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Decreased Frequency (decreased + frequency)
Selected AbstractsDecreased frequency of seizures in infantile spasms associated with lissencephaly by human herpes virus 7 infectionPEDIATRICS INTERNATIONAL, Issue 2 2002Jiro Ono No abstract is available for this article. [source] The germinal center response is impaired in the absence of T cell-expressed CXCR5EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Carrie Abstract Germinal centers support the differentiation of memory B cells and long-lived antibody-secreting cells during infection or upon vaccination. Here, we constructed mice with T cells that selectively lack the chemokine receptor CXCR5 to determine if expression of this receptor by T cells is mandatory for germinal center formation and function. In these animals, germinal centers that are properly localized in B cell follicles and contain T cells do form after immunization with a thymus-dependent antigen. However, fewer and smaller germinal centers form, resulting in a significant reduction in the frequency of germinal center B cells. The defect in germinal center formation is paralleled by decreased frequencies of isotype-switched antibody-secreting cells in the spleen and bone marrow and reduced serum concentrations of total and high-affinity hapten-specific IgG1. The results demonstrate that although CXCR5-dependent T cell positioning is important for maximal induction and expansion of germinal centers, stimulation of isotype class switching, and development of antibody-secreting cells that seed the spleen and bone marrow, it is not absolutely required for the formation and function of follicular germinal centers. [source] Effects of sex chromosome aneuploidy on male sexual behaviorGENES, BRAIN AND BEHAVIOR, Issue 6 2008J. H. Park Incidence of sex chromosome aneuploidy in men is as high as 1:500. The predominant conditions are an additional Y chromosome (47,XYY) or an additional X chromosome (47,XXY). Behavioral studies using animal models of these conditions are rare. To assess the role of sex chromosome aneuploidy on sexual behavior, we used mice with a spontaneous mutation on the Y chromosome in which the testis-determining gene Sry is deleted (referred to as Y,) and insertion of a Sry transgene on an autosome. Dams were aneuploid (XXY,) and the sires had an inserted Sry transgene (XYSry). Litters contained six male genotypes, XY, XYY,, XXSry, XXY,Sry, XYSry and XYY,Sry. In order to eliminate possible differences in levels of testosterone, all of the subjects were castrated and received testosterone implants prior to tests for male sex behavior. Mice with an additional copy of the Y, chromosome (XYY,) had shorter latencies to intromit and achieve ejaculations than XY males. In a comparison of the four genotypes bearing the Sry transgene, males with two copies of the X chromosome (XXSry and XXY,Sry) had longer latencies to mount and thrust than males with only one copy of the X chromosome (XYSry and XYY,Sry) and decreased frequencies of mounts and intromissions as compared with XYSry males. The results implicate novel roles for sex chromosome genes in sexual behaviors. [source] Foot abnormalities in Canadian Aboriginal adolescents with Type 2 diabetesDIABETIC MEDICINE, Issue 7 2007J. Chuback Abstract Aims To determine the profile of foot abnormalities in Canadian Aboriginal adolescents with Type 2 diabetes and the risk factors associated with these abnormalities. Methods Aboriginal adolescents with Type 2 diabetes underwent an interview, medical record review and foot examination in a tertiary care, paediatric hospital diabetes clinic and two geographically remote outreach clinics. The notes of 110 subjects were reviewed [mean age 15 ± 3 years; mean duration of diabetes, 30 ± 20 months; 71 (66%) female and 39 (34%) male] and 77 (70%) of the subjects were examined. Results Foot abnormalities were identified by either interview or notes review, and included poor toenail condition in 85 (77%), paronychia in 29 (26%), ingrowing toenails in 16 (15%) and neuropathic symptoms in 13 (12%) subjects. Foot abnormalities were identified by examination in many subjects, including poor toenail condition in 38 (49%), calluses in 34 (44%) and paronychia in 13 (17%) subjects. Eighteen (24%) of 75 subjects did not have running water in the home. Factors that significantly increased the presence of foot abnormalities included: foot care provided by a person other than self; absence of running water in the home; decreased frequency of bathing; and decreased frequency of nail clipping. A greater percentage of subjects living on a reservation or rural community had