the group with the highest SAA levels and in the group with middle and highest CRP levels. SAA and CRP levels were elevated in workers with asthma. Greenhouse workers did not have elevated serum levels of SAA and CRP compared to a reference group. However, occupational exposure to endotoxin was positively associated with serum levels of the acute phase proteins SAA and CRP. Preventive measures to reduce endotoxin exposure may be beneficial.

Elevated serum uric acid increases risks for developing high LDL cholesterol and hypertriglyceridemia: A five-year cohort study in Japan.

PubMed

Kuwabara, Masanari; Borghi, Claudio; Cicero, Arrigo F G; Hisatome, Ichiro; Niwa, Koichiro; Ohno, Minoru; Johnson, Richard J; Lanaspa, Miguel A

2018-06-15

High serum uric acid (SUA) is associated with the dyslipidemia, but whether hyperuricemia predicts an increase in serum low-density lipoprotein (LDL) cholesterol is unknown. This study is to evaluate whether an elevated SUA predicts the development of high LDL cholesterol as well as hypertriglyceridemia. This is a retrospective 5-year cohort study of 6476 healthy Japanese adults (age, 45.7 ± 10.1 years; 2.243 men) who underwent health examinations at 2004 and were reevaluated in 2009 at St. Luke's International Hospital, Tokyo, Japan. Subjects were included if at their baseline examination they did not have hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, or if they were on medication for hyperuricemia and/or gout. The analysis was adjusted for age, body mass index (BMI), smoking and drinking habits, baseline estimated glomerular filtration rate (eGFR), baseline SUA and SUA change over the 5 years. High baseline SUA was an independent risk for developing high LDL cholesterol both in men (OR: 1.159 per 1 mg/dL increase, 95% CI:1.009-1.331) and women (OR: 1.215, 95% CI:1.061-1.390). Other risk factors included a higher baseline LDL cholesterol, higher BMI, and higher baseline eGFR (the latter two in women only). Increased SUA over 5 years were also independent risks for developing high LDL cholesterol and hypertriglyceridemia, but not for low high-density lipoprotein (HDL) cholesterol. This is the first study to report that an elevated SUA increases the risk for developing high LDL cholesterol, as well as hypertriglyceridemia. This may shed light into the role of SUA in cardiovascular disease. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum Albumin Stimulates Protein Kinase G-dependent Microneme Secretion in Toxoplasma gondii.

PubMed

Brown, Kevin M; Lourido, Sebastian; Sibley, L David

2016-04-29

Microneme secretion is essential for motility, invasion, and egress in apicomplexan parasites. Although previous studies indicate that Ca(2+) and cGMP control microneme secretion, little is known about how these pathways are naturally activated. Here we have developed genetically encoded indicators for Ca(2+) and microneme secretion to better define the signaling pathways that regulate these processes in Toxoplasma gondii We found that microneme secretion was triggered in vitro by exposure to a single host protein, serum albumin. The natural agonist serum albumin induced microneme secretion in a protein kinase G-dependent manner that correlated with increased cGMP levels. Surprisingly, serum albumin acted independently of elevated Ca(2+) and yet it was augmented by artificial agonists that raise Ca(2+), such as ethanol. Furthermore, although ethanol elevated intracellular Ca(2+), it alone was unable to trigger secretion without the presence of serum or serum albumin. This dichotomy was recapitulated by zaprinast, a phosphodiesterase inhibitor that elevated cGMP and separately increased Ca(2+) in a protein kinase G-independent manner leading to microneme secretion. Taken together, these findings reveal that microneme secretion is centrally controlled by protein kinase G and that this pathway is further augmented by elevation of intracellular Ca(2.) © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

[Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level].

PubMed

Yan, Ling; Ye, Lu; Wang, Kun; Zhou, Jie; Zhu, Chunjia

2016-05-25

Objective: To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels. Methods: One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed. Results: Serum uric acid levels were decreased after treatment in both groups (all P <0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level ( P <0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group ( P <0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups ( P >0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels ( P <0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid ( P <0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI ( OR =1.01, 95% CI :1.01-1.11, P <0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) ( P <0

Effects of cafestol and kahweol from coffee grounds on serum lipids and serum liver enzymes in humans.

PubMed

Urgert, R; Schulz, A G; Katan, M B

1995-01-01

The diterpenes cafestol and kahweol are present in unfiltered coffee in oil droplets and floating fines. They elevate serum cholesterol and alanine aminotransferase (ALT). We measured fines in coffee brews, and examined diterpene availability from spent grounds in healthy volunteers. Turkish or Scandinavian boiled coffee contained 2-5 g fines/L and French press coffee contained 1.5 g fines/L. An intake of 8 g fine grounds/d for 3 wk increased cholesterol by 0.65 mmol/L (95% CI 0.41-0.89 mmol/L) and ALT by 18 U/L (95% CI 4-32 U/L) relative to control subjects (n = 7/group). In a crossover study (n = 15), mean serum cholesterol was 4.9 mmol/L after consumption of both fine and coarse grounds for 10 d (P = 0.43). Serum ALT activities were 29 U/L on fine and 21 U/L on coarse grounds (P = 0.02). Floating fines could contribute substantially to the hyperlipidemic and ALT-elevating effect of unfiltered coffee. Diterpene measurements in coffee brews should include the contribution of fines.

Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly.

PubMed

Lewerin, C; Ljungman, S; Nilsson-Ehle, H

2007-01-01

To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. Population-based study of 209 community-dwelling subjects, mean age 76 years. Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.

Association of ferroportin Q248H polymorphism with elevated levels of serum ferritin in African-Americans in the Hemochromatosis and Iron Overload Screening (HEIRS) Study

PubMed Central

Rivers, Charles A.; Barton, James C.; Gordeuk, Victor R.; Acton, Ronald T.; Speechley, Mark R.; Snively, Beverly M.; Leiendecker-Foster, Catherine; Press, Richard D.; Adams, Paul C.; McLaren, Gordon D.; Dawkins, Fitzroy W.; McLaren, Christine E.; Reboussin, David M.

2007-01-01

The ferroportin (FPN1) Q248H polymorphism has been associated with increased serum ferritin (SF) levels in sub-Saharan Africans and in African Americans (AA). AA participants of the HEIRS Study who did not have HFE C282Y or H63D who had elevated initial screening SF (≥300 μg/L in men and ≥200 μg/L in women) (defined as cases) were frequency-matched to AA participants with normal SF (defined as controls) to investigate the association of the Q248H with elevated SF. 10.4% of cases and 6.7% of controls were Q248H heterozygotes (P = 0.257). Q248H homozygosity was observed in 0.5% of the cases and none of the controls. The frequency of Q248H was higher among men with elevated SF than among control men (P = 0.047); corresponding differences were not observed among women. This appeared to be unrelated to self-reports of a previous diagnosis of liver disease. Men with elevated SF were three times more likely than women with elevated SF to have Q248H (P = 0.012). There were no significant differences in Q248H frequencies in men and women control participants. We conclude that the frequency of the FPN1 Q248H polymorphism is greater in AA men with elevated SF than in those with normal SF. PMID:17276706

Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal function.

PubMed

Yamoto, M; Imai, M; Otani, H; Nakano, R

1997-05-01

To determine whether serum inhibin A and inhibin B concentrations are lower in patients with luteal dysfunction than in women with normal luteal function. Serum samples were collected from seven healthy women with regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were collected from patients with luteal dysfunction. The diagnosis of luteal dysfunction was based on a luteal phase duration less than 11 days and a single midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin B, progesterone, estradiol (E2), FSH, and LH were measured. The serum inhibin A levels were increased toward the late follicular phase. The levels reached a maximum during the midluteal phase, followed by a fall during the late luteal phase. The serum inhibin B levels were high during the follicular phases and the early luteal phase. The levels decreased during the midluteal and late luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in patients with luteal dysfunction were significantly lower than those in women during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01) in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7 compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ significantly between normal women and those with luteal dysfunction. There also were no significant differences in the E2, FSH, and LH levels. Levels of inhibin A, but not of inhibin B, may reflect the human luteal function.

Bulk- and surface-modified combinable PDMS capillary sensor array as an easy-to-use sensing device with enhanced sensitivity to elevated concentrations of multiple serum sample components.

PubMed

Fujii, Yuji; Henares, Terence G; Kawamura, Kunio; Endo, Tatsuro; Hisamoto, Hideaki

2012-04-21

To enhance sensitivity and facilitate easy sample introduction into a combinable poly(dimethylsiloxane) (PDMS) capillary (CPC) sensor array, PDMS was modified in bulk and on its surface to prepare "black" PDMS coated with a silver layer and self-assembled monolayer (SAM). India ink, a traditional Japanese black ink, was added to the PDMS pre-polymer for bulk modification. The surface was modified by a silver mirror reaction followed by SAM formation using cysteine. These modifications enhanced the fluorescence signals by reflecting them from the surface and reducing background interference. A decrease in the water contact angle led to enhanced sensitivity and easy sample introduction. Furthermore, a CPC sensor array for multiplex detection of serum sample components was prepared that could quantify the analytes glucose, potassium, and alkaline phosphatase (ALP). When serum samples were introduced by capillary action, the CPC sensor array showed fluorescence responses for each analyte and successfully identified the components with elevated concentrations in the serum samples.

Grey matter abnormalities in untreated hyperthyroidism: a voxel-based morphometry study using the DARTEL approach.

PubMed

Zhang, Wei; Song, Lingheng; Yin, Xuntao; Zhang, Jiuquan; Liu, Chen; Wang, Jian; Zhou, Daiquan; Chen, Bing; Lii, Haitao

2014-01-01

Hyperthyroidism is frequently associated with pronounced neuropsychiatric symptoms such as impulsiveness, irritability, poor concentration, and memory impairments. Functional neuroimaging has revealed changes in cerebral metabolism in hyperthyroidism, but regional changes in cortical morphology associated with specific neurological deficits have not been studied so far. To investigate the pathophysiology underlying hyperthyroid-associated neural dysfunction, we compared grey matter volume (GMV) between adult hyperthyroid patients and matched healthy controls using voxel-based morphometry (VBM). High resolution 3D T1-weighted images were acquired by 3T MRI from 51 hyperthyroid patients and 51 controls. VBM analysis was performed using SPM8. Correlations between regional GMV and both serum free thyroid hormone (TH) concentrations and disease duration were assessed by multiple regression analysis. Compared to controls, GM volumes in the bilateral hippocampus, parahippocampal gyrus, calcarine, lingual gyrus, and left temporal pole were lower and bilateral supplementary motor area GMV higher in hyperthyroid patients. Serum free triiodothyronine (FT3) concentration was negatively correlated with the normalized regional volume (NRV) of the left parahippocampal gyrus and serum free thyroxine (FT4) concentration negatively correlated with the NRV of the left hippocampus and right parahippocampal gyrus. Disease duration was negatively correlated with the NRV of the left hippocampus, bilateral parahippocampal gyrus, and left temporal pole. Hyperthyroid patients exhibited reduced GMV in regions associated with memory, attention, emotion, vision, and motor planning. Negative correlations between GMV and both free TH and disease duration suggest that chronic TH elevation induces abnormalities in the adult cortex. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Relationships among the serum omega fatty acid levels, serum C-reactive protein levels and arterial stiffness/wave reflection in Japanese men.

PubMed

Tomiyama, Hirofumi; Matsumoto, Chisa; Odaira, Mari; Yamada, Jiko; Yoshida, Masanobu; Shiina, Kazuki; Nagata, Mikio; Yamashina, Akira

2011-08-01

We examined the relationship among the serum omega-3 and omega-6 fatty acid (O3FA and O6FA) levels, serum C-reactive protein (CRP) levels, and arterial stiffness/wave reflection (AS/WR) in healthy Japanese men. In 2206 Japanese healthy men, parameters related to the AS/WR (i.e., brachial-ankle pulse wave velocity and radial arterial pulse wave analysis) were measured. No significant inverse relationships were observed between the serum O3FA levels and the AS/WR-related parameters. Adjusted values of the AS/WR-related parameters and serum CRP levels were higher in the subjects with serum O6FA levels in the highest tertile than in those with serum O6FA levels in the lowest tertile. In healthy Japanese men with known high dietary intakes of O3FAs, the serum O3FA levels may not reflect the pathophysiological abnormalities related to AS/WR. Increased serum O6FA levels appeared to be independently associated with the unfavorable conditions related to AS/WR and inflammation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Serum sodium concentration, blood urea nitrogen, and outcomes in patients hospitalized for acute decompensated heart failure.

