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Selected AbstractsComment on "Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose"ACADEMIC EMERGENCY MEDICINE, Issue 5 2008Nima Majlesi DO No abstract is available for this article. [source] Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen OverdoseACADEMIC EMERGENCY MEDICINE, Issue 1 2008W. Stephen Waring PhD Abstract Objectives:, Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N -acetylcysteine (NAC) therapy after deliberate acetaminophen overdose. Methods:, This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC. Results:, There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi-square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the "200-line" and was independent of the interval between ingestion and assessment. Conclusions:, Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion. [source] Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimenCLINICAL TRANSPLANTATION, Issue 5 2010Jeffrey Allen Giullian Giullian JA, Cavanaugh K, Schaefer H. Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimen. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01129.x © 2009 John Wiley & Sons A/S. Abstract:, Background:, Urinary tract infections (UTI) are common in renal transplant recipients. Trimethoprim/sulfamethoxazole (TMP/SMZ) in moderate to high daily doses prevents Pneumocystis jiroveci (PCP) and reduces the risk of UTI in renal transplant patients. Low-dose TMP/SMZ also reduces the risk of PCP, although its ability to reduce the risk of UTI is uncertain. Design:, Retrospective review of 158 patients who received a renal transplant without corticosteroids for maintenance immunosuppression. Results:, Forty percent of patients initially prescribed TMP/SMZ ultimately stopped this medication early because of an adverse reaction. Urinary infection occurred in 16% without a significant difference in the risk of UTI between those treated with dapsone vs. those treated with TMP/SMZ (HR [95%CI]: 1.7 [0.75, 3.9], p = 0.2). In the subset of patients who were older than age 47 yr (mean age for this cohort, SD ± 6.2 yr), those treated with dapsone originally or who switched from TMP/SMZ to dapsone had a greater risk of UTI compared to patients who remained on TMP/SMZ (HR [95%CI]: 4.3 [1.2, 15.5], p = 0.024). Conclusions:, For renal transplant recipients over the age of 47 yr, treated without long-term glucocorticoids, our retrospective data suggest that low-dose TMP/SMZ is associated with a lower risk of UTI compared to dapsone prophylaxis. [source] Previous experience of spontaneous or elective abortion and risk for posttraumatic stress and depression during subsequent pregnancyDEPRESSION AND ANXIETY, Issue 8 2010Lydia Hamama Abstract Background: Few studies have considered whether elective and/or spontaneous abortion (EAB/SAB) may be risk factors for mental health sequelae in subsequent pregnancy. This paper examines the impact of EAB/SAB on mental health during subsequent pregnancy in a sample of women involved in a larger prospective study of posttraumatic stress disorder (PTSD) across the childbearing year (n=1,581). Methods: Women expecting their first baby completed standardized telephone assessments including demographics, trauma history, PTSD, depression, and pregnancy wantedness, and religiosity. Results: Fourteen percent (n=221) experienced a prior elective abortion (EAB), 13.1% (n=206) experienced a prior spontaneous abortion (SAB), and 1.4% (n=22) experienced both. Of those women who experienced either an EAB or SAB, 13.9% (n=220) appraised the EAB or SAB experience as having been "a hard time" (i.e., potentially traumatic) and 32.6% (n=132) rated it as their index trauma (i.e., their worst or second worst lifetime exposure). Among the subset of 405 women with prior EAB or SAB, the rate of PTSD during the subsequent pregnancy was 12.6% (n,51), the rate of depression was 16.8% (n=68), and 5.4% (n,22) met criteria for both disorders. Conclusions: History of sexual trauma predicted appraising the experience of EAB or SAB as "a hard time." Wanting to be pregnant sooner was predictive of appraising the experience of EAB or SAB as the worst or second worst (index) trauma. EAB or SAB was appraised as less traumatic than sexual or medical trauma exposures and conveyed relatively lower risk for PTSD. The patterns of predictors for depression were similar. Depression and Anxiety, 2010.© 2010 Wiley-Liss, Inc. [source] Hypoglycaemia in Type 2 diabetesDIABETIC MEDICINE, Issue 3 2008S. A. Amiel Abstract The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication,in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes,both direct hospital costs and indirect costs,are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications. [source] Atypical antipsychotics and weightgain , a systematic reviewACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2000D. M. Taylor Objective: To review systematically data relating to weight changes with atypical antipsychotics. Method: We conducted a Medline search on October 29 1999 and covered the period 1980,99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them. Results: Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes. Conclusion: All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed. [source] Obesity and lifestyle risk factors for gastroesophageal reflux disease, Barrett esophagus and esophageal adenocarcinomaDISEASES OF THE