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Predisposing
Kinds of Predisposing Terms modified by Predisposing Selected AbstractsEnvironmental Risk Factors Predisposing to the Development of Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 2004Malgorzata Zak-Prelich MD Background. Basal cell carcinomas (BCCs) are the most common malignancies in white people. The incidence varies depending on the region of the world, with the highest rate of 1% to 2% per year noted in Australia. It is estimated that BCC incidence increases by 5% annually. An increasing incidence of BCC is in line with the changes in the living style and exposure to various environmental factors. Objective. To present the environmental factors that may influence the development of BCCs. The influence of ultraviolet radiation exposure alone and in connection with immunosuppression, smoking, occupational factors, as well as arsenic and ionizing radiation exposure, was described. Conclusion. BCC is a very complex disease, with many factors influencing its development. Environmental factors are very important for the prevalence of BCC, and most of them can be avoided. The exposure to ultraviolet radiation is undoubtedly of great risk; therefore, the national campaigns against aggressive, seasonal sun exposure, especially in children and adolescents, as well as using sunscreens, are of great value in the fight against BCC development. [source] Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible Factors Predisposing to Sub-optimal Platelet Response to Aspirin?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Leszek Markuszewski Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75,150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8,15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45,50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313,728 pg/mg creatinine versus 321; 246,488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients. [source] The sex of the individual as a factor in allergic contact dermatitisCONTACT DERMATITIS, Issue 2 2004B. S. Modjtahedi Exogenous and endogenous factors have been implicated in allergic contact dermatitis (ACD); this review explores the sex of the individual as a possible endogenous factor. While there is a clinical impression that women are more skin-reactive than men, upon review this hypothesis appears oversimplified. This review explores sex differences in controlled testing of adult ACD, occupational ACD and juvenile ACD. Further, geographical location and socioeconomic and cultural factors in relation to sex differences in allergic contact dermatitis are discussed. We conclude that female sex could be a factor predisposing to allergic contact dermatitis not so much because of possible differences in intrinsic skin characteristics between the sexes, but more because of different exposure patterns. This conclusion has practical consequences regarding product labelling requirements, occupational risk assessment and legislation. [source] Pulmonary Artery Dissection: Echocardiographic Findings and DiagnosisECHOCARDIOGRAPHY, Issue 4 2003Daniel Areco Pulmonary artery dissection is a rare but life-threatening event, predisposing to sudden cardiac death or cardiogenic shock. It is often associated with underlying congenital disorders predisposing to pulmonary hypertension. Rarely, it is diagnosed by echocardiography or other image techniques. We present a case report of a pulmonary artery dissection, diagnosed primarily by echocardiography. The patient died soon after refusing any interventional approach after a short period under medication. (ECHOCARDIOGRAPHY, Volume 20, May 2003) [source] Superficial digital flexor tendon lesions in racehorses as a sequela to muscle fatigue: A preliminary studyEQUINE VETERINARY JOURNAL, Issue 6 2007M. T. Butcher Summary Reasons for performing study: Racing and training related lesions of the forelimb superficial digital flexor tendon are a common career ending injury to racehorses but aetiology and/or predisposing causes of the injury are not completely understood. Objectives: Although the injury takes place within the tendon, the lesion must be considered within the context of the function of the complete suspensory system of the distal limb, including the associated muscles. Methods: Both muscle and tendon function were investigated in vivo using implanted strain gauges in 3 Thoroughbred horses walking, trotting and cantering on a motorised treadmill. These data were combined with assessments of muscle architecture and fibre composition to arrive at an overview of the contribution of each muscle-tendon unit during locomotion. Results: The superficial digital flexor muscle has fatigue-resistant and high force production properties that allow its tendon to store and return elastic energy, predominantly at the trot. As running speed increases, deep digital flexor tendon force increases and it stabilises hyperextension of the fetlock, thus reinforcing the superficial digital flexor in limb load support. The deep digital flexor muscle has fast contracting properties that render it susceptible to fatigue. Conclusion: Based on these measurements