specialized consultations for retinal examination, footwear, or both than of those living in an urban or unknown residence. Conclusions A high prevalence of foot abnormalities was noted in Aboriginal adolescents with Type 2 diabetes. These findings highlight the associated comorbidities in this population, emphasizing the need for early detection and intervention. [source] Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studiesDRUG DEVELOPMENT RESEARCH, Issue 6 2009A.S. Manjappa Abstract Most ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti-inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH-triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo-plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] Altered primary CD8+ T,cell response to a modified virus Ankara(MVA)-vectored vaccine in the absence of CD4+ T,cell helpEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Marie Abstract T,cell receptor-transgenic F5 mice were used to assess primary CD8+ T,cell responses to a modified virus Ankara (MVA)-vectored vaccine in the absence of CD4+ T,cell help. Naive, CD8-enriched, CFSE-labelled F5 cells were transferred into normal or CD4+ cell-depleted mice and the mice were vaccinated with MVA.HIVA-NP. At different time points during the primary response, F5 cells were re-isolated and analysed on divisional basis for a number of parameters. We demonstrated that the primary CD8+ T,cell response in the absence of CD4+ T,cell help differed from that in normal CD4+ cell-undepleted mice. While in the absence of CD4+ T,cell help, the initial migratory progress from the local response to a systemic one was not grossly affected, the proportion of dying F5 cells during the expansion phase was markedly increased and resulted in an overall smaller expansion and significantly decreased frequency of CD8+ T,cell memory after contraction. T,cells primed without help displayed accelerated proliferation and activation, while expression of interferon-, remained similar. These phenomena were observed in the lymph nodes draining the MVA.HIVA-NP immunization site and were similar, but delayed by 2,3,days in spleen and non-draining lymph nodes. [source] Is the Sonoran Desert losing its cool?GLOBAL CHANGE BIOLOGY, Issue 12 2005Jeremy L. Weiss Abstract Freezing temperatures strongly influence vegetation in the hottest desert of North America, in part determining both its overall boundary and distributions of plant species within. To evaluate recent variability of freezing temperatures in this context, minimum temperature data from weather stations in the Sonoran Desert are examined. Data show widespread warming trends in winter and spring, decreased frequency of freezing temperatures, lengthening of the freeze-free season, and increased minimum temperatures per winter year. Local land use and multidecadal modes of the global climate system such as the Pacific decadal oscillation and the Atlantic multidecadal oscillation do not appear to be principal drivers of this warming. Minimum temperature variability in the Sonoran Desert does, however, correspond to global temperature variability attributed to human-dominated global warming. With warming expected to continue at faster rates throughout the 21st century, potential ecological responses may include contraction of the overall boundary of the Sonoran Desert in the south-east and expansion northward, eastward, and upward in elevation, as well as changes to distributions of plant species within and other characteristics of Sonoran Desert ecosystems. Potential trajectories of vegetation change in the Sonoran Desert region may be affected or made more difficult to predict by uncertain changes in warm season precipitation variability and fire. Opportunities now exist to investigate ecosystem response to regional climate disturbance, as well as to anticipate and plan for continued warming in the Sonoran Desert region. [source] Transformation Into Daily Migraine With Aura Following Transcutaneous Atrial Septal Defect ClosureHEADACHE, Issue 5 2003A. E. Yankovsky MD A link between migraine with aura and cardiac right-to-left shunting has been previously reported. Abortion or decreased frequency of migraine with aura attacks after atrial septal defect closure has been reported in the literature. We report the first case of transformation of migraine with aura into a daily pattern after atrial septal defect closure. A 48-year-old male who had been suffering from rather infrequent attacks of migraine with sensory and visual aura underwent transcutaneous closure of an atrial septal defect. His migraine attacks changed into a daily pattern the day following the procedure and remained