Modern pathophysiology and treatment of esophageal diverticula

Introduction  

Esophageal diverticula are rare. They may occur in the pharyngoesophageal area (Zenker's), midesophagus, or distally (epiphrenic). A motility disorder (either at the level of the esophageal sphincters or body) is frequently associated with esophageal diverticula. The risk of malignant transformation is low.     

Attentional bias and disinhibition toward gaming cues are related to problem gaming in male adolescents

PurposeThe aim of this study was to examine whether behavioral tendencies commonly related to addictive behaviors are also related to problematic computer and video game playing in adolescents. The study of attentional bias and response inhibition, characteristic for addictive disorders, is relevant to the ongoing discussion on whether problematic gaming should be classified as an addictive disorder.MethodsWe tested the relation between self-reported levels of problem gaming and two behavioral domains: attentional bias and response inhibition. Ninety-two male adolescents performed two attentional bias tasks (addiction-Stroop, dot-probe) and a behavioral inhibition task (go/no-go). Self-reported problem gaming was measured by the game addiction scale, based on the Diagnostic and Statistical Manual of Mental Disorders-fourth edition criteria for pathological gambling and time spent on computer and/or video games.ResultsMale adolescents with higher levels of self-reported problem gaming displayed signs of error-related attentional bias to game cues. Higher levels of problem gaming were also related to more errors on response inhibition, but only when game cues were presented.ConclusionsThese findings are in line with the findings of attentional bias reported in clinically recognized addictive disorders, such as substance dependence and pathological gambling, and contribute to the discussion on the proposed concept of “Addiction and Related Disorders” (which may include non–substance-related addictive behaviors) in the Diagnostic and Statistical Manual of Mental Disorders-fourth edition.     

Randomized trial of HPV4 vaccine assessing the response to HPV4 vaccine in two schedules among Peruvian female sex workers

Two hundred female sex workers (FSWs) in Lima, Peru were randomized to receive HPV4 vaccine in the standard (0, 2, 6 months) or a modified schedule (0, 3, 6 months). One hundred and eighty four (92%) participants completed 3 doses of vaccine. Baseline seropositive rates were 58% for HPV6, 22.5% for HPV11, 41.5% for HPV16, and 13% for HPV18. The final geometric mean antibody titer (GMT) following vaccination was significantly greater for women who were seropositive at baseline compared to seronegative women: HPV6 (GMT ratio=2.3, p<0.01), HPV11 (GMT ratio=2.7, p<0.01), HPV16 (GMT ratio=1.3, p=0.04), and HPV18 (GMT ratio=2.4, p<0.01). Antibody titers in the modified schedule were not inferior to those in the standard schedule, suggesting the modified schedule may be paired with required STD visits. Although all women benefit from vaccination, administration at a younger age and before sexual debut is needed to achieve maximum protection from vaccine.     

The platelet serotonin‐release assay

Few laboratory tests are as clinically useful as The platelet serotonin‐release assay (SRA): a positive SRA in the appropriate clinical context is virtually diagnostic of heparin‐induced thrombocytopenia (HIT), a life‐ and limb‐threatening prothrombotic disorder caused by anti‐platelet factor 4 (PF4)/heparin antibodies that activate platelets, thereby triggering serotonin‐release. The SRA's performance characteristics include high sensitivity and specificity, although caveats include indeterminate reaction profiles (observed in ～4% of test sera) and potential for false‐positive reactions. As only a subset of anti‐PF4/heparin antibodies detectable by enzyme‐immunoassay (EIA) are additionally platelet‐activating, the SRA has far greater diagnostic specificity than the EIA. However, requiring a positive EIA, either as an initial screening test or as an SRA adjunct, will reduce risk of a false‐positive SRA (since a negative EIA in a patient with a “positive” SRA should prompt critical evaluation of the SRA reaction profile). The SRA also provides useful information on whether a HIT serum produces strong platelet activation even in the absence of heparin: such heparin‐“independent” platelet activation is a marker of unusually severe HIT, including delayed‐onset HIT and severe HIT complicated by consumptive coagulopathy with risk for microvascular thrombosis. Am. J. Hematol. 90:564–572, 2015. © 2015 Wiley Periodicals, Inc.     

Effect of insulin and sulfonylurea therapy, at the same level of blood glucose control, on low density lipoprotein subfractions in type 2 diabetic patients

The aim of this study was to evaluate the effect of sc insulin (INS) compared with sulfonylurea (SUL) therapy, at the same level of blood glucose control, on the low density lipoprotein (LDL) subfraction profile in normolipidemic type 2 diabetic patients. Nine normolipidemic type 2 diabetic men (age, 56+/-3 yr; body mass index, 26.5+/-0.9 kg/m2; mean +/- SEM), after a 3-week wash-out period, were assigned to INS or SUL for 2 months in a randomized cross-over design. Doses were adjusted only during the first month and then were kept constant. At the end of the treatments, hemoglobin A1c, plasma lipids, LDL, and very low density lipoprotein (VLDL) subfraction profiles and plasma postheparin lipoprotein lipase and hepatic lipase (HL) activities were evaluated. Despite glucose control was similar at the end of both periods (hemoglobin A1c, 7.4+/-0.3% vs. 7.0+/-0.2%, INS vs. SUL), INS compared with SUL significantly reduced plasma triglyceride (0.9+/-0.1 vs. 1.1+/-0.1 mmol/L; P < 0.05). Although INS did not affect the LDL concentration, it induced a decrease in both the amount (59.0 = 9.8 vs. 76.1+/-16.8 mg/dL; P = NS) and the proportion (31.2+/-3.0% vs. 38.3+/-3.8%; P < 0.03) of small LDL. Moreover, the decrease in small LDL was positively related to the reduction of large VLDL (r = 0.67; P < 0.04) and HL (r = 0.69, P < 0.05) induced by insulin therapy. In conclusion, sc insulin therapy, independently of glucose control and even in the presence of quite low plasma triglyceride levels, is able to reduce small LDL particles in type 2 diabetic patients. This change is related to decreases in both HL activity and large VLDL particles.     