PubMed

Kajimoto, Katsuya; Minami, Yuichiro; Sato, Naoki; Takano, Teruo

2016-11-01

This study investigated the association of a low serum sodium and elevated blood urea nitrogen (BUN) with outcomes in acute decompensated heart failure (HF) patients. Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4438 patients discharged after hospitalization for acute decompensated HF were investigated to assess the association of a low serum sodium and/or elevated BUN at discharge with all-cause mortality. The patients were divided into four groups based on serum sodium (>136 or ≤136mEq/l) and BUN (<25 or ≥25mg/dl) at discharge. The median follow-up period after discharge was 517 (381-776) days. According to multivariate analysis, a low serum sodium (≤136mEq/l) or an elevated BUN (≥25mg/dl) was significantly associated with a higher risk of all-cause death compared with patients who had neither (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.22 to 1.94; P<0.001 and HR, 1.44; 95% CI, 1.19 to 1.73; P<0.001, respectively). Patients with both low serum sodium and elevated BUN had a higher risk of all-cause death relative to patients with neither (HR, 2.64; 95% CI, 2.17 to 3.20; P<0.001) and also relative to patients with either low serum sodium alone or elevated BUN alone (HR, 1.72; 95% CI, 1.36 to 2.18; P<0.001 and HR, 1.84; 95% CI, 1.53 to 2.21; P<0.001, respectively). These findings demonstrated that a low serum sodium and an elevated BUN may be additive risk factors for postdischarge mortality in acute decompensated HF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Elevation of cardiac troponin I during non-exertional heat-related illnesses in the context of a heatwave

PubMed Central

2010-01-01

Introduction The prognostic value of cardiac troponin I (cTnI) in patients having a heat-related illness during a heat wave has been poorly documented. Methods In a post hoc analysis, we evaluated 514 patients admitted to emergency departments during the August 2003 heat wave in Paris, having a core temperature >38.5°C and who had analysis of cTnI levels. cTnI was considered as normal, moderately elevated (abnormality threshold to 1.5 ng.mL-1), or severely elevated (>1.5 ng.mL-1). Patients were classified according to our previously described risk score (high, intermediate, and low-risk of death). Results Mean age was 84 ± 12 years, mean body temperature 40.3 ± 1.2°C. cTnI was moderately elevated in 165 (32%) and severely elevated in 97 (19%) patients. One-year survival was significantly decreased in patients with moderate or severe increase in cTnI (24 and 46% vs 58%, all P < 0.05). Using logistic regression, four independent variables were associated with an elevated cTnI: previous coronary artery disease, Glasgow coma scale <12, serum creatinine >120 μmol.L-1, and heart rate >110 bpm. Using Cox regression, only severely elevated cTnI was an independent prognostic factor (hazard ratio 1.93, 95% confidence interval 1.35 to 2.77) when risk score was taken into account. One-year survival was decreased in patients with elevated cTnI only in high risk patients (17 vs 31%, P = 0.04). Conclusions cTnI is frequently elevated in patients with non-exertional heat-related illnesses during a heat wave and is an independent risk factor only in high risk patients where severe increase (>1.5 ng.mL-1) indicates severe myocardial damage. PMID:20507603

A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children.

PubMed

Mostafa, Gehan Ahmed; Al-Ayadhi, Laila Yousef

2011-06-22

One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism. Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39). Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Lack of correlation between serum soluble Fas/APO-1 levels and autoimmune disease.

PubMed

Goel, N; Ulrich, D T; St Clair, E W; Fleming, J A; Lynch, D H; Seldin, M F

1995-12-01

To determine whether elevated soluble Fas/APO-1 (sFas/APO-1) levels are associated with either autoimmune disease or evidence of flares in autoimmune disease. Thirty-seven serum samples were retrospectively obtained from normal controls and patients with laboratory evidence of autoimmune disease activity. These samples were assayed for sFas/APO-1 levels by an enzyme-linked immunosorbent assay, and hospital medical records were retrospectively reviewed for clinical and laboratory characteristics of the patients. Soluble Fas/APO-1 levels did not correlate with clinical diagnoses or laboratory abnormalities. The mean and range of sFas/APO-1 levels were similar in systemic lupus erythematosus patients (including those with active disease), patients with other autoimmune diseases, and normal controls. These data strongly suggest that measurement of sFas/APO-1 levels is unlikely to hold clinical value or play a role in the pathogenesis of autoimmune disease.

[The value of serum free light chain in differential diagnosis of monoclonal gammopathy of renal significance].

PubMed

Li, C; Wen, Y B; Li, H; Su, W; Li, J; Cai, J F; Chen, L M; Li, X M; Li, X W

2017-08-08

Objective: To investigate the value of serum free light chain (FLC) in differential diagnosis of monoclonal gammopathy of renal significance (MGRS). Methods: Forty-nine hospitalized patients who underwent renal biopsy in Peking Union Medical College Hospital between January 2013 and December 2015 were included. Monoclonal gammopathy was detected by serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), urine IFE and serum FLC. All patients were classified as MGRS ( n =32) and monoclonal gammopathy of undetermined significance (MGUS) ( n =17). Results: Renal lesions in MGRS subgroup included light chain amyloidosis ( n =24, 75.0%), light chain deposition disease ( n =7, 21.9%), and fibrillary glomerulopathy ( n =1, 3.1%). Renal diseases in MGUS subgroup included membranous nephropathy ( n =10), focal segmental glomerulosclerosi (FSGS) ( n =3), diabetic glomerulopathy ( n =1), Henoch-Schonlein purpura nephritis ( n =1), anti-GBM disease concurrent with membranous nephropathy ( n =1) and glomerulomegaly ( n =1). Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGRS subgroup were 12, 16, 23 and 30, respectively. Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGUS subgroup were 11, 17, 6 and 3, respectively. MGRS and MGUS subgroups differed significantly in positive rate of serum IFE ( P <0.001), as well as positive rate of urine IFE ( P =0.02) and abnormal rate of serum FLC ratio ( P <0.001). The sensitivity, specificity, total consistent rate of serum FLC ratio for diagnosis of MGRS were 93.8%, 82.4%, and 89.8% respectively. The sensitivity for diagnosing MGRS could be increased to 100% by combining serum FLC ratio and urine IFE. Conclusions: The significance of monoclonal gammopathy in patients with renal disease should be evaluated by renal pathology.On the premise of excluding lymphoplasmacytic malignancy, serum FLC ratio had promising diagnostic value for MGRS

Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy.

PubMed

Ross, D S

1988-12-01

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.

Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?

PubMed

Nieto, F J; Iribarren, C; Gross, M D; Comstock, G W; Cutler, R G

2000-01-01

the evidence of a potential beneficial role of antioxidants in preventing atherosclerotic disease is not entirely consistent. to assess the longitudinal association of serum total antioxidant capacity and serum antioxidants with the presence of subclinical carotid atherosclerosis. Prospective case-control study nested within an historical cohort. Cases were 150 individuals with elevated carotid intimal-medial thickness measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities Study (1987-92). Controls were 150 age-gender-matched individuals with low carotid intimal-medial thickness. Serum antioxidant vitamins, uric acid, and serum total antioxidant capacity were measured in frozen serum samples collected from the same individuals in 1974 (13-15 years prior to the determination of case-control status). Compared to controls, atherosclerosis cases had significantly higher levels of serum total antioxidant capacity in 1974 than controls. This difference was almost entirely explained by increased serum concentration of uric acid in cases. In contrast with cross-sectional results, uric acid serum concentration in 1974, was significantly higher in cases than in controls, even after adjusting for the main cardiovascular risk factors. Cases had significantly lower levels of alpha-carotene in the 1974 sera than controls, but no other differences in serum antioxidant vitamin concentrations were observed. The higher serum uric acid concentration seemed associated with elevated total serum antioxidant capacity among individuals with atherosclerosis. This finding is consistent with experimental evidence suggesting that hyperuricemia may be a compensatory mechanism to counteract oxidative damage related to atherosclerosis and aging in humans.

Low cholesteryl ester transfer protein (CETP) concentration but normal CETP activity in serum from patients with short-term hypothyroidism Lack of relationship to lipoprotein abnormalities.

PubMed

Dedecjus, Marek; Masson, David; Gautier, Thomas; de Barros, Jean-Paul Pais; Gambert, Philippe; Lewinski, Andrzej; Adamczewski, Zbigniew; Moulin, Philippe; Lagrost, Laurent

2003-05-01

Hypothyroidism is associated with a number of abnormalities in lipoprotein metabolism. Although alterations in neutral lipid exchanges among plasma lipoproteins might be one characteristic feature of hypothyroidism, a few human studies of cholesteryl ester transfer protein (CETP) activity have led to heterogeneous and fragmentary observations. The aim of the present study was to analyse the influence of short-term hypothyroidism on CETP activity, as well as on the structure and composition of lipoproteins. PATIENTS, DESIGN AND MEASUREMENTS: Sixty-six thyroidectomized patients were withdrawn from L-thyroxine (L-T4) treatment for 5 weeks. Subsequently, L-T4 therapy was reinstated for 2 months and patients were compared to 61 matched normolipidaemic controls. Serum CETP activity and mass concentration, serum lipids, apolipoproteins and lipoprotein size distribution were determined in the three groups. Serum CETP mass concentration was significantly decreased in short-term hypothyroid patients, as compared to control subjects (3.22 +/- 0.98 vs. 3.79 +/- 1.2 mg/l, respectively; P < 0.001), and the values were normalized during L-T4 therapy. The ability of endogenous serum lipoproteins to interact with CETP was normal in short-term hypothyroid patients. Concordant observations were made regardless of whether neutral lipid transfers were measured from high-density lipoproteins (HDL) toward apo B-containing lipoproteins or from liposomes toward HDL. The size distribution of HDL was significantly different in short-term hypothyroid patients, compared to either the control or treated subgroups, with significant higher proportions of large-sized HDL2b and HDL2a (HDL2b: 13.6 +/- 6.5% before vs. 8.5 +/- 4.2% during L-T4 therapy, P < 0.05; HDL2a, 33.0 +/- 7.0% before vs. 29.3 +/- 6.9% during L-T4 therapy, P < 0.05). Although serum CETP mass concentration correlated negatively with the HDL2 to HDL3 ratio in control subjects (r = -0.588; P < 0.0001), no significant correlations

High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.

PubMed

Persson, G Rutger; Pettersson, Thomas; Ohlsson, Ola; Renvert, Stefan

2005-03-01

Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels. To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63). hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied. Subjects with AMI had higher hsC-rp levels than control subjects (p<0.001, Mann-Whitney U-test). The odds that subjects in the control group with periodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, p<0.05). Stepwise linear regression analysis failed to include periodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, p<0.001). Serum WBC counts were significantly higher in control subjects with periodontitis (p<0.03) but not in subjects in the AMI group (p<0.57). (1) As expected, elevated serum hsC-rp concentration and serum WBC counts are associated with acute coronary heart disease. (2) Elevated serum hsC-rp values are associated with radiographically defined periodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model. Copyright 2005 Blackwell Munksgaard.

A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer.

PubMed

Borniger, Jeremy C; Walker Ii, William H; Surbhi; Emmer, Kathryn M; Zhang, Ning; Zalenski, Abigail A; Muscarella, Stevie L; Fitzgerald, Julie A; Smith, Alexandra N; Braam, Cornelius J; TinKai, Tial; Magalang, Ulysses J; Lustberg, Maryam B; Nelson, Randy J; DeVries, A Courtney

2018-05-14

We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. We used a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

Idiopathic liver function test abnormality in pregnancy is associated with assisted reproduction techniques.

PubMed

Kopylov, Uri; Avidan, Benjamin; Papageorgiou, Neofytos P; Katz, Lior H; Sivan, Eyal; Zimlichman, Eyal; Hussein, Haya; Maor, Yaakov

2013-02-01

To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality. A retrospective case-control study using an electronic database and patients' files. Tertiary referral center. Women in the third trimester of pregnancy who were hospitalized for delivery. None. Development of significant elevation of alanine aminotransferase (ALT ≥ 100 IU/L). Secondary outcomes included development of maternal and fetal complications. The upper limit of normal of ALT was ≥ 1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥ 100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥ 100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications. A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

miR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

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

Wang, Baocan; Li, Wenxi; Guo, Kun

2012-04-27

Highlights: Black-Right-Pointing-Pointer miR-181a and miR-181b, especially, miR-181b could be induced by transforming growth factor-beta 1 (TGF-{beta}1) in hepatic stellate cells. Black-Right-Pointing-Pointer miR-181b could promote HSC-T6 cell proliferation by directly targeting the negative cell regulator-p27 in HSC-T6 cell. Black-Right-Pointing-Pointer miR-181b was identified as potential serum diagnostic marker for liver cirrhosis patients. -- Abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because ofmore » the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-{beta}1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-{beta}1 pathway by a currently unknown mechanism.« less

Viscous Energy Loss in the Presence of Abnormal Aortic Flow

PubMed Central

Barker, A.J.; van Ooij, P.; Bandi, K.; Garcia, J.; Albaghdadi, M.; McCarthy, P.; Bonow, R. O.; Carr, J.; Collins, J.; Malaisrie, C.; Markl, M.

2014-01-01

Purpose To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses, and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Methods 4D flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n=12, age=37±10), patients with aortic dilation (n=16, age=52±8), and patients with aortic valve stenosis matched for age and aortic size (n=14, age=46±15), using a relationship between the 3D velocity field and viscous energy dissipation. Results Viscous energy loss was significantly elevated in the thoracic aorta for patients with dilated aorta (3.6±1.3 mW, p=0.024) and patients with aortic stenosis (14.3±8.2 mW, p<0.001) compared to healthy volunteers (2.3±0.9 mW). The same pattern of significant differences were seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2±1.1 mW, p=0.021) and patients with aortic stenosis (10.9±6.8 mW, p<0.001) were elevated compared to healthy volunteers (1.2±0.6 mW). Conclusion This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow. PMID:24122967

Function of Serum Complement in Drinking Water Arsenic Toxicity

PubMed Central

Islam, Laila N.; Zahid, M. Shamim Hasan; Nabi, A. H. M. Nurun; Hossain, Mahmud

2012-01-01

Serum complement function was evaluated in 125 affected subjects suffering from drinking water arsenic toxicity. Their mean duration of exposure was 7.4 ± 5.3 yrs, and the levels of arsenic in drinking water and urine samples were 216 ± 211 and 223 ± 302 μg/L, respectively. The mean bactericidal activity of complement from the arsenic patients was 92% and that in the unexposed controls was 99% (P < 0.01), but heat-inactivated serum showed slightly elevated activity than in controls. In patients, the mean complement C3 was 1.56 g/L, and C4 was 0.29 g/L compared to 1.68 g/L and 0.25 g/L, respectively, in the controls. The mean IgG in the arsenic patients was 24.3 g/L that was highly significantly elevated (P < 0.001). Arsenic patients showed a significant direct correlation between C3 and bactericidal activity (P = 0.014). Elevated levels of C4 indicated underutilization and possibly impaired activity of the classical complement pathway. We conclude reduced function of serum complement in drinking water arsenic toxicity. PMID:22545044

Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

PubMed Central

Chan, Te-Fu; Lin, Wei-Ting; Chen, Yi-Ling; Huang, Hsiao-Ling; Yang, Wei-Zeng; Lee, Chun-Ying; Chen, Meng-Hsueh; Wang, Tsu-Nai; Huang, Meng-Chuan; Chiu, Yu-Wen; Huang, Chun-Chi; Tsai, Sharon; Lin, Chih-Lung; Lee, Chien-Hung

2014-01-01

Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r = 0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4. PMID:24475021

Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

PubMed Central

Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

2016-01-01

Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

[Regression analysis of serum bone metabolic markers and traditional Chinese medicine syndromes in patients with CKD-MBD].