so for 6 months. This change in pattern may be related to a changed intra-atrial pressure after the closure or some other unknown factor. [source] Improvement of Reflux Symptoms 3 Years After Cure of Helicobacter pylori Infection: A Case-Controlled Study in the Japanese PopulationHELICOBACTER, Issue 4 2002Hiroto Miwa Abstract Background. Development of reflux esophagitis is one of the adverse effects that cause concern in relation to curative treatment of Helicobacter pylori infection. However, recent studies present a rather negative association between curative treatment and development of reflux esophagitis or reflux symptoms. Therefore, this issue has remained controversial. Accordingly, we investigated the long-term adverse effects of H. pylori eradication treatment in special reference to development of reflux symptoms. Patients and Methods. We conducted a case controlled study by mailing structured questionnaires on past (before curative treatment or 3 years previously) and current status. A case was an endoscopically confirmed peptic ulcer patient with confirmed cure of the infection after eradication treatment 3 years previously and a control was one who had not undergone the eradication treatment during the same period. We studied 241 pairs who matched for age, gender, and type of ulcer disease (GU, DU or GDU). Of these pairs, 81.3% were male and the mean age was 52.6 ± 9.6 year (range 23,76). Results. The rates of patients with improved reflux symptoms in the case and control groups were 65.4% and 30.4%, respectively, with the rate being significantly greater in the case group. On the contrary, the rates of those with worsened reflux symptoms were similar (5.1% and 7.6%). Regarding general events, the rate of patients with decreased frequency of hospital visits and of those who regularly used antiacid medications were significantly decreased in the case group. Furthermore, the case group experienced significantly fewer hospital admissions for various diseases in this 3-year period. However, a significantly greater number of case group patients than control subjects gained weight. Conclusion. Reflux symptoms as well as general well-being were significantly improved after cure of H. pylori infection. [source] Esophageal motility in patients with sliding hiatal hernia and reflux esophagitisJOURNAL OF DIGESTIVE DISEASES, Issue 2 2002Ping YE OBJECTIVE: To study the radiographic and esophageal motility changes that are characteristic of patients with both sliding hiatus hernia (HH) and reflux esophagitis. METHODS: Thirty patients were diagnosed with HH by using gastroscopy. These patients were divided into two groups according to the severity of their esophagitis: group HH1 (grades A and B, n= 18); group HH2 (grades C and D, n= 12). Sliding HH was confirmed by barium meal examination. Radiographic techniques were used to test for spasms and strictures, the coarseness of the mucosa, and to study the types of reflux and clearance. Esophageal pH (24-h), lower esophageal sphincter pressure and the frequency and amplitude of esophageal peristalsis during reflux were also studied. RESULTS: Radiography revealed that the mucosa was coarse in all cases. Eighty percent of patients had sucking reflux and 36.7% had passive clearance. The percentages of total, supine and upright acid exposure times were greater in patients with HH than those in the controls (P < 0.01), but the difference between the HH1 and HH2 groups was not significant. Lower esophageal sphincter resting pressure was less in the HH group than that in the control group (P < 0.05). However, there were no differences in the length of the sphincter among groups. During episodes of acid reflux, the frequency and amplitude of peristalsis, and the percentage of normal primary esophageal peristalsis were all lower in HH patients than in the controls, and the duration of peristalsis was increased relative to that of the controls (P < 0.05). CONCLUSIONS: Sucking reflux and passive clearance are very important in HH. Esophageal acid exposure time does not correlate with the severity of esophagitis. Lowered lower esophageal sphincter resting pressure, decreased frequency and amplitude, and increased duration of esophageal peristalsis during the episode of reflux may play an important role in the pathogenesis of sliding HH. [source] Influence of slope and aspect on long-term vegetation change in British chalk grasslandsJOURNAL OF ECOLOGY, Issue 2 2006JONATHAN BENNIE Summary 1,The species composition of fragmented semi-natural grasslands may change over time due to stochastic local extinction and colonization events, successional change and/or as a response to changing management or abiotic conditions. The resistance of vegetation to change may be mediated through the effects of topography (slope and aspect) on soils and microclimate. 