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Control Population (control + population)
Kinds of Control Population Selected AbstractsEpilepsy and Language Development: The Continuous Spike-Waves during Slow Sleep SyndromeEPILEPSIA, Issue 6 2007Séverine Debiais Summary:,Background: Continuous spike-waves during slow sleep syndrome (CSWSS) is a rare epileptic syndrome occurring in children, which is characterized by the association of epilepsy, neuropsychological disorders, and abnormal paroxysmal electroencephalographic (EEG) discharges activated by sleep. Language can be affected but, to date, language disorders and their long-term outcome have been documented only rarely. Purposes: Description of language impairment in patients with the CSWSS. Methods: We performed a detailed language testing in 10 right-handed children and adolescents with the CSWSS. Their pragmatic performance was compared to that of a control population of 36 children aged 6,10 years. Results: Patients with CSWSS had lower scores in tests measuring their lexical, morphosyntactic, and pragmatic skills compared to controls. Comprehension remains unaffected. In addition, language impairment was found to be just as severe in patients in remission as those still in an active phase. Conclusions: We found severe language impairments in lexical and syntactic skills. The language profile is different from that observed in the Landau,Kleffner syndrome. Moreover patients in remission and those in an active phase of the CSWSS have the same language impairment profiles. This confirms the poor long-term neuropsychological prognosis. Our results raise points about the relationship between epileptic activity and language development. This pilot study underscores the need to assess language, and especially pragmatic skills, and to study long-term outcome in such childhood epileptic syndromes. [source] Prolonged Febrile Seizures Are Associated with Hippocampal Vasogenic Edema and Developmental ChangesEPILEPSIA, Issue 9 2006Rod C. Scott Summary:,Purpose: There is mounting evidence that a prolonged febrile seizure (PFS) can cause acute hippocampal edema although the nature of that edema remains uncertain. The principal aims of the current study were: (1) to use apparent diffusion coefficient (ADC) measurements to further characterize the hippocampal edema previously identified within 5 days of a PFS, and (2) to determine whether the age dependency of ADC in the hippocampus is different in patients when compared to a control population following a PFS. Methods: Diffusion weighted imaging was acquired in 23 children within 5 days of a PFS, and in 14 of these children a mean of 5.5 months later. Twenty-four control children were enrolled. Results: There was a reduction in ADC between the acute and follow-up investigations [mean reduction = 0.0072 mm2/s/month since PFS (95% confidence interval; 0.0001,0.014 mm2/s/month since PFS), p = 0.048] consistent with early vasogenic edema, followed by recovery in children investigated within 2 days of a PFS. In addition, the behavior of ADC with respect to age was different in patients when compared to control subjects [mean difference in slope =,0.155 mm2/s/log10 age (95% confidence interval; ,0.290,0.0203 mm2/s/log10 age), p = 0.029], in that the expected age dependence was observed only in the control subjects. Conclusion: We suggest that these latter findings are most consistent with a preexisting developmental hippocampal abnormality that may predispose individuals to having a PFS. [source] Heightened levels of circulating 20S proteasome in critically ill patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2005G. A. Roth Abstract Background, Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients. Material and methods, Case,control-study at a university hospital intensive care unit; 15 patients recruited within 24,48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean ± SEM. Mann,Whitney U -test was used to calculate significance and a P -value of 0·05 was considered to be statistically significant. Results, Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 ± 10 034 ng mL,1) as well as in trauma patients (29 669 ± 5750 ng mL,1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 ± 1767 ng mL,1) and in the healthy control population (2157 ± 273 ng mL,1). Conclusion, Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors. [source] Haemophilia and thrombophilia: an unexpected association!HAEMOPHILIA, Issue 4 2004Y. Dargaud Summary., In patients with haemophilia, a close correlation is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX clotting activity. However, some patients experience milder bleeding phenotypes than others, although they exhibit a similar biological profile. The high prevalence of some inherited thrombophilia risk factors offers the possibility of a co-inheritance in haemophilic patients which could influence the phenotypic expression of the disease. Rare thrombotic complications occurring in haemophiliacs could also be facilitated by the co-inheritance of modifier genes. The majority of thrombotic events occurring in haemophiliacs are in relation to clotting factor infusions or central venous catheters. Concerning surgical situations, in the absence of therapeutic recommendations, postoperative thromboprophylaxis is not systematically performed in haemophiliacs. However, substitutive treatment more or less completely corrects the coagulation defect and makes the venous thrombosis risk