Comparison of two cyclophosphamide treatment regimens in nephrotic patients with chronic glomerulonephritis

AIM: Comparison of two cyclophosphamide (CPA) treatment regimens in chronic glomerulonephritis (CGN) patients: oral daily CPA versus intravenous CPA pulses (IV-CPA) MATERIALS AND METHODS: 31 nephrotic patients entered the trial: 12, 16 and 3 with membraneous, mesangial proliferative and mesangiocapillary CGN, respectively. The patients were randomized into two groups. 13 patients of group 1 received oral CPA (1.5-2.0 mg/kg/day for 6 months, while 18 patients of group 2 received IV-CPA pulses (20 mg/kg/monthly, at least 6 pulses) combined with oral prednisolone (40-6-mg/day during 1.5 mo with subsequent tapering). At entry, no statistical differences (p > 0.05) were found between groups 1 and 2 by age, gender, duration of the renal disease, serum creatinine levels, frequency of arterial hypertension. Mean duration of follow-up was 27.6 and 22.6 mo (p > 0.05) for group 1 and 2, respectively. RESULTS: After 6 months of follow-up there was no difference in the rate of complete and partial remission between the groups (69 and 83% for group 1 and 2, respectively). The rate of renal function deterioration was also similar. Side effects occurred 3 times more frequently in group 1 than group 2. The mean cumulative course dose of CPA per 1 patient in group 1 was 35.6 g, in group 2--5.6 g. CONCLUSION: The effectiveness of methods was similar irrespective of CGN morphological form, but in spite of similar rates of remission of nephrotic syndrome, pulse CPA is preferable being more safe as to possible complications.     

An epidemic of besnoitiosis in cattle in Kenya

OBJECTIVE: Peptic ulcer disease is rare in the absence of Helicobacter pylori. Testing for H. pylori has recently become easier with the development of Near Patient Tests. However, the validity of many of these tests is unknown. The aim of this study was to assess the validity of the QuickVue one-step Near Patient Test for H. pylori in a group of patients attending for endoscopy at a tertiary referral hospital. METHODS: In a retrospective study the QuickVue one-step serum test (Quidel) was performed on the stored serum from 193 patients whose H. pylori status had been determined by a 'gold standard' using urease testing, histology, culture and 14C-urea breath testing. Twenty four other patients presenting to endoscopy were studied prospectively. For these patients QuickVue was performed on capillary and venous samples and the results were compared to a similar 'gold standard'. Enzyme immunoassay (Premier, H. pylori, Meridian Diagnostics, OH, USA) was used to define H. pylori status of patients with indeterminate H. pylori status by the above criteria. RESULTS: In the retrospective study the QuickVue one-step H. pylori test had a sensitivity (CI) of 82% (75-89) and specificity of 83% (74-92). In the prospective study on capillary blood its sensitivity (CI) was 89% (52-100) and its specificity 93% (68-100); and on venous blood, 78% (40-97) and 93% (68-100). Premier has previously been shown to have a sensitivity and specificity of 100%. CONCLUSION: In this group of patients the QuickVue one-step H. pylori Near Patient Test was less accurate than the Premier ELISA test, but its ease of use and availability in primary care make it useful for patient screening.     

Polymorphism in the alleles of tetranucleotide repeat SE33 in Udege and in two urban populations of Russia

Capillary electrophoresis was used to separate diastereomers and enantiomers of synthesized thiopyrans and thiinopyrroles. Separation conditions were optimized by varying the buffer parameters, i.e., kind and concentration of chiral selector, pH, main buffering component, micelle forming additives, and content of organic solvents. The interaction of thiopyrans and thiinopyrroles with beta- and gamma-cyclodextrins results in the separation of enantiomers and diastereomers. The magnitude of the resolution depends on the spatial requirements of the different substituents of the analytes and the dimensions of the cyclodextrin cavity. For well-separated enantiomers or diastereomers the identification and characterization of degradation products was possible.     

Retroviral-mediated gene transduction of human alkyltransferase complementary DNA confers nitrosourea resistance to human hematopoietic progenitors

