Methadone maintenance treatment: An update

Available data (this review includes old major articles and recent articles) show that, although results are heterogenous, methadone maintenance treatments (MMTs) have a real efficiency not only to reduce illicit opiate abuse (50–80% of patients under MMT did not use heroin in the preceding month) but also to reduce criminality, HIV risks and mortality, and to improve social rehabilitation, without inducing other alternative substance abuse. A minority of patients (perhaps 5–20%) stay on MMT on a very long-term basis (more than 10 years). Efficiency of MMTs are rather poorly related to patients' variables, with the exception of a moderately deleterious effect of a low age at onset of opiate dependance, a precocious or high involvement in criminality and an abuse of non-opiate drugs. On the other hand, variables related to treatment play a more important role in explaining heterogeneity of results. Optimal daily dose, high quality of medical and psycho-social services, clear orientation towards social rehabilitation and treatment retention (to allow a sufficient duration of treatment) and slow detoxification regimen of well-stabilized patients are all factors contributing to better results.     

Aminoterminal pro-brain natriuretic peptide and ventricular filling pressures in heart transplant recipients.

We tested the hypothesis that, in heart transplant recipients, plasma aminoterminal pro-brain natriuretic peptide (NT-proBNP) dosage is useful for diagnosis of high ventricular loading pressures in the absence of systolic dysfunction. We studied 60 consecutive transplanted heart recipients without systolic dysfunction at 1 to 16 years after transplantation. We found that, in these patients with frequent high ventricular filling pressures, plasma NT-proBNP was highly correlated with creatininemia and not correlated with ventricular loading pressures. These results do not support the hypothesis that NT-proBNP is useful for diagnosis of isolated diastolic dysfunction in transplanted heart recipients.     

Distribution of the cytogenetic abnormality +i(3)(q10) in persistent polyclonal B-cell lymphocytosis: a FICTION study in three cases

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity characterized by a moderate but sustained lymphocytosis where some binucleated or bilobulated circulating forms constitute, even if they are not entirely specific, the cytological hallmark of the disease. An additional chromosome long arm i(3)(q10) has recently been reported as a recurrent cytogenetic aberration, contrasting with a usual polyclonal immunoglobulin expression. To determine more precisely the distribution of the chromosomal abnormality within the peripheral lymphocyte population and study the relationship between the +i(3)(q10) and the bilobulated character, we investigated three new cases of PPBL displaying the cytogenetic abnormality on the karyotype, using a technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). We demonstrated that the +i(3)(q10) was restricted to the B lymphocytes, independently of the κ or λ light chain isotype and was present in both bilobulated and non-bilobulated cells. Therefore it is likely that the cytogenetic abnormality occurs at an early stage of lymphocyte differentiation in a precursor cell already committed to the B-cell lineage, before any rearrangement of immunoglobulin genes has taken place.     

Pharmacokinetics of bevacizumab in haemodialysis

Sir, Bevacizumab, a recombinant humanized monoclonal antibody againstVEGF (rhuMAb VEGF, Avastin®, Genentech, South San Francisco,CA), was approved as a treatment for metastatic renal cell carcinoma(RCC) [1]. However, no bevacizumab pharmacokinetic data areavailable for patients with renal failure. We report a pharmacokinetic     

A retro-inverso analog mimicks the cognate peptide epitope of a CD4+ T cell clone