closer to the control population. It should be emphasized that haemophilia does not fully protect against venous thromboembolic disease. Patients with haemophilia very infrequently experience thrombotic events. Thus, the management of thrombotic complications occurring in haemophilic patients should be discussed in each case according to the precipitating risk factors, the clinical context and the thrombo-haemorrhagic balance of the patient with respect to a particular clinical situation. [source] Quality of life in patients with primary biliary cirrhosisHEPATOLOGY, Issue 2 2004Renée Eugénie Poupon The impact of primary biliary cirrhosis (PBC) on health-related quality of life (HRQOL) is poorly documented. We assessed quality of life in a group of 276 unselected patients with PBC using the Nottingham Health Profile (NHP). This is a generic scale that assesses six major areas commonly associated with HRQOL. Data were compared with those of a sex- and age-matched control group. The associations between NHP scores and the severity of PBC were tested. Patients (86% women) had a median age of 62 years (range 33,87). Most patients were treated with UDCA. PBC patients showed a strong statistically significant difference in energy compared to controls (respectively, 40.6 vs. 22.9, P < .0001) and had worse scores for emotional reactions (22.2 vs. 16.1, P < .005). No other differences were observed. No associations of the dimension subscores were found with biochemical liver tests, histological stages, or duration of the disease. Among the signs or symptoms, fatigue was the finding most often associated with the dimension subscores. In conclusion, patients with PBC feel that their overall quality of life is worse than that of the control population. This difference is mainly due to the decrease in the subscores of energy and emotional reactions, both associated with fatigue. These effects must be taken into account by clinicians when treating these patients, as they constitute the clinical outcomes that have the most impact on patients' lifestyle and adherence to treatment. (HEPATOLOGY 2004;40:489,494.) [source] Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with incontinentia pigmenti,HUMAN MUTATION, Issue 9 2009Fusco Francesca Abstract The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found two recurrent nonpathological variants of IP locus, which were also present as rare polymorphism in control population: the IKBKGPdel, corresponding to the exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates the exon4_10 region downstream of the normal IKBKG gene. Using quantitative DNA analysis and microsatellite mapping, we established that both variants might promote the generation of the pathological IKBKGdel. Indeed, in family IP-516, the exon4_10 deletion was repositioned in the same allele from the pseudogene to the gene, whereas in family IP-688, the MER67Bdup generated the pathological IKBKGdel by recombination between two direct nonadjacent MER67Bs. Moreover, we found an instance of somatic recombination in a MER67Bdup variant, creating the IKBKGdel in an IP male. Our data suggest that the IP locus undergoes recombination producing recurrent variants that might be "at risk" of generating de novo IKBKGdel by NAHR during either meiotic or mitotic division. Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) , association with decreased enzyme function,,HUMAN MUTATION, Issue 9 2006Elke Schaeffeler Abstract The genetic polymorphism of the thiopurine S-methyltransferase, TPMT, comprises at least 21 alleles causing three distinct drug metabolism phenotypes termed normal/high, intermediate, and deficient methylators. In consequence, adverse drug reactions may occur if standard doses of thiopurines are applied routinely. Genetic prediction of the methylator phenotype as a basis for dose selection requires the extensive knowledge of single nucleotide polymorphisms occurring naturally in the population. Here we describe three novel missense variants in the TPMT gene which were associated with an intermediate red blood cell TPMT activity in three Caucasians. The following alleles were designated: TPMT*20 (c.712A>G), *21 (c.205C>G), and *22 (c.488G>C). No further genetic variations in remaining coding regions as well as the 5,flanking region of TPMT were identified. These sequence variants are present in highly conserved nucleotide positions of the TPMT gene throughout various mammalian species and in zebra fish, and are predicted to be intolerant when the functional consequences of variations were analyzed using SIFT (Sorting Intolerant From Tolerant) algorithm. In Caucasians the occurrence of these genetic variants appears to be extremely rare since none of these alleles were identified in a randomly selected control population of 1048 individuals. © 2006 Wiley-Liss, Inc. [source] Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 5 2007S. Ardizzone MD Abstract Background: Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane-bound efflux transporter P-glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. Methods: A total of 211 patients with Crohn's disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype,phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. Results: No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo-colonic CD (OR = 3.34; 95% CI: 1.34,8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20,0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13,0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. Conclusions: