Membranoproliferative glomerulonephritis and a rare bleeding disorder: factor X deficiency

Factor X (FX) deficiency is a rare hereditary coagulation disorder. This is the first case report on the association of FX deficiency and membranoproliferative glomerulonephritis (MPGN) type I. The patient, a 17-year-old male, presented with edema, hypertension, and microscopic hematuria, followed by a mild upper respiratory tract infection. Laboratory tests revealed: serum creatinine 1.6 mg/dl, serum albumin 2.80 g/dl, C3 16 mg/dl and proteinuria (1,800 mg/day). The renal biopsy showed MPGN type I. The coagulation profile prior to percutaneous renal biopsy revealed prolonged prothrombin time and activated partial thromboplastin time values. The patient was given fresh frozen plasma and vitamin K before the biopsy. Further evaluation showed the functional activity of FX was 7% of the norm. This case emphasizes the need for routine coagulation screening before percutaneous renal biopsy.     

Investigation of the functional characteristics of antibodies to therapeutic anti-human tumor necrosis factor alpha monoclonal antibody

Humanized antibody-based treatment modalities represent an active area of investigation. Included in these strategies are passive administrations of monoclonal antibodies, which recognize tumor necrosis factor alpha (TNF-alpha). However, several problems associated with these types of treatment strategies have been reported in the literature. We attempted to address the issue related to unresponsiveness to infliximab that might be induced by anti-idiotype response to the passively administered humanized monoclonal antibody. The characteristics and functional importance of antibodies to infliximab (ATI) were investigated in human sera. We studied the binding characteristics of ATI to infliximab, TNF-alpha Receptor-I (RI, p55) and Receptor-II (RII, p75). In addition, cytotoxicity effect on L929 cells and blocking effects on the binding of TNF-alpha with infliximab and etanercept were also analyzed. On the basis of the results obtained from the experiments, it seems that the target epitope for ATI is related with somewhere else not residing in the region capable of generating "mirror image". The results presented indicate that ATI does not mimic the functional characteristics of TNF-alpha. However, ATI inhibited the binding properties of infliximab to TNF-alpha.     

Acinar cell carcinoma of the pancreas and related neoplasms: a review

Acinar cell carcinomas (ACCs) are rare tumours of the exocrine pancreas, accounting for up to 2% of all pancreatic neoplasms in adults and 15% of those in children. They are typically solid, cellular, stroma-poor tumours composed of sheets of relatively uniform cells. This sheet-like arrangement is usually punctuated by variable numbers of acinar structures. Variable amounts of neuroendocrine elements in the form of scattered individual cells are quite common, and some cases have more significant neuroendocrine or ductal elements (mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma).Demonstration of acinar differentiation, usually by immunohistochemistry, is necessary for the diagnosis. Among the antibodies recognizing various pancreatic enzymes, trypsin and chymotrypsin are the most useful. Molecular alterations characteristic of ductal adenocarcinomas such as mutation in the KRAS oncogene are absent in ACCs. However, allelic loss on chromosomes 11p and mutations in the APC/β-catenin pathway have been identified in about 50% and 25% of cases, respectively.ACCs are fairly aggressive tumours, although they are not as dismal prognostically as ductal adenocarcinomas. Those patients who present with localized disease have a much better prognosis than those who present with metastases (5-year survival rate of 25% vs. 50%). Unfortunately, metastases, usually involving the liver, are present in 50% of patients at the time of diagnosis.     

Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients

It has been proposed that new atypical antipsychotics cause minimal prolactin (PRL) elevation compared to traditional antipsychotic agents because they spare dopamine blockade within the brain's tuberoinfundibular tract. The aim of this study was to compare the effects of olanzapine and haloperidol on PRL secretion in male schizophrenic patients. Twenty-nine male schizophrenic inpatients were included in the study. Fifteen of them were given olanzapine in a fixed dose of 10 mg/day PO and 14 of them were given haloperidol in a fixed dose of 10 mg/day PO for 6 weeks after a 2-week drug washout period. Fifteen age-matched healthy control subjects were used as control group. PRL levels were measured both before and after the 6-week treatment period in the patients. At the end of the 6th week, the PRL values observed with olanzapine treatment were significantly less than those observed with haloperidol, but not different from those of the controls. There was a significant positive correlation between the PRL values and the severity of extrapyramidal side effects in only the haloperidol group after the six week's treatment period. Our data indicate that short-term olanzapine treatment at doses of 10 mg/day PO causes minimal elevations in PRL secretion in male schizophrenic patients in contrast to haloperidol. This finding is consistent with the previous reports and may be attributed to olanzapine's differential effects on dopamine neurotransmission.     

Urinary N-acetyl B glucosaminidase as an earlier marker of diabetic nephropathy and influence of low-dose perindopril/indapamide combination

INTRODUCTION: Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. N-Acetyl B glucosaminidase (NAG) is derived from proximal tubular cells and is widely used to evaluate tubular renal function. OBJECTIVE: The objective of this study is whether NAG can be used as an early marker of diabetic nephropathy by comparing the urinary NAG levels between healthy controls and diabetic patients and determining changes in urinary NAG excretion after treatment with low-dose combination perindopril (2 mg)/ indapamide (0.625 mg)/o.d. MATERIALS AND METHODS: A total of 50 patients (29 female) with type II diabetes mellitus applying to our diabetes outpatient clinics for the first time were included in our study (Group 1). Diabetic patients were classified into three subgroups on the basis of their duration of diabetes: Group 1A (n = 15) < or = 3 years, Group 1B (n = 19) 3 to 5 years, and Group 1c (n = 16) > 5 years. The inclusion criteria were no prior use of antihypertensive agents; blood pressure < 130/85 mmHg; urinary albumin excretion < 30 mg/day; and absence of renal failure, diabetietes, and hypertensive retinopathy. A total of 30 healthy individuals (16 female) (Group 2) were assessed as the control group. Systolic and diastolic blood pressures, HbA1c, body mass index, 24-h microalbuminuria (MAU), and NAG measurements in urine samples were performed by using colorimetric assay method in an analyzer (Roche Cobas Mira). The assay defined as fragmentation of 3-cresolsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide molecule by NAG to 3-cresolsulphonphthalein and N-acetylglucosamine molecules and serum creatinine were measured in all groups. Type II diabetic patients were administered perindopril (2 mg)/indapamide (0.625 mg) combination once daily for 4 months, and urinary NAG levels were measured at the end of treatment. RESULTS: Statistically significant differences were observed between the groups 1 and 2 with respect to the levels of NAG and HbA1c (p < 0.05). In the treatment group, NAG levels decreased significantly (p < 0.05), whereas blood pressure and HbA1c levels did not change significantly (p > 0.05). In diabetic patients, pretreatment NAG were lowest in Group 1A and highest in Group 1c, although the difference between the treatment subgroups was not statistically significant (p > 0.05). CONCLUSION: Urinary NAG excretion is elevated in type II diabetic patients as compared with the healthy individuals. Perindopril/indapamide administration is effective in reducing urinary NAG excretion in these patients, and this effect seems to be independent from blood pressure and glycemia control. Presence of tubular proteinuria may be an early indicator of diabetic renal disease in patients without microalbuminuria. Perindopril (2 mg)/ indapamide (0.625 mg)/o.d. treatment may have beneficial effect on the tubulointerstitial damage in diabetic kidney disease.