Synthetic analogs of peptide epitopes may activate specific T helper cells, antagonize their antigen receptors, or block recognition by competing for major histocompatibility complex (MHC) class II binding sites. Rationally designed peptides may therefore prove useful as vaccines and for treatment of autoimmune diseases and allergies mediated by CD4⁺ T cells. However, their susceptibility to proteolytic degradation limits the applicability of conventional peptides in vivo. By contrast, retro-inverso analogs, in which a native sequence is substituted with D -amino acids linked with a reversed backbone, resist proteolysis and still maintain the side chain topology of the corresponding natural peptide. We report here that an end group-modified retro-inverso analog of the IgG2a^b heavy chain allopeptide determinant γ2a^b 435–447 was recognized by an I-A^d-restricted, γ2a^b 435–447-reactive T cell clone. The pseudopeptide elicited near-maximal interleukin-2 responses, although 300-fold higher concentrations were needed than the native determinant. The weaker antigenicity of the retro-inverso analog could be fully accounted for by an impaired I-A^d binding capacity, which might reflect reduced ability of the distorted main chain to form hydrogen bonds with I-A^d. Glycine substitution at the residue corresponding to the first primary anchor (P1) of the native peptide abrogated I-A^d binding and antigenicity of the retro-inverso analog. Thus, the pseudopeptide resembled the native determinant with respect to orientation in the class II binding site, configuration of the epitopic side chains, and the constraints that governed the interactions between a major anchoring side chain and I-A^d. In conclusion, proteolytically resistant compounds with predefined capacity to interact with MHC class II allelic products and T cell antigen receptors may be designed by retro-inverso modification of native determinants.     

Tinea Capitis in the United Arab Emirates

ABSTRACT: The authors reviewed the causative agents for tinea capitis in United Arab Emirates nationals attending Tawam Hospital, Al Ain, between 1981 and 1988. Microsporum canis was the most prevalent organism isolated. Oral griseofulvin remained the treatment of choice. The addition of isotretinoin appeared promising in the chronic inflammatory forms.     

Atazanavir: a novel inhibitor of HIV-protease in haemodialysis.

Sir, Atazanavir is a novel azapeptide protease inhibitor with highspecificity for, and activity against, HIV-1 protease. Atazanavirhas a pharmacokinetic profile that allows for once-daily oraladministration. It is a moderate inhibitor of hepatic cytochromeP450 enzymes and interacts with several drugs [1]. However,it has been shown that even drugs whose elimination is predominantlyhepatic may have altered pharmacokinetics in patients with renalimpairment [2]. Furthermore, both currently available proteaseinhibitors     

Hallucinations in Parkinson's disease: a follow-up study.

To study prevalence of hallucinations in patients with Parkinson's disease (PD) during a 1-year period, and identify factors predictive of the onset of hallucinations in patients who were hallucination-free at baseline, 141 unselected outpatients with PD were evaluated prospectively for a set of demographic, clinical, and therapeutic variables and the presence of hallucinations during the previous 3 months. Patient groups were compared with nonparametric tests, and logistic regression was applied to significant data. Follow-up data were available for 127 patients. The hallucination prevalence rates (%) at the first and second evaluation were, respectively, 41.7 and 49.6 for hallucinations of all types (NS), 29.1 and 40.2 for minor hallucinations (i.e., presence or passage hallucinations, and illusions) (P = 0.02), 22.8 and 21.2 for formed visual hallucinations (NS), and 8.7 and 8.7 for auditory hallucinations (NS). Hallucinations rarely started or ceased during the study. The most labile forms were minor hallucinations, which developed in 20% of patients and ceased in 9%. During follow-up, 15% of patients started to hallucinate. Three factors, all present at the first evaluation, independently predicted the onset of hallucinations in patients previously free of hallucinations at baseline (odds ratio; 95% confidence interval): severe sleep disturbances (14.3; 2.5-80.9), ocular disorders (9.1; 1.6-52.0), and a high axial motor score (5.7; 1.2-27.4). Hallucinations have a chronic course in most parkinsonian patients. Factors predicting the onset of hallucinations point to a role of extranigral brainstem involvement and a nonspecific, facilitating role of ocular disorders.     

First-Pass Metabolism of Diltiazem in Anesthetized Rabbits: Role of Extrahepatic Organs

Pharmaceutical Research - Purpose. The aim of this study was to assess in vivo which organs contribute to the first-pass metabolism of diltiazem. Methods. Anaesthetized rabbits received diltiazem...