PubMed

Yang, Hai-Ming; Meng, Xian-Jie; Wu, Wei; Liu, Ying-Lu; Zhai, Xiao-Juan

2017-10-01

To analyze the interdependent relationship between serum bone metabolic markers and traditional Chinese medicine (TCM) syndromes in patients with chronic kidney disease (stages 3 and 4)-related mineral and bone disorder (CKD-MBD), in order to provide the objective basis for exploring the rules of TCM syndrome differentiation in patients with CKD-MBD. The retrospective survey was conducted to collect 105 cases with CKD (stages 3 and 4)-MBD. General clinical indexes, frequency of TCM syndromes and distribution of TCM syndrome type were investigated. Furthermore, serum bone metabolic markers, including calcium (Ca2+), phosphonium (P3+), intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), procollagen type 1 amino-N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) were analyzed, respectively. Meanwhile, bone mineral density (BMD) was assessed. And then, the multivariate regression analysis was performed for serum bone metabolic markers and TCM syndromes. The results showed that the general clinical features of the 105 patients included old age, hypertension, fracture, loss of bone mass and mild abnormalities of serum bone metabolic markers. High-frequency TCM syndromes were related to Yang deficiency in Spleen and Kidney, Qi deficiency in Spleen and Kidney and blood stasis. Moreover, Yang deficiency in Spleen and Kidney and blood stasis were found as the most frequent characteristics of the distribution of TCM syndromes type. The clinical characteristics of patients with the syndrome type of Yang deficiency in Spleen and Kidney were probably old age, increase in TCM syndrome scores and abnormalities in iPTH and P1NP. In addition, the interdependent relationship between abnormality in Ca2+ and syndromes of hair loss, tooth shake and sexual dysfunction, abnormality in P3+ and syndromes of aches in waist and knees, abnormality in iPTH and syndromes of soreness and weakness in waist and knees, lassitude, fatigue and extreme chilliness, abnormality in ALP and

Elevated TGF β2 serum levels in Emery-Dreifuss muscular dystrophy: implications for myocyte and tenocyte differentiation and fibrogenic processes.

PubMed

Bernasconi, Pia; Carboni, Nicola; Ricci, Giulia; Siciliano, Gabriele; Politano, Luisa; Maggi, Lorenzo; Mongini, Tiziana; Vercelli, Liliana; Rodolico, Carmelo; Biagini, Elena; Boriani, Giuseppe; Ruggiero, Lucia; Santoro, Lucio; Schena, Elisa; Prencipe, Sabino; Evangelisti, Camilla; Pegoraro, Elena; Morandi, Lucia; Columbaro, Marta; Lanzuolo, Chiara; Sabatelli, Patrizia; Cavalcante, Paola; Cappelletti, Cristina; Bonne, Gisèle; Muchir, Antoine; Lattanzi, Giovanna

2018-04-25

Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF β2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF β2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss muscular dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF β2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF β2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF β2-dependent mechanisms were also determined in laminopathic cells, where TGF β2 activated AKT/mTOR phosphorylation. These data show that TGF β2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.

A patient with serum creatinine of 61 mg/dl

PubMed Central

Sriram, S.; Srinivas, S.; Naveen, P. S. R.

2017-01-01

Spurious elevation of serum creatinine by Jaffe assay is known to occur due to a variety of substances. This results in subjecting the patient to invasive and complicated procedures such as dialysis. We report a rare case of false elevation of this renal parameter following exposure to an organic solvent. PMID:28182048

Is abnormal liver function correlated with food sensitisation in adults? US NHANES, 2005-2006.

PubMed

Shiue, I

2015-01-01

Associations between liver function and serum IgE levels have recently been observed in children. However, the relationship in adults is unclear. Therefore, it was aimed to study associations of liver function and serum total and food-specific IgE concentrations in a national and population-based study. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2005-2006 including demographics, liver status tests, biomarkers, lifestyle factors, and serum total and food-specific IgE concentrations. Participants aged 20 and above were included. Analyses included t-test, chi-square test, and survey-weighted regression modelling. After adjusting for age, sex, ethnicity, vitamin D, waist circumference, family poverty income ratio, total cholesterol, ever asthma, total protein, and survey weighting, abnormal gamma glutamyl transpeptidase was significantly associated with food sensitisation (peanut: OR 2.17, 95%CI 1.60-2.94, P<0.001; egg: OR 2.55, 95%CI 1.32-4.90, P=0.008; milk: OR 2.59, 95%CI 1.56-4.31, P=0.001; shrimp: OR 1.81, 95%CI 1.29-2.55, P=0.002). Moreover, both abnormal albumin and alanine transaminase were associated with egg sensitisation (OR 1.96, 95%CI 1.12-3.43, P=0.022 and OR 2.06, 95%CI 1.04-4.09, P=0.040, respectively). Abnormal liver status tests were correlated with serum food-specific IgE concentrations in adults. Future research with longitudinal design or in clinical settings may be warranted confirming or refuting the observations made in the present epidemiological study. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

Factors associated with serum thyroglobulin levels in a population living in Belarus

PubMed Central

Cahoon, Elizabeth K; Rozhko, Alexander; Hatch, Maureen; Polyanskaya, Olga; Ostroumova, Evgenia; Tang, Min; Nadirov, Eldar; Yauseyenka, Vasilina; Savasteeva, Irina; McConnell, Robert J; Pfeiffer, Ruth M; Brenner, Alina V

2013-01-01

SUMMARY Objective Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to socio-demographic characteristics, iodine status, and thyroid function for individuals exposed to I-131. Design A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data, and physiological measurements. Participants Our analytic sample included 10,344 subjects of whom 7,890 had no thyroid disease and 2,454 had evidence of structural or functional thyroid abnormality. Measurements Standardized assays were used to measure serum Tg, urinary iodine, TSH, and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume. Results In the fully adjusted model, percent change in Tg was significantly increased among females, smokers, and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (p-values for trend < 0.0001), and presence of thyroid nodules (p < 0.05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities, and serum Tg (p < 0.0001). Conclusions In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study. PMID:23190420

Serum microRNA biomarker identification in a residential cohort with elevated polychlorinated biphenyl exposures

EPA Science Inventory

Exposure to liver toxicants can result in or exacerbate fatty liver disease. Recent evidence suggests that serum-derived microRNAs (miRs) may improve identification of chemical-induced fatty liver disease relative to traditional protein-based biomarkers alone. Historical serum sa...

Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease.

PubMed

Sin, Don D; Miller, Bruce E; Duvoix, Annelyse; Man, S F Paul; Zhang, Xuekui; Silverman, Edwin K; Connett, John E; Anthonisen, Nicholas A; Wise, Robert A; Tashkin, Donald; Celli, Bartolome R; Edwards, Lisa D; Locantore, Nicholas; Macnee, William; Tal-Singer, Ruth; Lomas, David A

2011-05-01

There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.

Factors contributing to the development of overt encephalopathy in liver cirrhosis patients.

PubMed

Iwasa, Motoh; Sugimoto, Ryosuke; Mifuji-Moroka, Rumi; Hara, Nagisa; Yoshikawa, Kyoko; Tanaka, Hideaki; Eguchi, Akiko; Yamamoto, Norihiko; Sugimoto, Kazushi; Kobayashi, Yoshinao; Hasegawa, Hiroshi; Takei, Yoshiyuki

2016-10-01

The aim of this study was to clarify the relationships among psychometric testing results, blood ammonia (NH3) levels, electrolyte abnormalities, and degree of inflammation, and their associations with the development of overt hepatic encephalopathy (HE) in liver cirrhosis (LC) patients. The relationships between covert HE and blood NH3, sodium (Na), and C-reactive protein (CRP) were examined in 40 LC patients. The effects of elevated NH3, hyponatremia, and elevated CRP on the development of overt HE were also investigated. The covert HE group had significantly lower serum Na levels and significantly higher serum CRP levels. During the median observation period of 11 months, 10 patients developed overt HE, and the results of multivariate analysis showed that covert HE and elevated blood NH3 were factors contributing to the development of overt HE. Electrolyte abnormalities and mild inflammation are involved in the pathogenesis of HE. Abnormal psychometric testing results and hyperammonemia are linked to subsequent development of overt HE.

Serum Free Light Chain Assay and κ/λ Ratio Performance in Patients Without Monoclonal Gammopathies:  High False-Positive Rate.

PubMed

Singh, Gurmukh

2016-08-01

Serum free light chain assay is a recommended screening test for monoclonal gammopathies. Anecdotal observations indicated a high rate of false-positive abnormal κ/λ ratios. This study was undertaken to ascertain the magnitude of the false-positive rate and factors contributing to the error rate. Results of serum protein electrophoresis, serum free light chains, and related tests, usually done for investigation of suspected monoclonal gammopathy, were reviewed retrospectively for 270 patients and 297 observations. Using the conventional κ/λ ratio, 36.4% of the ratios were abnormal, in the absence of monoclonal gammopathy. When the renal κ/λ ratio was used, the rate of abnormal κ/λ ratios was 30.1%. In patients with a γ-globulin concentration of 1.6 g/dL or more, the usual κ/λ ratio was abnormal in 54.8% of the patients. Urine protein electrophoresis was used in 53 (19.6%) instances, whereas bone marrow examination was done in 65 (24.1%) cases. Usual κ/λ ratio was abnormal in 36.4% of the observations in patients without evidence of monoclonal gammopathy, and an abnormal κ/λ ratio should not be used as the sole indicator for diagnosis of neoplastic proliferation of the lympho-plasmacytic system. Hypergammaglobulinemia is associated with a higher rate of false-positive abnormal κ/λ ratios. Examination of urine for monoclonal immunoglobulins may be underused, and recommendations by some to use serum free light chain assay in place of, rather than as an adjunct to, urine electrophoresis are not warranted. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

PubMed Central

Olivier, Alicia K.; Yi, Yaling; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Hu, Shanming; Xie, Weiliang; Fisher, John T.; Keiser, Nicholas W.; Lei, Diana; Zhou, Weihong; Yan, Ziying; Li, Guiying; Evans, Turan I.A.; Meyerholz, David K.; Wang, Kai; Stewart, Zoe A.; Norris, Andrew W.; Engelhardt, John F.

2012-01-01

Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. PMID:22996690

ABNORMAL ALDOSTERONE PHYSIOLOGY AND CARDIO-METABOLIC RISK FACTORS

PubMed Central

Vaidya, Anand; Underwood, Patricia C.; Hopkins, Paul N.; Jeunemaitre, Xavier; Ferri, Claudio; Williams, Gordon H.; Adler, Gail K.

2013-01-01

Abnormal aldosterone physiology has been implicated in the pathogenesis of cardio-metabolic diseases. Single aldosterone measurements capture only a limited range of aldosterone physiology. New methods of characterizing aldosterone physiology may provide a more comprehensive understanding of its relationship with cardio-metabolic disease. We evaluated whether novel indices of aldosterone responses to dietary sodium modulation, the Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI for serum and SAUSSI for urine), could predict cardio-metabolic risk factors. We performed cross-sectional analyses on 539 subjects studied on liberal (LIB) and restricted (RES) sodium diets with serum and urinary aldosterone measurements. SASSI and SAUSSI were calculated as the ratio of aldosterone on LIB (maximally suppressed aldosterone) to aldosterone on RES (stimulated aldosterone) diets, and associated with risk factors using adjusted regression models. Cardio-metabolic risk factors associated with either impaired suppression of aldosterone on LIB diet, or impaired stimulation on RES diet, or both; in all of these individual cases, these risk factors associated with higher SASSI or SAUSSI. In the context of abnormalities that comprise the metabolic syndrome (MetS), there was a strong positive association between the number of MetS components (0–4) and both SASSI and SAUSSI (P<0.0001) that was independent of known aldosterone secretagogues (angiotensin II, corticotropin, potassium). SASSI and SAUSSI exhibited a high sensitivity in detecting normal individuals with zero MetS components (86% for SASSI and 83% for SAUSSI). Assessing the physiologic range of aldosterone responses may provide greater insights into adrenal pathophysiology. Dysregulated aldosterone physiology may contribute to, and/or result from, early cardio-metabolic abnormalities. PMID:23399714

[Serum glycosaminoglycans in Graves' disease patients].