ESOPHAGUS, Issue 5 2006P. J. Veugelers SUMMARY., The aim of this study was to examine the association of obesity with esophageal adenocarcinoma, and with the precursor lesions Barrett esophagus and gastroesophageal reflux disease (GERD). This case-control study included cases with GERD (n = 142), Barrett esophagus (n = 130), and esophageal adenocarcinoma (n = 57). Controls comprised 102 asymptomatic individuals. Using logistic regression methods, we compared obesity rates between cases and controls adjusting for differences in age, gender, and lifestyle risk factors. Relative to normal weight, obese individuals were at increased risk for esophageal adenocarcinoma (Odds Ratio [OR] 4.67, 95% Confidence Interval [CI] 1.27,17.9). Diets high in vitamin C were associated with a lower risk for GERD (OR 0.40, 95% CI 0.19,0.87), Barrett esophagus (OR 0.44, 95% CI 0.20,0.98), and esophageal adenocarcinoma (OR 0.21, 95% CI 0.06,0.77). For the more established risk factors, we confirmed that smoking was a significant risk factor for esophageal adenocarcinoma, and that increased liquor consumption was associated with GERD and Barrett esophagus. In light of the current obesity epidemic, esophageal adenocarcinoma incidence rates are expected to continue to increase. Successful promotion of healthy body weight and diets high in vitamin C may substantially reduce the incidence of this disease. [source] Symptoms of nicotine dependence in a cohort of Swedish youths: a comparison between smokers, smokeless tobacco users and dual tobacco usersADDICTION, Issue 4 2010Ann Post ABSTRACT Aims To determine whether symptoms of nicotine dependence, addiction and withdrawal symptoms differ between exclusive smokers, exclusive snus (moist snuff) users and dual users. Design A cross-sectional survey of a cohort subsample. Setting County of Stockholm, Sweden. Participants Current exclusive smokers (n = 466), exclusive snus users (n = 209) and dual users (n = 144), mean age 17.6 years. Measurements Self-reported life-time experience of nicotine dependence and withdrawal symptoms in periods of discontinued tobacco use. Selected items from the modified Fagerstöm Tolerance Questionnaire (mFTQ), the Hooked on Nicotine Checklist (HONC) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Findings The odds ratio of endorsing each of four mFTQ items as well as the HONC item investigating the risk of feeling addicted to tobacco was two to five-fold higher for exclusive snus users and for dual users compared to exclusive smokers. One DSM-IV item (difficult to refrain from use) was elevated among dual users compared to smokers. Dual users reported the highest prevalence of any withdrawal symptom in contrast to exclusive snus users, who reported a lower risk of withdrawal symptoms compared to exclusive smokers. Conclusions Smokeless tobacco users show symptoms of nicotine dependence at least as frequently as cigarette smokers. Symptoms of nicotine dependence and of withdrawal during quit attempts are particularly frequent in the subgroup of users who combine smokeless tobacco with smoking. [source] Are adolescents who moderate their cannabis use at lower risk of later regular and dependent cannabis use?ADDICTION, Issue 5 2009Wendy Swift ABSTRACT Aims To examine whether moderation of cannabis use among adolescent cannabis users is associated with reductions in cannabis use frequency and risk of dependence in young adulthood. Design Ten-year representative cohort study with six surveys in adolescence (mean age 14.9,17.4 years) and two in young adulthood (mean age 20.7 and 24.1 years). Participants Inception cohort of 1943 Victorian secondary school students (96% response rate), with 1520 (78% of adolescent participants) interviewed in the final wave. Measurements Participants were classified into six groups according to the maximum level of adolescent use and the extent of subsequent moderation in such use: non-users, occasional to abstinence, occasional persisting, weekly to abstinence, weekly to occasional and weekly persisting. Outcome measures were weekly+ cannabis use and DSM-IV cannabis dependence at 20 and 24 years. Findings Thirty-one per cent reported cannabis use during adolescence. Most adolescent users had moderated their use: from occasional to abstinence (71% of occasional users), weekly to abstinence or weekly to occasional (28% and 48% of weekly+ users, respectively). By age 24, both occasional use groups were at similar, elevated risk of regular and dependent cannabis use compared to non-users. Weekly+ adolescent users were at greatest risk of these outcomes, although the weekly to abstinence group exhibited lower risk than those in the weekly persisting and weekly to occasional groups, who were at similar risk. Conclusions While many young people have dynamic cannabis use patterns, a pattern of moderating adolescent cannabis use was associated with less risk of later problematic use than among those persisting, but risks were still elevated substantially compared with never-users. [source] Longitudinal study of parental movie restriction on teen smoking and drinking in GermanyADDICTION, Issue 10 2008Reiner Hanewinkel ABSTRACT Aims To determine if adolescents who report that their parents restrict viewing movies based on rating have a lower risk of trying smoking and drinking alcohol in the future. Design Prospective observational study. A cohort of 2110 German adolescents younger