and supporting evidence from the literature, it is proposed that overloading of the superficial digital flexor tendon results from fatigue of the synergistic, faster contracting deep digital flexor muscle. Potential relevance: Future research investigating distal limb system function as a whole should help refine clinical diagnostic procedures and exercise training approaches that will lead to more effective prevention and treatment of digital flexor tendon injuries in equine athletes. [source] Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor functionFEBS JOURNAL, Issue 24 2002Jesús Sánchez Más The ,-melanocyte-stimulating hormone (,MSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of ,MSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent ,MSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships. [source] Oncogenetic tree model of somatic mutations and DNA methylation in colon tumorsGENES, CHROMOSOMES AND CANCER, Issue 1 2009Carol Sweeney Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis. © 2008 Wiley-Liss, Inc. [source] Obesity: a new disaster for haemophilic patients?HAEMOPHILIA, Issue 5 2008A nationwide survey Summary., The prevalence of obesity, an important risk factor for both cardiovascular disease and arthropathy, is strongly increasing in the general population, but data for the haemophilia population are scarce. Obesity may have a more profound effect on arthropathy and on cardiovascular disease in patients with haemophilia. To assess the prevalence of obesity in haemophilia patients and install adequate measures, if necessary. We performed a nationwide postal survey to measure the prevalence of overweight and obesity in Dutch haemophilia patients in 1992 (n = 980) and 2001 (n = 1066). A random sample of the Dutch male population served as the control group. In adult haemophiliacs, the prevalence of overweight (BMI 25,30 kg m,2) increased from 27% to 35% (95% CI 31.1,38.0) and the prevalence of obesity (BMI ,30 kg m,2) doubled from 4% to 8% (95% CI 6.0,10.1), which was comparable with the general population. The increased prevalence of obesity in boys with haemophiliacs, which tripled in 10 years, is alarming. The increased prevalence of overweight and obesity in patients with haemophilia may have a profound effect on morbidity and quality of life of haemophilia patients by aggravating pre-existing arthropathy and predisposing aged patients to cardiovascular disease. Measures to prevent overweight in haemophiliacs are therefore urgently needed. [source] Blood Flow Velocity and Pulsatility Index Differences in Patients With Unilateral MigraineHEADACHE, Issue 7 2001Oleg Y. Chernyshev MD Objective.,To evaluate blood flow velocity and pulsatility in unilateral migraine without aura during the headache-free period using transcranial Doppler (TCD) sonography. Methods.,Patients with unilateral headache were recruited during the headache-free period. Maximum mean flow velocity (MFV) and pulsatility index (PI) were measured in the middle cerebral (MCA) and basilar arteries. Controls were headache-free individuals without cerebrovascular disease. Results.,Twenty-five patients with right-sided migraine, 25 patients with left-sided migraine, and 19 controls were studied. The MCA PI was higher on the right headache side versus the left headache side (0.97 ± 0.2 versus 0.86 ± 0.1 cm/s, P = .02) and versus controls (0.9 ± 0.2 cm/s, NS). The basilar artery MFV was higher in patients with right-sided headache versus left-sided headache (39.5 ± 5.6 versus 34.7 ± 8.2 cm/s, P = .02) and versus controls (38.2 ± 8 cm/s, NS). No decrease in MFV with age was observed in patients with migraine. Conclusions.,Middle cerebral artery flow pulsatility and basilar artery velocity are higher in patients with right-sided migraine compared with left-sided migraineurs, during the headache-free period. Although these parameters were similar to controls, the differences found during the headache-free period in migraineurs may indicate vascular involvement predisposing to the unilateral headache recurrence. [source] The Effects of Health Sector Market Factors and Vulnerable Group Membership on Access to Alcohol, Drug, and Mental Health CareHEALTH SERVICES RESEARCH, Issue 3p1 2007Susan E. Stockdale Objective. This study adapts Andersen's Behavioral Model to determine if health sector market conditions affect vulnerable subgroups' use of alcohol, drug, and mental health services (ADM) differently than the general population, focusing specifically on community-level predisposing and enabling characteristics. Data Sources. Wave 2 data (2000,2001) from the Health Care for Communities study, supplemented with cases from wave 1 (1997,1998), were merged with area characteristics taken from Census, Area Resource File (ARF), and other data sources. Study Design. The study used four-level hierarchical logistic regression to examine access to ADM care from any provider and specialty ADM access. Interactions between community-level predisposing and enabling vulnerability characteristics with individual race/ethnicity, age, income category, and insurance type were explored. Principal Findings. Nonwhites, the