Loss of lineage antigens is a common feature of apoptotic lymphocytes

The analysis of apoptosis in cell populations involves the detection of their specific lineage antigen (LAg) expression. This experimental approach relies on their assumed constant expression, but it is unclear whether such expression is actually maintained during cell death. We examined whether the loss of LAgs is a common feature of apoptotic lymphocytes and whether some might completely lose their LAgs. The changes in the expression of CD3, CD5, CD8, CD4, CD28, CD56, and CD19 were monitored in highly purified lymphocyte populations obtained by negative selection in a fluorescence-activated cell sorter. These were cultured for 24 h with or without phytohemagglutinin or staurosporin. For each LAg-positive subset studied, apoptosis was consistently more common among cells showing partial or total loss of LAg expression compared with cells maintaining their initial LAg levels. The kinetics of expression loss was rapid for CD8, CD56, and CD28, and more than 80% of initial expression was lost in the early stages of apoptosis but was slower for CD3, CD5, and CD4. For CD3 and CD5, expression was dependent on the apoptotic stimulus used. It is interesting that loss of antigen expression was independent of cell size. This phenomenon was also found in nonmanipulated, highly pure CD19 B lymphocytes of peripheral blood mononuclear cells from B chronic lymphocytic leukemia patients. Loss of LAg expression appeared to be a common feature of apoptotic lymphocytes under all the conditions assayed. The different kinetic patterns of LAg loss suggest apoptotic cells might actively regulate this process.     

Determinants of the Consumption of Regular Soda,Sport, and Energy Beverages in Spanish Adolescents

Increasing sugar-sweetened beverages (SSB) consumption and associated health impacts warrant health-policy action. We assessed associations of socioeconomic and lifestyle variables with adolescents’ consumption of regular soda (RSD), sport (SD), and energy (ED) drinks. Cross-sectional study of 3930 Spanish adolescents (2089 girls, 1841 boys) aged 13–18 years). We compared frequency of consuming each SSB type (European Food Safety Authority questionnaire) with sociodemographic and lifestyle variables (standardized questions). RSD, SD, and ED were consumed at least weekly by 72.7%, 32.3%, and 12.3% of participants, respectively, and more frequently (p < 0.001) by boys, compared to girls. Multivariate ordinal logistic regression showed inverse association between RSD, SD, and ED consumption and parental occupation-based socioeconomic status (p < 0.01). Daily smoking was associated (p < 0.001) with higher ED (OR 3.64, 95% CI 2.39–5.55) and RSD (OR 2.15, 95% CI 1.56–2.97) consumptions. SD intake was associated inversely with smoking (OR 0.60, 95% CI 0.40–0.89, p = 0.012) and directly with physical activity (OR 2.93, 95% CI 2.18–3.95, p < 0.001). School performance was lower among ED (OR 2.14, 95% CI, 1.37–3.35, p = 0.001) and RSD (OR 1.81, 95% CI 1.24–2.64, p = 0.002) consumers, compared to SD. Maleness and low socioeconomic status predicted SSB consumption. Smoking and low school performance were associated with higher ED and RSD intakes.     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Validation of a screening test for alcohol use,the Russian Federation

ObjectiveTo validate a Russian-language version of the World Health Organization’s Alcohol Use Disorders Identification Test (AUDIT).MethodsWe invited 2173 patients from 21 rural and urban primary health-care centres in nine Russian regions to participate in the study (143 declined and eight were excluded). In a standardized interview, patients who had consumed alcohol in the past 12 months provided information on their sociodemographic characteristics and completed the Russian AUDIT, the Kessler Psychological Distress Scale and the Composite International Diagnostic Interview to identify problem drinking and alcohol use disorders. We assessed the feasibility of administering the test, its internal consistency and its ability to predict hazardous drinking and alcohol use disorders in primary health care in the Russian Federation.FindingsOf the 2022 patients included in the study, 1497 were current drinkers with Russian AUDIT scores. The test was internally consistent with good psychometric properties (Cronbach’s α : 0.842) and accurately predicted alcohol use disorders and other outcomes (area under the curve > 75%). A three-item short form of the test correlated well with the full instrument and had similar predictive power (area under the curve > 80%). We determined sex-specific thresholds for all outcomes, as non-specific thresholds resulted in few women being identified.ConclusionWith the validated Russian AUDIT, there is no longer a barrier to introducing screening and brief interventions into primary health care in the Russian Federation to supplement successful alcohol control policies.     