PubMed

Winsz-Szczotka, Katarzyna B; Olczyk, Krystyna Z; Koźma, Ewa M; Komosińska-Vassev, Katarzyna B; Wisowski, Grzegorz R; Marcisz, Czesław

2006-01-01

The aim of the study was to determine the blood serum sulfated glycosaminoglycans (GAGs) and hyaluronic acid (HA) concentration of Graves' disease patients before treatment and after attainment of the euthyroid state. The study was carried out on the blood serum obtained from 17 patients with newly recognised Graves' disease and from the same patients after attainment of the euthyroid state. Graves' patients had not any clinical symptoms neither of ophthalmopathy nor pretibial myxedema. GAGs were isolated from the blood serum by the multistage extraction and purification using papaine hydrolysis, alkali elimination, as well as cetylpyridium chloride binding. Total amount of GAGs was quantified by the hexuronic acids assay. HA content in obtained GAGs sample was evaluated by the ELISA method. Increased serum concentration of sulfated GAGs in non-treated Graves' disease patients was found. Similarly, serum HA level in untreated patients was significantly elevated. The attainment of euthyroid state was accompanied by the decreased serum sulfated GAGs level and by normalization of serum HA concentration. In conclusion, the results obtained demonstrate that the alterations of GAGs metabolism connected with Graves' disease can lead to systemic changes of the extracellular matrix properties.

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.

A lack of association between hyperserotonemia and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children

PubMed Central

2011-01-01

Background One of the most consistent biological findings in autism is the elevated blood serotonin levels. Immune abnormalities, including autoimmunity with production of brain specific auto-antibodies, are also commonly observed in this disorder. Hyperserotonemia may be one of the contributing factors to autoimmunity in some patients with autism through the reduction of T-helper (Th) 1-type cytokines. We are the first to investigate the possible role of hyperserotonemia in the induction of autoimmunity, as indicated by serum anti-myelin-basic protein (anti-MBP) auto-antibodies, in autism. Methods Serum levels of serotonin and anti-MBP auto-antibodies were measured, by ELISA, in 50 autistic patients, aged between 5 and 12 years, and 30 healthy-matched children. Results Autistic children had significantly higher serum levels of serotonin and anti-MBP auto-antibodies than healthy children (P < 0.001 and P < 0.001, respectively). Increased serum levels of serotonin and anti-MBP auto-antibodies were found in 92% and 80%, respectively of autistic patients. Patients with severe autism had significantly higher serum serotonin levels than children with mild to moderate autism (P < 0.001). Serum serotonin levels had no significant correlations with serum levels of anti-MBP auto-antibodies in autistic patients (P = 0.39). Conclusions Hyperserotonemia may not be one of the contributing factors to the increased frequency of serum anti-MBP auto-antibodies in some autistic children. These data should be treated with caution until further investigations are performed. However, inclusion of serum serotonin levels as a correlate may be useful in other future immune studies in autism to help unravel the long-standing mystery of hyperserotonemia and its possible role in the pathophysiology of this disorder. PMID:21696608

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.

The Effects of Curcumin and Curcumin-Phospholipid Complex on the Serum Pro-oxidant-Antioxidant Balance in Subjects with Metabolic Syndrome.

PubMed

Ghazimoradi, Maryam; Saberi-Karimian, Maryam; Mohammadi, Farzane; Sahebkar, Amirhossein; Tavallaie, Shima; Safarian, Hamideh; Ferns, Gordon A; Ghayour-Mobarhan, Majid; Moohebati, Mohsen; Esmaeili, Habibollah; Ahmadinejad, Malihe

2017-11-01

Metabolic syndrome (MetS) is defined by a clustering of metabolic and anthropometric abnormalities and is associated by an increased risk of cardiovascular disease. We have investigated the effect of curcumin supplementation on the serum pro-oxidant-antioxidant balance (PAB) in patients with MetS. This double-blind, randomized, placebo-controlled trial was conducted over 6 weeks. Subjects (n = 120) were randomly allocated to one of three groups (curcumin, phospholipidated curcumin, and placebo). The curcumin group received 1 g/day of simple curcumin, the phospholipidated curcumin group received 1 g/day of phospholipidated curcumin (containing 200 mg of pure curcumin), and the control group received 1 g/day of placebo. Serum PAB was measured before and after the intervention (at baseline and at 6 weeks). Data analyses were performed using spss software (version 16.0). Serum PAB increased significantly in the curcumin group (p < 0.001), but in the phospholipidated curcumin group, elevation of PAB level was not significant (p = 0.053). The results of our study did not suggest any improvement of PAB following supplementation with curcumin in MetS subjects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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.

Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level.

PubMed

Zheng, Qin; Zhou, Feifei; Cui, Xinyuan; Liu, Mulin; Li, Yulin; Liu, Shuai; Tan, Jichun; Yan, Qiu

2018-01-01

Polycystic ovary syndrome (PCOS), characterized by female infertility and metabolic abnormalities, is one of the most common endocrine disorders. The etiology of PCOS remains unknown. The comprehensive analysis of protein alterations in PCOS patients is meaningful for identifying diagnostic biomarkers of PCOS. Here, we explored the clinical value of serum proteins as novel biomarkers to detect PCOS with low progesterone level. A total of 43 patients with PCOS and 30 healthy women were enrolled. Protein array was used to detect the variations of serum proteins between PCOS patients and healthy women. The level of five serum proteins was further confirmed by ELISA and western blot. The human ovarian granulosa cells (KGN) was cultured to examine the underlying mechanism of PCOS. CCK8 assay and western blot were carried out to evaluate the alterations in proliferative ability, TUNEL assay and DAPI staining to detect the apoptosis of KGN cells. Among the 507 proteins, we identified 76 differentially expressed serum proteins (≧1.5 fold), with 40 elevated and 36 decreased proteins. Moreover, 47 proteins were newly reported in PCOS. The alterations in the five significantly decreased proteins (EREG, inhibin βA, IDE, PDGF-D and KNG1) were further confirmed by ELISA and western blot. The level of these proteins were directly associated with the low progesterone, and the expression could be upregulated by progesterone. EREG and inhibin βA also promoted the proliferation and inhibited the apoptosis of ovarian granulosa cells. The study highlights that serum proteins are differentially expressed in PCOS patients and healthy women, and EREG and inhibin βA levels are upregulated by progesterone, which are correlated with ovarian functions. The study suggests that EREG and inhibin βA may be applied as novel potential biomarkers for PCOS with low progesterone level. © 2018 The Author(s). Published by S. Karger AG, Basel.

Pretreatment with human serum butyrylcholinesterase alone prevents cardiac abnormalities, seizures, and death in Göttingen minipigs exposed to sarin vapor.

PubMed

Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

2011-12-15

Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a prophylactic countermeasure against organophosphorus nerve agents. This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed blood gas and acid-base disturbances and the onset of cardiac and neural toxic signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu BChE, however, completely prevented toxic signs, with blood chemistry and ECG and EEG parameters indistinguishable from control during and after GB exposure. GB bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased survivability, but also prevented cardiac abnormalities and neural toxicity in minipigs exposed to a lethal dose of GB vapor. Published by Elsevier Inc.

Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin.

PubMed

Morfeld, Kari A; Brown, Janine L

2016-04-01

The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

NASA Technical Reports Server (NTRS)

Spatz, J. M.; Fields, E. E.; Yu, E. W.; Divieti, Pajevic P.; Bouxsein, M. L.; Sibonga, M. L.; Zwart, S. R.; Smith, S. M.

2011-01-01

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin

Gross placental morphology and foal serum biochemistry as predictors of foal health.

PubMed

Pirrone, A; Antonelli, C; Mariella, J; Castagnetti, C

2014-06-01

The aim of this study was to verify if changes in blood glucose, creatinine, urea, and fibrinogen concentrations evaluated at birth reflect gross placenta abnormalities, and are useful to identify foals that suffered from placental dysfunction. A total of 92 mares were included in the present study: 68 delivered healthy foals and they were included in group 1; 24 delivered sick foals and they were included in group 2. In group 2, foals' clinical diagnoses included perinatal asphyxia syndrome (PAS; n = 20) and prematurity and/or dysmaturity (n = 4). The proportion of sick foals was greater when placental abnormalities were observed (χ(2) [1, n = 89] = 5.00; P = 0.025). Serum creatinine concentration at birth was higher in sick than in healthy foals (P = 0.003), and blood glucose concentrations at birth was smaller in sick than in healthy foals (P = 0.007). No difference was found in blood chemistry results between survivors and nonsurvivors of group 2. Serum creatinine concentration was higher in foals born from grossly abnormal than in foals born from grossly normal placenta (P = 0.029), and it was higher in foals affected by PAS (311.17 μmol/L) than in healthy foals (238.24 μmol/L) (P = 0.004). In a clinical setting, serum creatinine and blood glucose concentrations should be evaluated at birth, particularly in foals born from grossly abnormal placenta. The association of clinical and laboratory data could be particularly important to promptly identify and treat foals with a higher risk to develop PAS. Copyright © 2014 Elsevier Inc. All rights reserved.

Serum levels of innate immunity cytokines are elevated in dogs with metaphyseal osteopathy (hypertrophic osteodytrophy) during active disease and remission.

PubMed

Safra, Noa; Hitchens, Peta L; Maverakis, Emanual; Mitra, Anupam; Korff, Courtney; Johnson, Eric; Kol, Amir; Bannasch, Michael J; Pedersen, Niels C; Bannasch, Danika L

2016-10-15

Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multifocal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children. Copyright © 2016 Elsevier B.V. All rights reserved.

Elevated serum levels of endothelin-1 in patients with chronic inflammatory demyelinating polyneuropathy.

PubMed

Chang, Chun-Wei; Wu, Hsiu-Chuan; Lyu, Rong-Kuo; Lo, Yen-Shi; Chen, Chiung-Mei; Ro, Long-Sun; Chang, Hong-Shiu; Huang, Ching-Chang; Liao, Ming-Feng; Wu, Yih-Ru; Kuo, Hung-Chou; Chu, Chun-Che; Weng, Yi-Ching; Wei, Pei-Tsi; Lo, Ai-Lun; Chang, Kuo-Hsuan

2018-01-01

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, or non-hereditary, chronic demyelinating neuropathy. Currently, there is no reliable molecular biomarker that can identify CIDP patients as well as monitor disease severity. We measured serum levels of endothelin-1 (ET-1), a factors involved in vasoconstrictive, inflammatory and nerve regenerative processes, in 20 CIDP, 21 acute inflammatory demyelinating polyneuropathy (AIDP), 37 multiple sclerosis (MS), and 10 Alzheimer's disease (AD) patients, as well as 26 healthy control (HC) subjects. Patients with CIDP demonstrated higher serum levels of ET-1 (2.07±1.07pg/mL) than those with AIDP (0.75±0.62ng/mL, P<0.001), AD (0.78±0.49pg/mL, P<0.001), as well as HCs (1.16±0.63pg/mL, P=0.002), while levels of ET-1 in patients with MS (2.10±0.81pg/mL) and CIDP were similar. Furthermore, the serum ET-1 levels significantly correlated with Inflammatory Neuropathy Cause And Treatment (INCAT) disability scale in CIDP patients. Receiver operating characteristic (ROC) curve showed good discrimination ability for ET-1 to distinguish CIDP patients from AIDP (AUC=0.883) or HCs (AUC=0.763). This study discloses the potential of serum ET-1 as a biomarker for CIDP. Copyright © 2017 Elsevier B.V. All rights reserved.

[Electrocardiographic abnormalities in acute olanzapine poisonings].

PubMed

Ciszowski, Krzysztof; Sein Anand, Jacek

2011-01-01

Olanzapine is an atypical antipsychotic used for many years in the treatment of schizophrenia and bipolar disorder. Poisonings with this medicine can results with cardiotoxic effects in the form of ECG abnormalities. To evaluate the nature and incidence of electrocardiographic abnormalities in patients with acute olanzapine poisoning. 23 adult (mean age 38.4 +/- 15.5 years) patients with acute olanzapine poisoning, including 10 men (30.4 +/- 8.1 years) and 11 women (45.7 +/- 17.2 years), where 1 man and 1 woman were poisoned twice. The toxic serum level of olanzapine (above 100 ng/mL) was confirmed in each patient. Evaluation of electrocardiograms performed in patients in the first day of hospitalization with automatic measurement of durations of PQ, QRS and QTc and the identification of arrhythmias and conduction disorders on the basis of visual analysis of the ECG waveforms. Statistical analysis of the results using the methods of descriptive statistics. The mean durations of PQ, QRS and QTc in the study group were as follows: 135 +/- 23 ms, 91 +/- 12 ms, and 453 +/- 48 ms, respectively. The most common ECG abnormalities were prolonged QTc and supraventricular tachycardia (including sinus tachycardia) - each 22%; less common were ST-T changes (17%) and supraventricular premature complexes (9%), and only in individual cases (4%) ventricular premature complexes, bundle branch block, sinus bradycardia and atrial fibrillation were present. In the course of acute olanzapine poisonings: (1) prolonged QTc interval is quite common, but rarely leads to torsade de pointes tachycardia; (2) fast supraventricular rhythms are also common, but rarely cause irregular tachyarrhythmias, eg. atrial fibrillation; (3) conduction disorders (atrioventricular blocks, bundle branch blocks) are not typical abnormalities; (4) the observed ECG abnormalities emphasize the need of continuous ECG monitoring in these patients.

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.

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.

Serum Levels of IGF-1 and IGFBP-3 in Relation to Clinical and Pathobiological Aspects of Head and Neck Squamous Cell Carcinomas.

PubMed

Kalfert, David; Ludvikova, Marie; Topolcan, Ondrej; Celakovsky, Petr; Kucera, Radek; Windrichova, Jindra; Ludvik, Jaroslav; Skalova, Katerina; Kulda, Vlastimil; Pesta, Martin; Plzak, Jan

2017-06-01

Head and neck squamous cell carcinoma (HNSCC) includes tumors of various anatomical sites sharing multifactorial etiopathogenesis and generally dismal response to conventional treatment. The objective of this study was to determine the clinical significance of serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) in HNSCC. A total of 46 patients, with histologically-confirmed diagnosis of HNSCC (21 oropharyngeal, 21 laryngeal, and 4 hypopharyngeal cancers) were enrolled in this study. IGF-1 and IGFBP-3 serum levels were measured by an immunoradiometric assay using commercial kits. The adjustment of serum levels at 60 years of age was performed. Significant differences were found in IGF-1 serum concentrations between patients with p16 positive and p16 negative HNSCC (p=0.0062), with higher IGF-1 levels in p16 positive tumors, between low-grade and high-grade cancers (p=0.0323) only in larynx, with elevated IGF-1 concentrations associated with high-grade and between recurrent and non-recurrent HNSCC (p=0.0354), with lower IGF-1 levels in recurrent tumors. The conflicting results of this study may reflect some abnormality of IGF axis regulation in HNSCC, as well as the influence of other etiological factors (e.g. smoking, HPV infection). Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Acid-base and hormonal abnormalities in dogs with naturally occurring diabetes mellitus.

