Vitamin D receptor BsmI and TagI gene polymorphisms in a Turkish ESRD population: influences on parathyroid hormone response.

BACKGROUND: Clinical presentation and complications of end-stage renal disease patients are influenced by many environmental and genetic factors. In this study we sought to define the frequencies of BsmI and TagI vitamin D receptor gene polymorphisms and their influences on clinical presentations in the Turkish end-stage renal disease population. METHODOLOGY AND PATIENTS: Hemodialyzed patients (n = 186; 111 male, 75 female) were genotyped for the insertion/deletion BsmI (B --> b, restriction site, exon VIII --> IX), TagI (T --> t, 352 exon IX) vitamin D receptor gene polymorphisms. The previous 12 months of laboratory values (C-reactive protein, intact parathyroid hormone, albumin, calcium, phosphorus, CaxP product) and clinical findings (vitamin D requirement, body weight) were analyzed retrospectively. RESULTS: Mean age and follow-up periods were 42.1 +/- 12.6 years and 76.3 +/- 43.9 months, respectively. Polymorphism percentages were BsmI; BB/Bb/bb: 28.9/65.3/5.8% and TagI; TT/Tt/tt: 36.7/60.5/2.8%, respectively. Further analysis revealed that the TT variant of TagI was related to hyperparathyroidism (P < .05). Analysis of the data after regrouping patients according to iPTH levels (0 to 249; 250 to 499; > or =500 pg/mL) and hemodialysis duration (<60 versus > or =60 months) revealed an influence of TT variation on hyperparathyroidism as a function of increased hemodialysis duration and higher iPTH levels (P < .005). CONCLUSION: TT variants of the TagI vitamin D receptor gene influence the development of hyperparathyroidism in hemodialysis patients, an influence that becomes more evident in patients with longer hemodialysis duration.

Angiotensin-converting enzyme and endothelial constitutive nitric oxide synthase polymorphisms in Turkish renal transplant population and possible influence on renal artery atherosclerosis and graft survival.

BACKGROUND: Renal transplant recipients are prone to accelerated atherosclerosis secondary to immunosuppressants, which may decrease graft survival. We sought to analyze the effects on renal graft survival of atherosclerotic degeneration in the renal artery and the influence of angiotensin-converting enzyme (ACE) endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms. METHODS AND PATIENTS: Thirty three renal transplant recipients (25 men) of mean age 28.4 +/- 9.6 years, received organs from 11 living related donors and were followed for at least 36 months. Genotyping was performed for the insertion/deletion ACE (I/D), angiotensin (AGT) (M-->T, 235), angiotensine 1 receptor (A-->C, 1166), angiotensin 2-receptor (A-->G, 1223), and ecNOS (b-->a, intron4) gene polymorphisms. Renal artery biopsies were performed during transplantation surgery to analyze the presence of atherosclerosis. RESULTS: Pathological examination indicated that 18 donor specimens and nine recipient specimens had atherosclerotic degeneration. Survival analysis (36 months) indicated that graft survival rates of recipients who had atherosclerosis in the renal artery and who received an organ from donors with an atherosclerotic renal artery were shorter than in their counterparts (P = .02, P = .04, respectively). Comparison of genetic variations of recipients revealed that CC/TC variation of AGT was higher in patients with atherosclerosis (81% vs 53%, P = .03). There was no significant difference between groups in means of other gene polymorphisms. CONCLUSION: Renin-angiotensin system gene polymorphism analysis of patients in renal transplantation waiting list may provide information about allograft survival and posttransplant atherosclerotic degeneration at graft vasculature of young transplant recipients.

Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9) polymorphism with bleeding complication.

Drug metabolism may be perturbed by genetically determined differences in the metabolic activity of cytochrome P450 enzymes. The authors encountered extensive bleeding in a patient receiving warfarin for anticoagulation after the introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme metabolises these drugs, it was determined whether variant alleles were responsible for altering warfarin handling. Genetic analysis established that the patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which exhibit lower drug metabolising capacity and enhance susceptibility to drug toxicity.

Gallbladder vasculitis associated with type-1 cryoglobulinemia.

A patient with type I cryoglobulinemia and monoclonal gammopathy of uncertain significance was found to have acute gallbladder vasculitis. The most prominent manifestation was upper abdominal pain in the setting of normal liver tests. An abdominal ultrasound demonstrated a thickened gallbladder wall, along with gallstones. HIDA scanning showed a nonfunctioning gallbladder with an edematous and thickened wall. There was characteristic leukocytoclastic vasculitis affecting the gallbladder. The patient recovered uneventfully subsequent to cholecystectomy. Gallbladder vasculitis should be considered in patients with unexplained upper abdominal pain and systemic vasculitis.

