The Shanghai Women's Asthma and Allergy Study: objectives, design, and recruitment results

The Shanghai Women's Asthma and Allergy Study is the first population-based incidence study designed to assess the associations of dietary antioxidant intake and measures of oxidative stress and antioxidant enzyme activity with development of adult-onset asthma and allergic rhinitis. A total of 65,732 participants in the Shanghai Women's Health Study, an ongoing cohort study in seven districts of Shanghai, People's Republic of China, were recruited to the Shanghai Women's Asthma and Allergy Study from 2003 to 2007. Dietary intake was assessed in the parent study by using a validated and quantitative food frequency questionnaire at baseline recruitment and at the first biennial follow-up survey. Blood and urine samples were collected to measure baseline oxidative stress, antioxidant enzyme activity, and nutrient levels at the baseline survey. Incident asthma and allergic rhinitis were assessed by using a modification of the International Study of Asthma and Allergies in Childhood questionnaire during the biennial in-person survey of the Shanghai Women's Health Study. Diagnosis of asthma was confirmed by either methacholine challenge testing or test of reversibility to beta-agonists. Dietary antioxidant intake, plasma antioxidants, antioxidant enzymes, and urinary isoprostanes, a marker of oxidative stress, were measured prior to disease onset. This paper describes the study objectives, design, population demographics, and recruitment results.     

Transarterial chemoembolization for liver metastases from solid pseudopapillary epithelial neoplasm of pancreas: A case report

Solid pseudo-papillary epithelial neoplasm(SPEN) is a rare epithelial tumor of pancreas with a low malignant potential occurs most commonly in young females. We report a case of 40 years old woman presented withextensive liver metastasis from SPEN of pancreatic body for which she was operated four years ago. Due to the extensive nature of metastatic disease she was offered Transarterial chemoembolisation(TACE) using gemcitabine as chemotherapeutic agent. Short term follow up after a month of TACE with multiphase computed tomography showed > 90% resolution in the viable tumor with significant clinical improvement. TACE ensures targeted delivery of chemotherapeutic drugs in higher doses with least systemic toxicity and is more effective and safe than systemic chemotherapy. TACE with gemcitabine was found to be very effective in our patient with numerous liver metastasis.     

One-stage revision in two cases of Salmonella prosthetic hip infection

We describe two cases of prosthetic joint infection (PJI) of the hip due to Salmonella. The first patient presented with an early infection 5 d after being discharged following a total hip replacement and the second patient presented at the emergency ward with a late infection, thirteen years following a total hip replacement. Both cases occurred within one month of each other at our institution and both were successfully treated with a one-stage revision. PJI caused by Salmonella species is very rare: so far only 20 Salmonella PJIs of the hip have been described. Therefore, full consensus on the best treatment approach has not yet been reached. An aggressive two-stage approach is advised because of the virulence of Salmonella, although a limited number of successful one-stage approaches have been described as well. According to the latest guidelines, one-stage revision has comparable success rates and less morbidity compared to two-stage treatment, when selecting the right patients. In our opinion, PJI caused by Salmonella should be treated just as PJI caused by other bacteria, with consideration of the selection criteria as mentioned in several treatment guidelines. As illustrated by these two cases, one-stage revision can be successful in both early and late Salmonella PJI of the hip.     

Seroprevalence and factors associated with herpes simplex virus type 2 among HIV-negative high-risk men who have sex with men from Rio de Janeiro, Brazil: a cross-sectional study

Background  

Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease in developing countries, including Brazil, and is especially prevalent among men who have sex with men (MSM). HSV-2 infection represents a risk factor for the acquisition and transmission of other sexually transmitted diseases. The goal of the present cross-sectional study was to estimate HSV-2 seroprevalence and to determine the factors associated with HSV-2 seropositivity in HIV-negative high-risk MSM from Rio de Janeiro, Brazil.     

Highlights from the annual scientific assembly: patient-centered approaches to asthma management: strategies for treatment and management of asthma

Asthma is a chronic inflammatory disease in which the genetic predisposition to allergic disease is the strongest identifiable predisposing factor. (1) Optimal outpatient treatment of asthma includes identifying and minimizing exposure to asthma triggers, whether they Me allergens or irritants. When these triggers are not obvious, referral to an allergist may be appropriate to ideniify potential exacerbating factors. In addition, pulmonary consultation may be helpful in patients who do not have the typical features of asthma on chest radiograph or pulmonary function testing, or who are not responding well to standard therapy. The primary care physician is the most important component in the care of the asthmatic patient, however, managing acute exacerbations, determining long-term medical therapy, and providing preventive measures, such as yearly influenza vaccinations.     