poor, uninsured, and elderly had lower likelihoods of service use, but interactions between race/ethnicity, income, age and insurance status with community-level vulnerability factors were not statistically significant for any service use. For ADM specialty care, those with Medicare, Medicaid, private fully managed, and private partially managed insurance, the likelihood of utilization was higher in areas with higher HMO penetration. However, for those with other insurance or no insurance plan, the likelihood of utilization was lower in areas with higher HMO penetration. Conclusions. Community-level enabling factors explain part of the effect of disadvantaged status but, with the exception of the effect of HMO penetration on the relationship between insurance and specialty care use, do not modify any of the residual individual-level effects of disadvantage. Interventions targeting both structural and individual levels may be necessary to address the problem of health disparities. More research with longitudinal data is necessary to sort out the causal direction of social context and ADM access outcomes, and whether policy interventions to change health sector market conditions can shift ADM treatment utilization. [source] The Effects of Geography and Spatial Behavior on Health Care Utilization among the Residents of a Rural RegionHEALTH SERVICES RESEARCH, Issue 1 2005Thomas A. Arcury Objective. This analysis determines the importance of geography and spatial behavior as predisposing and enabling factors in rural health care utilization, controlling for demographic, social, cultural, and health status factors. Data Sources. A survey of 1,059 adults in 12 rural Appalachian North Carolina counties. Study Design. This cross-sectional study used a three-stage sampling design stratified by county and ethnicity. Preliminary analysis of health services utilization compared weighted proportions of number of health care visits in the previous 12 months for regular check-up care, chronic care, and acute care across geographic, sociodemographic, cultural, and health variables. Multivariable logistic models identified independent correlates of health services utilization. Data Collection Methods. Respondents answered standard survey questions. They located places in which they engaged health related and normal day-to-day activities; these data were entered into a geographic information system for analysis. Principal Findings. Several geographic and spatial behavior factors, including having a driver's license, use of provided rides, and distance for regular care, were significantly related to health care utilization for regular check-up and chronic care in the bivariate analysis. In the multivariate model, having a driver's license and distance for regular care remained significant, as did several predisposing (age, gender, ethnicity), enabling (household income), and need (physical and mental health measures, number of conditions). Geographic measures, as predisposing and enabling factors, were related to regular check-up and chronic care, but not to acute care visits. Conclusions. These results show the importance of geographic and spatial behavior factors in rural health care utilization. They also indicate continuing inequity in rural health care utilization that must be addressed in public policy. [source] High-frequency haplotypes in the X chromosome locus TLR8 are associated with both CD and UC in femalesINFLAMMATORY BOWEL DISEASES, Issue 3 2009Masayuki Saruta MD Abstract Background: TNF-, and IL-1 have been associated with mucosal inflammation in both Crohn's disease (CD) and ulcerative colitis (UC). Innate immune defects have been associated with CD, specifically CARD15/NOD2. Recently, Toll-like receptor 8 (TLR8) signaling has been shown to enhance generation of both cytokines. Interestingly, TLR8 is located on the X chromosome and inflammatory bowel disease (IBD) has been associated with abnormalities of the X chromosome. The aim was to test whether TLR8 haplotypes are associated with IBD. Methods: Subjects (735 CD, 343 UC, 245 controls) were genotyped. Single nucleotide polymorphisms (SNPs) were chosen to tag common Caucasian haplotypes. Results: Both "risk (H4)" and "protective (H1)" TLR8 haplotypes were observed associated with CD in females. Eighteen percent of CD females had H4 compared with 9% of controls (P = 0.02). Fifty-nine percent of CD females had H1 compared with 72% of controls (P = 0.01). H1 was also negatively associated with UC in females (59% of UC, 72% of controls P = 0.03). Diplotype analysis of CD, UC, and all IBD in females revealed that 2 protective haplotypes (H1/H1) had a markedly diminished odds ratio, 0.4,0.5. The presence of a risk haplotype (H4 / not H1) had a significantly increased odds ratio, 2.0,2.2. Thus, the risk for IBD was 4,5 times higher in females with 1 risk haplotype than with the protective/protective diplotype. Conclusions: TLR8 is an X-linked IBD susceptibility gene with both common predisposing and protecting haplotypes. These associations further emphasize the importance of genetic variation in innate immunity as determinants, not only of CD, but of UC as