than 15 years who had never smoked or drunk alcohol at baseline were surveyed 12,13 months later to determine smoking and binge drinking initiation. Risk of substance use was assessed as a function of parental restriction on viewing FSK-16 movies (movies that only those aged 16 years and over would be allowed to see in theaters). Findings The percentage of students who tried smoking was 16.3%, 10.9% initiated binge drinking and 5.0% used both substances during the follow-up period. There was a significant effect of parental movie restriction on each substance use outcome measure after controlling for covariates. Compared with adolescents whose parents never allowed them to view FSK-16 movies, the adjusted relative risk [(RR) (95% confidence interval (CI)] for use of both substances were 1.64 (1.05,2.58) for adolescents allowed to view them once in a while, 2.30 (1.53,3.45) for sometimes and 2.92 (1.83,4.67) for all the time. FSK-16 restrictions were associated with lower viewership of all classes of movies, but especially FSK-16/18 movies; in addition, FSK-16 restrictions were associated with substantially lower exposure to movie depiction of tobacco and alcohol use, suggesting a mediational mechanism for the association. Conclusions Among young adolescents, parental restriction from viewing movies rated for older adolescents/adults decreases the risk of substance use in the future. [source] Exposure to opioid maintenance treatment reduces long-term mortalityADDICTION, Issue 3 2008Amy Gibson ABSTRACT Aims To (i) examine the predictors of mortality in a randomized study of methadone versus buprenorphine maintenance treatment; (ii) compare the survival experience of the randomized subject groups; and (iii) describe the causes of death. Design Ten-year longitudinal follow-up of mortality among participants in a randomized trial of methadone versus buprenorphine maintenance treatment. Setting Recruitment through three clinics for a randomized trial of buprenorphine versus methadone maintenance. Participants A total of 405 heroin-dependent (DSM-IV) participants aged 18 years and above who consented to participate in original study. Measurements Baseline data from original randomized study; dates and causes of death through data linkage with Births, Deaths and Marriages registries; and longitudinal treatment exposure via State health departments. Predictors of mortality examined through survival analysis. Findings There was an overall mortality rate of 8.84 deaths per 1000 person-years of follow-up and causes of death were comparable with the literature. Increased exposure to episodes of opioid treatment longer than 7 days reduced the risk of mortality; there was no differential mortality among methadone versus buprenorphine participants. More dependent, heavier users of heroin at baseline had a lower risk of death, and also higher exposure to opioid treatment. Older participants randomized to buprenorphine treatment had significantly improved survival. Aboriginal or Torres Strait Islander participants had a higher risk of death. Conclusions Increased exposure to opioid maintenance treatment reduces the risk of death in opioid-dependent people. There was no differential reduction between buprenorphine and methadone. Previous studies suggesting differential effects may have been affected by biases in patient selection. [source] Probabilistic risk assessment of reproductive effects of polychlorinated biphenyls on bottlenose dolphins (Tursiops truncatus) from the Southeast United States coastENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2002Lori H. Schwacke Abstract High levels of polychlorinated biphenyls (PCBs) have been reported in the tissues of some species of marine mammals. The high concentrations are of concern because a growing body of experimental evidence links PCBs to deleterious effects on reproduction, endocrine homeostasis, and immune system function. Much of the recent research has focused on determining the exposure of marine mammal populations to PCBs, but very little effort has been devoted to the actual risk assessments that are needed to determine the expected impacts of the documented exposures. We describe a novel risk assessment approach that integrates measured tissue concentrations of PCBs with a surrogate dose-response relationship and leads to predictions of health risks for marine mammals as well as to the uncertainties associated with these predictions. Specifically, we use PCB tissue residue data from three populations of bottlenose dolphins (Tursiops truncatus), study the feasibility of published dose-response data from a surrogate species, and combine this information to estimate the risk of detrimental reproductive effects in female dolphins. Our risk analyses for dolphin populations near Beaufort (NC, USA), Sarasota (FL, USA), and Matagorda Bay (TX, USA) indicate a high likelihood that reproductive success, primarily in primiparous females, is being severely impaired by chronic exposure to PCBs. Excess risk of reproductive failure, measured in terms of stillbirth or neonatal mortality, for primiparous females was estimated as 60% (Beaufort), 79% (Sarasota), and 78% (Matagorda Bay). Females of higher parity, which have previously off-loaded a majority of their PCB burden, exhibit a much lower risk. [source] Decision support systems used in the Netherlands for reduction in the input of active substances in agricultureEPPO