PubMed

Durocher, Lawren L; Hinchcliff, Kenneth W; DiBartola, Stephen P; Johnson, Susan E

2008-05-01

To examine acid-base and hormonal abnormalities in dogs with diabetes mellitus. Cross-sectional study. 48 dogs with diabetes mellitus and 17 healthy dogs. Blood was collected and serum ketone, glucose, lactate, electrolytes, insulin, glucagon, cortisol, epinephrine, norepinephrine, nonesterified fatty acid, and triglyceride concentrations were measured. Indicators of acid-base status were calculated and compared between groups. Serum ketone and glucose concentrations were significantly higher in diabetic than in healthy dogs, but there was no difference in venous blood pH or base excess between groups. Anion gap and strong ion difference were significantly higher and strong ion gap and serum bicarbonate concentration were significantly lower in the diabetic dogs. There were significant linear relationships between measures of acid-base status and serum ketone concentration, but not between measures of acid-base status and serum lactate concentration. Serum insulin concentration did not differ significantly between groups, but diabetic dogs had a wider range of values. All diabetic dogs with a serum ketone concentration > 1,000 micromol/L had a serum insulin concentration < 5 microU/mL. There were strong relationships between serum ketone concentration and serum glucagon-insulin ratio, serum cortisol concentration, and plasma norepinephrine concentration. Serum beta-hydroxybutyrate concentration, expressed as a percentage of serum ketone concentration, decreased as serum ketone concentration increased. Results suggested that ketosis in diabetic dogs was related to the glucagon-insulin ratio with only low concentrations of insulin required to prevent ketosis. Acidosis in ketotic dogs was attributable largely to high serum ketone concentrations.

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

Serum Analysis of Tryptophan Catabolism Pathway: Correlation with Crohn’s Disease Activity

PubMed Central

Gupta, Nitin K; Thaker, Ameet I; Kanuri, Navya; Riehl, Terrence E; Rowley, Christopher W; Stenson, William F; Ciorba, Matthew A

2011-01-01

BACKGROUND Indoleamine 2,3 dioxygenase 1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn’s disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine. METHODS Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by physician’s global assessment. Serum tryptophan and kynurenine were measured by high pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks. RESULTS 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. CONCLUSIONS IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity. PMID:21823214

Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma.

PubMed

Fu, Yucheng; Lan, Tao; Cai, Hongliu; Lu, Anwei; Yu, Wei

2018-05-01

A large number of studies have reported the relationships between serum lactate dehydrogenase (LDH) and prognosis of osteosarcoma. However, the result is still controversial and no consensus has been reached. Therefore, we performed a meta-analysis to evaluate the prognostic role of serum LDH in osteosarcoma patients. We performed the systematic computerized search for eligible articles from PubMed, Embase, and Cochrane databases until December 21, 2017. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) of overall survival (OS) and event-free survival (EFS) were obtained to assess the prognostic value of serum LDH. A total of 18 studies with 2543 osteosarcoma patients were included. Overall, 15 studies assessed the elevated serum LDH level on OS and the pooled HR was 1.87 (95% CI = 1.58-2.20). Meanwhile, the pooled HR to evaluate the relationship between serum LDH and EFS in 9 studies was 1.78 (95% CI = 1.51-2.10). The same results were acquired when these studies were stratified by Enneking stage, geographic region, and sample size. No heterogeneity existed between these subgroups (P > .05). Begg's funnel plot and Egger's test (OS: P = .04; EFS: P = .34) showed that possible publication bias might exist in OS studies. Sensitivity analysis suggested the pooled HR was robust. This meta-analysis demonstrates that elevated serum LDH level is apparently associated with lower EFS rate and serum LDH could be a prognostic biomarker for osteosarcoma patients.

Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism.

PubMed

Nir, I; Meir, D; Zilber, N; Knobler, H; Hadjez, J; Lerner, Y

1995-12-01

An abnormal circadian pattern of melatonin was found in a group of young adults with an extreme autism syndrome. Although not out of phase, the serum melatonin levels differed from normal in amplitude and mesor. Marginal changes in diurnal rhythms of serum TSH and possibly prolactin were also recorded. Subjects with seizures tended to have an abnormal pattern of melatonin correlated with EEG changes. In others, a parallel was evidenced between thyroid function and impairment in verbal communication. There appears to be a tendency for various types of neuroendocrinological abnormalities in autistics, and melatonin, as well as possibly TSH and perhaps prolactin, could serve as biochemical variables of the biological parameters of the disease.

Alfalfa dodder (Cuscuta campestris) toxicity in horses: clinical, haematological and serum biochemical findings.

PubMed

Abutarbush, S M

2013-07-27

The objective of this observational study is to describe clinical, haematological and serum biochemical findings of horses affected with alfalfa dodder (Cuscuta campestris) toxicity. Twenty horses naturally exposed to alfalfa dodder toxicity were examined and information was collected on history and clinical signs. Physical examination was done on horses in the premises (n=20), and venous blood samples of 12 horses were submitted for haematology and serum biochemical examination for each horse. Abnormal clinical signs started around 36 hours after horses were fed the contaminated alfalfa. Abnormal signs were seen in 11 horses and those included diarrhoea (n=8), decreased appetite (n=7), neurological signs (n=4) and abdominal pain (n=1). Some horses had multiple clinical signs of the above. The results of complete blood cell count revealed leukocytopenia, neutropenia and thrombocytopenia. Serum biochemical analysis revealed decreased ALP, AST and CPK levels and increased direct bilirubin level. The used alfalfa was stopped immediately and a different alfalfa from a new container that did not contain any weeds was fed. Horses on the premises were observed closely, and the abnormal clinical signs resolved within three days. No treatment was implemented. Knowledge about toxicity of horses by Cuscuta species is scarce in the English veterinary literature and very limited.

Serum PARC/CCL-18 Concentrations and Health Outcomes in Chronic Obstructive Pulmonary Disease

PubMed Central

Sin, Don D.; Miller, Bruce E.; Duvoix, Annelyse; Man, S. F. Paul; Zhang, Xuekui; Silverman, Edwin K.; Connett, John E.; Anthonisen, Nicholas A.; Wise, Robert A.; Tashkin, Donald; Celli, Bartolome R.; Edwards, Lisa D.; Locantore, Nicholas; MacNee, William; Tal-Singer, Ruth; Lomas, David A.

2011-01-01

Rationale: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. Objectives: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. Methods: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. Measurements and Main Results: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. Conclusions: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552). PMID:21216880

Polyfluoroalkyl Chemicals in the Serum and Milk of ...

EPA Pesticide Factsheets

Polyfluoroalkyl chemicals (PFCs) comprise a group of man-made organic compounds, some of which are persistent contaminants with developmental toxicity shown in laboratory animals. There is a paucity of human perinatal exposure data. The US EPA conducted a pilot study (Methods Advancement in Milk Analysis) including 34 breastfeeding women in North Carolina. Milk and serum samples were collected at 2-7 weeks and 3-4 months postpartum; 9 PFCs were assessed in milk and 7 in serum. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were found in nearly 100% of the serum samples. PFOS and PFOA were found at the highest concentrations. PFCs were below the limit of detection in most milk samples. Serum concentrations of PFOS, PFOA and PFHxS were lower (p<0.01) at the second visit compared to the first visit, and living in North Carolina 10 years or longer was related to elevated PFOS, PFOA and PFNA (p<0.03). These pilot data support the need to further explore perinatal PFC exposures and potentially related health effects, as planned in the upcoming National Children’s Study which provided the framework for this investigation. These data demonstrate very low transfer of perfluorinated chemicals (PFCs) to breast milk, even though PFCs are readily detected in the sera of lactating NC women. Our data correlation statistics suggest that there is an elevation of average serum PFCs i

Elevated IL-8 levels during sickle cell crisis.

PubMed

Duits, A J; Schnog, J B; Lard, L R; Saleh, A W; Rojer, R A

1998-11-01

The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.

G-protein coupled receptor 56 promotes myoblast fusion through serum response factor- and nuclear factor of activated T-cell-mediated signalling but is not essential for muscle development in vivo.

PubMed

Wu, Melissa P; Doyle, Jamie R; Barry, Brenda; Beauvais, Ariane; Rozkalne, Anete; Piao, Xianhua; Lawlor, Michael W; Kopin, Alan S; Walsh, Christopher A; Gussoni, Emanuela

2013-12-01

Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the gene for G-protein coupled receptor 56 (GPR56) was transiently up-regulated during the early fusion of human myoblasts. Human mutations in the gene for GPR56 cause the disease bilateral frontoparietal polymicrogyria; however, the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, a loss of GPR56 expression in muscle cells results in decreases or delays in the expression of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56-mediated serum response element and NFAT signalling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase compared to wild-type. In agreement with these findings, clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed mild serum creatine kinase increase in only two patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this G-protein coupled receptor during muscle development and that the motor delay observed in these patients is likely not a result of primary muscle abnormalities. © 2013 FEBS.

Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

PubMed

Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

1983-04-01

Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

PubMed

Li, Jinmiao; Xu, Fan; Zeng, Rui; Gong, Haijun; Lan, Yuqing

2016-02-01

This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 μmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 μmol/L (95% CI, -1.98, 0.74), 5.81 μmol/L (95% CI, -3.53, 15.14), and -16.79 μmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

Serum biochemical markers in lung cancer.

PubMed Central

Burt, R. W.; Ratcliffe, J. G.; Stack, B. H.; Cuthbert, J.; Kennedy, R. S.; Corker, C. S.; Franchimont, P.; Spilg, W. G.; Stimson, W. H.

1978-01-01

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy. PMID:77672

Derivation and Validation of Predictive Factors for Clinical Deterioration after Admission in Emergency Department Patients Presenting with Abnormal Vital Signs Without Shock

PubMed Central

Henning, Daniel J.; Oedorf, Kimie; Day, Danielle E.; Redfield, Colby S.; Huguenel, Colin J.; Roberts, Jonathan C.; Sanchez, Leon D.; Wolfe, Richard E.; Shapiro, Nathan I.

2015-01-01

Introduction Strategies to identify high-risk emergency department (ED) patients often use markedly abnormal vital signs and serum lactate levels. Risk stratifying such patients without using the presence of shock is challenging. The objective of the study is to identify independent predictors of in-hospital adverse outcomes in ED patients with abnormal vital signs or lactate levels, but who are not in shock. Methods We performed a prospective observational study of patients with abnormal vital signs or lactate level defined as heart rate ≥130 beats/min, respiratory rate ≥24 breaths/min, shock index ≥1, systolic blood pressure <90mm/Hg, or lactate ≥4mmole/L. We excluded patients with isolated atrial tachycardia, seizure, intoxication, psychiatric agitation, or tachycardia due to pain (ie: extremity fracture). The primary outcome was deterioration, defined as development of acute renal failure (creatinine 2× baseline), non-elective intubation, vasopressor requirement, or mortality. Independent predictors of deterioration after hospitalization were determined using logistic regression. Results Of 1,152 consecutive patients identified with abnormal vital signs or lactate level, 620 were excluded, leaving 532 for analysis. Of these, 53/532 (9.9±2.5%) deteriorated after hospital admission. Independent predictors of in-hospital deterioration were: lactate >4.0mmol/L (OR 5.1, 95% CI [2.1–12.2]), age ≥80 yrs (OR 1.9, CI [1.0–3.7]), bicarbonate <21mEq/L (OR 2.5, CI [1.3–4.9]), and initial HR≥130 (OR 3.1, CI [1.5–6.1]). Conclusion Patients exhibiting abnormal vital signs or elevated lactate levels without shock had significant rates of deterioration after hospitalization. ED clinical data predicted patients who suffered adverse outcomes with reasonable reliability. PMID:26759655

Co-ingestion of methanol and nitromethane: using falsely elevated creatinine as indicator for methanol antidote use.

PubMed

Leonard, Charlene P; Akhtar, Javed

2007-07-01

To report a case of co-ingestion of methanol and nitromethane in a child in order to heighten the awareness of false elevation of serum creatinine from nitromethane ingestion. Case report. Pediatric intensive care unit. A 4-yr-old previously healthy girl ingested an unknown quantity of "Blue Thunder" model-engine fuel, which consisted of methanol and nitromethane. The patient was treated with fomepizole for methanol ingestion using elevated creatinine level as a reason for treatment. The patient was asymptomatic but her creatinine level increased ten-fold (from 0.4 mg/dL to 4 mg/dL) within 6 hrs. Blood urea nitrogen, anion gap, and osmolar gap remained within normal limits. When the serum creatinine level was measured with enzymatic method instead of Jaffe's method, a normal creatinine level was obtained. The falsely elevated creatinine level was due to nitromethane. The falsely elevated serum creatinine levels due to nitromethane ingestion can lead to unnecessary therapeutic interventions. We intend to heighten awareness of this potential misstep by reporting this case.

The DD genotype of the angiotensin converting enzyme gene independently associates with CMR-derived abnormal microvascular perfusion in patients with a first anterior ST-segment elevation myocardial infarction treated with thrombolytic agents.