The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P-glycoprotein 170, in the regulation of host,bacteria interactions and in the pathogenesis of IBD. (Inflamm Bowel Dis 2007) [source] Epstein-Barr virus infection and risk of lymphoma: Immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controlsINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Silvia de Sanjosé Abstract Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case,control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15,1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22,3.95). Lower levels of ab_EBV were observed for follicular lymphoma (OR = 0.38, 95%CI = 0.15,0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceeding or paralleling possible EBV associated oncogenic events. © 2007 Wiley-Liss, Inc. [source] Self-reported severity of taste disturbances correlates with dysfunctional grade of TMD painJOURNAL OF ORAL REHABILITATION, Issue 11 2009D. R. NIXDORF Summary, Altered central neural processing of sensory information may be associated with temporomandibular disorders (TMD) pain. The objectives of this study were to compare the prevalence of self-reported taste disturbances in TMD pain patients and in a control population, and to determine whether frequency of taste disturbances was correlated with dysfunctional grade of TMD pain. Subjects were 2026 people within a German population sample and 301 consecutive TMD patients diagnosed using the Research Diagnostic Criteria. Taste disturbances were measured using two questions from the Oral Health Impact Profile. Dysfunctional grade of TMD pain was measured with the Graded Chronic Pain Scale. A two-sample test of proportions revealed that TMD patients reported a greater frequency of taste disturbances, 6%, than did the general population subjects, 2% (P < 0·001). Moreover, the frequency of taste disturbances correlated with the dysfunctional grade of TMD pain. For each 1 unit increase in taste disturbance, the odds of observing a higher grade of TMD pain increased by 29% (95% CI: 3,63%, P = 0·03). Analysis by individual taste question and adjustment for age and gender did not substantially affect the results. These findings are consistent with a central neural dysfunction in TMD pain and suggest that a common neural substrate may underlie sensory disturbances of multiple modalities in chronic pain patients. Further research regarding taste disturbances and trigeminally mediated pains such as in TMD is warranted. [source] A Haplotype of the DRD1 Gene Is Associated With Alcohol DependenceALCOHOLISM, Issue 4 2008P. Batel Background:, The D1 dopamine receptor has been involved in a number of brain functions, including motor control, inattentive symptoms and reward and reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking behavior and the acquisition of cocaine-cue associations. The D1.1/r4532 marker of the DRD1 gene has been associated with a large set of phenotypes including addictive behaviors, but none with alcohol dependence per se. Methods:, We analyzed a population of 134 patients with alcohol dependence, also assessing more homogeneous (severe) phenotypes, comparing this sample with a healthy control population, assessing two SNPs within the DRD1 gene in order to depict the role of DRD1 polymorphisms and haplotypes. Results:, The T allele of the rs686 polymorphism within DRD1 gene was significantly more frequent in patients with alcohol dependence (p = 0.0008), with a larger excess for patients with severe dependence (p = 6 × 10,6), and even more for patients with severe complications such as withdrawal seizures (p = 7 × 10,7). A specific haplotype rs686*T-rs4532*G within the DRD1 gene was significantly more precisely associated with alcohol dependence in our sample (p = 5 × 10,6). Conclusions:, Even though chance finding cannot be ruled out, convergent evidence is given that the DRD1 gene is a susceptibility gene in alcohol dependence, regarding the fact that relying on more homogeneous phenotypes (i.e., more severe patients) and more informative genetic markers (i.e., haplotypes) reinforce the initial association. [source] A study of environmental and behavioural factors that may be associated with feline idiopathic cystitisJOURNAL OF SMALL ANIMAL PRACTICE, Issue 3 2004M. E. Cameron The cause of cystitis in many cats remains unknown. The aim of this study was to determine whether or not any environmental or behavioural factors, particularly those that could be considered potentially stressful, were associated with feline idiopathic cystitis (FIC). The questionnaire-based study involved comparing 31 cats with FIC to 24 cats in the same households that did not have cystitis. They were also compared with a control population of 125 clinically healthy cats. Compared with the live-in controls and the control population, the cats with FIC were significantly more likely to be male, overweight and pedigree. Several stress factors were found to be associated with FIC. The factor that stood out most prominently was living with another cat with which there was conflict. The findings support the hypothesis that stress may be implicated in some cases of FIC. [source] Evaluation of Abdominal Fluid: Peripheral Blood Creatinine and Potassium Ratios for Diagnosis of Uroperitoneum in DogsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2001Chad Schmiedt DVM, DACVS Objective:To determine the clinical efficacy of abdominal fluid to peripheral blood ratios of