Danger of systemic cyclosporine for corneal graft

PURPOSE: To report a case of posttransplant lymphoproliferative disorder (PTLD) in a patient receiving oral cyclosporine (CS) for immunosuppression in a high-risk keratoplasty. METHODS: A systemic CS therapy was given to prevent graft rejection of a keratoplasty. Risk rejection was high in regard to a previous graft rejection and persistence of a corneal vascularization. One year after the keratoplasty, the patient developed a gastric Epstein-Barr virus (EBV)-induced B cell lymphoma. The outcome was favorable after chemotherapy. CONCLUSIONS: This unique case of lymphoma (PTLD) in the course of corneal graft management questions the indications and the follow-up of patients with CS therapy and raises the issue of topical CS treatment.     

Intrarenal detection of nitric oxide using electron spin resonance spectroscopy in hypertensive lipopolysaccharide-treated rats

The inhibition of nitric oxide (NO) synthesis by chronic administration of NG-nitro-l-arginine methyl ester (l-NAME) in rats is responsible for systemic hypertension. However, the mechanisms involved in this hypertension remain unclear. The effects of chronic l-NAME on kidney and blood NO production were studied in rats in a state of endotoxic shock due to lipopolysaccharide (LPS). A nitric oxide spin trapping technique using electron spin resonance (ESR) spectroscopy has been used to identify and measure the production of NO in the kidney. This method is based on the trapping of nitric oxide by a metal-chelator complex consisting of N-methyl-d-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) forming a water-soluble NO-FeMGD complex detected by ESR. After LPS injection (14 mg/kg, IV, 6 h before the sacrifice) to rats pretreated with l-NAME (10 mg/kg/d over 14 days), the NO-FeMGD complex was evaluated in the kidney (arbitrary units [AU]/g of kidney) and the density of polynuclear neutrophils was counted by light microscopy. Chronic inhibition of NO synthase by l-NAME, a nonspecific inhibitor, was responsible for a decrease of the NO-FeMGD complex levels in the kidney (24.9 +/- 1.6 AU versus 13.8 +/- 1.3 AU). LPS administration was responsible for a large increase in both NO-FeMGD complex and neutrophil levels in the kidney of normotensive rats (332.6 +/- 12.8 AU versus 24.9 +/- 1.6 AU for NO-FeMGD complex and 1.36 +/- 0.41 versus 0.11 +/- 0.03 for neutrophils). Conversely, LPS administration in hypertensive, l-NAME-pretreated rats was linked to a smaller increase in the NO-FeMGD complex (85.1 +/- 7.9 AU versus 332.6 +/- 12.8 AU) and a larger increase in glomerular neutrophils (2.48 +/- 0.36 versus 1.36 +/- 0.41) compared with normotensive rats. These results are in agreement with a direct implication of NO during LPS-and l-NAME-induced kidney injuries.     

Non-transferrin-bound iron in untreated and ribavirin-treated chronic hepatitis C patients

BACKGROUND: In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress-related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non-transferrin-bound iron can appear. Therefore, we determined non-transferrin-bound iron levels in untreated chronic hepatitis C patients and in patients during interferon-ribavirin treatment. MATERIALS AND METHODS: In 10 untreated and 19 interferon-ribavirin-treated chronic hepatitis C patients, we examined non-transferrin-bound iron levels by a colorimetric method using nitrilotriacetic acid as a ligand and sodium triscarbonatecobalt (III) to block free iron binding sites on transferrin. RESULTS: Despite the presence of high serum iron saturation and ferritin levels, non-transferrin-bound iron was absent in the majority of hepatitis C virus patients (25/29, 86%). There was no difference in non-transferrin-bound iron levels between untreated and treated patients. Four patients with high non-transferrin-bound iron levels were distinguished by higher serum iron levels. In two of these patients, hepatocytic iron was present on liver biopsy. CONCLUSIONS: In the majority of chronic hepatitis C patients, non-transferrin-bound iron levels are normal. Treatment with ribavirin does not induce high non-transferrin-bound iron levels. Non-transferrin-bound iron levels are only higher than normal in hepatitis C patients with higher serum iron levels.     

