Reinvestigation of the Branimycin Stereochemistry at Position 17-C.

A conformational study of branimycin was performed using single-crystal X-ray crystallography to characterize the solid-state form, while a combination of NMR spectroscopy and molecular modeling was employed to gain information about the solution structure. Comparison of the crystal structure with its solution counterpart showed no significant differences in conformation, confirming the relative rigidity of the tricyclic system. However, these experiments revealed that the formerly proposed stereochemistry of branimycin at 17-C should be revised.

[Amyloidosis and pleural calcification]. / Amylose et calcinose pleurale.

INTRODUCTION: Pulmonary diseases during the course of generalised amyloidosis are principally represented by tracheobronchial involvement and diffuse parenchymal localizations. CASE REPORT: The authors report the case of a 66-year-old woman presenting with pleural amyloidosis in the context of generalised amyloidosis. Thoracoscopy performed in the investigation of recurrent transudative pleural effusions found evidence of an inflamed parietal pleura with areas of calcification. Pleural biopsies confirmed amyloid infiltration pleural ossification. Talc pleurodesis was performed. CONCLUSIONS: The authors' conclusion is that, meeting an unexplained pleural effusion even transudative during the course of a generalised amyloidosis, the thoracoscopy is the diagnosis key test as it allows moreover a pleural pleurodesis to be performed.

Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity.

BACKGROUND: Reactive oxygen species (ROS) are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to correlate this with parameters of inflammatory activity. METHODS: In 25 patients with Crohn's disease (CD), 20 patients with ulcerative colitis (UC) and 65 age- and sex-matched healthy volunteers ROS production was measured using the whole blood luminol enhanced chemiluminescence assay (LECA). Disease activity was assessed using the Crohn's disease activity index and the Ulcerative Colitis Symptoms Score (UCSS) for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. RESULTS: LECA was significantly higher in CD and UC patients compared with healthy controls (7.1+/-4.7 and 9.8+/-6 vs. 5.2+/-2.8 x 10(3) counts per minute (cpm), p<0.05 and <0.001). In CD, relative LECA (patient/control) was correlated with the Crohn's disease activity index and C-reactive protein (CRP) (r=0.54, p=0.001 and r=0.51, p=0.01). In UC, CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score (C-reactive protein: r=0.42, p=0.01). Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. CONCLUSION: Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical.

Granulocyte function in women with diabetes and asymptomatic bacteriuria.

OBJECTIVE: To study whether diabetic women with asymptomatic bacteriuria have impaired granulocyte function and compare them with nonbacteriuric diabetic women. RESEARCH DESIGN AND METHODS: A prevalence study with granulocyte function testing in a randomly selected number of patients was conducted; the setting was the university. The patients consisted of 63 women visiting the outpatient clinic for routine control of their diabetes. Measurements of routine blood controls and urine cultures were conducted in all patients. Granulocyte function testing (chemotaxis, opsonization, oxidative burst, phagocytosis, and killing) was performed in the first 20 patients (10 with and 10 without asymptomatic bacteriuria) and in 7 healthy control subjects. RESULTS: The prevalence of bacteriuria was 32%. Demographic characteristics were not significantly different between bacteriuric and nonbacteriuric women. Leukocytes were found more often in the urine of bacteriuric women (P < 0.05). No differences in any of the granulocyte function tests were documented among diabetic women with true asymptomatic bacteriuria, nonbacteriuric women, and healthy control subjects. CONCLUSIONS: The prevalence of asymptomatic bacteriuria is increased in women with diabetes. Granulocyte function impairment, however, cannot be the explanation for this finding.

[Neonatal rhinopharyngeal obstruction due to craniopharyngioma]. / Obstruction rhinopharyngée néonatale par craniopharyngiome.