well. (Inflamm Bowel Dis 2008) [source] The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastomaINTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Jasmien Hoebeeck Abstract Deletions of the short arm of chromosome 3 are often observed in a specific subset of aggressive neuroblastomas (NBs) with loss of distal 11q and without MYCN amplification. The critical deleted region encompasses the locus of the von Hippel-Lindau gene (VHL, 3p25). Constitutional loss of function mutations in the VHL gene are responsible for the VHL syndrome, a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, including pheochromocytoma. Pheochromocytomas are, like NB, derived from neural crest cells, but, unlike NB, consist of more mature chromaffin cells instead of immature neuroblasts. Further arguments for a putative role of VHL in NB are its function as oxygen sensitizer and the reported relation between hypoxia and dedifferentiation of NB cells, leading to a more aggressive phenotype. To test the possible involvement of VHL in NB, we did mRNA expression analysis and sought evidence for VHL gene inactivation. Although no evidence for a classic tumor suppressor role for VHL in NB could be obtained, a strong correlation was observed between reduced levels of VHL mRNA and low patient survival probability (p = 0.013). Furthermore, VHL appears to have predictive power in NTRK1 (TRKA) positive tumor samples with presumed favorable prognosis, which makes it a potentially valuable marker for more accurate risk assessment in this subgroup of patients. The significance of the reduced VHL expression levels in relation to NB tumor biology remains unexplained, as functional analysis demonstrated no clear effect of the reduction in VHL mRNA expression on protein stability of its downstream target hypoxia-inducible factor ,. © 2006 Wiley-Liss, Inc. [source] Excessive exercise in anorexia nervosa and bulimia nervosa: Relation to eating characteristics and general psychopathologyINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 4 2002Eva Peñas-Lledó Abstract Objective Excessive exercise is a well-known phenomenon in anorexia nervosa, but less is known about its role in bulimia nervosa. In addition, there is little evidence regarding the psychopathological processes that might act as predisposing, triggering, or maintaining factors for such exercise. The present study examined the presence of excessive exercise in different women with eating disorders, and its psychopathological correlates. Methods Case notes from 63 anorexia nervosa and 61 bulimia nervosa patients were examined. Two-way multivariate analyses of variance (diagnosis × use of excessive exercise) were used to determine the impact of the two factors upon eating characteristics (EAT-40 and BITE) and psychopathological symptoms (SCL-90-R). Results While high levels of depression were more likely among all patients who used excessive exercise, levels of anxiety and somatization were particularly high only among those anorexics who exercised excessively. Discussion Possible explanatory models are advanced to account for this pattern of findings, focusing on the possible use of exercise as an affect regulation strategy among anorexia nervosa patients. Further research is suggested to test and develop this model, and possible clinical implications are outlined. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 370,375, 2002. [source] Predicting needs for nursing home admission , does sense of coherence delay nursing home admission in care dependent older people?INTERNATIONAL JOURNAL OF OLDER PEOPLE NURSING, Issue 1 2009A longitudinal study Objectives., This study examined predisposing, enabling and need variables (Andersen's Behavioral Model) influencing the need for nursing home admission (NHA) in older people receiving home nursing care. In particular, the potential role of coping ability, measured as ,sense of coherence' (SOC), was studied. Design, sample, and measurements., A survey with baseline- and follow-up data after a 2-year period was undertaken with 208 patients aged 75+. The measures used were: gender, education, age, social visits, SOC, social provision scale (SPS), self-rated health (SRH), general health questionnaire (GHQ), clinical dementia rating (CDR), Barthel activities of daily living (ADL) index, and registered illnesses (RI). A Cox proportional model was used to examine factors that could explain risk of NHA. Results., Measures with predictive properties were Barthel ADL index, SPS, SRH, and gender. SOC, along with subjective health complaints, general health questionnaire, RI and social visits did not predict NHA. Conclusions., It is concluded that the patients' subjective evaluations of both their health and perceived social support were important predictors of future NHA needs, and should be seriously taken into consideration, along with the more commonly used objective measures of ADL and CDR. [source] Provider Characteristics Related to Antidepressant Use in Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2006Gerda G. Fillenbaum PhD OBJECTIVES: To determine whether the characteristics of the usual medical care providers of older