PubMed

Bodi, Vicente; Sanchis, Juan; Nunez, Julio; Aliño, Salvador F; Herrero, Maria J; Chorro, Francisco J; Mainar, Luis; Lopez-Lereu, Maria P; Monmeneu, Jose V; Oltra, Ricardo; Chaustre, Fabian; Forteza, Maria J; Husser, Oliver; Riegger, Günter A; Llacer, Angel

2009-12-01

The role of the angiotensin converting enzyme (ACE) gene on the result of thrombolysis at the microvascular level has not been addressed so far. We analyzed the implications of the insertion/deletion (I/D) polymorphism of the ACE gene on the presence of abnormal cardiovascular magnetic resonance (CMR)-derived microvascular perfusion after ST-segment elevation myocardial infarction (STEMI). We studied 105 patients with a first anterior STEMI treated with thrombolytic agents and an open left anterior descending artery. Microvascular perfusion was assessed using first-pass perfusion CMR at 7+/-1 days. CMR studies were repeated 184+/-11 days after STEMI. The ACE gene insertion/deletion (I/D) polymorphism was determined using polymerase chain reaction amplification. Overall genotype frequencies were II-ID 58% and DD 42%. Abnormal perfusion (> or = 1 segment) was detected in 56% of patients. The DD genotype associated to a higher risk of abnormal microvascular perfusion (68% vs. 47%, p=0.03) and to a larger extent of perfusion deficit (median [percentile 25 - percentile 75]: 4 [0-6] vs. 0 [0-4] segments, p=0.003). Once adjusted for baseline characteristics, the DD genotype independently increased the risk of abnormal microvascular perfusion (odds ratio [95% confidence intervals]: 2.5 [1.02-5.9], p=0.04). Moreover, DD patients displayed a larger infarct size (35+/-17 vs. 27+/-15 g, p=0.01) and a lower ejection fraction at 6 months (48+/-14 vs. 54+/-14%, p=0.03). The DD genotype associates to a higher risk of abnormal microvascular perfusion after STEMI.

Prevalence of Abnormal Vitamin D Levels Among Division I NCAA Athletes

PubMed Central

Villacis, Diego; Yi, Anthony; Jahn, Ryan; Kephart, Curtis J.; Charlton, Timothy; Gamradt, Seth C.; Romano, Russ; Tibone, James E.; Hatch, George F. Rick

2014-01-01

Background: Up to 1 billion people have insufficient or deficient vitamin D levels. Despite the well-documented, widespread prevalence of low vitamin D levels and the importance of vitamin D for athletes, there is a paucity of research investigating the prevalence of vitamin D deficiency in athletes. Hypothesis: We investigated the prevalence of abnormal vitamin D levels in National Collegiate Athletic Association (NCAA) Division I college athletes at a single institution. We hypothesized that vitamin D insufficiency is prevalent among our cohort. Study Design: Cohort study. Level of Evidence: Level 1. Methods: We measured serum 25-hydroxyvitamin D (25(OH)D) levels of 223 NCAA Division I athletes between June 2012 and August 2012. The prevalence of normal (≥32 ng/mL), insufficient (20 to <32 ng/mL), and deficient (<20 ng/mL) vitamin D levels was determined. Logistic regression was utilized to analyze risk factors for abnormal vitamin D levels. Results: The mean serum 25(OH)D level for the 223 members of this study was 40.1 ± 14.9 ng/mL. Overall, 148 (66.4%) participants had sufficient 25(OH)D levels, and 75 (33.6%) had abnormal levels. Univariate analysis revealed the following significant predictors of abnormal vitamin D levels: male sex (odds ratio [OR] = 2.83; P = 0.0006), Hispanic race (OR = 6.07; P = 0.0063), black race (OR = 19.1; P < 0.0001), and dark skin tone (OR = 15.2; P < 0.0001). Only dark skin tone remained a significant predictor of abnormal vitamin D levels after multivariate analysis (adjusted OR = 15.2; P < 0.0001). Conclusion: In a large cohort of NCAA athletes, more than one third had abnormal vitamin D levels. Races with dark skin tones are at much higher risk than white athletes. Male athletes are more likely than female athletes to be vitamin D deficient. Our study demonstrates a high prevalence of vitamin D deficiency among healthy NCAA athletes. Clinical Relevance: Many studies indicate a significant prevalence of vitamin-D insufficiency

Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

PubMed

Nagy, Béla; Nagy, Béla; Fila, Libor; Clarke, Luka A; Gönczy, Ferenc; Bede, Olga; Nagy, Dóra; Újhelyi, Rita; Szabó, Ágnes; Anghelyi, Andrea; Major, Miklós; Bene, Zsolt; Fejes, Zsolt; Antal-Szalmás, Péter; Bhattoa, Harjit Pal; Balla, György; Kappelmayer, János; Amaral, Margarida D; Macek, Milan; Balogh, István

2016-09-01

Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF. Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR. Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator

Risk factors for abnormal liver function tests in patients with ileal pouch-anal anastomosis for underlying inflammatory bowel disease.

PubMed

Navaneethan, Udayakumar; Remzi, Feza H; Nutter, Benjamin; Fazio, Victor W; Shen, Bo

2009-10-01

Liver involvement is common in patients with inflammatory bowel disease (IBD). However, the frequency and the significance of liver function test (LFT) abnormalities in patients with ileal pouch-anal anastomosis (IPAA) for underlying IBD have not been studied. The aim of this study was to evaluate the prevalence and to identify risk factors for abnormal LFTs in patients with IPAA and underlying IBD. All patients were identified from our prospectively maintained Pouchitis Database between 2002 and 2008. Abnormal LFTs were classified as the following: (i) any abnormal elevation of transaminases, and/or alkaline phosphatase (ALP), and/or bilirubin; (ii) hepatitis, if there was more than twice the elevation of transaminases; and (iii) cholestatic, if there was more than 1.5 times elevation of ALP. Clinical, endoscopic, and histological variables were assessed using Cox proportional hazard models for evaluating risk for abnormal LFTs. A total of 545 IPAA patients with underlying IBD were identified from the database, of which 373 patients who had LFTs done after their pouch surgery were included. This included 346 patients with ulcerative colitis, 25 with indeterminate colitis, and 2 with Crohn's colitis before surgery. Their mean age was 45.9+/-13.8 years. A total of 65 patients (17.4%) (40 men, 25 women, median age: 47 years) had abnormal LFTs. Of the patients, 52 (13.9%) had abnormal transaminases, whereas 15 (4%) were classified as having hepatitis. Thirty-five (9.4%) patients had an abnormal ALP level, with 18 (4.8%) classified as cholestatic. The most common cause of an abnormal LFT was transient elevation in 32 (49.2%) patients, followed by fatty liver (fatty change on imaging with body mass index (BMI) > or =25 kg/m(2) in the absence of other causes, including alcohol abuse and drug-induced hepatitis) in 10 (15.4%), drug-induced abnormal LFTs in 7 (10.7%), and chronic hepatitis B or C in 6 (9.2%). Primary sclerosing cholangitis (PSC) was responsible for abnormal

Elevated levels of serum sICAM-1 in asphyxiated low birth weight newborns

PubMed Central

Huseynova, Saadat; Panakhova, Nushaba; Orujova, Pusta; Hasanov, Safikhan; Guliyev, Mehman; Orujov, Agil

2014-01-01

Perinatal hypoxia results in neuronal and endothelial cell damage. The main purpose of this study was to investigate the correlation of soluble intercellular adhesion molecule 1 (sICAM-1) expression and peripheral blood changes in perinatal asphyxia with neuronal injury markers in low birth weight (LBW) neonates. We compared the concentrations of serum sICAM-1, neuron-specific enolase (NSE) and antibodies specific for NR2 glutamate receptors in 29 asphyxiated and 20 control infants using standard enzyme immunoassay procedures. The mean total concentrations of sICAM-1 and neuron-specific proteins (NSE and NR2-specific antibodies) were higher in the asphyxiated infants than in the control infants. The serum sICAM-1 concentrations significantly correlated with Apgar scoring and with the pH and lactate data from capillary or arterial cord blood. No significant correlation between serum concentrations of neuron specific proteins and blood changes of asphyxia was found. Therefore, endothelial sICAM-1 expression levels might be accepted as an indicator of the severity of perinatal asphyxia in LBW infants. PMID:25358349

Amelioration of Abnormalities Associated with the Metabolic Syndrome by Spinacia oleracea (Spinach) Consumption and Aerobic Exercise in Rats.

PubMed

Panda, Vandana; Mistry, Kinjal; Sudhamani, S; Nandave, Mukesh; Ojha, Shreesh Kumar

2017-01-01

The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE) in abnormalities associated with the metabolic syndrome (MetS) in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20%  w / v ) in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po), the standard drug gemfibrozil (60 mg/kg, po), aerobic exercise (AE), and a combination of NAOE 400 mg/kg and AE (NAOEAE) daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB) in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS.

Amelioration of Abnormalities Associated with the Metabolic Syndrome by Spinacia oleracea (Spinach) Consumption and Aerobic Exercise in Rats

PubMed Central

Mistry, Kinjal; Sudhamani, S.

2017-01-01

The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE) in abnormalities associated with the metabolic syndrome (MetS) in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20% w/v) in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po), the standard drug gemfibrozil (60 mg/kg, po), aerobic exercise (AE), and a combination of NAOE 400 mg/kg and AE (NAOEAE) daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB) in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS. PMID:28798859

Polycystic Ovary-Like Abnormalities (PCO-L) in women with functional hypothalamic amenorrhea.

PubMed

Robin, G; Gallo, C; Catteau-Jonard, S; Lefebvre-Maunoury, C; Pigny, P; Duhamel, A; Dewailly, D

2012-11-01

In the general population, about 30% of asymptomatic women have polycystic ovary-like abnormalities (PCO-L), i.e. polycystic ovarian morphology (PCOM) at ultrasound and/or increased anti-Müllerian hormone (AMH) serum level. PCOM has also been reported in 30-50% of women with functional hypothalamic amenorrhea (FHA). The aim of this study was to verify whether both PCOM and excessive AMH level indicate PCO-L in FHA and to elucidate its significance. We conducted a retrospective analysis using a database and comparison with a control population. Subjects received ambulatory care in an academic hospital. Fifty-eight patients with FHA were compared to 217 control women with nonendocrine infertility and body mass index of less than 25 kg/m(2). There were no interventions. We measured serum testosterone, androstenedione, FSH, LH, AMH, and ovarian area values. The antral follicle count (AFC) was used as a binary variable (i.e. negative or positive) because of the evolution of its sensitivity over the time of this study. The ability of these variables (except AFC) to detect PCO-L in both populations was tested by cluster analysis. One cluster (cluster 2) suggesting PCO-L was detected in the control population (n = 52; 24%), whereas two such clusters were observed in the FHA population (n = 22 and n = 6; 38 and 10%; clusters 2 and 3, respectively). Cluster 2 in FHA had similar features of PCO-L as cluster 2 in controls, with higher prevalence of positive AFC (70%) and PCOM (70%), higher values of ovarian area and higher serum AMH (P < 0.0001 for all), and testosterone levels (P < 0.01) than in cluster 1. Cluster 3 in FHA was peculiar, with frankly elevated AMH levels. In the whole population (controls + FHA), PCO-L was significantly associated with lower FSH values (P < 0.0001). PCO-L in FHA is a frequent and usually incidental finding of unclear significance, as in controls. The association of PCO-L with hypothalamic amenorrhea should not lead to a mistaken diagnosis of

Metastatic lung adenocarcinoma related α-Fetoprotein elevation in a patient with HBV-related cirrhosis.

PubMed

Hamamci, Mevlut; Karaahmet, Fatih; Akinci, Hakan; Kilincalp, Serta; Acıkgoz, Ruchan; Coban, Sahin; Yuksel, Ilhami

2015-12-01

HCC is the most common type of primary liver tumor. The Practice Guideline, AASLD, for HCC recommended surveillance of HBV carriers at high risk of HCC with US every 6-12 months. Laboratory surveillance option is the measurement of serum α-fetoprotein level which has long been used for the diagnosis of HCC. But, increased serum levels of α-fetoprotein are also seen in acute hepatitis, cirrhosis, and malignancies include yolk sac carcinoma, neuroblastoma, hepatoblastoma, gastric and lung carcinoma. Because of elevation α-fetoprotein in these malignancies, liver mass with an elevated α-fetoprotein does not directly indicate HCC. For these reason, clinicians evaluating patient with liver mass and HBV-related cirrhosis should be vigilant for other case of α-fetoprotein elevation. © Acta Gastro-Enterologica Belgica.

Elevation of serum CA 125 and D-dimer levels associated with rupture of ovarian endometrioma.

PubMed

Uharcek, P; Mlyncek, M; Ravinger, J

2007-01-01

Patients with endometriosis rarely have a serum CA 125 concentration >100 IU/mL. A raised plasma level of D-dimer indicates active fibrinolysis, either secondary to clot formation or primarily activated. This condition is seldom diagnosed in patients with endometriosis. A 53-year-old woman was referred to our institution for acute abdominal pain. Laparoscopic surgery revealed a large ovarian cyst with rupture on the left side. Preoperative laboratory tests detected high serum CA 125 and D-dimer levels. Adnexectomy was performed, resulting in a sharp decrease in serum CA 125 and D-dimer concentration. We describe the clinical course of the patient. Rupture of a large ovarian endometrioma can lead to a high serum concentration of CA 125, a condition which, in addition to the detected pelvic mass, may mimic a malignant process. The increased D-dimer plasma level indicated that a ruptured endometriotic cyst can induce coagulation reactions.

Higher serum sTNFR1 level predicts conversion from mild cognitive impairment to Alzheimer's disease.

