Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Is the political system really related to health?

We analyze whether the political system and its stability are related to cross-country differences in health. We apply factor analysis on various national health indicators for a large sample of countries over the period 2000–2005 and use the outcomes of the factor analysis to construct two new health measures, i.e., the health of individuals and the quality of the health care sector. Using a cross-country structural equation model with various economic and demographic control variables, we examine the relationship between the type of regime and political stability on the one hand and health on the other. The political variables and the control variables are measured as averages over the period 1980–1999. Our results suggest that democracy has a positive relationship with the health of individuals, while regime instability has a negative relationship with the health of individuals. Government instability is negatively related to individual health via its link with the quality of the health care sector, while democracy is positively related with individual health through its link with income. Our main findings are confirmed by the results of a panel model and various sensitivity tests.     

Monotherapy with enoxaparin for the prevention of recurrent venous thromboembolism.

This study aimed to determine whether a weight-adjusted dose of subcutaneous enoxaparin is as effective and safe as oral acenocoumarol for the secondary prophylaxis of pulmonary embolism. Three hundred and eighty consecutive noncancer outpatients hospitalized with an episode of symptomatic pulmonary embolism selected treatment with acenocoumarol or enoxaparin at a dose of 1 mg/kg once daily after being informed of the type of administration and expected frequency of laboratory monitoring for both medicinal products. Endpoints were symptomatic recurrent thromboembolic events evaluated by standard objective testing, and a composite endpoint of recurrent venous thromboembolism, major bleeding, and death from any cause. One hundred and ninety-nine patients (52%) chose acenocoumarol therapy and 181 chose enoxaparin monotherapy. Four patients in the enoxaparin group (2.2%) and six patients in the acenocoumarol group (3%) had an objective thromboembolic recurrence (hazard ratio, 1.35; 95% confidence interval, 0.38-4.79; P = 0.64). Nine patients in the enoxaparin group (5.0%) had a hemorrhagic complication compared with 11 in the acenocoumarol group (5.5%) (P = 0.81). The hospital length of stay was shorter with enoxaparin compared with acenocoumarol (11 versus 16 days, P = 0.0001). Enoxaparin is as effective and safe as acenocoumarol in the secondary prevention of recurrent thromboembolic disease and is associated with shorter hospitalization.     

The 6-min walking distance: long-term follow up in patients with COPD.

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m.yr(-1)) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m.yr(-1)) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Dipyridamole and RA-642 inhibit the production of superoxide anion and free radical damage to rat lens.

We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.     

Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials.

PURPOSE: Current treatment for febrile neutropenia (FN) includes hospitalization for evaluation, empiric broad-spectrum antibiotics, and other supportive care. Clinical trials have reported conflicting results when studying whether the colony-stimulating factors (CSFs) improve outcomes in patients with FN. This Cochrane Collaboration review was undertaken to further evaluate the safety and efficacy of the CSFs in patients with FN. METHODS: An exhaustive literature search was undertaken including major electronic databases (CANCERLIT, EMBASE, LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All randomized controlled trials that compare CSFs plus antibiotics versus antibiotics alone for the treatment of established FN in adults and children were sought. A meta-analysis of the selected studies was performed. RESULTS: More than 8,000 references were screened, with 13 studies meeting eligibility criteria for inclusion. The overall mortality was not influenced significantly by the use of CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally significant result was obtained for the use of CSF in reducing infection-related mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49 to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI, 0.23 to 0.46; P < .00001). CONCLUSION: The use of the CSFs in patients with established FN caused by cancer chemotherapy reduces the amount of time spent in hospital and the neutrophil recovery period. The possible influence of the CSFs on infection-related mortality requires further investigation.