2,To assess long-term vegetation change in British chalk grasslands, 92 plots first surveyed by F. H. Perring in 1952,53, and distributed across four climatic regions, were re-surveyed during 2001,03. Changes in vegetation since the original survey were assessed by comparing local colonization and extinction rates at the plot scale, and changes in species frequency at the subplot scale. Vegetation change was quantified using indirect ordination (Detrended Correspondence Analysis; DCA) and Ellenberg indicator values. 3,Across all four regions, there was a significant decrease in species number and a marked decline in stress-tolerant species typical of species-rich calcareous grasslands, both in terms of decreased plot occupancy and decreased frequency within occupied plots. More competitive species typical of mesotrophic grasslands had colonized plots they had not previously occupied, but had not increased significantly in frequency within occupied plots. 4,A significant increase in Ellenberg fertility values, which was highly correlated with the first DCA axis, was found across all regions. The magnitude of change of fertility and moisture values was found to decrease with angle of slope and with a topographic solar radiation index derived from slope and aspect. 5,The observed shift from calcareous grassland towards more mesotrophic grassland communities is consistent with the predicted effects of both habitat fragmentation and nutrient enrichment. It is hypothesized that chalk grassland swards on steeply sloping ground are more resistant to invasion by competitive grass species than those on flatter sites due to phosphorus limitation in shallow minerogenic rendzina soils, and that those with a southerly aspect are more resistant due to increased magnitude and frequency of drought events. [source] Pharmacodynamics of Insulin Detemir and Insulin Glargine Assessed by an Isoglycemic Clamp Method in Healthy CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2010C. Gilor Background: Insulin detemir and insulin glargine are synthetic long-acting insulin analogs. In people, insulin glargine is longer acting and has a relatively flat time-action profile, while insulin detemir has significantly less within-subject variability. Insulin detemir is also associated with less undesired weight gain and decreased frequency of hypoglycemic events. Objectives: To compare the pharmacodynamics of insulin detemir and insulin glargine in healthy cats. Animals: Ten young, healthy, neutered, purpose-bred cats. Methods: Randomized, cross-over design. Pharmacodynamics of insulin detemir and insulin glargine were determined by the isoglycemic clamp method after a 0.5 U/kg SC injection. Results: The only significant difference in the pharmacodynamics of insulin detemir and insulin glargine was onset of action (1.8 ± 0.8 and 1.3 ± 0.5 hours for insulin detemir and insulin glargine, respectively, P= .03). End of action of insulin detemir was reached at 13.5 ± 3.5 hours and for insulin glargine at 11.3 ± 4.5 hours (P= .18). Time-to-peak action of insulin detemir was reached at 6.9 ± 3.1 hours and for insulin glargine at 5.3 ± 3.8 hours (P= .7). The time-action curves of both insulin analogs varied between relatively flat curves in some cats and peaked curves in others. Conclusion and Clinical Importance: Insulin detemir and insulin glargine have shorter durations of action than in people when assessed by the clamp method, but in some cats these insulin analogs could be useful as once-a-day drugs. Peak effects of both insulin analogs are pronounced in some cats. [source] Pulsed Radiofrequency Ablation for Residual and Phantom Limb Pain: A Case SeriesPAIN PRACTICE, Issue 5 2010Matt West MD Abstract Residual limb pain (RLP) and phantom limb pain (PLP) can be debilitating and can prevent functional gains following amputation. High correlations have been reported between RLP and the stump neuromas following amputation. Many treatment methods including physical therapy, medications, and interventions, have been used with limited success. Pulsed radiofrequency ablation (PRFA) has shown promise in treating neuropathic pain because of the inhibition of evoked synaptic activity. We present 4 amputees who were treated with PRFA after failing conservative management for their RLP and PLP. All 4 patients underwent PRFA and demonstrated at least 80% relief of RLP for over 6 months. One patient reported a complete resolution of phantom sensation while another patient had significantly