Localization of non-specific X-linked mental retardation gene (MRX73) to Xp22.2

Clinical and molecular studies are reported on a family (MRX73) of five males with non-specific X-linked mental retardation (XLMR). A total of 33 microsatellite and RFLP markers was typed. The gene for this XLMR condition was been linked to DXS1195, with a lod score of 2.36 at theta = 0. The haplotype and multipoint linkage analyses suggest localization of the MRX73 locus to an interval of 2 cM defined by markers DXS8019 and DXS365, in Xp22.2. This interval contains the gene of Coffin-Lowry syndrome (RSK2), where a missense mutation has been associated with a form of non-specific mental retardation. Therefore, a search for RSK2 mutations was performed in the MRX73 family, but no causal mutation was found. We hypothesize that another unidentified XLMR gene is located near RSK2.     

Patience is a virtue: Multiple preoperative visits are associated with decreased recurrence in pediatric pilonidal disease

Background/PurposeThis study aimed to compare preoperative management strategies for patients undergoing trephination for pilonidal disease and evaluate risk factors for recurrence.MethodsA retrospective review was performed of children undergoing index surgical treatment with trephination for pilonidal disease between September 2017 and April 2019. Intraoperative and postoperative management were standardized. Demographic and perioperative data were collected and analyzed.ResultsOne-hundred twenty patients were identified with a median follow-up time of 7.5 months (interquartile range 4.1–13.2 months). Overall, 24 (20%) patients had a postoperative recurrence of pilonidal disease. Patients with multiple preoperative surgery clinic visits were less likely to have recurrent disease compared to those seen only once preoperatively (11% vs 26%, p = 0.040). Compared to patients without recurrence, those who recurred went to the operating room sooner from the time of initial surgical consultation (32 days vs 54 days, p < 0.001). Perioperative antibiotics, history of acute infection, and prior drainage procedures were not risk factors for recurrence.ConclusionsMultiple preoperative clinic visits are associated with a lower recurrence rate in children undergoing trephination for pilonidal disease. An increased duration of preoperative medical management may be responsible for this finding. Prospective study is needed to confirm these findings and identify additional factors that influence recurrence.Type of StudyTreatment Study.Level of EvidenceIII (Retrospective Comparative).     

Surrogate end-points: the case of trials on coronary atherosclerotic plaque regression

The experimental progression-regression human model offers an excellent opportunity for testing the pathophysiological hypotheses that have arisen in the study of atherosclerosis. Nevertheless, it is still necessary to demonstrate that the modifications of angiographic patterns are strictly related to changes in coronary events, and this evidence is not yet supported to date by performed trials. Ten randomized controlled trials designed with the aim of angiographically evaluating the evolution of coronary lesions in patients with coronary heart disease made over the past 13 years were reviewed to perform a meta-analysis. Quality of design and execution of the trials, and the analysis of the primary and secondary end-points chosen for each trial, as well as the methods used to measure the changes in atherosclerotic plaques were also assessed. The phenomenon of plaque regression in human beings seems to occur, but clinical, methodological and physiopathologic heterogeneity between examined trials made it unfeasible to perform a meta-analysis. Coronary events are the consequence of the interaction of known and unknown factors, and coronary arterial narrowing from a mild to moderate degree is only one of these factors. The choice of the regression of atherosclerotic plaques as the primary end-point of a trial should probably be confined to phase 2 studies, while proof of clinical efficacy should be based on harder end-points that are representative of the very objective of medical interventions: amelioration and/or prolongation of a patient's life.     

Coinfections by HIV, hepatitis B and hepatitis C in imprisoned injecting drug users

In order to know the prevalence and risk factors for coinfections by human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among injecting drug users (IDUs), a cross-sectional study was carried out in two prisons of the province of Cantabria, northern Spain. Three hundred and sixty-two IDU inmates were recruited. All inmates were interviewed and their blood tested for HIV, HBV and HCV. Crude and multiple risk factor adjusted for (by polychotomous logistic regression) odds ratios were calculated. Prevalence of HBV-HCV coinfection (42.5%) was higher than HIV-HBV-HCV coinfection (37.3%), whereas monoinfections were very uncommon (overall: 13%). Long-term injectors and reincarceration were the foremost risk factors for both coinfections, showing a trend between the degree of association and the number of viruses infecting a patient. No significant relationship between coinfection status and sexual practices was observed. The results related to coinfections are consistent with previous studies of prevalence and risk factors for HIV, HBV and HCV, in indicating that the high rates of coinfections among IDU inmates emphasise the need to harm-reduction policy across prisons in Spain.     

Risk factors for monoinfections and coinfections with HIV,hepatitis B and hepatitis C viruses in northern Spanish prisoners.

A cross-sectional study was conducted in prisons of Cantabria (northern Spain) from June 1992 to December 1994. Inmates were asked to participate in a survey on prevalence and risk factors for monoinfections and coinfections with HIV, HBV and HCV. Crude and multiple odds ratios of risk factors were calculated (by polychotomous logistic regression). Prevalence of coinfections was higher than that of monoinfections. IDU risk factors were the main independent variables associated with monoinfections and coinfections with these agents. The strength of association increased with the degree of coinfection for IDU risk factors and penal status, e.g. duration of injecting drug use for more than 5 years yielded an adjusted OR ranging from 1.3 (95% CI: 0.4-5.1) for HBV monoinfection to 180 (95% CI: 61.0-540.0) for HIV-HBV-HCV coinfection. In comparison, sexual behaviours were less important than IDU risk factors.     

Polymorphism analysis of the VNTR locus D17S5 in Central Spain

The fragment length polymorphism YNZ22 (D17S5) was analysed for a sample of 207 unrelated individuals living in Madrid (Spanish Caucasians) using PCR-methodology and high resolution separation. Hardy-Weinberg expectations (HWE) were calculated after pooling alleles into four groups. No deviations from HWE were detectable using the conventional ²-test. The power of discrimination was estimated as 0.96 and the mean paternity exclusion chance as 0.7587. A comparison of the allele frequency distribution with those of other Caucasian groups revealed no major differences.     

Identification and characterization of a T-helper peptide from carcinoembryonic antigen.

PURPOSE: The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas. EXPERIMENTAL DESIGN: Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo. RESULTS: Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264). CONCLUSIONS: CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.