LTA4H rs2660845 association with montelukast response in early and late-onset asthma.

Leukotrienes play a central pathophysiological role in both paediatric and adult asthma. However, 35% to 78% of asthmatics do not respond to leukotriene inhibitors. In this study we tested the role of the LTA4H regulatory variant rs2660845 and age of asthma onset in response to montelukast in ethnically diverse populations. We identified and genotyped 3,594 asthma patients treated with montelukast (2,514 late-onset and 1,080 early-onset) from seven cohorts (UKBiobank, GoSHARE, BREATHE, Tayside RCT, PAGES, GALA II and SAGE). Individuals under montelukast treatment experiencing at least one exacerbation in a 12-month period were compared against individuals with no exacerbation, using logistic regression for each cohort and meta-analysis. While no significant association was found with European late-onset subjects, a meta-analysis of 523 early-onset individuals from European ancestry demonstrated the odds of experiencing asthma exacerbations by carriers of at least one G allele, despite montelukast treatment, were increased (odds-ratio = 2.92, 95%confidence interval (CI): 1.04-8.18, I2 = 62%, p = 0.0412) compared to those in the AA group. When meta-analysing with other ethnic groups, no significant increased risk of asthma exacerbations was found (OR = 1.60, 95% CI: 0.61-4.19, I2 = 85%, p = 0.342). Our study demonstrates that genetic variation in LTA4H, together with timing of asthma onset, may contribute to variability in montelukast response. European individuals with early-onset (≤18y) carrying at least one copy of rs2660845 have increased odd of exacerbation under montelukast treatment, presumably due to the up-regulation of LTA4H activity. These findings support a precision medicine approach for the treatment of asthma with montelukast.

Anti-hyperalgesic properties of ethanolic crude extract from the peels of Citrus reticulata (Rutaceae).

The therapeutic effects from Citrus reticulata on painful inflammatory ailments are associated to its flavonoids constituent and phytochemical studies with Citrus genus affirm that the peels have important amounts of it. These bioactive compounds have been a considerable therapeutic source and evaluate potential application of the peel extract is significant. This research aims to investigate the influence of ethanolic crude extract from the peels of Citrus reticulata and its possible mechanism of action in different animal models of pain. The extract reduced hyperalgesia in the second phase of formalin test (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s), in the carrageenan model (vehicle at 4th h: 82.5 ± 9.6 %; C. reticulata extract 300 mg/kg at 4th h: 47.5 ± 6.5 %) and in Complete Freund's Adjuvant model (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s). The possible contribution of opioidergic and adenosinergic systems in the anti-hyperalgesic effect of C. reticulata extract was observed after treatment, with non-selective antagonists for both systems, which produced reversal effects. In conclusion, these properties of C. reticulata extract suggest a potential therapeutic benefit in treating painful conditions.

Hypertensive emergencies of pregnancy.

Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.

Micronutrient levels in children exposed to secondhand tobacco smoke.

INTRODUCTION: Antioxidant micronutrients are the body's primary defense against the oxidative stress of secondhand smoke (SHS). Micronutrient levels have been associated with lung function; decreased levels of vitamin C and ß-carotene have been associated with SHS exposure in children. We sought to determine the association between SHS exposure and micronutrient levels in children. METHODS: Data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Serum cotinine levels were categorized into no (<0.015 ng/mL), moderate (0.015 to <2.0 ng/mL), and high (2.0-15.0 ng/mL) smoke exposure; t-tests determined associations between exposure and levels of micronutrients. Significant bivariate associations were tested further using linear regression. RESULTS: In all, 2,218 children, aged 6-18 years, were included (response rate of 82%); 17% had no, 76% moderate, and 7% high exposure. Children with no exposure had higher levels of vitamin A, C, and E, cis- and trans-ß-carotene, and folate, while levels of vitamins B(6), B(12), and D did not differ. In regression analysis, higher cotinine levels were negatively associated with levels of vitamin C (ß = -.03; p < .01), cis-ß-carotene (ß = -.04; p < .01), trans-ß-carotene (ß = -.7; p < .01), folate (ß = -.5; p < .001) and vitamin A (ß = -.6; p < .01). CONCLUSIONS: Children exposed to SHS have lower levels of antioxidants controlling for dietary and supplement intake. This antioxidant depletion may increase systemic inflammation and sensitivity to other oxidant stresses. Parents should be counseled on these specific risks from SHS exposure for their children, and the importance of smoking cessation and eliminating children's exposure to tobacco smoke.

Silver carbonate nanoparticles stabilised over alumina nanoneedles exhibiting potent antibacterial properties.

A simple method of preparing Ag2CO3 nanoparticles utilising high area gamma-alumina nanoneedles has been developed; these are promising antimicrobial agents against diverse bacterial strains.