decreased frequency of spontaneous PLP and resolution of evoked PLP. In addition, all patients reported improved overall function including increased prosthetic tolerance and decreased oral pain medications. This case series suggests that PRFA is a viable treatment option which might be used for long-term relief of intractable RLP and/or PLP. [source] HLA-DRB1*08 allele may help to distinguish between type 1 diabetes mellitus and type 2 diabetes mellitus in Mexican childrenPEDIATRIC DIABETES, Issue 1 2007Ana L Rodríguez-Ventura Background:, It may be difficult to distinguish type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM) in the pediatric population. Autoantibodies may help to differentiate both types of diabetes, but sometimes these are positive in patients with T2DM and negative in patients with T1DM. The human leukocyte antigen (HLA)-DR genotype has been associated with T1DM and with T2DM only in adults and in determined cases. Aim:, To determine the differences in HLA class II allele frequencies in Mexican children with T1DM and T2DM. Methods:, We included 72 children with T1DM, 28 children with T2DM, and 99 healthy controls. All were Mexican, and diabetes was diagnosed according to the clinical and laboratory criteria established by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. The HLA-DRB1 typing was performed using polymerase chain reaction,sequence-specific oligonucleotide probe and polymerase chain reaction sequence-specific primers. Results:, We found an increased frequency of HLA-DRB1*08 and a decreased frequency of HLA-DRB1*04 in the group with T2DM vs. T1DM [p = 0.0001, odds ratio (OR) = 10.58, 95% confidence interval (CI) = 3,40.8 and p = 0.0006, OR = 0.24, 95% CI = 0.11,0.53, respectively]. No significant differences were found between HLA-DRB1 alleles in T2DM vs. controls. In the group with T1DM, there was a significantly increased frequency of the HLA-DR4 and HLA-DR3 alleles relative to controls (p = 0.0000001, OR = 3.59, 95% CI = 2.2,5.8 and p = 0.00009, OR = 4.66, 95% CI = 2.1,10.3, respectively). Conclusion:, There are significant differences in the HLA profile in Mexican children with T1DM and T2DM. HLA typing could play a role in the differentiation between both types of diabetes in this population. [source] Diagnosis and treatment of gastroesophageal reflux disease in Ohio Medicaid patients: practice patterns and temporal trends,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2004Gregory S. Cooper MD Abstract Purpose There is a paucity of data about the use of procedures and prescription medications in the treatment of gastroesophageal reflux disease (GERD) in actual clinical practice. Methods Outpatient Ohio Medicaid claims from 1994 to 1998 were searched to identify patients with an initial diagnosis of GERD along with associated prescriptions and gastrointestinal procedures. Complications of GERD and comorbid illnesses were also determined. Results A total of 5579 patients were identified. Histamine-2 receptor antagonists (H2RA') were prescribed in 59%, followed by proton pump inhibitors (PPI's) (30%) and prokinetic drugs (17%). PPI's were more frequently prescribed to patients with GERD-related complications, peptic ulcer disease and major comorbidities, and patients who received PPI's were also more likely to undergo upper gastrointestinal endoscopy. The frequencies of upper endoscopy and barium studies were 20% and 11% respectively, with no change over the study period. There was an increased frequency of PPI therapy (17,43%) and decreased frequency of H2RA therapy (72,47%) from 1994 to 1998 which persisted after adjusting for potential differences in case mix. Conclusions In this population-based study, prescription of PPI's increased over time which likely reflected changes in clinician practice rather than patient mix. Despite a greater awareness of GERD complications, use of upper endoscopy did not increase. Although the cohort consists of predominantly low socioeconomic status, female patients, further studies should be conducted in other populations to confirm these findings. Copyright © 2003 John Wiley & Sons, Ltd. [source] Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2005Cristiam M. Alvarez The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (,9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells. [source] Premature aging of the immune system in children with juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 7 2008Martina Prelog Objective Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence. Methods To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation. Results JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67,positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04). Conclusion Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies. [source] Decreased incidence of nonmelanoma skin cancer in patients with type 2 diabetes mellitus using insulin: a pilot studyBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2005T-Y. Chuang Summary Background, In order to prevent the propagation of genetic mutations, human keratinocytes irradiated with ultraviolet (UV) B light in vitro undergo premature stress-induced senescence or apoptosis. This response to UVB irradiation is dependent on the functional activation of the insulin-like growth factor-1 receptor (IGF-1R). Based on this in vitro functional data, we hypothesized that the increased serum levels of insulin in patients with type 2 diabetes may activate the IGF-1R in skin and lead to a decreased frequency of skin cancer in these patients. Objectives, To determine whether the use of insulin by patients with type 2 diabetes correlated with a change in the incidence in nonmelanoma skin cancer (NMSC). Methods, A historical cohort study identifying the incidence of NMSC following the use of two different pharmacological therapies. The patient population was restricted to caucasians who were at least 50 years old when they began the indicated pharmacological therapy. The first group consisted of 1440 patients who used insulin therapy to treat type 2 diabetes and the second group comprised 4135 patients who used cimetidine to treat their gastrointestinal ailments. An additional group of 6131 patients with diabetes who used noninsulin antidiabetics was added to examine the effect of noninsulin therapies. All patients had regular follow-up visits at the Regenstrief Clinics during the study period between 1980 and 1999. The Regenstrief Clinics is an outpatient facility which serves the general population in Metro-Indianapolis, Indiana, U.S.A. Results, The incidence of NMSC in patients using insulin was significantly lower than in patients using cimetidine (1·25% vs. 2·35%, P < 0·02). The decrease in NMSC in patients with type 2 diabetes correlated specifically with the use of insulin (NMSC incidence insulin-only patients with diabetes: 1·40% vs. those with diabetes using noninsulin therapies: 2·35%, P = 0·11). Conclusions, Patients using exogenous insulin had a lower risk of developing NMSC and the protective effect of insulin use becomes more distinct with increasing age. [source] CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial cancer susceptibilityCANCER, Issue 9 2008Hiroshi Hirata MD Abstract BACKGROUND. In estrogen biosynthetic pathways, many enzymes are important for metabolism, detoxification, and bioavailability. Polymorphisms in these genes may have an effect on the enzymes' function. For example, higher expression and activation of biosynthetic enzymes and lower expression and activation of conjugation enzymes may lead to high toxicity or carcinogenesis. The authors hypothesized that single nucleotide polymorphisms (single nucleotide polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes may be risk factors for endometrial cancer. METHODS. DNA samples from 150 cases of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase chain reaction,restriction fragment length polymorphism (PCR-RFLP) to determine the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2, m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His, 14A/G, 85C/T in the 3, flanking region), SULT1E1-64G/A promoter region, and SHBG genes. Genotyping was validated by direct DNA sequencing. The authors also investigated the relation between expression of CYP1A1 in endometrial cancer tissues and genotypes of CYP1A1 m1. RESULTS. A decreased frequency of TC + CC genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer patients compared with controls (OR = 0.42; 95% CI, 0.27,0.69). The T-A haplotype of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P = .009). The authors also found that individuals carrying the variants of SULT1A1 codon213 and 2 single nucleotide polymorphisms in the 3, flanking region (14A/G and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C and A-G-T haplotypes of these 3 variants were higher in endometrial cancer patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients. (OR, 4.58; 95% CI, 2.35,8.93). CONCLUSIONS. This is the first report on the combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer that suggests a decreased single nucleotide polymorphism of CYP1A1 and an increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be risk factors for endometrial cancer in Caucasians. Cancer 2008. © 2008 American Cancer