BULLETIN, Issue 3 2003E. Bouma Since the middle of the 1980s, Dutch farmers have been using decision support systems (DSS) as an aid in the control of pests. This started with EPIPRE, then weather-related potato blight warning systems were developed (Prophy and Plant-Plus). In the 1990s, many weather-based DSS were developed against pests of orchards, flower bulbs, arable crops and field-produced vegetables. Also, a DSS was developed to predict and check the effect of meteorological conditions on the effectiveness of application timing of plant protection products (GEWIS). The use of these systems resulted in more sustainable crop protection: sustainable because the use of DSS led to a lower risk of crop damage and, in many cases, to a lower input of active substances, by optimization of the product and dose to actual phytosanitary and meteorological conditions. The use of GEWIS to ensure application at the right time of day further reduced the input of active substances and increased efficacy. [source] Avian Risk Assessment: Effects of Perching Height and DetectabilityETHOLOGY, Issue 4 2004Daniel T. Blumstein We studied two components of predator risk assessment in birds. While many species are limited to seeking safety under cover or under ground, some birds can fly away from their predators and escape to trees. If birds in fact ,feel' safer (e.g. perceive less risk) in trees, we would expect them to tolerate closer approach by a potential terrestrial predator. Another component of safety is at which point the animal detects an approaching threat, which we expected to increase with eye size, assuming eye size is a surrogate for visual acuity. We used the distance birds moved away from an approaching human [flight initiation distance (FID)] as a metric to determine whether birds associated a lower risk of predation by being in trees, and we used the distance at which birds first displayed alert behaviors from an approaching human (alert distance) to determine if birds with larger eyes had higher detection distances. Although some species were affected by tree height, we found no clear pattern that birds assessed themselves to be at a lower risk of predation when they were ,3 m above the ground compared with being <3 m above ground. In the 10 species for which height had any significant effect on FID, birds ,3 m off the ground had greater FIDs in six species, but the remaining three species had the opposite response. While we found a significant positive relationship between eye size and alert distance in 23 species, the relationship was not present in a phylogenetic analysis using independent contrasts, which suggests that the apparent relationship was influenced strongly by the association between the studied species. Together, these results suggest that birds do not obviously associate being in a tree with safety, and that variations in visual acuity, per se, cannot be used as a general indicator of differences in alert distances, as previously suggested in the literature. [source] Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2009Anna Lönnqvist Abstract The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance. [source] Biological phenotypes associated with individuals at high risk for developing alcohol-related disorders.ADDICTION BIOLOGY, Issue 1 2000Part This paper reviews comparisons of populations at higher and lower risk for alcoholism on biological phenotypes. The results of studies must be considered in the context of the research methods used including the need for large, carefully defined samples and longitudinal designs. Comparisons of children of alcoholics and controls have revealed potentially important differences on level of response to alcohol, cognitive attributes and differences in alcohol-metabolizing and other enzyme systems responsible for various aspects of the body's reaction to alcohol. Many opportunities for future research in this area exist, including large-scale, longitudinal studies that simultaneously evaluate multiple domains of influence, and searches for candidate genes or other biological material that will simplify procedures and increase the accuracy of measurement. [source] Pimecrolimus , an anti-inflammatory drug targeting the skinEXPERIMENTAL DERMATOLOGY, Issue 12 2004M. Grassberger Abstract:, Pimecrolimus is the most recent member of calcineurin inhibitors available for the therapy for inflammatory skin diseases. It targets T-cells and mast cells and inhibits the production and release of cytokines and other inflammatory mediators, as well as the expression of signals essential for the activation of inflammatory T-lymphocytes. Pimecrolimus has a cell-selective mode of action. In contrast to corticosteroids, it does not affect, e.g., Langerhans'cells/dendritic cells (LC/DC), as demonstrated in vitro with human monocyte-derived DC and in vivo with epidermal LC in mice, nor human primary fibroblasts. As shown in vitro with human skin and by comparison of clinical pharmacokinetic data from patients with atopic dermatitis, pimecrolimus permeates less through skin than tacrolimus and much less than corticosteroids. It, thus, has a lower potential for transcutaneous resorption after topical administration, resulting in a lower risk of systemic effects. Pimecrolimus has high anti-inflammatory activity in animal models of skin inflammation, including a model reflecting neurogenic inflammation, but a more