Spinocerebellar ataxia type 3/Machado–Joseph disease: segregation patterns and factors influencing instability of expanded CAG transmissions

Controversies about Mendelian segregation and CAG expansion (CAGexp) instabilities during meiosis in spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) need clarification. Additional evidence about these issues was obtained from the cohort of all SCA3/MJD individuals living in South Brazil. A survey was carried out to update information registered since 2001. Deaths were checked with the Public Information System, and data was made anonymous. Anticipation and delta‐CAGexp from parent–offspring pairs, and delta‐CAGexp between siblings were obtained. One hundred and fifty‐nine families (94% of the entire registry) were retrieved, comprising 3725 living individuals as of 2015, 625 of these being symptomatic. Minimal prevalence was 6:100,000. Carriers of a CAGexp represented 65.6% of sibs in the genotyped offspring (p < 0.001). Median instability was larger among paternal than maternal transmissions, and instabilities correlated with anticipation (r = 0.38; p = 0.001). Age of the parent correlated to delta‐CAGexp among 115 direct parent–offspring CAGexp transmissions (ρ = 0.23, p = 0.014). In 98 additional kindreds, the delta‐CAGexp between 269 siblings correlated with their delta‐of‐age (ρ = 0.27, p < 0.0001). SCA3/MJD was associated with a segregation distortion favoring the expanded allele in our cohort. Instability of expansion during meiosis was weakly influenced by the age of the transmitting parent at the time of conception.     

Small bowel obstruction in the virgin abdomen: the need for a mandatory laparotomy explored

Background

A laparotomy is still considered mandatory for patients without previous abdominal surgery presenting with a small bowel obstruction (SBO) because of a perceived high incidence of underlying lesions. However, there is no evidence in literature to support this assumption. We analyzed the etiology of SBO in this subgroup of patients to establish the need for a mandatory laparotomy.

Methods

A retrospective analysis was conducted over a 5-year period. Basic demographics, radiology results, operative findings, and outpatient investigations were analyzed.

Results

Of 689 patients presenting with an SBO, a total of 62 patients, 9.0%, had a virgin abdomen. A known underlying disease (inflammatory bowel disease, malignancy) was the cause in 13 patients. The remaining 49 patients had adhesions in 75.5% and a newly diagnosed malignancy in 10.2% as a cause.

Conclusions

Adhesions are by far the most likely cause of SBO in patients without previous abdominal surgery followed by a small number of newly diagnosed malignancies. Both prevalences are in equal proportion to patients with previous abdominal surgery. A trial of nonoperative management may therefore be justified.     

Identifying maternal risk factors associated with Fetal Alcohol Spectrum Disorders: a systematic review

To identify the demographic, psychological, and social maternal risk factors associated with the development of Fetal Alcohol Spectrum Disorders (FASD). A bibliographic search was conducted in PubMed, SciELO, Lilacs, Web of Knowledge, and PsycINFO. The Newcastle–Ottawa Quality Assessment Scale (NOS) was used to evaluate the quality of the studies with case–control design. Articles were selected based on their relevance and presentation of data related to statistical comparisons of at least one or more demographic, psychological, or social maternal risk factors for FASD. 738 references were identified, of which 15 met the criteria to be included in the present review. Mothers of FASD children tend to: be older at the time of birth of the affected child, present lower educational level, have other family relatives with alcohol abuse, have other children with FASD, present a pattern of little prenatal care and a distinguishing pattern of alcohol consumption (alcohol use before and during pregnancy, failure to reduce alcohol use during pregnancy, and frequent episodes of binge drinking). Application of the NOS scale of methodological quality indicated that 8 studies (53 %) met the criterion for selection, 4 (27 %) were suitable for the criterion for comparability and only 4 studies were suitable for the exposition criterion. Mothers of FASD children have a distinctive pattern of drinking and accumulate several social risk factors. Maternal age at birth of the child seems to accentuate the risk. There are, however, few controlled studies that are adequate according to the NOS requirements for methodological quality. Fewer are based on the verification of a theoretical model. Clinicians should be aware of the relevance of preventive assessment of FASD risk mothers.     

Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10–4.59 and P = 0.032 OR 2.32 CI 1.07–5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.     

Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance

The Cerebellum - Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to...     

Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind,Double Dummy,Randomized Study

Background

Proton-pump inhibitors (PPIs) are often prescribed to patients receiving dual antiplatelet therapy (DAPT). However, this class of medication, especially omeprazole, has been associated with a reduction in clopidogrel efficacy, leading many clinicians to substitute omeprazole with ranitidine.

Objectives

Our objective was to compare the antiplatelet effect of clopidogrel before and after the addition of omeprazole or ranitidine.

Methods

We measured platelet aggregability at baseline and after 1 week of clopidogrel 75 mg daily. Subjects were then randomized in a double-blinded, double-dummy fashion to omeprazole 20 mg twice daily (bid) or ranitidine 150 mg bid. We repeated aggregability tests after 1 additional week, using VerifyNow P2Y12? (Accumetrics; San Diego, CA, USA), depicting aggregability as percent inhibition of platelet aggregation (IPA).

Results

We enrolled 41 patients in the omeprazole group and 44 in the ranitidine group. IPA was significantly decreased after the addition of omeprazole to clopidogrel (from 26.3 ± 32.9 to 17.4 ± 33.1 %; p = 0.025), with no statistical significant changes observed in the ranitidine group (from 32.6 ± 28.9 to 30.1 ± 31.3 %; p = 0.310). The comparison of IPA in both groups at the end of the follow-up showed a trend toward significance (p = 0.07, 95 % confidence interval [CI] ?1.19 to 26.59); after excluding homozygous patients for 2C19*2 genotype, the comparison of IPA between the groups reached statistical significance (32.7 ± 30.8 vs. 17.7 ± 33.4 %, respectively, for ranitidine and omeprazole groups; p = 0.04).

Conclusions

Unlike omeprazole, ranitidine did not influence platelet aggregability response to clopidogrel.

Clinical Trial Registration

NCT01896557.