Economic evaluation of pharmaceuticals: a European perspective

In recent years there has been a large increase in the number of economic evaluations of pharmaceuticals. Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. In 2 countries, Australia and Canada (in the province of Ontario), draft guidelines issued by the government have outlined the requirements for economic evaluations to be submitted in support of requests for reimbursement (government subsidy) of particular products. One consequence of the guidelines is that they clarify what is required, and in specifying the procedure for submission of dossiers, identify a clear audience for the economic evaluation. In contrast, the situation in Europe is diverse. A wide range of healthcare systems exist, including national health services and more liberal systems, involving a wide range of insurers and providers. European countries also differ widely in their approach to the pricing and reimbursement of pharmaceuticals. Because of this diversity, the nature, conduct and impact of economic evaluation in Europe is not clear. It is therefore difficult for pharmaceutical companies to develop appropriate strategies for economic evaluation and for analysts to decide on appropriate study methodology. This article reviews the nature of any official guidance or requirements for economic evaluation, the potential for use of economic evaluation, the range of studies carried out and the identifiable impacts. There is currently no official guidance in any country, although some countries are considering issuing guidelines. In some countries there is official encouragement to pharmaceutical companies to undertake studies, and where economic data have been presented they have been considered by the relevant committees. The potential uses of economic evaluation vary widely from country to country. These can be classified in terms of a potential role in undertaking national price negotiations, deciding on reimbursement status or copayment level, deciding on inclusion in local formularies or in treatment guidelines, or in improving prescribing decisions. Approximately 80 economic evaluations of pharmaceutical products have been conducted to date in Europe, covering a wide range of clinical areas. There are relatively few examples of identifiable effects of such studies. In part this is because it is often difficult to assess the part played by various items of data. Nevertheless, the overriding conclusion is that economic evaluation of medicines is likely to be more relevant in Europe in the future. The problem for the pharmaceutical industry is in determining when and how.     

Cost-effectiveness analysis of hepatitis B vaccination strategies in Catalonia, Spain

Hepatitis B virus (HBV) infection is an important public health problem all over the world. Vaccination is one way to prevent it, and several strategies can be used depending on endemicity, the main pattern of HBV transmission and the demographic structure of the population. In this study, an economic comparison of 3 vaccination strategies (mass adolescent vaccination, mass infant vaccination and mass combined vaccination) was performed in Catalonia, Spain. Screening pregnant women for HBV infection in combination with these strategies was also evaluated. Epidemiological models to analyse patterns of HBV infection with and without vaccination and to calculate HBV-associated costs were designed. Comparison between strategies was done using cost-effectiveness analysis from the perspective of the healthcare system. Epidemiological model results indicate that implementation of HBV vaccination could prevent as many as 104,778 new acute infections, and avoid up to 5239 chronic infections, 2096 cases of cirrhosis and 419 cases of hepatocarcinoma over a 20-year period in Catalonia. Cost-effectiveness analysis shows that mass adolescent vaccination is the most efficient strategy, with lower costs per avoided case than the other 2 strategies. When any of these strategies is complemented by screening for HBV in pregnant women, the number of avoided cases is always higher and the cost per avoided case decreases or remains unchanged.     

Gating of α3β4 neuronal nicotinic receptor can be controlled by the loop M2-M3 of both α3 and β4 subunits

Previous studies have shown that the gating mechanism of alpha3beta4 neuronal nicotinic receptors is affected by a residue in the middle of the M2-M3 loop of the beta4 subunit. We have extended the study of the same location to the alpha3 subunit. Bovine alpha3beta4 receptors were mutated in position 268, substituting the residue present in wild-type receptors, i.e. leucine in alpha3 and asparagine in beta4, for an aspartate. Wild-type and mutated alpha3 and beta4 subunits were combined to form four different receptors. We have measured macroscopic currents in Xenopus oocytes elicited by nicotine, and related them to surface receptor expression measured with an epibatidine-binding essay. We also obtained single-channel recordings of the receptors to study their kinetic behaviour. The results were analysed in terms of an allosteric model with three states. We found that the effect of the mutation in the alpha3 subunit on the gating of the receptor was similar to the corresponding mutation in the beta4 subunit. The effect when both subunits were mutated was additive, suggesting that the contribution of each subunit to the gating mechanism is independent.     

Hyperacute spinal subdural haematoma as a complication of lumbar spinal anaesthesia: MRI

We report two cases of hyperacute spinal subdural haematoma secondary to lumbar spinal anaesthesia, identified with MRI. Prompt diagnosis of this infrequent, potentially serious complication of spinal anaesthesia is essential, as early surgical evacuation may be needed. Suggestive MRI findings in this early phase include diffuse occupation filling of the spinal canal with poor delineation of the spinal cord on T1-weighted images, and a poorly-defined high-signal lesion with a low-signal rim on T2-weighted images. Received: 10 November 1998 Accepted: 6 April 1999