favourable balance of anti-inflammatory vs. immunosuppressive activity than tacrolimus. Pimecrolimus does not affect sensitization in a murine model of allergic contact dermatitis and has a lower potency in various models of immunosuppression after systemic administration, compared to tacrolimus. In conclusion, the results of preclinical studies show that pimecrolimus has a selective pharmacological profile, suited for effective and safe treatment for inflammatory skin diseases. [source] PERSPECTIVE: Rethinking the value of high wood densityFUNCTIONAL ECOLOGY, Issue 4 2010Markku Larjavaara Summary 1.,Current thinking holds that wood density mediates a tradeoff between strength and economy of construction, with higher wood density providing higher strength but at higher cost. 2.,Yet the further away wood fibres are from the central axis of the trunk, the more they increase the strength of the trunk; thus, a fat trunk of low-density wood can achieve greater strength at lower construction cost than a thin trunk of high-density wood. 3.,What then are the countervailing advantages of high wood density? 4.,We hypothesize that high wood density is associated with lower maintenance costs due to lower trunk surface area, as surface area correlates with maintenance respiration. 5.,This advantage would be particularly important to long-lived trees and could in part explain why they tend to have high wood density. 6.,High wood density has also been associated with lower risk of trunk breakage, xylem implosion and pathogen invasion, but we argue that these relationships are not causal and instead reflect correlated selection on other traits of value to long-lived trees. 7.,This revaluation of the costs and benefits of high wood density has important implications for understanding tree life-history evolution, functional diversity, forest carbon stocks and the impacts of global change. [source] Lifetime Prevalence and Characteristics of Recurrent Primary Headaches in a Population-Based Sample of Swedish TwinsHEADACHE, Issue 8 2002Dan A. Svensson MSc Objective.,To examine the lifetime prevalence and other characteristics of recurrent primary headaches in twins. Background.,The twin model may provide insights into the role of genetic and environmental influences in headache disorders. However, assumptions as to whether twins are representative of the general population, and whether monozygotic and dizygotic twins are similar have rarely been addressed. Methods.,The study population consisted of a random sample of 17- to 82-year-old twins from the Swedish Twin Registry (n = 1329). Structured interviews on the telephone by lay personnel and the International Headache Society criteria were used for assessment and diagnosis of recurrent primary headaches. Prevalence data of the general population for migraine and tension-type headache was obtained from various published reports. Results.,A total of 372 subjects (29%) had ever had recurrent headaches. In total, 241 recurrent headache sufferers fulfilled the criteria for migraine or tension-type headache, and the lifetime prevalence was 7.1% for migraine without aura, 1.4% for migraine always with aura, 1.9% for migraine occasionally with aura, 9.4% for episodic tension-type headache, and 1.3% for chronic tension-type headache. The lifetime prevalence of all migraine and all tension-type headache, including another 84 subjects fulfilling all but one of the criteria for migraine or tension-type headache, was 13.8% and 13.5%, respectively. The corresponding prevalence risk for women was 2.4 (95% confidence interval [CI] 1.7, 3.4) and 1.5 (95% CI 1.1, 2.1), respectively. Zygosity was not a significant predictor for migraine. In tension-type headache, the prevalence risk for dizygotic twins and unlike-sexed twins as compared with monozygotic twins was 1.9 (95% CI: 1.2, 3.1) and 1.8 (95% CI: 1.1, 2.9), respectively. Conclusion.,There is no twin-singleton or monozygotic-dizygotic difference for the risk of migraine. In tension-type headache, twins seem to have a lower risk than singletons, and this is especially true for monozygotic twins. [source] Obstetric Complications in Women with Diagnosed Mental Illness: The Relative Success of California's County Mental Health SystemHEALTH SERVICES RESEARCH, Issue 1 2010Dorothy Thornton Objective. To examine disparities in serious obstetric complications and quality of obstetric care during labor and delivery for women with and without mental illness. Data Source. Linked California hospital discharge (2000,2001), birth, fetal death, and county mental health system (CMHS) records. Study Design. This population-based, cross-sectional study of 915,568 deliveries in California, calculated adjusted odds ratios (AORs) for obstetric complication rates for women with a mental illness diagnosis (treated and not treated in the CMHS) compared with women with no mental illness diagnosis, controlling for sociodemographic, delivery hospital type, and clinical factors. Results. Compared with deliveries in the general non,mentally ill population, deliveries to women with mental illness stand a higher adjusted risk of obstetric complication: AOR=1.32 (95 percent confidence interval [CI]=1.25, 1.39) for women treated in the CMHS and AOR=1.72 (95 percent CI=1.66, 1.79) for women not treated in the CMHS. Mentally ill women treated in the CMHS are at lower risk than non-CMHS mentally ill women of experiencing