The prevention of cisplatin-induced renal dysfunction by hydroxyl-containing dithiocarbamates.

Two hydroxyl containing dithiocarbamates, sodium N-methyl-D-glucamine dithiocarbamate (NaG) and sodium dihydroxyethyl dithiocarbamate (NaY) have been examined as agents for the control of the renal dysfunction in rats given cisplatin. Of these, NaG was found to be the more effective in controlling such renal dysfunction when administered at 1 and 3 h after 5 mg cisplatin kg-1, i.p. Renal function was examined 5 days after the administration of cisplatin by measurement of serum and urinary levels of creatinine and urea, creatinine clearance, serum and urinary levels of Na+, K+, Mg2+, Ca2+, as well as the concentrations of these ions in the renal medulla and cortex. Treatment of rats given cisplatin with NaG at 1 and 3 h post cisplatin resulted in indices of renal function which were not significantly different from those of animals which had received no cisplatin. The sole difference was found to be a slight increase in renal cortical Na+ concentration.     

Neurotoxic envenoming by an immigrant spider (Steatoda nobilis) in southern England.

A young woman was bitten on the shoulder by a female Steatoda nobilis spider, in Worthing on the south coast of England. She noticed intense radiating pain, local sweating (indicating parasympathetic stimulation) and feverishness. This immigrant species from the Canary Islands has established itself along the south coast of England in recent years. Like the related Mediterranean species S. paykulliana, S. nobilis may be of medical importance and deserves further study.     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Imipenem/cilastatin therapy of infections in cancer patients

Imipenem/cilastatin was administered during 153 febrile episodes occurring in cancer patients and the response rate was 68%. Considering only documented infections the response rate was 71%. Patients who received imipenem as initial therapy had a higher response rate than patients who received it after failing other antibiotics (77% versus 68%). The overall response rates for septicemias and pneumonias were 75% and 58%. Among the 57 gram-negative infections 77% responded, but the response rate was substantially higher if imipenem was used as initial therapy (94% versus 69%). The poorest response rate was observed when imipenem was given as secondary therapy for Pseudomonas infections (50%), but most of these patients had failed to respond to other appropriate antibiotics. The only serious side effect was seizures which occurred in ten patients, although eight of them had other predisposing factors. Imipenem appears to be a useful antibiotic for treatment of infections, even in neutropenic cancer patients.     

Bone levels of cephradine and cefuroxime after intravenous administration in patients undergoing total hip replacement

Summary A randomised, comparative study is reported of single intravenous doses of cephradine 2 g or cefuroxime 1.5 g given as prophylactic cover for total hip replacements in 40 patients. The serum and bone levels of cephalosporin achieved were higher in the cephradine treated group in proportion to the higher dose employed. Both agents provided adequate bone levels on average, cephradine 25.34 mcg/g, cefuroxime 17.39 mcg/g, although bone penetration was more variable with cefuroxime.

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Résumé Dans cette étude comparative randomisée, 40 patients ont reçu une dose intraveineuse unique de 2 g de céphradine ou de 1,5 g de céfuroxime en tant que couverture prophylactique d'arthroplastie totale de hanche. Les concentrations sériques et osseuses de céphalosporine ont été plus élevées dans le groupe traité par la céphradine, en rapport avec l'utilisation d'une dose plus importante. Des concentrations osseuses adéquates ont été obtenues en moyenne avec les deux produits (25,34 mcg/g avec la céphradine et 17,39 mcg/g avec le céfuroxime) bien que la pénétration osseuse ait été plus variable avec le céfuroxime.

     

Hospital acquired native valve endocarditis caused by Acinetobacter calcoaceticus and treated with imipenem/cilastin

A case of hospital acquired endocarditis due to Acinetobacter calcoaceticus in a severely burned patient is presented. Both aortic and mitral native valves were affected and the organism was resistant to most antimicrobial agents.     

Common pancreaticobiliary channels and their relationship to gallstone size in gallstone pancreatitis.

Bile reflux into the pancreatic duct after impaction of a stone in a common pancreaticobiliary channel has been suggested to be the initiating factor in gallstone pancreatitis. Such reflux would require that the impacted stone be smaller than the length of the common channel. The incidence of common channels was studied and gallstone size was compared with common channel length in patients with gallstone pancreatitis and those with cholelithiasis or choledocholithiasis without pancreatitis. Sixty-seven per cent of patients with gallstone pancreatitis had a common channel present on intraoperative cholangiography versus 32% of patients with cholelithiasis or choledocholithiasis without pancreatitis (p less than 0.005). Common channel length was greater than the diameter of the smallest stone in nine of 27 patients with gallstone pancreatitis and in 13 of 109 patients with cholelithiasis or choledocholithiasis without pancreatitis (p less than 0.025). In conclusion, common channels are more frequent in patients with gallstone pancreatitis than in patients with other biliary tract disease. Furthermore, gallstone pancreatitis is associated with stones that are smaller than the common channel, which favors obstruction of both pancreatic and bile ducts while allowing reflux of contents between them.     

Predicting medical students' intentions to take up rural practice after graduation

Objectives Using a novel longitudinal tracking project, this study develops and evaluates the performance of a predictive model and index of rural medical practice intention based on the characteristics of incoming medical students. Methods Medical school entry survey data were obtained from the Medical Schools Outcome Database (MSOD) project implemented in all Australian and New Zealand medical schools and coordinated through Medical Deans Australia and New Zealand, the representative body for the Deans of 18 Australian and two New Zealand medical schools and faculties. The medical school commencement survey collects data on students’ education and family background, including rural upbringing, personal circumstances and scholarships, and on their practice intentions in terms of location and specialty. The MSOD will also allow tracking of medical graduates after graduation. Logistic regression modelling was used to develop a predictive model of rural practice intention. Split‐sample validation was used to gain some insight into the stability of performance of the model. Results Response rates to the MSOD survey exceeded 90% on average. The model findings confirm and extend previous research examining the association of medical student characteristics with intention to take up rural medical practice. The statistically significant independent factors in the model included students’ rural backgrounds, financial arrangements and intentions regarding specialist versus generalist practice upon graduation. Model performance was good, with an area under the receiver‐operator characteristics curve of 0.86, and reproducible, with an area in a validation sample of 0.83. Conclusions The model and related index provide important insights into individual factors associated with rural practice intention among students commencing medical studies. The model can also provide a means for optimising the use of scarce medical programme resources, thereby helping to improve the supply of rural medical practitioners. This study illustrates the power and potential of a robust, consistent, systematic longitudinal tracking project.     

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR 相似文献