Flumazenil vs. placebo in hepatic encephalopathy in patients with cirrhosis: a meta-analysis

BACKGROUND: Randomized controlled trials testing flumazenil in hepatic encephalopathy have shown conflicting results. AIM: To compare flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis. METHODS: An overview of randomized controlled trials comparing flumazenil and placebo in hepatic encephalopathy in patients with cirrhosis was performed. For each end-point, heterogeneity and treatment efficacy were assessed by Peto and Der Simonian methods. As most trials were crossover in nature, a sensitivity analysis was performed including the two treatment periods. RESULTS: Six double-blind randomized controlled trials, including 641 patients (326 treated with flumazenil and 315 with placebo), were identified. The treatment duration ranged from 5 min to 3 days. Heterogeneity tests between control groups were not significant. The mean percentages of patients with clinical improvement (five trials) were 27% in treated groups and 3% in placebo groups. This difference was significant by both methods (Peto: odds ratio=6.15; 95% confidence interval, 4.0-9.5; P < 0.001; Der Simonian: mean rate difference, 29%; 95% confidence interval, 17-41; P < 0.001). The mean percentages of patients with electroencephalographic improvement were 19% in treated groups and 2% in placebo groups. This difference was significant only with the Peto method (odds ratio=5.8; 95% confidence interval, 3.4-9.7; P < 0.001). The sensitivity analysis showed similar results. CONCLUSIONS: This meta-analysis shows that flumazenil induces clinical and electroencephalographic improvement of hepatic encephalopathy in patients with cirrhosis.     

Active and passive smoking in breast cancer: prospective results from the Nurses' Health Study

BACKGROUND: The role of active and passive smoking in breast cancer remains controversial. METHODS: Using data collected in the prospective Nurses' Health Study, we examined the influence of active and passive smoking on the incidence of invasive breast cancer. The analysis was based on women responding to the 1982 questionnaire, which included questions on passive smoking exposure. Information on active smoking was collected in biennial questionnaires. A total of 78,206 women were followed prospectively from 1982 until June 1996. RESULTS: Of these women, 3,140 reported a diagnosis of invasive breast cancer during follow-up. Compared with never active smoking, relative risks (RR) of breast cancer were 1.04 (95% CI = 0.94-1.15) for current active smoking and 1.09 (95% CI = 1.00-1.18) for past active smoking. The RR for regular passive exposure at work and at home was 0.90 (95% CI = 0.67-1.22). For active smoking, a modest increase in risk was confined to women who began smoking before the age of 17 (RR = 1.19; 95% CI = 1.03-1.37). CONCLUSION: Results suggest that passive smoking is unrelated to breast cancer. However, results for active smoking are compatible with a small increase in risk when smoking is initiated at young ages.     

Perceived benefits of word prediction intervention on written productivity in children with spina bifida and hydrocephalus

Word prediction has been commonly used as a tool to enhance written productivity. However, the effectiveness of word prediction as a strategy to meet this targeted outcome has not been established. Using a single-subject alternating treatments design, this study evaluated the effect of word prediction on written productivity from the users' perspectives. Three girls and one boy aged 10-12 with spina bifida and hydrocephalus participated in the study over a period of 20 days. The Canadian Occupational Performance Measure (COPM) was used to measure changes in perception of written productivity. Analysis of individual participant data showed that participants perceived word prediction to have the potential to influence written productivity on some writing tasks. Quantitative analysis using a randomization test did not reveal any significant changes in COPM scores after using word prediction. The varied abilities of the participants in the study and the small sample size may be the reasons why statistical analysis did not show any changes. The limitations of this study included use of a copy task, lack of a supporting measure to COPM and limited generalizability. Further studies with a larger sample are necessary to explore the skills required for successful use of word prediction and the impact of word prediction on specific tasks.