conditions associated with suboptimal intrapartum care (postpartum hemorrhage, major puerperal infections) and inadequate prenatal care (acute pyelonephritis). Conclusion. Since mental disorders during pregnancy adversely affect mothers and their infants, care of the mentally ill pregnant woman by mental health and primary care providers warrants special attention. [source] Sexual activity as a risk factor for hepatitis CHEPATOLOGY, Issue S1 2002M.P.H., Norah A. Terrault M.D. The accumulated evidence indicates that hepatitis C virus (HCV) can be transmitted by sexual contact but much less efficiently than other sexually transmitted viruses, including hepatitis B virus and human immunodeficiency virus (HIV). However, because sex is such a common behavior and the reservoir of HCV-infected individuals is sizable, sexual transmission of HCV likely contributes to the total burden of infection in the United States. Risk of HCV transmission by sexual contact differs by the type of sexual relationship. Persons in long-term monogamous partnerships are at lower risk of HCV acquisition (0% to 0.6% per year) than persons with multiple partners or those at risk for sexually transmitted diseases (0.4% to 1.8% per year). This difference may reflect differences in sexual risk behaviors or differences in rates of exposure to nonsexual sources of HCV, such as injection drug use or shared razors and toothbrushes. In seroprevalence studies in monogamous, heterosexual partners of HCV-infected, HIV-negative persons, the frequency of antibody-positive and genotype-concordant couples is 2.8% to 11% in Southeast Asia, 0% to 6.3% in Northern Europe, and 2.7% in the United States. Among individuals at risk for sexually transmitted diseases (STDs), the median seroprevalence of antibody to HCV (anti-HCV) is 4% (range, 1.6% to 25.5%). HIV coinfection appears to increase the rate of HCV transmission by sexual contact. Current recommendations about sexual practices are different for persons with chronic HCV infection who are in steady monogamous partnerships versus those with multiple partners or who are in short-term sexual relationships. (HEPATOLOGY 2002;36:S99,S105). [source] Tenascin-C in primary malignant melanoma of the skinHISTOPATHOLOGY, Issue 4 2004S Ilmonen Aims :,To investigate the expression and the prognostic role of glycoprotein Tenascin-C (Tn-C) in primary melanoma of the skin. Methods and results :,The immunohistochemical expression of Tn-C was studied in 98 primary melanomas and related to inflammation, invasion, and patient outcome. Patients were followed up for disease recurrence for 0.04,7.4 years (median 3.9) and for survival for 0.5 to 12.1 years (median 9.3). The expression of Tn-C was evaluated for each tumour invasion border; the stromal and intracytoplasmic Tn-C of the melanoma islets were also recorded. Tn-C is widely expressed in primary melanoma samples, the staining pattern varying from focal to diffuse in different parts of the tumour. No correlation existed between intensity of Tn-C staining and inflammation. No stromal Tn-C was detected at the upper dermal lateral border in 12 patients, nor at the deep, dermal or subcutaneous border in 14 patients. These patients showed better disease-free survival (DFS) than did those cases with focal or diffuse staining (P = 0.06, P = 0.05). Also, absence of intracytoplasmic Tn-C was a beneficial prognostic factor for DFS (P = 0.04). In multivariate analysis, tumour ulceration and intracytoplasmic Tn-C expression of melanoma cells were independent adverse prognostic factors for DFS. Conclusions :,In primary melanoma of the skin, absence of Tn-C in the stroma of invasion fronts and within tumour cells seems to be related to a more benign disease behaviour with a lower risk of developing metastases. [source] Risk factors and occurrence of rash in HIV-positive patients not receiving nonnucleoside reverse transcriptase inhibitor: data from a randomized study evaluating use of protease inhibitors in nucleoside-experienced patients with very low CD4 levels (<50 cells/m,L)HIV MEDICINE, Issue 1 2004M Floridia Background Most of the studies evaluating rash in HIV-positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI. Methods We evaluated all cases of rash observed during a 48-week randomized multicentre trial in 1251 nucleoside-experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/,L. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrolment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log-rank test in a Kaplan-Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model. Results During a follow-up period of 9690 person-months, 66 patients (5.3%) developed rash (0.68 events/100 person-months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow-up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00,2.72, P=0.048) and use of a non-HAART regimen (risk for non-HAART patients compared to HAART: 2.73, 95% CI: 1.49,5.02, P=0.001). Conclusions In our study, about 5% of HIV-positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI. [source] Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9 -related disease,HUMAN MUTATION, Issue 3 2008Alessandro Pecci Abstract MYH9 -related disease (MYH9 -RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts, and/or progressive nephritis leading to end-stage renal failure. No consistent correlations have been identified between the 27 different MYH9 mutations identified