antidepressant users changed between 1986 and 1997 with the introduction of selective serotonin reuptake inhibitors. DESIGN: Longitudinal study. SETTING: Five-county Piedmont area of North Carolina. PARTICIPANTS: Stratified random sample of African-American (n=2,261) and white (n=1,875) community residents aged 65 to 105. MEASUREMENTS: Sample members provided information on prescription medications, demographic and health status, and usual medical care provider (matched to North Carolina Health Professions Data Systems files to ascertain provider characteristics) in 1986/87, 1989/90, 1992/93, and 1996/97. Most (77.5%) named a provider (name unmatchable for 4.1%). Sample member characteristics were aggregated into probability (propensity) scores summarizing predisposing (demographic), enabling (medical care access), and need (health status) categories. Along with wave of study and whether a provider was named, these were entered as control variables in generalized estimating equation models that examined the association between provider race (white vs nonwhite), sex, age, location of practice, and primary versus specialist care and antidepressant use. RESULTS: The characteristics of the usual medical care providers remained stable over the decade, although prevalence of antidepressant use increased. Two provider characteristics,race and area of practice (but not the interaction between them),were significantly associated with patients' use of antidepressants. Patients of white physicians and of physicians with urban practices were more likely to use antidepressants. CONCLUSION: Although use of antidepressants has increased over time, there has been little change in the characteristics of users' usual medical care providers. [source] Osteological features in pure-bred dogs predisposing to cervical spinal cord compressionJOURNAL OF ANATOMY, Issue 5 2001S. BREIT Relative to body size, midsagittal and interpedicular diameters of the cranial and caudal aspects of cervical vertebral foramina (C3,C7) were found to be significantly (P < 0·05) larger in small breeds than in large breeds and Dachshunds, and also larger in Dachshunds (P < 0·05) than in large breeds. This condition increases the risk for spinal cord compression resulting from relative stenosis of the cervical vertebral foramina, especially in large dogs, and this is also exacerbated by the typical shape of the vertebral foramina (i.e. dorsoventrally flattened cranially and bilaterally narrowed caudally). Within large dogs those breeds highly predisposed to cervical spinal cord compression were Great Danes (the breed with the smallest midsagittal vertebral foramen diameters from cranial C6 to cranial T1) and Doberman Pinschers, because of the most strikingly cranially dorsoventrally narrowed cone-shaped vertebral foramina at C6 and C7. The existence of a small midsagittal diameter in the cranial cervical spine was a high risk factor predisposing to spinal cord compression in small breeds and Dachshunds. Remarkable consistency was noted between the spinal level of the maximum enlargement of the spinal cord which previously was reported to be at C6, and the site of maximum enlargement of the vertebral canal currently stated in Dachshunds and small breeds. In large breeds the maximum enlargement of the vertebral canal tended to be located more caudally at the caudal limit of C7. The average age at which large dogs were most susceptible to noxious factors causing abnormal growth of the pedicles was determined to be 16 wk. [source] The Effect of Antihistamine Cetirizine on Ventricular Repolarization in Congenital Long QT SyndromeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 7 2007ANNA-MARI HEKKALA M.D. Introduction: Many drugs are known to block cardiac potassium channels, thus prolonging QT interval and predisposing to malignant arrhythmias. Patients with congenital long QT syndrome are particularly vulnerable, but usually electrophysiological effects of drugs have not been assessed in these patients at risk. Methods: Fifteen asymptomatic patients with type 1 (LQT1), 15 patients with type 2 (LQT2) long QT syndrome, and 15 healthy volunteers took a placebo and cetirizine 10 mg. In addition, healthy volunteers took cetirizine 50 mg. The study was single-blinded and randomized. Exercise tests were performed during stable plasma concentrations. The electrocardiogram was recorded with a body surface potential mapping system (BSPM). Data were analyzed with an automated analyze program. QT intervals to the T wave apex and T wave end and their difference (Tp-e) were determined at rest and at specified heart rates during and after exercise. Results: Cetirizine did not lengthen the QT intervals at rest or during exercise and recovery in any group. It shortened Tp-e at rest in LQT1 and LQT2 patients and during exercise test in LQT1 patients, thus slightly decreasing electrocardiographic transmural dispersion of repolarization. Conclusions: Cetirizine does not adversely modify ventricular repolarization in types 1 and 2 long QT syndrome, suggesting that it might be used safely in these long QT syndrome patients. [source] Fanconi anemia protein complex is a novel target of the IKK signalsomeJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2002Tetsuya Otsuki Abstract Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the I,B kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K,>,M). When exposed to mitomycin C, cells expressing IKK2 K,>,M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. J. Cell. Biochem. 