BACKGROUND: Craniopharyngioma, the most common tumor of the sellar and suprasellar regions in childhood, can exceptionally develop in the infrasellar area. CASE REPORT: A premature girl (GA: 30 weeks) weighing 1240 g required intubation and ventilation because she suffered from a neonatal respiratory distress syndrome. Nasal endoscopy showed total obstruction of rhinopharynx by a tumor resembling adenoid tissue. This tumor was successfully excised and its histological examination showed a craniopharyngioma. CONCLUSION: A wide range of intranasal tumors has to be examined, endoscopy and CT scan are necessary for a precise localization and to eliminate meningocele.

Pharmacokinetics of single-dose intravenous, oral, and intraperitoneal pefloxacin in patients on chronic ambulatory peritoneal dialysis.

Comparison of plasma and dialysate concentrations of pefloxacin after intravenous, oral, or intraperitoneal administration shows excellent bidirectional diffusion of the quinolone through the peritoneal membrane, demonstrating that therapeutical concentrations can be achieved in the dialysate after intravenous or oral administration. In this study, the half-life of the drug was 18.8 +/- 1.4 h, i.e., apparently longer than that reported for normal controls or uremic patients on hemodialysis.

Uncoupling of oxidative and non-oxidative mechanisms in human granulocyte-mediated cytotoxicity: use of cytoplasts and cells from chronic granulomatous disease patient.

Human polymorphonuclear leukocytes (PMN) and granule-free cytoplasts were compared for their cytotoxic capacities against red blood cells (RBC) and K562 tumor cells. Phorbol myristate acetate (PMA) stimulated PMN to efficient lysis of RBC targets, while cytotoxicity against the tumor cell line K562 was moderate. Activated cytoplasts also lysed RBC targets but were not able to kill K562 tumor cells, even at high cell numbers. Suppression of the glutathione redox cycle of the K562 tumor targets markedly increased their susceptibility to lysis by PMA-activated PMN. Despite the enhanced susceptibility of antioxidant-depleted K562 tumor cells to oxygen radical-induced damage, PMA-stimulated cytoplasts did not kill these targets. Addition of exogenous myeloperoxidase or lactoferrin to cytoplasts devoid of granule did not improve the lysis of RBC and K562 tumor cells. Coating K562 targets with specific antibodies induced efficient PMN-mediated killing in comparison to PMA-stimulated lysis of non-coated targets. Cytoplasts, however, did not kill antibody-coated K562 tumor cells; this was not improved by glutathione depletion but showed some lysis of antibody-coated RBC. PMN from a patient with chronic granulomatous disease (CGD) showed normal antibody-dependent cell-mediated cytotoxicity (ADCC) against K562 tumor cells but were not able to lyse these targets after PMA stimulation. The analysis of target cell killing by cytoplasts and PMN from a CGD patient indicated that granular constituents are important mediators in the killing of nucleated target cells and that PMN-mediated ADCC does not require the release of reactive oxygen species. Differences in the susceptibility of target cells to oxygen-mediated lysis indicates that target cell antioxidant mechanisms play an important role in the outcome of the cytotoxic response.

[Epidemiology of primary glomerulonephritis in Picardie]. / Epidémiologie des glomérulopathies primitives en Picardie.

Between 1 January 1976 and 31 December 1986, primary glomerulonephritis was histologically diagnosed in 319 patients, living in a region of 675,000 inhabitants at the time of renal biopsy. The prevalence of primary glomerulopathy was 0.4/1000 inhabitants. The annual incidence was determined during two 5 year periods: period A (1976-1980) and period B (1981-1985): they were, respectively, 3.4 and 4.5 for 100,000 inhabitants. Berger's focal glomerulonephritis was the most common (30 p. 100) and its incidence was increasing. In contrast, membranoproliferative and acute glomerulonephritides were sharply decreased (almost disappeared), while membranous glomerulonephropathies and glomerulopathies with minimal glomerular lesions or proliferative forms with crescents increased. All primary glomerulonephritides were more prevalent in men and their frequencies increased with age. Our findings lead to the following conclusions: a) the low prevalence and incidence of primary glomerulopathies (3 times less than in other published studies) probably reflect the under medicalization of our region and the attractiveness of neighbouring metropolis, rather than a real decrease in the disease; b) the quasi- disappearance of acute and membranoproliferative glomerulonephropathies and the high incidence of IgA glomerulonephropathies suggest that their pathogenetic associations with infections sensitive to antibiotics are different; c) the increased frequency of membranous glomerulonephropathy and the glomerulopathy with minimal glomerular lesions in aged subjects is most likely due to their polymedication.