so far and the variable clinical evolution of the disease. We have evaluated 108 consecutive MYH9 -RD patients belonging to 50 unrelated pedigrees. The risk of noncongenital manifestations associated with different genotypes was estimated over time by event-free survival analysis. We demonstrated that all subjects with mutations in the motor domain of NMMHC-IIA present with severe thrombocytopenia and develop nephritis and deafness before the age of 40 years, while those with mutations in the tail domain have a much lower risk of noncongenital complications and significantly higher platelet counts. We also evaluated the clinical course of patients with mutations in the four most frequently affected residues of NMMHC-IIA (responsible for 70% of MYH9 -RD cases). We concluded that mutations at residue 1933 do not induce kidney damage or cataracts and cause deafness only in the elderly, those in position 702 result in severe thrombocytopenia and produce nephritis and deafness at a juvenile age, while alterations at residue 1424 or 1841 result in intermediate clinical pictures. These findings are relevant not only to patients' clinical management but also to the elucidation of the pathogenesis of the disease. Hum Mutat 29(3), 409,417, 2008. © 2007 Wiley-Liss, Inc. [source] Outcome prediction and risk assessment by quantitative pyrosequencing methylation analysis of the SFN gene in advanced stage, high-risk, neuroblastic tumor patientsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2010Barbara Banelli Abstract The aim of our study was to identify threshold levels of DNA methylation predictive of the outcome to better define the risk group of stage 4 neuroblastic tumor patients. Quantitative pyrosequencing analysis was applied to a training set of 50 stage 4, high risk patients and to a validation cohort of 72 consecutive patients. Stage 4 patients at lower risk and ganglioneuroma patients were included as control groups. Predictive thresholds of methylation were identified by ROC curve analysis. The prognostic end points of the study were the overall and progression-free survival at 60 months. Data were analyzed with the Cox proportional hazard model. In a multivariate model the methylation threshold identified for the SFN gene (14.3.3,) distinguished the patients presenting favorable outcome from those with progressing disease, independently from all known predictors (Training set: Overall Survival HR 8.53, p = 0.001; Validation set: HR 4.07, p = 0.008). The level of methylation in the tumors of high-risk patients surviving more than 60 months was comparable to that of tumors derived from lower risk patients and to that of benign ganglioneuroma. Methylation above the threshold level was associated with reduced SFN expression in comparison with samples below the threshold. Quantitative methylation is a promising tool to predict survival in neuroblastic tumor patients. Our results lead to the hypothesis that a subset of patients considered at high risk,but displaying low levels of methylation,could be assigned at a lower risk group. [source] Biological indicators of prognosis in Ewing's sarcoma: An emerging role for lectin galactoside-binding soluble 3 binding protein (LGALS3BP)INTERNATIONAL JOURNAL OF CANCER, Issue 1 2010Diana Zambelli Abstract Starting from an experimental model that accounts for the 2 most important adverse processes to successful therapy of Ewing's sarcoma (EWS), chemoresistance and the presence of metastasis at the time of diagnosis, we defined a molecular signature of potential prognostic value. Functional annotation of differentially regulated genes revealed 3 major networks related to cell cycle, cell-to-cell interactions and cellular development. The prognostic impact of 8 genes, representative of these 3 networks, was validated in 56 EWS patients. High mRNA expression levels of HINT1, IFITM2, LGALS3BP, STOML2 and c-MYC were associated with reduced risk to death and lower risk to develop metastasis. At multivariate analysis, LGALS3BP, a matricellular protein with a role in tumor progression and metastasis, was the most important predictor of event-free survival and overall survival. The association between LGALS3BP and prognosis was confirmed at protein level, when expression of the molecule was determined in tumor tissues but not in serum, indicating a role for the protein at local tumor microenvironment. Engineered enhancement of LGALS3BP expression in EWS cells resulted in inhibition of anchorage independent cell growth and reduction of cell migration and metastasis. Silencing of LGALS3BP expression reverted cell behavior with respect to in vitro parameters, thus providing further functional validation of genetic data obtained in clinical samples. Thus, we propose LGALS3BP as a novel reliable indicator of prognosis, and we offer genetic signatures to the scientific communities for cross-validation and meta-analysis, which are indispensable tools for a rare tumor such as EWS. [source] Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers from 3 populations with different risks of lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Kiersten S. Derby Abstract Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower risk of lung cancer (LC), compared with white smokers, even after accounting for smoking history. Because variation in carcinogen exposure/metabolism may occur separately of smoking amount, we compared urinary