Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Central and peripheral changes in catecholamine-synthesizing enzyme activities after systemic administration of the neurotoxin DSP-4

In brain regions containing noradrenergic (NA) cell bodies or terminals, DSP-4 induces changes in the activity of catecholamine-synthesizing enzymes which suggest that central NA neurons are lesioned by this neurotoxin. In contrast, the lack of change in the same enzymatic activities in an area containing mostly adrenergic (A) neurons (C2 region), favors the hypothesis of a resistance of the A neurons to DSP-4. Furthermore, the enzymatic changes observed in peripheral organs suggest a peripheral activation of the NA cell bodies in response to lesioning of the sympathetic terminals by DSP-4.     

Non-cultured cell transplantation in an ovine model of non-ischemic heart failure.

OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. METHODS: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.     

Inhibition of coronary artery thrombosis by SIN-1, a donor of nitric oxide.

Molsidomine and its metabolite, SIN-1, a donor of nitric oxide, are potent coronary vasodilator and anti-ischemic agents. Recently, SIN-1 and nitric oxide have also been shown to inhibit platelet adhesion and aggregation in vitro. The present study in dogs was designed to evaluate the in vivo antithrombotic properties of SIN-1. Coronary intimal damage and stenosis are known to induce coronary cyclic flow variations that reflect platelet thrombus formation followed by disaggregation and embolization (Folts preparation). This model of coronary artery thrombosis appears to simulate the combination of some of the factors contributing to unstable angina and myocardial infarction in human. SIN-1 infusion (10 micrograms/kg/min) significantly reduced the frequency of cyclic flow variations: 4.9 +/- 6.2/h vs. 14 +/- 4.6/h (before treatment, p less than 0.03, n = 6). Results were similar to those obtained with aspirin (5 mg/kg, bolus i.v.: 1.5 +/- 0.6/h vs. 11.7 +/- 3/h, p less than 0.03, n = 5) whereas saline had no effect (17.8 +/- 2.2/h vs. 19.3 +/- 2.4/h, n = 5). As expected, blood pressure was decreased only in the SIN-1 group: 56.2 +/- 7.8 vs. 87.3 +/- 9.3 mm Hg (p less than 0.02) (mean arterial blood pressure). The present results suggest that the well-documented anti-ischemic properties of SIN-1 could be partly due to its antithrombotic activity, clearly demonstrated with the model of coronary thrombosis used here in the dog.     

Computed tomography of mediastinal lymph nodes in nonsmall cell lung cancer. A new approach based on the lymphatic pathway of tumor spread

Computed tomography was used to evaluate mediastinal lymph nodes in 97 patients with nonsmall cell lung cancer. All patients had thorough surgical-pathological determination of mediastinal node status. Twenty-three patients were found to have metastatic lymph nodes. The usual lymphatic pathways of tumor spread into the mediastinum were defined using the node mapping scheme suggested by the American Thoracic Society. We considered mediastinal nodes abnormal when the short axis of the largest mediastinal node in the lymphatic drainage territory of the cancer was greater than or equal to 10 mm and the difference between this node and the largest node in the other territories is greater than 5 mm. The sensitivity was 78%, the specificity 99%, the positive predictive value 95%, the negative predictive value 94%, and the accuracy 94%. Comparing our method to those that used the size criterion alone, the number of false positives was reduced.     

Evaluation of larvicides for the control of Simulium damnosum s.l. (Diptera: Simuliidae) in West Africa

The Onchocerciasis Control Program of the World Health Organization is carrying out an extensive screening program in a search for new larvicides to be used for control of Simulium damnosum s.l. Emphasis has been given to finding a pyrethroid and a carbamate to supplement the organophosphates currently in use. These chemicals with differing modes of action, together with Bacillus thuringiensis H-14, are being used in an attempt to cope with the development and spread of resistance to the organophosphates temephos and chlorphoxim.     

Heart-type fatty acid-binding proteins (H-FABP): a reliable tool for initial risk stratification of pulmonary embolism?

The severity of pulmonary embolism (PE) ranges from asymptomaticto cardiogenic shock with corresponding short-term mortalitybetween 2 and 95%. Whereas the former could be discharged earlyor managed entirely as outpatients using low-molecular-weightheparin, those with greater severity of PE require rapid echocardiographyto evaluate for indications for immediate thrombolysis or embolectomy.^2,3However, most patients with PE fall between these two extremes.Patients with PE who do not initially present with life-threateningcriteria are usually admitted to a hospital ward where thosewith intermediate risk might experience a life-threatening recurrentepisode requiring emergent thrombolysis and critical care. Therefore,among patients with intermediate clinical severity, it is criticalto accurately identify those at risk for adverse medical outcome. Despite recent advances in risk stratification,     

Comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients

BACKGROUND: Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures. METHODS: The consumption of substances was investigated using biological measures (urine cotinine, cannabis, opiates, cocaine, amphetamines and barbiturates; blood carbohydrate-deficient transferrin [CDT] and gamma-glutamyl transferase [GGT]) in 486 consecutively admitted psychiatric patients, one day following their hospitalization. Patients' self-reports of alcohol, tobacco and illicit drugs consumption were recorded. Socio-professional and familial data were also recorded. RESULTS: The results show a low correlation between biological measures and self-reported consumption of alcohol and illicit drugs. Fifty-two percent of the patients under-reported their consumption of illicit drugs (kappa=.47). Patients with schizophrenia and personality disorders were more likely to disclose their illicit drug consumption relative to patients suffering from mood disorders and alcohol dependence. Fifty-six percent of patients underreported alcohol use, as evaluated by CDT (kappa=.2), and 37% underreported when using the CDT+GGT measure as an indicator. Smoking appeared to be reported adequately. In the study we observed a strong negative correlation between cannabis use and age, a strong correlation between tobacco and cannabis use, and correlations between tobacco, cannabis and alcohol consumption. CONCLUSION: This study is the first to compare self-reports and biological measures of alcohol, tobacco and illicit drug uses in a large sample of inpatients suffering from various categories of psychiatric illnesses, allowing for cross-diagnosis comparisons.