PubMed

Diniz, Breno Satler; Teixeira, Antonio Lucio; Ojopi, Elida Benquique; Talib, Leda Leme; Mendonça, Vanessa Amaral; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2010-01-01

The activation of inflammatory cascades has been consistently demonstrated in the pathophysiology of Alzheimer's disease (AD). Among several putative neuroinflammatory mechanisms, the tumor necrosis factor α (TNF-α) signaling system has a central role in this process. Recent evidence indicates that the abnormal production of inflammatory factors may accompany the progression from mild cognitive impairment (MCI) to dementia. We aimed to examine serum levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in patients with MCI and AD as compared to cognitively unimpaired elderly subjects. We further aimed to investigate whether abnormal levels of these cytokines predict the progression from MCI to AD upon follow-up. We utilized cross-sectional determination of serum levels of TNF-α, sTNFR1, and sTNFR2 (ELISA method) in a test group comprising 167 older adults (31 AD, 72 MCI, and 64 healthy controls), and longitudinal reassessment of clinical status after 18.9 ± 10.0 months. At baseline, there were no statistically significant differences in serum TNF-α, sTNFR1, and sTNFR2 between patients with MCI and AD as compared to controls. Nevertheless, patients with MCI who progressed to AD had significantly higher serum sTNFR1 levels as opposed to patients who retained the diagnosis of MCI upon follow-up (p = 0.03). Cox regression analysis showed that high serum sTNFR1 levels predicted the conversion from MCI to AD (p = 0.003), whereas no significant differences were found with respect to serum levels of TNF-α and sTNFR2. Abnormal activation of TNF-α signaling system, represented by increased expression of sTNFR1, is associated with a higher risk of progression from MCI to AD.

Total alpha-fetoprotein and Lens culinaris agglutinin-reactive alpha-fetoprotein in fetal chromosomal abnormalities.

PubMed

Yamamoto, R; Azuma, M; Kishida, T; Yamada, H; Satomura, S; Fujimoto, S

2001-11-01

To examine the differences in multiples of the median (MoM) of total alpha-fetoprotein, and the proportion of Lens culinaris agglutinin reactive alpha-fetoprotein (% alpha-fetoprotein-L2 + L3) in the maternal serum and amniotic fluid of pregnant women whose fetuses were diagnosed with autosomal or sex chromosomal abnormalities. Prospective consecutive series. University hospital. Maternal sera and amniotic fluids from 46 pregnant women with trisomy 21 fetuses, 10 pregnant women with trisomy 18 fetuses, one pregnant woman with a trisomy 13 fetus, six pregnant women with fetal sex chromosomal abnormalities, and 100 pregnant women for whom the fetal karyotype was diagnosed as normal following a genetic amniocentesis. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum for trisomy 21 (40.3%. P < 0.0001) and trisomy 18 (39.8%, P < 0.05) showed a significantly higher value compared with normal (32.6%). The proportion of alpha-fetoprotein-L2 + L3 in amniotic fluid was significantly higher (P < 0.0001) for trisomy 21 (46.6%) than for a normal karyotype (41.5%). Only for the trisomy 21 group was there a strong correlation in the % alpha-fetoprotein-L2 + L3 between maternal serum and amniotic fluid (r = 0.840, P < 0.0001). For all groups, there was no correlation between alpha-fetoprotein MoM and % alpha-fetoprotein-L2 + L3 in maternal serum and amniotic fluid. The proportion of alpha-fetoprotein-L2 + L3 in maternal serum is an appropriate choice for a trisomy 21 biochemical marker, and it is possible that combining alpha-fetoprotein-L2 + L3 analysis with assays of alpha-fetoprotein in maternal serum could further improve the sensitivity and specificity of multiple marker screening.

Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

PubMed

Grover, V P B; Southern, L; Dyson, J K; Kim, J U; Crossey, M M E; Wylezinska-Arridge, M; Patel, N; Fitzpatrick, J A; Bak-Bol, A; Waldman, A D; Alexander, G J; Mells, G F; Chapman, R W; Jones, D E J; Taylor-Robinson, S D

2016-11-01

Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Elevated EGF Levels in the Blood Serum of Dogs with Periodontal Diseases and Oral Tumours.

PubMed

Sobczyńska-Rak, Aleksandra; Żylińska, Beata; Polkowska, Izabela; Szponder, Tomasz

2018-01-01

Paradontopathy and neoplasms of the oral cavity represent one of the greatest challenges in human and animal dentistry. EGF plays a key role in maintaining the integrity and proper rate of cell proliferation in normal oral epithelium. The aim of the present study was to study serum levels of EGF in dogs diagnosed with periodontal diseases and oral cavity tumours. The samples comprised of cancerous tissue sections and serum obtained from dogs of various breeds, aged between 5-13 years. Serum EGF concentrations were measured by an immunoenzymatic method. The median for EGF concentration in serum of dogs suffered from severe periodontal diseases was greater when compared to the control group. EGF concentration in dogs with malignant tumours was significantly higher than in those with non-malignant growths. A positive correlation between EGF concentration and tumour size was also observed. EGF level in dogs diagnosed with benign tumours was comparable to the control group. The blood serum level of EGF increases significantly in patients with malignant oral tumours and advanced periodontal disease. In malignant tumours, the high level of EGF correlates with the size and invasiveness of the neoplasm. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Association of serum uric acid level and blood pressure in type 2 diabetes mellitus

NASA Astrophysics Data System (ADS)

Savira, M.; Rusdiana; Syahputra, M.

2018-03-01

Uric acid is an end product of purine degradation in humans and primarily excreted through urine. In adulthood, concentrations rise steadily over time and vary with height, body weight, blood pressure, renal function, and alcohol intake. Uric acid is known as anti-oxidant, it has a beneficial role in diseases. Elevated serum uric acid associated with anincreased risk of cardiovascular disease. It has been found that elevated levels of uric acid associated with high risks of acomplication of type 2 diabetes mellitus and It has astrong association between elevated uric acid levels and obesity, metabolic syndrome, diabetes mellitus, hypertension, cardiovascular and renal disorders. The aim of the study analyzed the association between serum uric acid level and blood pressure in type 2 diabetes mellitus patients. This research is descriptive analytic research with a cross sectional design included 50 diabetic subjects aged over 40 years old. Subjects picked by consecutive sampling then we examined the weight, height, waist size, blood pressure, fasting blood sugar, and serum uric acid level. Statistical analysis using chi-square found that there was no significant association between serum uric acid level and systole and diastole pressure in type 2 diabetes mellitus patients (p>0.005).

Glucose-6-phosphate transporter gene therapy corrects metabolic and myeloid abnormalities in glycogen storage disease type Ib mice

PubMed Central

Yiu, Wai Han; Pan, Chi-Jiunn; Allamarvdasht, Mohammad; Kim, So Youn; Chou, Janice Y.

2008-01-01

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate transporter (G6PT), an endoplasmic reticulum-associated transmembrane protein that is ubiquitously expressed. GSD-Ib patients suffer from disturbed glucose homeostasis and myeloid dysfunctions. To evaluate the feasibility of gene replacement therapy for GSD-Ib, we have infused adenoviral (Ad) vector containing human G6PT (Ad-hG6PT) into G6PT-deficient (G6PT-/-) mice that manifest symptoms characteristics of the human disorder. Ad-hG6PT-infusion restores significant levels of G6PT mRNA expression in the liver, bone marrow, and spleen and corrects metabolic as well as myeloid abnormalities in G6PT-/- mice. The G6PT-/- mice receiving gene therapy exhibit improved growth; normalized serum profiles for glucose, cholesterol, triglyceride, uric acid, and lactic acid; and reduced hepatic glycogen deposition. The therapy also corrects neutropenia and lowers the elevated serum levels of granulocyte colony stimulating factor. The development of bone and spleen in the infused G6PT-/- mice is improved and accompanied by increased cellularity and normalized myeloid progenitor cell frequencies in both tissues. This effective use of gene therapy to correct metabolic imbalances and myeloid dysfunctions in GSD-Ib mice holds promise for the future of gene therapy in humans. PMID:17006547

Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma.

PubMed

Hume, Kelly R; Sylvester, Skylar R; Borlle, Lucia; Balkman, Cheryl E; McCleary-Wheeler, Angela L; Pulvino, Mary; Casulo, Carla; Zhao, Jiyong

2018-01-01

Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 ( n  = 6) or 7.5 ( n  = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro , trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p  < 0.0001; Wilcoxon signed rank test, p  = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline

Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma

PubMed Central

Hume, Kelly R.; Sylvester, Skylar R.; Borlle, Lucia; Balkman, Cheryl E.; McCleary-Wheeler, Angela L.; Pulvino, Mary; Casulo, Carla; Zhao, Jiyong

2018-01-01

Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 (n = 6) or 7.5 (n = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro, trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p < 0.0001; Wilcoxon signed rank test, p = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy

Adult-onset glutaric aciduria type I presenting with white matter abnormalities and subependymal nodules.

PubMed

Pierson, T M; Nezhad, Mani; Tremblay, Matthew A; Lewis, Richard; Wong, Derek; Salamon, Noriko; Sicotte, Nancy

2015-10-01

A 55-year-old female presented with a 6-year history of paresthesias, incontinence, spasticity, and gait abnormalities. Neuroimaging revealed white matter abnormalities associated with subependymal nodules. Biochemical evaluation noted increased serum C5-DC glutarylcarnitines and urine glutaric and 3-hydroxyglutaric acids. Evaluation of the glutaryl-CoA dehydrogenase (GCDH) gene revealed compound heterozygosity consisting of a novel variant (c.1219C>G; p.Leu407Val) and pathogenic mutation (c.848delT; p.L283fs). Together, these results were consistent with a diagnosis of adult-onset type I glutaric aciduria.

Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

PubMed Central

Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

2013-01-01

Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P<0.001), <1 year (82% versus 8%; P<0.001), 1–4 years (53% versus 0%; P<0.001), and >4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

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.

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.

Radiographic abnormalities among construction workers exposed to quartz containing dust

PubMed Central

Tjoe, N; Burdorf, A; Parker, J; Attfield, M; van Duivenbooden, C; Heederik, D

2003-01-01

Background: Construction workers are exposed to quartz containing respirable dust, at levels that may cause fibrosis in the lungs. Studies so far have not established a dose-response relation for radiographic abnormalities for this occupational group. Aims: To measure the extent of radiographic abnormalities among construction workers primarily exposed to quartz containing respirable dust. Methods: A cross sectional study on radiographic abnormalities indicative of pneumoconiosis was conducted among 1339 construction workers mainly involved in grinding, (jack)-hammering, drilling, cutting, sawing, and polishing. Radiological abnormalities were determined by median results of the 1980 International Labour Organisation system of three certified "B" readers. Questionnaires were used for assessment of occupational history, presence of respiratory diseases, and symptoms and smoking habits. Results: An abnormality of ILO profusion category 1/0 and greater was observed on 10.2% of the chest radiographs, and profusion category of 1/1 or greater on 2.9% of the radiographs. The average duration of exposure of this group was 19 years and the average age was 42. The predominant type of small opacities (irregularly shaped) is presumably indicative of mixed dust pneumoconiosis. The prevalence of early signs of nodular silicosis (small rounded opacities of category 1/0 or greater) was low (0.8%). Conclusions: The study suggests an elevated risk of radiographic abnormalities among these workers with expected high exposure. An association between radiographic abnormalities and cumulative exposure to quartz containing dust from construction sites was observed, after correction for potentially confounding variables. PMID:12771392

Diel CO2 cycles reduce severity of behavioural abnormalities in coral reef fish under ocean acidification.

PubMed

Jarrold, Michael D; Humphrey, Craig; McCormick, Mark I; Munday, Philip L

2017-08-31

Elevated CO 2 levels associated with ocean acidification (OA) have been shown to alter behavioural responses in coral reef fishes. However, all studies to date have used stable pCO 2 treatments, not considering the substantial diel pCO 2 variation that occurs in shallow reef habitats. Here, we reared juvenile damselfish, Acanthochromis polyacanthus, and clownfish, Amphiprion percula, at stable and diel cycling pCO 2 treatments in two experiments. As expected, absolute lateralization of A. polyacanthus and response to predator cue of Am. percula were negatively affected in fish reared at stable, elevated pCO 2 in both experiments. However, diel pCO 2 fluctuations reduced the negative effects of OA on behaviour. Importantly, in experiment two, behavioural abnormalities that were present in fish reared at stable 750 µatm CO 2 were largely absent in fish reared at 750 ± 300 µatm CO 2 . Overall, we show that diel pCO 2 cycles can substantially reduce the severity of behavioural abnormalities caused by elevated CO 2 . Thus, past studies may have over-estimated the impacts of OA on the behavioural performance of coral reef fishes. Furthermore, our results suggest that diel pCO 2 cycles will delay the onset of behavioural abnormalities in natural populations.

Serum ferritin concentrations and body iron stores in a multicenter, multiethnic primary-care population

PubMed Central

Gordeuk, Victor R.; Reboussin, David M.; McLaren, Christine E.; Barton, James C.; Acton, Ronald T.; McLaren, Gordon D.; Harris, Emily L.; Reiss, Jacob A.; Adams, Paul C.; Speechley, Mark; Phatak, Pradyumna D.; Sholinsky, Phyliss; Eckfeldt, John H.; Chen, Wen-Pin; Passmore, Leah; Dawkins, Fitzroy W.