biomarkers of uptake and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK),a potent lung carcinogen,among 578 smokers in these ethnic/racial groups in Hawaii. We measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL + NNAL-Gluc) and the NNAL detoxification ratio (NNAL-Gluc:NNAL). Native Hawaiians and Japanese,Americans had lower age- and sex-adjusted mean total NNAL, compared with whites. When further adjusting for urinary nicotine equivalents (the sum of nicotine, cotinine, trans -3,-hydroxycotinine and their respective glucuronides), only the difference between Japanese,Americans and whites was eliminated. Therefore, consistent with their lower LC risk, a lower cigarette smoke exposure explains the lower NNK dose of Japanese,Americans, but it does not explain that of Native Hawaiians. The mean detoxification ratio was also lower in Native Hawaiians and Japanese,Americans, compared with whites, even after adjusting for nicotine equivalents (p < 0.0001). Lower NNAL glucuronidation in Native Hawaiians might contribute to their increased LC risk; however, this is inconsistent with the low glucuronidation ratio similarly observed in the low-risk Japanese-American group and because Native Hawaiians had lower total NNAL levels. Thus, exposure and detoxification of NNK are unlikely to explain, by themselves, the differences in LC risk among the 3 populations studied. © 2009 UICC [source] Physical activity and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohortINTERNATIONAL JOURNAL OF CANCER, Issue 4 2009Nina Føns Johnsen Abstract The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In our study, including 127,923 men aged 20,97 years from 8 European countries, 2,458 cases of prostate cancer were identified during 8.5 years of followup. Using the Cox proportional hazards model, we investigated the associations between prostate cancer incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk of advanced stage prostate cancer (ptrend = 0.024). In conclusion, our data support the hypothesis of an inverse association between advanced prostate cancer risk and occupational physical activity, but we found no support for an association between prostate cancer risk and leisure time physical activity. © 2009 UICC [source] Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese womenINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Cai-Xia Zhang Abstract The effect of vegetable and fruit consumption on breast cancer risk is controversial. We examined the association between vegetable and fruit intake and breast cancer risk in a hospital-based case,control study conducted in Guangdong, China. Four hundred and thirty-eight cases were frequency matched to 438 controls by age (5-year interval) and residence (rural/urban). Dietary intake was assessed by face-to-face interviews using a validated food frequency questionnaire. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) after adjusting for various potential confounders. Total vegetable and fruit intake was found to be inversely associated with breast cancer risk. The ORs of the highest quartile relative to the lowest quartile of total vegetable and fruit intake were 0.28 (95% CI 0.18,0.43) and 0.53 (95% CI 0.34,0.82), respectively. Consumption of individual vegetable and fruit groups such as dark green leafy vegetables, cruciferous vegetables, carrots and tomatoes, banana, watermelon/papaya/cantaloupe were all inversely and significantly related with breast cancer risk. An inverse association was also observed for vitamin A, carotene, vitamin C, vitamin E, and fiber intake. These data indicate that greater intake of vegetables and fruits is associated with a decreased risk of breast cancer among Chinese women residing in Guangdong. © 2009 UICC [source] Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and NutritionINTERNATIONAL JOURNAL OF CANCER, Issue 8 2009Alina Vrieling Abstract Many case-control studies have suggested that higher consumption of fruit and vegetables is associated with a lower risk of pancreatic cancer, whereas cohort studies do not support such an association. We examined the associations of the consumption of fruits and vegetables and their main subgroups with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is comprised of over 520,000 subjects recruited from 10 European countries. The present study included 555 exocrine pancreatic cancer cases after an average follow-up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models, stratified by age at recruitment, gender, and study center, and adjusted for total energy intake, weight, height, history of diabetes mellitus, and smoking status. Total consumption of fruit and vegetables, combined or separately, as well as subgroups of vegetables and fruits were unrelated to risk of pancreatic cancer. Hazard ratios (95% CI) for the highest versus the lowest quartile were 0.92 (0.68,1.25) for total fruit and vegetables combined, 0.99 (0.73,1.33) for total vegetables, and 1.02 (0.77,1.36) for total fruits. Stratification by gender or smoking status, restriction to microscopically verified cases, and exclusion of the first 2 years of follow-up did not materially change the results. These results from a large European prospective cohort suggest that higher consumption of fruit and vegetables is not associated with decreased risk of pancreatic cancer. © 2008 Wiley-Liss, Inc. 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