Quantitation of conjugate formation between human polymorphonuclear leukocytes and antibody-coated target cells by flow cytometry: the role of Fc receptor and LFA-1 antigen.

The specific binding of human polymorphonuclear leukocytes (PMN) to antibody-coated target cells was characterized by flow cytometry. PMN were labeled with phycoerythrin-E (PE) via a granulocyte-specific monoclonal antibody (leu-M1) and mixed with fluorescein isothiocyanate-labeled K562 tumor cells sensitized with rabbit antiserum. Specific conjugates were formed as analyzed by two-color fluorescence in a flow cytometer. The formation of stable conjugates was dependent on initiation of contact, temperature, time, and antiserum concentration. Studies with inhibitors implicate that microfilaments, but not microtubules, Ca2+, Mg2+, or energy-dependent processes were a prerequisite for binding of PMN to the antibody-coated target cells. No conjugates were formed when uncoated target cells were used or when the experiment was performed in the presence of protein A, indicating that binding was specifically mediated through Fc receptors (FcR). Monoclonal antibodies against the FcRII and FcRIII were used to address the role of these receptors in conjugation. One of the two anti-FcRIII antibodies and an anti-FcRII antibody effectively prevented conjugation. A monoclonal antibody directed against the common beta-chain of the adhesion molecule family and a combination of antibodies against the alpha-chain of LFA-1 and Mo-1 also blocked conjugation when target cells were sensitized under suboptimal conditions. The antibody against the beta-chain also diminished killing of antibody-coated K562, as measured by chromium release when included in the cytotoxicity assay. These results indicate that flow cytometry permits accurate quantitation and characterization of the binding between PMN and antibody-coated target cells, which in principle, can be prevented by monoclonal antibodies against surface receptors. Binding is primarily established by both the FcRII and FcRIII. Adhesion-associated molecules on the PMN surface contribute to optimal binding.

Comparison of dilevalol and enalapril administered once daily for mild hypertension.

This was a multicenter, randomized, double-blind, parallel-group study of the efficacy and safety of dilevalol, 200 mg (n = 86), compared with enalapril, 20 mg (n = 92), administered once daily to patients with mild hypertension. Three weeks of placebo washout were followed by 4 weeks of comparative treatment. Beginning with the first week of treatment, both drugs substantially decreased blood pressure from baselines of approximately 160/100 mm Hg. Decreases in systolic pressure were comparable throughout treatment, but dilevalol tended to have a greater effect on diastolic pressure. At the end of double-blind treatment, average decreases in blood pressure with dilevalol and enalapril were 16/13 and 16/11 mm Hg supine and 15/13 and 15/10 mm Hg standing (p = 0.03 for between-group comparisons of standing diastolic pressure). More dilevalol- than enalapril-treated patients achieved a diastolic pressure less than 90 mm Hg; 73 vs 55% (p = 0.02) supine, and 69 vs 43% (p less than 0.01) standing. The safety profiles of the 2 drugs were comparable. The incidence of adverse effects was low, and few patients discontinued treatment. Headache and gastrointestinal discomfort were reported in both groups. Average postural changes in blood pressure were similar to baseline. Electrocardiographic changes were rare and not treatment related. Changes in laboratory test results were minor. Heart rate decreased modestly with dilevalol relative to enalapril (6 vs 2 to 3 beats/min; p less than 0.01), but no bradycardia was observed.

Antibody-coated target cell membrane-induced chemiluminescence by human polymorphonuclear leukocytes.

Activation of the oxidative metabolic burst of human polymorphonuclear leukocytes (PMN) by antibody-coated crude membrane fragments of K562 tumor cells was measured in a luminometer. Induction of the chemiluminescence (Cl) response was measured in the presence of luminol and lucigenin. The Cl was dependent on the concentration of PMN, the enhancer luminol or lucigenin, and the amount of tumor cell fragments and anti-K562 serum. PMN were not triggered to a Cl response in the absence of antibodies. The lucigenin-enhanced Cl involved superoxide anion detection while the luminol-enhanced Cl was dependent on the presence of myeloperoxidase and involved hydroxyl radicals. An intact cytoskeleton and energy were necessary for an optimal Cl response.

Prevention of osteitis fibrosa, aluminium bone disease and soft-tissue calcification in dialysis patients: a long-term comparison of moderate doses of oral calcium +/- Mg(OH)2 vs Al(OH)3 +/- 1 alpha OH vitamin D3.

Since 1980, moderately large doses of oral calcium (80 +/- 35 mmol/day as CaCO3 +/- calcium polystyrene sulphonate), in association if necessary with Mg(OH)2 (2.5 +/- 1 g/day), with a reduction in the dialysate Mg concentrations from 0.75 to 0.375 mmol/24 h, have replaced A1(OH)3 as phosphate binders in our centre. A1(OH)3 was previously given to our haemodialysis patients in association with small doses of Ca CO3 (less than or equal to 3 g/day) and if necessary with 1 alpha OH vitamin D3. To compare the long-term efficacy of this new approach with the former one in the prevention of renal osteodystrophy and soft-tissue calcification, 32 current patients were selected on the basis of at least 24 months of treatment in our centre and availability of a yearly bone survey (profile of lumbar spine and anteroposterior view of the pelvis, shoulders and hands). A group of 30 patients treated before 1980 were then selected on the same criteria and matched for age, sex, and duration on dialysis. Linear calcifications of the anterior and posterior walls of the aorta in front of L2, L3, L4 and on the lateral walls of the iliac and femoral arteries were measured and the para-articular calcifications and subperiosteal resorptions of the hands evaluated. The initial extent and the subsequent increase of the ocular and para-articular calcification were comparable in the two groups. Plasma alkaline phosphatase was stable in the normal range in both groups, as was plasma concentration of calcium. Plasma phosphate was slightly elevated (1.7 mmol/l) but stable and comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-molecular-weight heparin Fraxiparin in chronic hemodialysis. A dose-finding study.

A two-step dose-ranging study was undertaken with CY216 (Fraxiparin) in 8 patients on 7 sessions each. The different doses were administered each time as a single bolus injection at the start of hemodialysis without heparinized priming nor further administration during the 4-hour session. In the first step, the clinical efficacy of 4 different doses of Fraxiparin was compared with that of standard heparin on the percentage of sessions free of clot formation in the extracorporeal circulation (ECC). Safety was evaluated by the compression time for hemostasis at the puncture sites. The second step was a randomized comparison of 3 Fraxiparin dosages. In addition to the clinical assessment of efficacy, the following biological parameters were measured: fibrinopeptide A (FPA), anti-Xa (AXa) activity calibrated against Fraxiparin, thrombin time (TT), activated partial thromboplastin time, blood counts, hemoglobin, hematocrit, plasma creatinine and urea, and residual blood volume in the dialyzer. A 'standard' dosage of 10,000 AXa Institut Choay units of Fraxiparin was shown to prevent clot formation in the ECC. It resulted in a marked increase in TT, without any lengthening of the puncture site compression time. After 4 h, AXa and FPA levels in the venous line were related to the doses used (p less than 0.05). After 48 h AXa activity was very low. Dialysance and tolerance were excellent. Thus, a single dose of Fraxiparin unrelated to body weight and not determined by the measurement of the whole-blood activated clotting time appeared to be a safe and effective means for preventing fibrin formation in 4-hour dialysis sessions.