86: 613,623, 2002. © 2002 Wiley-Liss, Inc. [source] Altering women's relationships with food: A relational, developmental approachJOURNAL OF CLINICAL PSYCHOLOGY, Issue 11 2001Margo Maine Eating disorders, ranging from body-image distortions to full-blown anorexia nervosa and bulimia nervosa, reflect developmental issues and significant deficits in feelings of self-efficacy. The relational model, an outgrowth of theoretical work specific to the psychology of women, is an appropriate treatment approach. This model appreciates the social context and pressures that foster disconnection from the self and helps the woman to reconnect with self and others, decreasing the need for obsessive control over food and weight. Treatment emphasizes empathy, connection, mutuality, and authenticity and views disconnections and disruptions as the predisposing, precipitating, and perpetuating factors related to eating disorders. The client,therapist relationship is central to this model as demonstrated by a case illustration. © 2001 John Wiley & Sons, Inc. J Clin Psychol/In Session 57: 1301,1310, 2001. [source] The neurobiology and genetics of eating and weight regulationJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 10 2008J. Hebebrand Over the past 15 years tremendous advances have been made in the elucidation of pathways relevant to eating behaviour and body weight regulation. It has become evident that these pathways are intricately interwoven with those underlying mood and anxiety regulation, motor activity, cognition, sleep, fertility and libido. In addition, advances have been made in determining genetic variation underlying inter-individual differences in body weight. To illustrate these novel findings we will focus on: 1) Monogenic and oligogenic obesity: The underlying genes were initially detected in animal models. Based on mutation screens of the human homologues functionally relevant mutations were detected in the genes coding for leptin, its receptors and the melanocortin-4 receptor (MC4R). The effect of such mutations is large. Leptin gene mutations lead to hyperphagia and subsequently obesity. Hyperphagia, albeit of a substantially reduced magnitude, has also been observed in obese children with mutations in the MC4R. 2) Polygenic obesity: The advent of genome wide association studies has led to the detection of single polygenes, among which FTO features prominently. Typically, a variant predisposing to obesity accounts for a body weight elevated by on average 200 to 1500 grams. Such polygenes act in concert to account for inter-individual differences in body weight. 3) Leptin has been shown to have profound implications for anorexia nervosa. Serum leptin levels in this eating disorders are annormaly low. The hypoleptinemia entails a down-regulation of the hypothalamic-pituitary-gonadal-axis, which underlies the amenorrhea characteristic of anorexia nervosa. Furthermore, the hypoleptinemia induces hyperactivity in a rat model of anorexia nervosa. In patients, leptin levels are inversely correlated with activity levels. [source] Linking impulsivity to dysfunctional thought control and insomnia: a structural equation modelJOURNAL OF SLEEP RESEARCH, Issue 1-Part-I 2010RALPH E. SCHMIDT Summary According to cognitive models of insomnia, excessive mental activity at bedtime may be viewed as an important impediment to the process of falling asleep. A further assumption of these models is that ,cognitive arousal' may be perpetuated and exacerbated by counterproductive strategies of thought management. As yet, little is known about factors that may predispose people to rely on these strategies when confronted with thoughts that keep them awake at night. This study examined the relations between impulsivity, use of different thought-control strategies and insomnia severity. A sample of 391 university students completed the UPPS Impulsive Behavior Scale, the Thought Control Questionnaire Insomnia-Revised and the Insomnia Severity Index. Correlation analyses revealed that two facets of impulsivity (urgency and lack of perseverance), two strategies of thought control (aggressive suppression and worry) and insomnia severity were positively associated. Follow-up structural equation modeling analyses showed that the two mentioned thought-control strategies mediated the effects of the two facets of impulsivity on sleep problems. These findings extend existing cognitive accounts of insomnia by suggesting how predisposing and perpetuating factors may be related: specific personality traits may incline individuals to respond with dysfunctional thought-control strategies to unwanted mental activity at night. [source] Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowthALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2010M. Furnari Aliment Pharmacol