Elimination of racial differences in invasive pneumococcal disease in young children after introduction of the conjugate pneumococcal vaccine

BACKGROUND: Racial differences in the epidemiology of invasive pneumococcal disease (IPD) have been widely recognized, but the impact of conjugate pneumococcal vaccine (PCV) introduction in 2000 on these differences has not been extensively studied. METHODS: IPD episodes in 5 Tennessee counties from January 1995 through December 2002 were collected prospectively using the Centers for Disease Control and Prevention's Active Bacterial Core Surveillance system (ABCs). Trained nurses collected clinical data, and antibiotic susceptibility testing was performed on available isolates. RESULTS: Before vaccine licensure, IPD rates were highest in children younger than 2 years and in blacks. The disparity in IPD rates between blacks and whites younger than 2 years of age substantially diminished after PCV introduction. In 1999, the IPD rate in black children younger than 2 years was 340.2 per 100,000, representing 176.5 more events per 100,000 than in white children (P < 0.001). In 2002, this rate had decreased 83% to 57.4 per 100,000, similar to the rate in white children (39.6 per 100,000; P = 0.31). Before vaccine licensure, a higher percentage of isolates from whites were antibiotic-nonsusceptible. In 2002, the proportion of antibiotic-nonsusceptible pneumococcal isolates was similar in whites and blacks of all ages for the first time during the study period (P > 0.05 for separate comparisons of penicillin, cephalosporin and erythromycin nonsusceptibility). These changes occurred despite a lower PCV vaccination coverage in Tennessee in blacks than in whites (31.2% versus 47.6%). CONCLUSIONS: With conjugate pneumococcal vaccine introduction in Tennessee, racial differences in the incidence rates of IPD have largely been eliminated, particularly in young children.     

N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine formation by peroxidative metabolism

N'-(3'-Monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ) is thought to play an important role in initiation of benzidine-induced bladder cancer in humans. This report assesses the possible formation of this adduct by peroxidatic activation of N-acetylbenzidine (ABZ). Adduct formation was measured by 32P-post-labeling. Ram seminal vesicle microsomes were used as a source of prostaglandin H synthase (PHS). The peroxidatic activity of PHS was compared with that for horseradish peroxidase. Both peroxidases converted ABZ to dGp-ABZ whether DNA or 2'- deoxyguanosine 3'-monophosphate (dGp) was present. Following 32P-post- labeling, the enzymatic and synthetic adduct were extracted from PEI- cellulose plates and were shown to have the same HPLC elution profiles for the bisphosphate adduct (32P-dpGp-ABZ). Treatment of the enzymatic and synthetic bisphosphate adduct with nuclease P1 yielded a product that eluted at the same time from the HPLC (32P-dpG-ABZ). Additional experiments demonstrated that the PHS-derived 5'-monophosphate (dpG- ABZ) and 3'-monophosphate (dGp-ABZ) adducts were also identical to their corresponding synthetic standard. With comparable amounts of total ABZ metabolism, PHS produced approximately 40-fold more dGp-ABZ than horseradish peroxidase (1943 +/- 339 versus 49 +/- 7.8 fmol/mg dGp). Adduct formation was dependent upon the presence of peroxidase and the specific substrate, i.e. arachidonic acid or H2O2. Adduct formation by PHS was inhibited by indomethacin (0.1 mM), ascorbic acid (1 mM) and glutathione (10 mM), but not by 5,5-dimethyl-1-pyrroline N- oxide (DMPO) (100 mM), a radical scavenger. Horseradish peroxidase adduct formation was also inhibited by ascorbic acid and glutathione. In addition, DMPO elicited greater than a 96% inhibition. Results demonstrate peroxidatic metabolism of ABZ to form dGp-ABZ. The mechanism of dGp-ABZ formation by PHS and horseradish peroxidase may be different.      

Pilot study of MK-462 in migraine

MK-462 is a potent, selective 5HT_1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg ( n = 8) and 40 mg ( n =36) vs placebo ( n =21), administered to 65 male and post-menopausal female migraine patients aged 22–51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly ( p <0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (10 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine.     

Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection. Autophagy was assayed in H. pylori‐infected human gastric epithelium and the functional role of autophagy was determined via genetic or pharmacological ablation of autophagy in mouse and cell line models of H. pylori infection. Here, we showed that H. pylori inhibited lysosomal function and thereby promoted the accumulation of autophagosomes in gastric epithelial cells. Importantly, inhibiting autophagosome formation by pharmacological inhibitors or genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival, whereas inhibition of lysosomal functions exerted an opposite effect. Further experiments demonstrated that H. pylori inhibited lysosomal acidification and the retrograde trafficking of mannose‐6‐phosphate receptors, both of which are known to positively regulate lysosomal function. We conclude that H. pylori subverts autophagy into a pro‐survival mechanism through inhibition of lysosomal clearance of autophagosomes. Disruption of autophagosome formation offers a novel strategy to reduce H. pylori colonization in human stomachs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.