The cost of renal dialysis in a UK setting--a multicentre study.

BACKGROUND: The UK National Health Service (NHS) will fund renal services using Payment by Results (PbR), from 2009. Central to the success of PbR will be the creation of tariffs that reflect the true cost of medical services. We have therefore estimated the cost of different dialysis modalities in the Cardiff and Vale NHS Trust and six other hospitals in the UK. METHODS: We used semi-structured interviews with nephrologists, head nurses and business managers to identify the steps involved in delivering the different dialysis modalities. We assigned costs to these using published figures or suppliers' published price lists. The study used mixed costing methods. Dialysis costs were estimated by a combination of microcosting and a top-down approach. Where we did not have access to detailed accounts, we applied values for Cardiff. RESULTS: The most efficient modalities were automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD), the mean annual costs of which were pound21 655 and pound15 570, respectively. Hospital-based haemodialysis (HD) cost pound35 023 per annum and satellite-unit-based HD cost pound32 669. The cost of home-based HD was pound20 764 per year (based on data from only one unit). The main cost drivers for PD were the costs of solutions and management of anaemia. For HD they were costs of disposables, nursing, the overheads associated with running the unit and management of anaemia. CONCLUSIONS: Renal tariffs for PbR need to reflect the true cost of dialysis provision if choices about modalities are not to be influenced by erroneous estimates of cost. Knowledge of the true costs of modalities will also maximize the number of established renal failure patients treated by dialysis within the limited funds available from the NHS.

Use of high-dose ibuprofen in a pediatric cystic fibrosis center.

Despite its apparent benefits, high-dose ibuprofen has been infrequently applied to children with cystic fibrosis. We have noted a decrease in the use of high-dose ibuprofen at our pediatric cystic fibrosis center during the past decade. In this retrospective study, we examined our clinical experience with high-dose ibuprofen and other anti-inflammatory drugs in cystic fibrosis patients. The medical records of all patients, ages 5 to 18 years, followed at the cystic fibrosis center from 1995 to 2002, were reviewed and children were classified into two cohorts: ibuprofen-treated and untreated groups. Patterns of ibuprofen use and pharmacokinetics in treated patients, and for patients who discontinued ibuprofen, the reasons for stopping the medication, including adverse effects, were assessed. Pulmonary function decline and hospitalization rates for each group were compared, examining both intent to treat and patients who continued therapy for at least 4 years. Nearly half of the patients in our pediatric cystic fibrosis center who were prescribed with high-dose ibuprofen discontinued therapy due to adverse events, not because of poor adherence or patient choice. Neither use of high-dose ibuprofen nor its cessation resulted in a significant change in the rate of decline in pulmonary function or influenced hospitalization rates.

Structural studies of high dispersion H3PW12O40/SiO2 solid acid catalysts.

Highly dispersed H(3)PW(12)O(40)/SiO(2) catalysts with loadings between 3.6 and 62.5 wt% have been synthesised and characterised. The formation of a chemically distinct interfacial HPW species is identified by XPS, attributed to pertubation of W atoms within the Keggin cage in direct contact with the SiO(2) surface. EXAFS confirms the Keggin unit remains intact for all loadings, while NH(3) adsorption calorimetery reveals the acid strength >0.14 monolayers of HPW is loading invariant with initial DeltaH(ads) = approximately -164 kJ mol(-1). Lower loading catalysts exhibit weaker acidity which is attributed to an inability of highly dispersed clusters to form crystalline water. For reactions involving non-polar hydrocarbons the interfacial species where the accessible tungstate is highest confer the greatest reactivity, while polar chemistry is favoured by higher loadings which can take advantage of the H(3)PW(12)O(40) pseudo-liquid phase available within supported multilayers.

Herbal products and their association with substance use in adolescents.

PURPOSE: To describe the prevalence of herbal product use in adolescents and the association between herbal product use and tobacco, alcohol, and other drug use. METHODS: The 1999 Monroe County, New York Youth Risk Behavior Survey provided data on a random sample of 2,006 high school students. Herbal product use was defined by lifetime use of "herbal or other natural products--to feel better, or perform better in sports or school." Bivariate analyses using chi2 tests and logistic regressions were used to describe the independent associations between herbal product use and substance use. RESULTS: Overall, 28.6% reported using herbal products. Herbal product use increased with age (24.5% of 9th graders to 29.9% of 12th graders; p < .04) and varied by ethnicity (33% of Hispanics, 30.9% of Caucasians, 28.8% of Asians, Native Americans, or Pacific Islanders, and 12.1% of African Americans; p < .001), but not by gender. After controlling for gender, grade, and ethnicity, logistic regression models showed herbal product use to be associated with lifetime use of: cigarettes (OR = 2.2; 95% CI = 1.8-2.8), alcohol (OR = 3.5; 2.5-4.9), marijuana (OR = 2.2; 1.8-2.7), and other drugs (odds ratios from 4.4 to 14.5). All p values were < .001. CONCLUSIONS: Over one-quarter of high school students report herbal product use, and this use is associated with drug use. Health care providers should inquire about adolescents' herbal product use, and disclosure should prompt an in-depth substance use history.