Ther 2010; 32: 1000,1006 Summary Background, Abnormal intestinal clearance is involved in the pathogenesis of small intestinal bacterial overgrowth (SIBO). It is known that partially hydrolysed guar gum affects intestinal motility. Eradication therapy of SIBO is based on antibiotic treatment: no data are available on the role of fibre supplementation in eradicating SIBO. Aim, To assess whether the combination of partially hydrolysed guar gum and rifaximin is more effective than rifaximin alone in the treatment of SIBO. Methods, A 50 g-glucose breath test was given to 500 consecutive patients. Patients with a positive glucose breath test and predisposing conditions to SIBO entered into the study, and were randomized to receive rifaximin 1200 mg/day or rifaximin 1200 mg/day plus partially hydrolysed guar gum 5 g/day for 10 days. Patients completed a symptom questionnaire and glucose breath test both in basal condition and 1 month after withdrawal of therapy. Results, Seventy-seven patients had SIBO. Eradication rate of SIBO was 62.1% in the rifaximin group (both on per-protocol and intention-to-treat analyses), and 87.1% (per-protocol, P = 0.017) and 85.0% (intention-to-treat, P = 0.036) in the rifaximin-plus-partially hydrolysed guar gum group. Clinical improvement was observed in 86.9% and 91.1% of eradicated cases in rifaximin and rifaximin-plus-partially hydrolysed guar gum groups respectively (P = 0.677). Conclusion, The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone. [source] Use of mental health treatment among veterans filing claims for posttraumatic stress disorderJOURNAL OF TRAUMATIC STRESS, Issue 1 2007Nina A. Sayer This study examines predictors of current mental health service use in a sample of 154 veterans filing claims for Veterans Affairs (VA) disability benefits based on Posttraumatic Stress Disorder (PTSD). Our conceptual framework was the behavioral model that classifies predictors of service utilization into predisposing (background), enabling (e.g., insurance) and need (e.g., symptoms) factors. Slightly more than half of the PTSD claimants were receiving mental health treatment at the time of claim initiation. Mean symptom levels were clinically significant in both users and nonusers of mental health treatment. In a multivariate logistic regression analysis, mental health treatment use was associated with younger age, marriage, and dependence on public insurance. Implications for future research are discussed. [source] The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-upALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009C. W. LEES Summary Background, Anti-TNF agents are now widely used in Crohn's disease (CD), and in ulcerative colitis (UC). Aim, To review the safety profile of anti-TNF agents in all patients treated with infliximab in Edinburgh from 1999 to 2007. Methods, Complete data were available on 202/207 patients comprising 157 CD, 42 UC and three coeliac disease. Median follow-up was 2.4 years (1.0,4.9) with a total of 620 patient-years follow-up. About 19.1% of CD patients were subsequently treated with adalimumab. Results, Seven deaths (3.3%) occurred in follow-up; only one death was <1 year post-infliximab (at day 72, from lung cancer). A total of six malignancies (three haematological, three bronchogenic) and six cases of suspected demyelination (three with confirmed neurological disease) were reported. In the 90 days following infliximab, 95 adverse events (36 serious) occurred in 58/202 (28.7%) patients. In all, 42/202 (20.8%) had an infectious event (22 serious) and 27/202 (13.4%) of patients had an infusion reaction: 19 acute (four serious) and eight delayed (three serious). Conclusions, Serious infections, malignancies and neurological disease complicate anti-TNF use in clinical practice. Although evidence for causality is unclear, potential mechanisms and predisposing factors need to be explored. In individual patients, the risk/benefit analysis needs to be carefully assessed and discussed prior to commencement of therapy. [source] Personal view: food for thought , western lifestyle and susceptibility to Crohn's disease.ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2005The FODMAP hypothesis Summary Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking. A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short-chain carbohydrates and polyols (designated FODMAPs , Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health-promoting effects of FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor. [source] Is affluence a risk factor for bronchial asthma and type 1 diabetes?PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Alberto Tedeschi In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (rsp: 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (rsp: 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (rsp: ,0.66, p < 0.0001 for type 1 diabetes; rsp:, 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (rsp: ,0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (rsp: ,0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes. [source] Thromboembolism in children with sarcomaPEDIATRIC BLOOD & CANCER, Issue 2 2007Uma