Myelosuppression is the dose-limiting toxicity for nitrosourea chemotherapy due to low levels of the DNA repair protein O6-alkylguanine-DNA alkyltransferase in myeloid precursors. We have shown that high-efficiency myeloproliferative sarcoma virus (vM5MGMT)-mediated transduction of the human MGMT cDNA into murine bone marrow (BM) cells leads to high MGMT expression and increased progenitor resistance to 1,3-bis-(2-chloroethyl) nitrosourea (BCNU) in vitro immediately after infection and after BM transplantation. These experiments were designed to increase MGMT expression in human hematopoietic progenitors. CD34(+) BM cells were isolated over an immunoaffinity column (CEPRATE, CellPro, Inc.), resulting in a mean 66-fold enrichment in clonogenic progenitors (colony-forming unit granulocyte-macrophage + burst-forming unit erythroid + colony-forming unit granulocyte erythroid macrophage = megakaryocyte), with an average progenitor yield of 58 +/- 11.5% and a final population that was 54% CD34(+). Seventy % of progenitors derived from CD34(+) cells were transduced after coculture with AM12-vM5MGMT retroviral producers. vM5MGMT-transduced progenitors were over 2-fold more resistant to concentrations of BCNU between 30 and 50 micrometer than were concurrently LacZ-transduced progenitors (P < 0.003). In vitro selection of transduced, cytokine-stimulated CD34(+) cells with 20 micrometer BCNU resulted in survival of 4.7% of MGMT+ clonogenic progenitors compared to 0.05% of LacZ+ progenitors. These studies indicate that MGMT-transduced human hematopoietic progenitors have increased resistance to nitrosoureas, and in a clinical transplant setting, this strategy may reduce alkylating agent myelosuppression.     

The risk of infection with HIV and hepatitis B in individuals who inject steroids in England and Wales

The present study was designed to ascertain whether the negative effects on reproductive potential of post-ovulatory ageing in vitro of oocytes can be prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were aged in vitro for 12 h prior to insemination in the presence of varying concentrations of L-ascorbic acid, 6-methoxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta-mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was associated with lower fertilization rate, higher proportion of concepti exhibiting cellular fragmentation at 24 h post-insemination and lower percentage of concepti reaching the blastocyst stage. Ascorbic acid, Trolox and EDTA had no effect on cellular fragmentation or potential of oocytes for development. However, the probability of an oocyte reaching the blastocyst stage was decreased (P < or = or = 0.05) in oocytes incubated in the presence of L-cystine (50 and 500 microM) and beta-mercaptoethanol (5, 50 and 500 microM) when compared to control aged oocytes. Age-associated cellular fragmentation at 24 h post-insemination was partially prevented (P < or = 0.05) by incubating oocytes in the presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM) increased (P < or = 0.05) fertilization rate and number of cells at 81 h post-insemination to levels similar to those exhibited by control oocytes. Furthermore, both age-associated fragmentation at 24 h post-insemination (P < or = 0.05) and decreased potential of oocytes for development to the blastocyst stage (P < or = 0.05) were prevented, at least in part, by culturing oocytes in the presence of DTT (50 microM). Although the mechanism by which DTT exerts its beneficial effects on aged oocytes remains to be elucidated, it may protect oocytes by preventing oxidation of free thiol groups and/or altering a redox-independent signalling pathway that mediates cellular fragmentation and death.     

Factors in the persistence of opportunistic microorganisms in dysbacteriosis of the gastrointestinal tract

The presence of correlation between the quantitative content of individual carboxylic acids and aromatic compounds of microbial origin in feces and the degree of the antagonistic activity of feces was proved in experiments on conventional laboratory rats receiving therapeutic doses of tetracyclin and pefloxacin for 8 days. Antagonistic activity was regarded as one of the factors of the colonization resistance of the intestine to the invasion of opportunistic microorganisms, and microbial metabolites studied in this work were regarded as factors contributing to the persistence of these microorganisms.     

Management of varicella infection during the course of inflammatory bowel disease

OBJECTIVE: To study the natural history and outcome of varicella infection developing in steroid treated inflammatory bowel disease. BACKGROUND: Varicella infection occurring in immunosuppressed or immunocompromised patients is a common problem with a significant mortality. Varicella infection during the course of inflammatory bowel disease has been reported in a small number of patients with at least one fatality. METHODS: Four young patients with inflammatory bowel disease who developed varicella infection while on immunosuppressive therapy, steroids, or azathioprine were studied. In each patient the infection was severe, and the three most recently treated patients received acyclovir. RESULTS: All four patients developed severe varicella infection while receiving immunosuppressive therapy for their disease. Three patients were treated with intravenous acyclovir with concomitant reduction of steroid dosage and recovered completely. One patient, treated in 1980 with antibiotics and reduction in steroids, did not receive acyclovir and also survived. CONCLUSIONS: Varicella infection is a relatively uncommon occurrence in inflammatory bowel disease. If varicella infection occurs, prompt diagnosis and treatment with acyclovir and concomitant reduction in immunosuppressive therapy (reduction in steroid dosage and discontinuation of azathioprine) should be initiated immediately to limit viremia and avoid fatal complications.