Effect of some uremic toxins on oxygen consumption of rats in vivo and in vitro

In rats, oxygen consumption is reduced by about 40-50% 24 h after bilateral nephrectomy. This is also the case when the animals are pretreated with triiodothyronine, 3 x 0.75 mg/kg body weight orally, for 2-3 days. Indole, cresol, putrescine, methylguanidine or acetoine was given intraperitoneally to normal rats at doses of between 5 and 300 mg/kg body weight. Only low single doses of indole (5 mg/kg) reduced oxygen consumption significantly. Single doses of the other substances studied were ineffective even at tenfold higher doses. Some combinations of these substances, however, (10 mg/kg each), reduced the metabolic rate significantly. In contrast to the results in vivo, plasma of uremic rats, as well as the uremic toxins, dissolved in Krebs-phosphate buffer pH 7.4 at concentrations of 30 mg/dl each, had no influence on respiration of rat diaphragma or liver slices in vitro (single substances and different combinations).     

Do insecticide-treated curtains reduce all-cause child mortality in Burkina Faso?

To evaluate whether insecticide-treated netting (ITN) reduces child mortality in different epidemiological settings, 4 large, randomized, controlled trials were conducted in Africa. Here we report the findings from the trial in Burkina Faso, in an area of hyperendemic and markedly seasonal malaria transmission. The trial involved 158 villages, with a total population of some 90,000, grouped into 16 geographical clusters. Ascertainment of mortality among children aged 6–59 months began in early 1993. In June/July 1994, 8 of the clusters, randomly selected, received permethrin-treated curtains. Follow-up of children and ascertainment of mortality continued until May 1996. A 15% reduction in all-cause mortality among children aged 6–59 months was observed over the 2-year period following the installation of the curtains (95% c.i. – 4% to 30%). In the first year, post-intervention mortality was substantially lower in the clusters receiving curtains compared with the control clusters (rate ratio = 0.74; 95% c.i. 0.57, 0.95) but in the second year, there was no difference between mortality in the two groups (rate ratio = 0.99). The overall two-year impact of the intervention is consistent with the impacts observed in other trials which have demonstrated reductions in child mortality of from 17% to 33%. However, the year-by-year analysis raises some concerns about the long-term effect of ITN. Further follow-up of this population is warranted.     

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range 0.015 mg/1 to 8 mg/1). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.Die klinische Wirksamkeit und Sicherheit von Ciprofloxacin wurde bei 92 Patienten (Alter 26 bis 83 Jahre, im Mittel 57,5 Jahre), die an verschiedenen Leberkrankheiten litten, bei interkurrent aufgetretenen Harnwegs- und Atemwegsinfektionen geprüft. Ciprofloxacin wurde in verschiedenen Dosierungen oral verabreicht. Zur Behandlung von Harnwegsinfektionen wurden Dosierungen von 500 mg zweimal täglich (22 Fälle), 250 mg zweimal täglich (20 Fälle) oder 500 mg in einer täglichen Einzeldosis (20 Fälle) verabreicht. Atemwegsinfektionen wurden mit zweimal täglich 500 mg (10 Fälle) oder mit zweimal täglich 250 mg (20 Fälle) behandelt. Die Dosen wurden nicht nach dem Schweregrad der Erkrankung gewählt. Die Behandlungsdauer betrug fünf bis 15 Tage. Alle aus Sputum oder Urin vor der Therapie isolierten Bakterien waren für Ciprofloxacin empfindlich (MHK-Werte 0,015 mg/l bis 8 mg/l). Bei einem hohen Prozentsatz der Patienten mit Atemwegs- und Harnwegsinfektionen wurden unabhängig von der Dosierung günstige klinische und bakteriologische Ergebnisse erzielt. Nebenwirkungen traten selten auf (7%) und waren leicht (Übelkeit, Magenschmerzen, orale Candidiasis). Ein Therapieabbruch war in keinem Fall nötig. Bei keiner der angewandten Dosierungen waren Änderungen in den klinisch-chemischen Parametern festzustellen.     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.     

Haplotype analysis of BRCA1 gene reveals a new gene rearrangement: characterization of a 19.9 KBP deletion

Germ-line mutations in the BRCA1 gene cause hereditary predisposition to breast and ovarian cancer. BRCA1 and BRCA2 mutations account for about 40% of high-risk families. Mutation-screening methods generally focus on genomic DNA and are usually PCR based; they enable the detection of sequence alterations such as point mutations and small deletions and insertions. However, they do not allow the detection of partial or entire exon(s) loss, because the presence of the homologous allele results in a positive PCR signal, giving rise to a false-negative result. Identification of unusual haplotypes in patient samples by an expectation maximization algorithm has recently been suggested as a method for identifying hemizygous regions caused by large intragenic deletions. Using a similar approach, we identified a novel BRCA1 genomic rearrangement in a breast/ovarian cancer family negative at the first mutation screening; we detected a deletion encompassing exons 14-19, probably due to replication slippage between Alu sequences.     

Human ORFeome Version 1.1: A Platform for Reverse Proteomics

The advent of systems biology necessitates the cloning of nearly entire sets of protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional studies of the corresponding proteomes. Here, we describe the generation of a first version of the human ORFeome using a newly improved Gateway recombinational cloning approach. Using the Mammalian Gene Collection (MGC) resource as a starting point, we report the successful cloning of 8076 human ORFs, representing at least 7263 human genes, as mini-pools of PCR-amplified products. These were assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After assessing the overall quality of this version, we describe the use of hORFeome v1.1 for heterologous protein expression in two different expression systems at proteome scale. The hORFeome v1.1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome.     

Pathogenesis of pancreatic atrophy by avian influenza a virus infection

Specific-pathogen-free (SPF), 2-day-old chicks were inoculated with type A influenza virus (A/whistling swan/Shimane/499/83/(H5N3)) into their caudal thoracic air sac. The original isolate of the virus was of low virulence (ICPI 0. 20 to 0.40), and was passaged 10 times through the respiratory organs of SPF chicks. Most of the chicks inoculated with the passaged virus (strain 499) showed respiratory and alimentary signs. Three of 30 chicks died on days 2, 6 and 7 post-inoculation (p.i.). Almost half of the infected chicks showed poor growth, and the variation of body size in the flock became prominent from day 10 p.i. Infected chicks consistently had pathological changes in the pancreas, liver, kidneys and respiratory tracts, and occasionally in the brain, duodenum and bone marrow. Positive immunoreaction to avian influenza virus (AIV) antigen and recovery of the virus persisted for longer period in the pancreas than in other organs. The pancreatic lesions were caused by a direct, lytic virus infection of the acinar cells and contributed to poor growth of the chicks.