Athale MD Abstract Background Thromboembolism (TE) is a common complication and cause of death in adults with cancer. Cancer has been identified as a major risk factor in children with TE. However, the information regarding the epidemiology of TE in children with cancer, especially in association with childhood solid tumors, is scant. Objective To define the prevalence and epidemiology of TE in children with sarcoma. Procedure Hospital records of children ,18 years of age with sarcoma diagnosed and treated at McMaster Children's Hospital during January 1990 to December 2005 were reviewed for demographic details, details of diagnosis and therapy for sarcoma, and details of diagnosis and management of TE. Statistical analysis was performed using Fisher's exact t -test. Results Ten of 70 (14.3%; 95% CI; 7.1, 24.7) patients with sarcoma developed symptomatic TE. Patients with CVL-dysfunction (n,=,9) were at significantly higher risk for symptomatic TE compared to those without CVL dysfunction (n,=,61) (55.5 vs. 8.2%; P,=,0.002, 95% CI; 14.2, 80.5). Patients with pulmonary disease (n,=,23) had higher prevalence of TE compared to those without pulmonary disease (n,=,47) (26 vs.8.5%; P,=,0.07, 95% CI; ,2.06, 37.2). Older patients, patients with metastatic disease and those with Ewing sarcoma had higher prevalence of TE. Conclusions TE is a significant complication in children with sarcoma. Over 50% of patients with CVL dysfunction had symptomatic TE; such patients may warrant careful evaluation for associated TE. Large prospective studies are needed to define the epidemiology and identify risk factors predisposing to TE in children with sarcoma. Pediatr Blood Cancer 2007;49:171,176. © 2006 Wiley-Liss, Inc. [source] Physiologic, bronchoscopic, and bronchoalveolar lavage fluid findings in young children with recurrent wheeze and cough,PEDIATRIC PULMONOLOGY, Issue 8 2006John Saito MD Abstract Assessing airway disease in young children with wheeze and/or cough is challenging. We conducted a prospective, descriptive study of lung function in children <3 years old with recurrent wheeze and/or cough, who had failed empiric antiasthma and/or antireflux therapy and subsequently underwent flexible bronchoscopy. Our goals were to describe radiographic, anatomical, microbiological, and physiological findings in these children, and generate hypotheses about their respiratory physiology. Plethysmography and raised-volume rapid thoracoabdominal compression (RVRTC) techniques were performed prior to bronchoscopy. Mean Z-scores (n,=,19) were ,1.34 for forced expiratory volume at 0.5 sec (FEV0.5), ,2.28 for forced expiratory flows at 75% of forced vital capacity (FVC) (FEF75), ,2.25 for forced expiratory flows between 25,75% of FVC (FEF25,75), 2.53 for functional residual capacity (FRC), and 2.23 for residual volume divided by total lung capacity (RV/TLC). Younger, shorter children had markedly depressed FEF75 and FEF25,75 Z-scores (P,=,0.002 and P,=,<0.001, respectively). As expected, lower airway anatomical abnormalities, infection, and inflammation were common. Elevated FRC was associated with anatomical lower airway abnormalities (P,=,0.03). FVC was higher in subjects with neutrophilic inflammation (P,=,0.03). There was no association between other physiologic variables and bronchoscopic/bronchoalveolar lavage fluid findings. Half of those with elevated RV/TLC ratios (Z-score >2) had no evidence of chest radiograph hyperinflation. We conclude that in this population, plethysmography and RVRTC techniques are useful in identifying severity of hyperinflation and airflow obstruction, and we hypothesize that younger children may have relatively small airways caliber, significantly limiting airflow, and thus impairing secretion clearance and predisposing to lower airway infection. Pediatr Pulmonol. 2006; 41: 709,719. © 2006 Wiley-Liss, Inc. [source] Intensified Screening and Treatment of the Metabolic Syndrome for Cardiovascular Risk ReductionPREVENTIVE CARDIOLOGY, Issue 1 2005Nathan D. Wong PhD The metabolic syndrome (MetS), characterized by a clustering of risk factors associated with insulin resistance and abdominal obesity, is associated with an increased risk of coronary heart disease and cardiovascular disease mortality. Persons with MetS have a wide spectrum of coronary heart disease risk and appropriate evaluation of risk using global risk algorithms. Measurement of other risk markers and subclinical disease is potentially needed to best set treatment goals and accompanying treatment regimens. The presence of MetS risk factors should be considered in global risk assessment. Clinical management emphasizes addressing underlying risk factors predisposing to MetS-specifically overweight/obesity and physical inactivity. Further recommendations are given for clinical risk factors, including atherogenic dyslipidemia, elevated blood pressure, insulin resistance/hyperglycemia, prothrombotic state, and proinflammatory state. Clinicians are recommended to assess MetS in their routine practice and to intensify efforts to adequately treat accompanying lifestyle and clinical risk factors. [source] | ||||||||||||||||||||||||||||||||||