2013-01-01

How often elevated serum ferritin in primary-care patients reflects increased iron stores (normally 0.8 g in men, 0.4 g in women) is not known. The Hereditary Hemochromatosis and Iron Overload Screening (HEIRS) study screened 101,168 primary-care participants (44% Caucasians, 27% African-Americans, 14% Asians/Pacific Islanders, 13% Hispanics, 2% others). Follow-up clinical evaluation was performed in 302 of 333 HFE C282Y homozygotes regardless of iron measures and 1,375 of 1,920 nonhomozygotes with serum ferritin >300 μg/L (men), >200 μg/L (women) and transferrin saturation >50% (men), >45% (women). Quantitative phlebotomy was conducted in 122 of 175 C282Y homozygotes and 122 of 1,102 nonhomozygotes with non-transfusional serum ferritin elevation at evaluation. The estimated prevalence in the Caucasian population of C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 20 per 10,000 men and 4 per 10,000 women; this constellation was predictive of iron stores >4 g in men and >2 g in women. The estimated prevalence per 10,000 of non-C282Y homozygotes with serum ferritin >900 μg/L at evaluation was 7 among Caucasians, 13 among Hispanics, 20 among African Americans, and 38 among Asians and Pacific Islanders, and this constellation was predictive of iron stores >2 g but <4 g. In conclusion, serum ferritin >900 μg/L after initial elevations of both serum ferritin and transferrin saturation is predictive of mildly increased iron stores in multiple ethnic populations regardless of HFE genotype. Serum ferritin >900 μg/L in male C282Y homozygotes is predictive of moderately increased iron stores. PMID:18429050

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

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

Incidence of abnormal offspring from cloning and other assisted reproductive technologies.

PubMed

Hill, Jonathan R

2014-02-01

In animals produced by assisted reproductive technologies, two abnormal phenotypes have been characterized. Large offspring syndrome (LOS) occurs in offspring derived from in vitro cultured embryos, and the abnormal clone phenotype includes placental and fetal changes. LOS is readily apparent in ruminants, where a large calf or lamb derived from in vitro embryo production or cloning may weigh up to twice the expected body weight. The incidence of LOS varies widely between species. When similar embryo culture conditions are applied to nonruminant species, LOS either is not as dramatic or may even be unapparent. Coculture with serum and somatic cells was identified in the 1990s as a risk factor for abnormal development of ruminant pregnancies. Animals cloned from somatic cells may display a combination of fetal and placental abnormalities that are manifested at different stages of pregnancy and postnatally. In highly interventional technologies, such as nuclear transfer (cloning), the incidence of abnormal offspring continues to be a limiting factor to broader application of the technique. This review details the breadth of phenotypes found in nonviable pregnancies, together with the phenotypes of animals that survive the transition to extrauterine life. The focus is on animals produced using in vitro embryo culture and nuclear transfer in comparison to naturally occurring phenotypes.

Per- and polyfluoroalkyl substances in human serum and urine samples from a residentially exposed community.

PubMed

Worley, Rachel Rogers; Moore, Susan McAfee; Tierney, Bruce C; Ye, Xiaoyun; Calafat, Antonia M; Campbell, Sean; Woudneh, Million B; Fisher, Jeffrey

2017-09-01

Per- and polyfluoroalkyl substances (PFAS) are considered chemicals of emerging concern, in part due to their environmental and biological persistence and the potential for widespread human exposure. In 2007, a PFAS manufacturer near Decatur, Alabama notified the United States Environmental Protection Agency (EPA) it had discharged PFAS into a wastewater treatment plant, resulting in environmental contamination and potential exposures to the local community. To characterize PFAS exposure over time, the Agency for Toxic Substances and Disease Registry (ATSDR) collected blood and urine samples from local residents. Eight PFAS were measured in serum in 2010 (n=153). Eleven PFAS were measured in serum, and five PFAS were measured in urine (n=45) from some of the same residents in 2016. Serum concentrations were compared to nationally representative data and change in serum concentration over time was evaluated. Biological half-lives were estimated for perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) using a one-compartment pharmacokinetic model. In 2010 and 2016, geometric mean PFOA and PFOS serum concentrations were elevated in participants compared to the general U.S. In 2016, the geometric mean PFHxS serum concentration was elevated compared to the general U.S. Geometric mean serum concentrations of PFOA, PFOS, and perfluorononanoic acid (PFNA) were significantly (p≤0.0001) lower (49%, 53%, and 58%, respectively) in 2016 compared to 2010. Half-lives for PFOA, PFOS, and PFHxS were estimated to be 3.9, 3.3, and 15.5years, respectively. Concentrations of PFOA in serum and urine were highly correlated (r=0.75) in males. Serum concentrations of some PFAS are decreasing in this residentially exposed community, but remain elevated compared to the U.S. general population. Published by Elsevier Ltd.

Independent association of elevated serum hepatocyte growth factor levels with development of insulin resistance in a 10-year prospective study.

PubMed

Tsukagawa, Eri; Adachi, Hisashi; Hirai, Yuji; Enomoto, Mika; Fukami, Ako; Ogata, Kinuka; Kasahara, Akiko; Yokoi, Kanako; Imaizumi, Tsutomu

2013-07-01

Hepatocyte growth factor (HGF) receptors form a hybrid complex with insulin receptors in the liver of mice, which lead to robust signalling to regulate glucose metabolism. Serum HGF levels are high in subjects with metabolic syndrome and/or obesity. Accordingly, we prospectively investigated the relationship between HGF and the development of insulin resistance (IR) in a general population without IR at baseline. A total of 1492 subjects received health examinations. After excluding subjects with diabetes and/or IR (n = 402) at baseline, the remaining subjects (n = 1090) were followed-up 10 years later. Complete data sets were available from 716 subjects for prospective analysis. Logistic regression was performed to determine factors associated with the development of IR after 10 years. In subjects without diabetes at baseline, serum HGF levels were higher (0·26 ± 0·10 ng/ml, n = 259) in subjects with IR than without it (0·22 ± 0·09 ng/ml, n = 1090). After deleting subjects who developed liver disease during follow-up, 188 were found to have developed IR at 10 years after the original screening. HGF (P < 0·05), age (P < 0·001), homoeostasis model assessment index (P < 0·001), HDL-c (P < 0·05; inversely) and hypertensive medication (P < 0·05) were significantly associated with the development of IR by multivariate stepwise logistic regression analysis. A significant (P < 0·05) relative risk [1·75 (95%CI: 1·01-3·12)] for the development of IR was observed in the highest (≥0·30 ng/ml) vs the lowest categories (<0·15 ng/ml) of HGF after adjustments for confounders. Our 10-year prospective study suggests that elevated serum HGF levels were significantly associated with the development of IR. © 2012 John Wiley & Sons Ltd.

Changes in Peripheral Serum Creatine Phosphokinase (CPK) and Lactic Dehydrogenase (LDH) in Acute Experimental Colonic Infarction

PubMed Central

Graeber, Geoffrey M.; Wukich, Dane K.; Cafferty, Patrick J.; O'Neill, John F.; Wolf, Robert E.; Ackerman, Norman B.; Harmon, John W.

1981-01-01

No satisfactory laboratory test for the early diagnosis of bowel infarction exists at this time. We have delineated changes in serum CPK levels after acute superior mesenteric artery infarction; whether or not comparable changes occur with inferior mesenteric artery infarction has not yet been determined. Furthermore, the changes in LDH associated with acute bowel infarction have not been documented. To determine the changes in serum CPK and LDH in acute colonic infarction, laparotomies were performed on dogs after peripheral baseline blood samples were drawn and each subject was randomly placed in one of three groups: laparotomy alone, acute colonic obstruction, and acute colonic infarction by ligation of the inferior mesenteric artery. The marginal artery of the colon was ligated at the peritoneal reflection and at the cecum to interrupt arterial collaterals. Blood samples were taken from each subject at intervals of three hours for 48 hours after injury. Serum from each sample was analyzed for total CPK and LDH by automated spectrophotometry. Isoenzymes were determined by agarose gel electrophoresis. Necropsies were conducted on all the dogs to confirm that the intended condition had been produced and that no intercurrent disease was present. The data support the conclusion that total CPK, total LDH and their isoenzymes become elevated in the peripheral serum after colonic infarction. The maximal elevations were all seen within the first 12 hours after acute colonic infarction. Total LDH and LDH3, the most prevalent isoenzyme of LDH in bowel, do not become elevated in the serum to as high a level as CPK, but the combination of serum elevations in both enzyme systems may prove to be of diagnostic significance. PMID:7305484

Analysis of the effects of exposure to polychlorinated biphenyls and chlorinated pesticides on serum lipid levels in residents of Anniston, Alabama

PubMed Central

2013-01-01

Background Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study. Methods Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis. Results We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196–203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components. Conclusions Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These

Progressive periodontal disease has a simultaneous incremental elevation of gingival crevicular fluid and serum CRP levels.

PubMed

Pradeep, A R; Manjunath, R G Shiva; Kathariya, Rahul

2010-11-01

Increased C-reactive protein levels have been found in all active inflammations, including periodontitis. This study aims to assess the C-reactive protein levels in periodontal disease progression. Forty-five patients were divided into the following three groups (n=15) based on gingival index, probing pocket depth, and clinical attachment level: healthy (group I), gingivitis (group II), and chronic periodontitis (group III). Gingival crevicular fluid and serum samples were quantified for C-reactive protein using enzyme-linked immunosorbent assay. The mean C-reactive protein concentration in gingival crevicular fluid and serum was found to be highest in group III (1233.33ng/mL for gingival crevicular fluid, 5483.33ng/mL for serum), and least in group I (60 ng/mL and 413 ng/mL for gingival crevicular fluid and serum, respectively) The mean C-reactive protein concentration in group II (453.33ng/mL for gingival crevicular fluid and 3565.33 ng/mL for serum) was found to be intermediate. C-reactive protein levels in gingival crevicular fluid and serum increased proportionately with the severity of periodontal disease. They correlated positively with clinical parameters, including gingival index, probing pocket depth, and clinical attachment level. Thus, it can be considered as a periodontal inflammatory biomarker and deserves further consideration. © 2010 Blackwell Publishing Asia Pty Ltd.

Hypotension, bedridden, leukocytosis, thrombocytopenia and elevated serum creatinine predict mortality in geriatric patients with fever.

PubMed

Chung, Min-Hsien; Chu, Feng-Yuan; Yang, Tzu-Meng; Lin, Hung-Jung; Chen, Jiann-Hwa; Guo, How-Ran; Vong, Si-Chon; Su, Shih-Bin; Huang, Chien-Cheng; Hsu, Chien-Chin

2015-07-01

The geriatric population (aged ≥65 years) accounts for 12-24% of all emergency department (ED) visits. Of them, 10% have a fever, 70-90% will be admitted and 7-10% of will die within a month. Therefore, mortality prediction and appropriate disposition after ED treatment are of great concern for geriatric patients with fever. We tried to identify independent mortality predictors of geriatric patients with fever, and combine these predictors to predict their mortality. We enrolled consecutive geriatric patients visiting the ED between 1 June and 21 July 2010 with the following criteria of fever: a tympanic temperature ≥37.2°C or a baseline temperature elevated ≥1.3°C. We used 30-day mortality as the primary end-point. A total of 330 patients were enrolled. Hypotension, bedridden, leukocytosis, thrombocytopenia and serum creatinine >2 mg/dL, but not age, were independently associated with 30-day mortality. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) ranged from 18.2% to 90.9%, 34.7% to 100%, 9.0% to 100% and 94.5% to 98.2%, respectively, depending on how many predictors there were. The 30-day mortality increased with the number of independent mortality predictors. With at least four predictors, 100% of the patients died within 30 days. With none of the predictors, just 1.8% died. These findings might help physicians make decisions about geriatric patients with fever. © 2014 Japan Geriatrics Society.

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.

Association between serum antibodies to periodontal bacteria and rheumatoid factor in NHANES III

PubMed Central

Goh, Charlene E.; Kopp, Jacob; Papapanou, Panos N.; Molitor, Jerry A.; Demmer, Ryan T.

2016-01-01

Objective Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population-based. We investigated the association between elevated serum IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults. Methods The Third National Health and Nutrition Examination Survey is a cross-sectional sample of the non-institutionalized US population (n=33,994). Our study population included all dentate participants ≥60 years, who did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n=2461). Results Adjusted odds ratios (ORs) (95% CI) summarizing the relationship between the 19 periodontal serum IgGs and RF seropositivity ranged from 0.53 (0.29, 0.97) to 1.27 (0.79, 2.06), and 17 of the 19 observed ORs were < 1.0. The ORs for RF seropositivity among participants with elevated Prevotella intermedia [0.53 (0.29, 0.97)] and Capnocytophaga ochracea [0.54 (0.31, 0.95)] IgG were statistically significant. Conclusion We have found elevated periodontal IgGs to be mostly unassociated with RF seropositivity in the nationally representative NHANES III. Elevated antibody levels to P. intermedia and C. ochracea were associated with lower odds of RF seropositivity. PMID:27110949

Co-administration of trientine and flaxseed oil on oxidative stress, serum lipids and heart structure in diabetic rats.

PubMed

Rezaei, Ali; Heidarian, Esfandiar

2013-08-01

The administration of flaxseed oil or flaxseed oil plus trientine in diabetic rats reduced triglyceride, very low density lipoprotein, and total cholesterol. Furthermore, the combined treatment significantly increased superoxide dismutase activity and attenuated serum Cu2+. The results suggest that the administration of flaxseed oil plus trientine is useful in controlling serum lipid abnormalities, oxidative stress, restoring heart structure, and reducing serum Cu2+ in diabetic rats.

Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly.

PubMed

Arpaci, Dilek; Karakas Celik, Sevim; Can, Murat; Ermiş, Esra; Kuzu, Fatih; Kokturk, Furuzan; Hamamcioglu, Ayse Ceylan; Dursun, Ahmet; Bayraktaroglu, Taner

2016-11-01

Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly. A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined. No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 ± 63.36 U/l in the case group and 63 ± 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively). Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters.