Molecular Characterization of a Full Genome Turkish Hepatitis C Virus 1b Isolate (HCV-TR1): A Predominant Viral Form in Turkey

Based on direct sequencing information from 5UTR and NS5B regions, we identified subtype 1b as a predominant hepatitis C virus genome in Turkey, which affected more than 91% of 79 patients studied. Next, the full genome sequence of a Turkish 1b isolate was obtained by the cloning of polypeptide-encoding region into 7 overlapping fragments. Turkish 1b isolate, which was named HCV-TR1, comprises 9361 nucleotides, including 306 nucleotides of 5UTR, a single long open reading frame of 9033 nucleotides, and 22 nucleotides of 3UTR. When compared to HCV 1b polypeptide sequences available at GenBank, the predicted polypeptide displayed a total of 36 amino acid substitutions, of which 16 was specific for HCV-TR1 isolate. Despite these changes, major structural and functional motifs of HCV proteins were maintained in HCV-TR1. In contrast, HCV-TR1 displayed amino acid substitutions in 6 out of 9 major cytotoxic T-cell epitopes. These data suggest that HCV-TR1 encodes functionally intact viral proteins, but it also encodes altered viral epitopes, which may affect host immune-response.     

Renal functional reserve in insulin dependent diabetic children

Abstract Background: Microalbuminuria has been shown to be predictive for clinical diabetic nephropathy. Renal functional reserve (RFR), as a response to protein loading in a short period of time, is a parameter to assess the ability of kidneys to increase the glomerular filtration rate (GFR). The aim of this study was to predict the early phase of diabetic nephropathy by measuring urinary albumin level and RFR capacity in patients with insulin-dependent diabetes mellitus (IDDM).
Methods: Twenty-two patients with IDDM were studied: 11 with a disease duration of less than 5 years (group 1) and 11 with a disease duration of more than 5 years (group 2). As the control group, 15 healthy children (group 3) were included in the study. At the beginning of the study, glucose was measured and the urinary albumin/creatinine ratio was calculated. Average glycosylated hemoglobin (HbA₁c) over 1 year was determined. After protein loading (red meat containing 2 g/kg of protein), the creatinine clearance was calculated at each hour for a duration of 4 h. The RFR was accepted as the peak percentage increase in GFR over the baseline value.
Results: Although metabolic control in group 2 was better, the RFR in group 2 was significantly lower than in group 1 (P < 0.05). Urinary microalbumin levels between the groups did not differ (P < 0.05). In two patients in whom microalbuminuria was detected, the RFR was much lower.
Conclusions: Detecting lower RFR levels in patients with normal urinary albumin excretion, as well as in patients with microalbuminuria, may support the idea that the RFR capacity is more sensitive than microalbuminuria in assessing the early phase of diabetic nephropathy.     

The clinical significance of JAK2V617F mutation for Philadelphia-negative chronic myeloproliferative neoplasms in patients with splanchnic vein thrombosis

Polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF), collectively known as Philadelphia-negative (Ph-negative) chronic myeloproliferative neoplasms (MPNs), MPNs represent the most common causes of splanchnic vein thrombosis (SVT), including Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT). The JAK2V617F mutation has been demonstrated in most of the Ph-negative chronic MPNs. The study objective was to assess the diagnostic value of JAK2V617F mutation in patients with SVT in a group of 68 patients with SVT (42 PVT,19 BCS, 7 combined PVT and BCS). By DNA-melting curve analysis, the JAK2V617F mutation was detected in 42.1 % of BCS, 38.1 % of PVT and 71.4 % of combined PVT and BCS groups. Thirteen of 15 (86.6 %) SVT patients with overt MPN and 16 of 53 (30.1 %) SVT patients without overt MPN (patients with either normal blood counts or cytopenias), including 6 of 16 with BCS (37.5 %), 7 of 33 with PVT (21.2 %) and 3 of 4 with combined BCS and PVT (75 %) possessed JAK2V617F mutation. A substantial proportion of patients with SVT were recognized as carriers of the JAK2V617F mutation despite the absence of overt signs of MPN. Receiver Operating Characteristic (ROC) curve analysis determined a platelet count of 190,000?mm(3) (area under the curve; AUC?=?0.724, p?=?0.002) and a white blood cell (WBC) count of 8,150?mm(3) (AUC?=?0.76, p?=?0.001) as the best cut-off values for the highest sensitivity and specificity ratios of the JAK2V617F mutation in patients with SVT. A significant positive correlation existed between the JAK2V617F mutational status of SVT patients and the WBC and platelet counts. Our results imply that JAK2V617F mutation screening should be an initial test for MPN in patients with SVT.     

Fatal Fever of Unknown Origin in Acute Cervical Spinal Cord Injury: Five Cases

Background/Objective: Patients with traumatic upper thoracic and cervical spinal cord injuries are at increased risk for the development of autonomic dysfunction, including thermodysregulation. Thermoregulation is identified as an autonomic function, although the exact mechanisms of thermodysregulation have not been completely recognized. Quad fever is a hyperthermic thermoregulatory disorder that occurs in people with acute cervical and upper thoracic spinal cord injuries. First described in 1982, it has not been widely discussed in the literature.

Methods: Case reports of 5 patients with cervical spinal cord injury (SCI).

Results: Five of 18 patients (28%) with acute cervical SCI who were admitted during a 1-year period had fatal complications caused by persistent hyperthermia of unknown origin.

Conclusions: Patients with acute traumatic cervical and upper thoracic SCI are at risk for thermoregulatory dysfunction. Changes in the hypothalamic axis may be implicated, especially in the light of modification in hypothalamic afferent nerves, but this hypothesis has not yet been explored. Thermodysregulation may be an early sign of autonomic dysfunction. A comprehensive guideline is needed for the management of elevated body temperature in critically ill patients with cervical SCI, because this condition may be fatal.     

Effect of clozapine on serum leptin,insulin levels,and body weight and composition in patients with schizophrenia

OBJECTIVE: Weight gain frequently occurs during treatment with clozapine. However, the pathophysiology of clozapine-induced weight gain remains unclear. The aim of this study was to investigate the influence of clozapine on hormones leptin and insulin in relation to body weight and composition measures to determine their contribution to clozapine-induced weight gain. METHOD: Data are reported on 19 patients with schizophrenia (11 women and 8 men) who completed 10 weeks of treatment with clozapine. Insulin levels, weight measurements, body mass index (BMI), and body composition measurements were evaluated at baseline and at the end of treatment. Leptin levels were assessed at baseline and after 4 and 10 weeks of treatment. Analysis of variance with repeated measures was used to evaluate changes in weight, body composition measures, leptin, and insulin. The Pearson correlations were used to assess the relationships between changes in hormone levels and weight along with body composition measurements. The correlations of change in Positive and Negative Syndrome Scale (PANSS) score with changes in hormone levels, weight gain and body composition measures were evaluated with Pearson correlations. RESULTS: Leptin and insulin levels did not show any significant alterations across time. The use of clozapine was associated with significant increases in BMI (F=19.8, P<.001), lean muscle mass (F=8.2, P=.01), and fat mass (F=15.4, P=.001), while total body fluid percentage (F=4.1, P=.05) significantly decreased. Improvement in PANSS scores was not correlated to change in leptin, insulin, weight, BMI, or body composition measurements. The change in leptin levels was correlated to change in body fat mass. CONCLUSION: The role of leptin in weight gain induced by clozapine might be a regulatory mechanism rather than being etiologic.     

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010. © 2010 Wiley‐Liss, Inc.     

Decreased adrenomedullin and total nitrite levels in breast milk of preeclamptic women

OBJECTIVE: To observe the adrenomedullin (AM) and total nitrite levels in the milk of preeclamptic and normal pregnant women. DESIGN AND METHODS: Fifteen women with preeclampsia and 15 normal pregnant women were included in the study. Total nitrite was quantitated by Griess reaction, while AM was measured by HPLC. RESULTS: The levels of AM and total nitrite in colostrum and 30th-day breast milk were decreased in preeclamptics. Total nitrite levels (micromol/l) were 56.09 +/- 11.18 vs. 82.20 +/- 12.01, P < 0.05, in colostrum of preeclamptics and controls, respectively. The level of total nitrite was 37.75 +/- 12.10 vs. 53.28 +/- 10.25, P < 0.05, in 30th-day milk of same patients. AM levels (pg/ml) were 11.18 +/- 1.11 vs. 16.59 +/- 1.24, P < 0.0001, in colostrum of preeclamptics and controls, respectively. In 30th-day milk of same patients, AM levels were 8.41 +/- 1.39 vs. 12.18 +/- 1.48, P < 0.005, respectively. CONCLUSION: This report shows for the first time that human milk has decreased levels of AM and total nitrite in preeclampsia.     

Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension

OBJECTIVES: Aim of this study was to evaluate implication of pregnancy induced hypertension on maternal plasma lipid, lipoprotein, apolipoprotein concentrations and lipid peroxidation products by a comparison of normal pregnancy vs. preeclampsia. DESIGN AND METHODS: Thirty-four women with preeclampsia and 32 healthy pregnant women (controls) in the third trimester were recruited for this study. RESULTS: In the preeclamptic group plasma total triglyceride, low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and apolipoprotein B (apo-B) were significantly increased, while plasma high density lipoprotein cholesterol (HDL-C) was significantly decreased compared to that of control group. There was no significant difference in total cholesterol and apolipoprotein A1 (apo-A1) concentrations. CONCLUSION: Our findings suggest that preeclampsia share some metabolic characteristics with coronary artery disease such as dislipidemia and increased lipid peroxidation. However lipoprotein concentrations may be better biochemical markers of dislipidemia in the preeclamptic state than the corresponding apolipoproteins.