Use of complementary medicine and dietary supplements among U.S. adolescents.

PURPOSE: Use of complementary and alternative medicine (CAM) is increasing, but some dietary supplements have potentially negative side effects. This study examines CAM and dietary supplement use among a national sample of adolescents. METHODS: A total of 1280 adolescents 14-19 years old completed an online survey in 2002 about lifetime and past-30-day use of all CAM modalities, and specifically about use of herbal medicines and dietary supplements. We e-mailed invitations to 12,353 members of Harris Interactive's national Youth Query panel, and filled age/gender quotas sample targets. Data were then weighted to reflect the U.S. adolescent population by gender, race/ethnicity, urbanicity, region, parents' education, propensity to be online, and likelihood of nonresponse. Chi-square and logistic regression analyses were done using SPSS. RESULTS: Seventy-nine percent of adolescents had used CAM in their lifetime, 48.5% in the previous month; 46.2% had used dietary supplements in their lifetime, 29.1% in the previous month; 9.3% reported concurrent use of supplements and prescription medication in the previous month. Factors associated with CAM and supplement use included being female, positive attitudes towards CAM, and being age 16-17 years (rather than in younger or older age groups). Commonly used supplements included ginseng, zinc, echinacea, ginkgo, weight loss supplements, and creatine. CONCLUSIONS: Many adolescents use CAM and dietary supplements, including a significant number concurrent with prescription medications. Commonly used supplements (weight loss supplements and creatine) are closely linked to attempts to change body shape. Health care providers should be aware of CAM and supplement use by adolescents.

Adolescents' knowledge of and beliefs about herbs and dietary supplements: a qualitative study.

OBJECTIVE: To explore adolescents' knowledge of and beliefs about dietary supplements, including herbs, and over-the-counter (OTC) medications. METHODS: Eighteen focus groups with 81 adolescents in Monroe County, New York, explored teens' familiarity with and beliefs about CAM, specifically dietary supplements. We asked about general health beliefs and opinions of OTC medications to provide a framework for understanding how dietary supplements are conceptualized. Groups were conducted with suburban adolescents, urban minority adolescents, adolescents with chronic illness, (asthma, eating disorders, and diabetes), and patients of complementary/alternative practitioners ("CAM practitioners"). Transcripts were analyzed for themes relating to prevention ("staying healthy") and treatment of illness ("getting better"); direct quotations are used to illustrate adolescents' views. RESULTS: Most adolescents are familiar with "herbal medicine," "herbal remedies," or "nutritional supplements," and are able to name specific products or complementary/alternative medicine (CAM) therapies; however, many are unfamiliar with the term "alternative medicine." Adolescents are more familiar with remedies or CAM therapies commonly used by people from their own cultural or ethnic background. Older suburban females and those with chronic illnesses are more familiar with herbs and supplements than other adolescents. Most supplement use is conceptually linked with treating illness rather than with preventive care. CONCLUSIONS: Most adolescents are familiar with culturally based herbal products and nutritional supplements, used for treatment of illnesses, and not for preventive care. Providers and researchers should consider chronic illness status and culture/family tradition, and clarify terms, when asking adolescents about self-care, OTCs, or CAM.

Adolescents' use of complementary and alternative medicine.

OBJECTIVE: To examine the prevalence of complementary and alternative medicine (CAM) use in a random sample of adolescents living in Monroe County, New York. METHODS: Questions about use of a variety of CAM therapies in the previous 6 months were asked of adolescents during a random-digit-dial telephone survey. RESULTS: A total of 54% of the 361 adolescents surveyed had used at least 1 CAM remedy. The most frequently used therapies were massage (13.2%), prayer or faith healing (13.1%), herbs (11.5%), megadose vitamins (10.6%), and special exercises (10.1%). Natural performance enhancers were used by 14.7% of the boys, but less than 1% of the girls (P <.001). Use of health care without parental knowledge, time spent in school clubs, and perceived parental use and friend use of CAM were all associated with CAM use in a logistic regression model. CONCLUSION: More than half of the adolescents in this county use CAM therapies, and a significant number use pharmacologically active substances. Physicians treating adolescents should ask adolescents about CAM use.