Clinically important improvements in asthma-specific quality of life,but no difference in conventional clinical indexes in patients changed from conventional beclomethasone dipropionate to approximately half the dose of extrafine beclomethasone dipropionate

STUDY OBJECTIVE: Clinical trials of asthma treatments usually use measures of asthma control to assess efficacy. However, it is also important to determine whether patients themselves benefit from interventions. The aim of this study was to evaluate health-related quality of life in patients with asthma switched from conventional chlorofluorocarbon (CFC) beclomethasone dipropionate (BDP) to hydrofluroalkane-134a (HFA) BDP extrafine aerosol at half the daily dose. DESIGN: Open-label, 12-month, parallel-group, randomized trial. SETTING: Fifty-seven centers in four countries (United States, Belgium, the Netherlands, and United Kingdom). PATIENTS: Four hundred seventy-three patients with a > or = 6-month history of asthma, stable symptoms, and maintained on CFC-BDP, 400 to 1,600 microg/d. INTERVENTIONS: HFA-BDP, 200 to 800 microg/d (n = 354), or CFC-BDP, 400 to 1,600 microg/d (n = 119). MEASUREMENTS AND RESULTS: The Asthma Quality of Life Questionnaire (AQLQ) and pulmonary function tests were completed at months 0, 2, 4, 8, and 12. For 1 month before each visit, patients made daily recordings of symptoms, peak expiratory flow, and beta(2)-agonist use. Two hundred ninety-six patients completed the study (HFA-BDP, 83.6%; CFC-BDP, 83.2%). At month 12, improvements in overall AQLQ scores were greater in the HFA-BDP group than in the CFC-BDP group (p = 0.0024). The number of patients who need to be treated with HFA-BDP for one to have a clinically important improvement in overall asthma-specific quality of life compared with CFC-BDP was 7.3. There was no evidence of differences (p > 0.05) between treatment groups for airway caliber, symptoms, or beta(2)-agonist use. CONCLUSION: Clinically important improvements in the AQLQ score were observed at month 12 for HFA-BDP vs CFC-BDP, while conventional clinical indexes of pulmonary function and asthma control were similar in the two groups.     

Family history of diabetes is a major determinant of endothelial function.

OBJECTIVES: We evaluated whether endothelial dysfunction was present in nondiabetic persons with a family history (FH) of diabetes and assessed its relationship with insulin resistance and atherosclerosis risk factors. BACKGROUND: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. METHODS: Oral glucose tolerance and brachial artery flow-mediated, endothelium-dependent vasodilation (EDV) were assessed in 38 nondiabetic subjects; offspring of two parents with T2D (FH+) or with no first-degree relative with diabetes (FH-). RESULTS: Although fasting glucose was higher in FH+ than FH- (5.3 +/- 0.1 mmol/l vs. 4.9 +/- 0.1 mmol/l, p < 0.03), glycemic burden assessed as 2-h or area-under-the-curve glucose after glucose load or glycosylated hemoglobin (HbA1c), and measures of insulin sensitivity or inflammation did not differ. Brachial artery flow-mediated EDV was reduced in FH+ (7.1 +/- 0.9% vs. 11.7 +/- 1.6%, p < 0.02), with no difference in nitroglycerin-induced endothelium-independent vasodilatation. In the combined cohort, only FH+ (r2 = 0.12, p < 0.02) and HbA1c (r2 = 0.14, p < 0.02) correlated with EDV. Insulin resistance, assessed by tertile of homeostasis model assessment of insulin resistance (HOMA-IR), was associated with impaired endothelium-dependent vasodilatation in FH- (p < 0.03, analysis of variance), but not in FH+, as even the most insulin-sensitive FH+ offspring had diminished endothelial function. In multiple regression analysis, including established cardiac risk factors, blood pressure and lipids, HbA1c, and HOMA-IR, FH remained a significant determinant of EDV (p = 0.04). CONCLUSIONS: Bioavailability of nitric oxide is lower in persons with a strong FH of T2D. Glycemic burden, even in the nondiabetic range, can contribute to endothelial dysfunction. Abnormalities of endothelial function may contribute to atherosclerosis before development of overt diabetes.     

Prevalence and distribution of high-risk human papilloma virus (HPV) types in invasive squamous cell carcinoma of the cervix and in normal women in Andhra Pradesh,India

Background  

Despite the high incidence of cervical cancer reported from India, large scale population based studies on the HPV prevalence and genotype distribution are very few from this region. In view of the clinical trials for HPV vaccine taking place in India, it is of utmost importance to understand the prevalence of HPV genotypes in various geographical regions of India. We investigated the genotype distribution of high-risk HPV types in squamous cell carcinomas and the prevalence of high-risk HPV in cervicovaginal samples in the southern state of Andhra Pradesh (AP), India.