Distinct Haplotype in Non-Ashkenazi Gaucher Patients with N370S Mutation

ABSTRACT: A new polymorphism, in intron 7 of glucocerebrosidase gene, has been identified in Gaucher Disease patients. It seems to appear only in Pv1.1^-alleles bearing the N370S mutation. This new sub-haplotype was only identified in Portuguese patients, of origins spanning all of the Portuguese continental territory. This finding indicates that, in the Portuguese, mutation N370S has existed in the context of two slightly different haplotypes and thus must be relatively ancient.     

Prevalence of rheumatoid arthritis in Tucumán,Argentina

OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucumán, Argentina. METHODS: The study was conducted between January 1, 1998, and December 31, 1999, in Tucumán province in northwest Argentina. Outpatient and hospitalization medical records for all patients with RA aged > or = 16 years were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR) criteria for RA and the population data were based on the 1991 national census. Prevalence rates, with 95% CI, were calculated using the number of San Miguel de Tucumán residents who fulfilled the 1987 ACR criteria for RA as numerator, and the city population aged > or = 16 as denominator. Crude and age-specific prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS: We identified 695 cases of RA. Sex-specific and overall prevalence rates (per 1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95% CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of Tucumán, Argentina, and comparable with rates observed in epidemiological surveys from Southern European countries.     

Scintigraphic evaluation of gallbladder motor functions in H pylori positive and negative patients in the stomach with dyspepsia

AIM：To evaluate the relationship between gallbladder （GB） motor function and H pylori infection in the stomach.
METHODS： All cases （86） underwent the 14C urea breath test （UBT）. ^14C-UBT was found as positive in 58 and negative in 28 dyspeptic patients. ^14C- UBT was accepted as a gold standard test. Clo test and histopathologic examination were compared with the results of ^14C-UBT in cases who tolerated upper gastrointestinal endoscopy procedure. Cholescintigraphy with ^99mTc-mebrofenin was used to determine the parameters of GB motor function （GB filling and emptying time, half of the emptying time, ejection fraction at 30th and 60th min） in all patients.
RESULTS： We found the sensitivity and specificity as 88% and 86% for Clo test and as 89% and 80% for histologic evaluation, respectively. The parameters of GB function were not significantly different in H pylori positive and negative patients. The GB emptying was normal in both groups. Minimum GB filling time was 30 min in 34 of 86 cases （39.5%）, filling was not observed in 2 cases. The GB ultrasonography （USG） results were normal for all cases and bile composition abnormality was not determined.
CONCLUSION： Our study showed that ^14C-UBT is highly reliable method to detect the presence of H pylori. The presence of H pylori infection does not directly affect the GB function.     

Detection of Pathogen-Specific Antibodies by Loop-Mediated Isothermal Amplification

Loop-mediated isothermal amplification (LAMP) is a method for enzymatically replicating DNA that has great utility for clinical diagnosis at the point of care (POC), given its high sensitivity, specificity, speed, and technical requirements (isothermal conditions). Here, we adapted LAMP for measuring protein analytes by creating a protein-DNA fusion (referred to here as a “LAMPole”) that attaches oligonucleotides (LAMP templates) to IgG antibodies. This fusion consists of a DNA element covalently bonded to an IgG-binding polypeptide (protein L/G domain). In our platform, LAMP is expected to provide the most suitable means for amplifying LAMPoles for clinical diagnosis at the POC, while quantitative PCR is more suitable for laboratory-based quantification of antigen-specific IgG abundance. As proof of concept, we measured serological responses to a protozoan parasite by quantifying changes in solution turbidity in real time. We observed a >6-log fold difference in signal between sera from vaccinated versus control mice and in a clinical patient sample versus a control. We assert that LAMPoles will be useful for increasing the sensitivity of measuring proteins, whether it be in a clinical laboratory or in a field setting, thereby improving acute diagnosis of a variety of infections.     

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01226758","term_id":"NCT01226758"}}NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.)     

Adipokines in Breast Milk: An Update

Epidemiological surveys indicate that nutrition in infancy is implicated in the long-term tendency to obesity and that a longer duration of breastfeeding is associated with a protective effect against metabolic disorders later in life. However, the precise cause of this association is not well understood. Recent studies on the compounds present in human breast milk have identified various adipokines, including leptin, adiponectin, resistin, obestatin, nesfatin, ghrelin and apelins. Some of these compounds are involved in the regulation of food intake and energy balance. The presence of these adipokines in breast milk suggests that they may be responsible for the regulation of growth in early infancy and that they could influence the energy balance and development of metabolic disorders in childhood and adulthood.     

Cardiac anatomy pertinent to the catheter and surgical treatment of atrial fibrillation

In the 1980s when surgery was first introduced for the treatment of atrial fibrillation (AF), one would often hear comments like “Every little old grandmother has AF. Why on earth would you operate on someone like that?”.