Society. [source] MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinomaCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2008Ivan Nisevic Abstract Chronic pancreatitis and pancreatic adenocarcinoma are extensively studied as common and potentially lethal disorders. However, their causes and genetic background in most cases remain unclear. The C677T polymorphism in 5,,10,-methylenetetrahydrofolate reductase (MTHFR) gene may modulate the risk of pancreatic disorders. In this study, we tested whether MTHFR C677T polymorphism is associated with chronic pancreatitis and pancreatic adenocarcinoma in the Serbian population. DNA was extracted from blood samples of 51 chronic pancreatitis patients, 21 pancreatic adenocarcinoma patients, and a control group consisting of 50 healthy smokers. The MTHFR C677T polymorphism was analyzed by polymerase chain reaction,restriction fragment length polymorphism (PCR,RFLP) technique. Although, no statistically significant differences were observed in the distribution of MTHFR genotype or allele frequencies between patients and control groups, the results showed an increased frequency of homozygotes for MTHFR C677T polymorphism in chronic pancreatitis patients (14%) and a decreased frequency in pancreatic adenocarcinoma patients (5%) in comparison to the control group (8%). We speculate that the MTHFR C677T polymorphism could act as a possible risk factor for chronic pancreatitis and a possible protective factor in pancreatic adenocarcinoma. This observation needs further investigation in prospective studies on a larger number of patients, in which the effect of other genetic and environmental factors should also be taken into consideration. Copyright © 2008 John Wiley & Sons, Ltd. [source] The Development of Argument SkillsCHILD DEVELOPMENT, Issue 5 2003Deanna Kuhn This work sought to obtain experimental evidence to corroborate cross-sectional patterns of development in argument skills and to evaluate the effectiveness of an intervention designed to foster development of these skills in academically at-risk 13- to 14-year-olds. Students participated in 16 sessions of a collaborative, goal-based activity providing dense exercise of argumentive thinking. One condition included peer dialogues; another did not. The former was the more effective, although both groups progressed. Participants showed increased frequency of usage of powerful argumentive discourse strategies, such as counterargument, and decreased frequency of less effective strategies. Quality of individual arguments (for or against a claim) also improved, supporting the existence of a close relation between these two kinds of argument skills. [source] Developmental, behavioural and somatic factors in pervasive developmental disorders: preliminary analysisCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 1 2004P. Whiteley Abstract Objectives To ascertain the frequency of parental reporting of selected variables related to development, behaviour and physiology in subgroups diagnosed with pervasive developmental disorders (PDDs) and identify any significant intragroup differences. Design Retrospective cross-sectional analysis of records of patients (n = 512) held on a computerized database with a chronological age between 3 and 11 years resident in the UK/Republic of Ireland and with a formal diagnosis of autism, Asperger syndrome (AS) or autism spectrum disorder (ASD). Methods Non-parametric analysis (P > 0.01) of the frequency of specific variables for PDD subgroups reported by parents/primary caregiver. Variables included timing of symptom onset, presence of skills acquired prior to symptom onset, indications of regression and regression events, current language, history of viral infections, history of ear problems, achievement of continence, current skin complaints, current bowel habits and adverse events at parturition. Results Preliminary results showed general agreement with the principle diagnostic differences between the PDD subgroups with patients diagnosed with AS showing an increased frequency of skills acquired before symptom onset (two- to three-word phrase speech, toileting skills) and a decreased frequency of regression in acquired skills when compared with other PDD subgroups. Developmental milestones such as the achievement of bowel and bladder continence were also more frequently reported for the AS group. Infantile feeding problems defined as vomiting, reflux, colic and failure to feed were more frequently reported for the AS group as was a reported history of the bacterial skin infection impetigo. Results are discussed with reference to relationships between behavioural and somatic factors in PDD. [source] | |||||||||||||||||||||||||