In vitro differentiation of human endometrial stromal cells: effect of transforming growth factor beta 1 on prolactin secretion.

OBJECTIVE: To investigate the role of Transforming Growth Factor beta 1 on differentiation of human endometrial stromal cells. STUDY DESIGN: A prospective study. MATERIAL AND METHODS: Human endometrial cells obtained from 9 women were cultured in DMEM-HAMs F12 media to adequate cell confluence and then the flasks were cultured in the presence and absence of TGF b 1. The influence of TGF beta 1 were measured by prolactin production expressed as nanograms of prolactin/mg of total DNA in cells measured by diphenylamine reaction. RESULTS: The levels of prolactin in the culture medium with and without TGF beta 1 were 0.16 +/- 0.27 ng/microgram DNA/day and 0.24 +/- 0.41 ng/microgram DNA/day respectively. There was no significant difference between groups. CONCLUSION: There is no direct effect of TGF beta 1 on differentiation of human endometrial stromal cells. However it may involve in more complex relationship in this process.

Paraproteinemia, plasmacytoma, myeloma and HIV infection.

We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.

Novel antiplatelet therapies for treatment of patients with ischemic heart disease: inhibitors of the platelet glycoprotein IIb/IIIa integrin receptor.

Blood platelets play essential roles in normal coagulation and in coronary atherosclerotic disease and its complications. Various antiplatelet therapies, including aspirin, ticlopidine, and dipyridamole, have been developed for use in patients with known coronary artery artery disease to prevent ischemic complications. More recently a more complete anti-aggregation effect has been accomplished by the use of monoclonal antibodies and specific peptide and nonpeptide compounds that bind to the platelet GP IIb/IIIa surface receptor. This receptor becomes activated by platelet stimulation and binds fibrinogen molecules between platelets in the aggregation process. These new antiplatelet drugs are now being evaluated in clinical trials in patients undergoing balloon coronary angioplasty, in whom fewer ischemic events occur when the receptor blocker is used intravenously than with standard therapy, and in patients with stable and unstable angina. Excessive bleeding is an important problem with these agents, and efforts must be made to eliminate this side effect.

Hematologic changes in massive burn injury.

OBJECTIVE: To study and report the striking hematologic changes that occur in patients with massive burn injury. DESIGN: Case reports and description of hematologic studies. SETTING: A municipal general hospital burn unit. PATIENTS: Three severely burned patients who survived, respectively, 45 mins, 22 hrs, and 57 hrs after hospitalization. METHODS: Routine clinical hematologic laboratory studies. RESULTS: The patients had intravascular hemolysis, and their RBCs exhibited spherocytosis, fragmentation, and vesiculation. Numerous fragments of red cell membranes were originally present in the blood and cleared within 4 hrs. These fragments may have contributed to the renal failure seen in these patients. The patients also had marked pseudothrombocytosis, presumably owing to "incorrect recognition" by the automatic counter of red cell microvesicles as platelets. CONCLUSIONS: Pseudothrombocytosis should be anticipated with massive burn injury. Despite high or normal platelet counts reported by the laboratory, evidence of intravascular coagulation should be promptly investigated.

Metastatic tumor: the complementary role of the marrow aspirate and biopsy.

To determine whether bone marrow aspiration or biopsy is more sensitive in the detection of nonhematologic metastatic involvement of marrow, all 1569 consecutive paired biopsy and aspirate samples obtained between January 1975 and January 1, 1986 in an 800 bed municipal hospital were reviewed. At least eight aspirate slides and 10 biopsy cross sections were examined for each pair. In 39 samples, both biopsy and aspirate identified metastatic tumor. No biopsies contained tumor that was not also seen on the aspirate. However, five aspirate slides contained metastatic malignancies not identified on biopsy. The hematologist or oncologist viewing individual cells in a monolayer at 1000 x magnification has the advantage of identifying very small clusters of tumor cells. That accounted for three of the five positive aspirate samples in which the biopsies were negative. The other two positive aspirate slides each contained tumor on only one of eight slides. The results of our study indicate that when carefully reviewed, the aspirate is at least as sensitive as the marrow biopsy for identifying metastatic tumor. Our results indicate that marrow aspirates and biopsies are useful and complementary examinations for identifying metastatic malignancy.