creatinine and potassium concentrations to diagnose uroperitoneum in dogs. Design:Records of 13 dogs with confirmed uroabdomen were retrospectively analyzed. Prospective evaluation of 8 dogs with nonrenal ascites provided data for a control population. Setting:Veterinary Medical Teaching Hospital. Animals:Client owned dogs. Interventions:None Measurements and Main Results:Abdominal fluid potassium (mEq/L) and creatinine concentrations (mg/dl) were recorded. Peripheral blood potassium and creatinine concentrations were also recorded. Ratios were calculated based on these values. An abdominal fluid creatinine concentration to peripheral blood creatinine concentration ratio of > 2:1 was predictive of uroabdomen in dogs (specificity 100%, sensitivity 86%). An abdominal fluid potassium concentration to peripheral blood potassium concentration of > 1.4:1 is also predictive of uroabdomen in dogs (specificity 100%, sensitivity 100%). All dogs with uroabdomen had an abdominal fluid creatinine concentration that was at least 4 times normal peripheral blood levels. Conclusion:Abdominal fluid to peripheral blood potassium and creatinine ratios provide a means to diagnose uroperitoneum in dogs without elevated peripheral blood creatinine. [source] The ,670A > G polymorphism in the promoter region of the FAS gene is associated with necrosis in periportal areas in patients with chronic hepatitis CJOURNAL OF VIRAL HEPATITIS, Issue 6 2005J. Aguilar-Reina Summary., Evidence suggests that apoptosis of liver cells may play a significant role in the pathogenesis of hepatitis C virus (HCV) infection. One of the best characterized apoptotic pathway is that mediated by the death receptor Fas. Fas expression has been found to be up-regulated on hepatocytes in chronic HCV infection, particularly in periportal areas. Recently, two polymorphisms have been identified in the promotor region of the FAS gene, ,1377G > A and ,670A > G. We have evaluated the involvement of these variants in the susceptibility to HCV infection, the severity of liver damage and progression of fibrosis in chronic hepatitis C. A cohort of 197 patients with chronic hepatitis C and 100 controls were analysed for both polymorphisms by Fluorescence Resonance Energy Transfer using specific probes and the LightcyclerTM system. In addition, liver biopsies were taken in 167 patients and scored using the Knodell classification system. We have found that the allele frequencies and the distribution of both polymorphisms do not differ significantly in the HCV cohort and in the control population. Thus, none of the polymorphisms seems to be related with susceptibility to HCV infection. However, we have examined the possible association between the two variants and the grade of necroinflammatory activity and the stage of fibrosis and we have detected an under-representation of the ,670A > G variant among those patients with higher Knodell's scores (P = 0.049) and necroinflammatory activity (P = 0.036). The ,670A allele was associated with higher levels of periportal necrosis (P = 0.012). In conclusion, our findings suggest an association between the ,670A > G polymorphism and the grade of necrosis in periportal areas in patients with chronic hepatitis C. [source] Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 3 2006Sigal Fishman Abstract: Objective: Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Methods: Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, ,fast fibrosers' and ,slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Results: Forty-two patients were classified as ,fast fibrosers' and 33 patients as ,slow fibrosers'. The frequency of CYP2D6*4 allele in the ,fast fibrosers' (34.5%) was significantly higher compared with the ,slow fibrosers' (15%) (P -value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the ,slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). Conclusion: This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients. [source] There are no reliable symptoms for erosive oesophagitis and Barrett's oesophagus: endoscopic diagnosis is still essentialALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2002B. Avidan Aims: To evaluate the sensitivity and specificity of different symptoms in erosive reflux oesophagitis and Barrett's oesophagus. Methods: The presence of reflux symptoms was compared between a case population of 306 patients with endoscopically determined erosive reflux oesophagitis, 235 patients with biopsy-proven Barrett's oesophagus and a control population of 198 subjects without reflux disease. Results: Heartburn at any time and heartburn at night represented the only two symptoms to be simultaneously sensitive and specific. Symptoms that were induced by various foods, such as fat, tomato, chocolate, citrus or spices, tended to cluster in the same sub-group of patients. Similarly, heartburn induced by exercise, lying down or bending over tended to occur in the same sub-groups. The frequency of symptoms was influenced more by the presence of mucosal erosions than by the presence of Barrett's oesophagus. Reflux symptoms occurred more frequently in the presence rather than the absence of Barrett's oesophagus, and in long segment rather than short segment of Barrett's mucosa. Conclusions: Endoscopic inspection of the oesophageal mucosa remains the only certain method by which to reliably diagnose erosive reflux oesophagitis and Barrett's oesophagus. [source] Reflux symptoms are associated with psychiatric diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2001B. Avidan Methods: To evaluate the frequency of reflux symptoms in patients with a diagnosed psychiatric disorder and to assess potential risk factors for symptom occurrence. Methods: The presence of reflux symptoms was compared between a case population of 94 psychiatric patients and a control population of 198 non-psychiatric patients. Results: Heartburn, exercise-induced heartburn, cough and dysphagia were all reported significantly more frequently by subjects with psychiatric disorders than by control subjects. The presence of any psychiatric diagnosis exerted an increased risk for both heartburn (odds ratio, 2.71; 95% confidence interval, 1.01,7.30) and exercise-induced heartburn (3.34; 1.12,9.96). The type of psychiatric disorder, the type of psychotropic medication and the lifestyle did not influence the presence of reflux symptoms. Conclusions: Reflux symptoms occur more frequently in patients with than without a diagnosed psychiatric disorder. The reflux symptoms are not associated with any specific type of medication and may reflect a generally reduced threshold for or distorted perception of symptoms. [source] Parkinson's disease and LRRK2: Frequency of a common mutation in U.S. movement disorder clinicsMOVEMENT DISORDERS, Issue 4 2006Denise M. Kay PhD Abstract The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (± 2SE) in patients was 0.013 ± 0.006 overall, 0.030 ± 0.019 in familial PD, 0.007 ± 0.005 in nonfamilial PD, 0.016 ± 0.013 in early-onset PD, and 0.012 ± 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. © 2005 Movement Disorder Society [source] Do fungi play a role in psoriatic nails?MYCOSES, Issue 6 2007Jacek C. Szepietowski Summary Onychomycosis is the most common disease of the nails and constitutes about a half of all nail abnormalities. Some factors like increasing age, male sex, repeated nail damage, genetic predispositions and underlying conditions, such as diabetes, immunodeficiency or peripheral arterial disease may predispose to develop onychomycosis. It is also suggested that abnormalities in nail morphology are the predisposing factors to onychomycosis. Psoriasis is one of the most common reasons of disturbed nail morphology and the spectrum of nail changes in psoriasis is very wide. Thus, there were suggestions that dystrophic nails in psoriatic patients lose their natural preventing barrier and therefore are more predisposed to fungal infection. This paper summarizes the knowledge about prevalence of onychomycosis among psoriatic patients and contains a literature review concerning this problem. Most authors report that the prevalence of onychomycosis in psoriatic patients is not higher than that in control population. However, especially yeasts and maybe moulds, probably as concomitant pathogens, are more often isolated from psoriatic patients than from non-psoriatic population. In reasonable cases, the mycological examination is required, especially when the clinical picture of the nails suggests the presence of fungal infection. In these cases, antifungal treatment may be beneficial for psoriatic patients. [source] Impact of off-pump coronary artery bypass surgery on postoperative renal dysfunction: Current best available evidence (Review Article)NEPHROLOGY, Issue 4 2006SHAHZAD G RAJA SUMMARY: Renal dysfunction is a serious complication after coronary artery bypass surgery with cardiopulmonary bypass. Cardiopulmonary bypass-related non-pulsatile flow, hypothermia, haemolysis, systemic inflammatory reactions and emboli are mentioned as possible causes for this postoperative renal dysfunction. In an attempt to avoid these deleterious effects of cardiopulmonary bypass, off-pump coronary artery bypass surgery has been rediscovered. Resurgence of interest in off-pump coronary artery bypass surgery is associated with the expectation that avoiding deleterious effects of the cardiopulmonary bypass leads to better outcomes and possibly decreased costs and resource use. We are currently practising in an era of evidence-based medicine that mandates the prospective randomized controlled trial as the most accurate tool for determining a treatment benefit compared with a control population. The present review article attempts to evaluate the current best available evidence from randomized controlled trials on the impact of off-pump coronary artery bypass surgery on postoperative renal dysfunction. [source] Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010Angela Dispenzieri We evaluated the capability of soluble cardiac biomarkers to predict tolerability and outcomes of IMiD-containing treatments among 106 patients treated on clinical trials. Baseline elevations in troponin T (TnT) and N-terminal brain naturietic protein (NT-proBNP) predicted for an inability to tolerate IMiD-based regimens. The best predictors for early attrition during cycle 1 were TnT , 0.07 ,g/L and NT-proBNP , 11,939 ng/L. NT-proBNP-response underperformed TnT-response as a predictor for overall survival (OS), but both predicted for early protocol attrition. Despite hematologic response, IMiD-treated patients were at higher risk for NT-proBNP rises and early drug discontinuation than a control population but not for early death. These observations prompt two questions: (1) does IMiD-based therapy lead to increased fluid retention and/or cardiac toxicity and (2) is an NT-proBNP-driven cardiac response system valid in IMiD-treated amyloidosis patients? Recognition of potential drug-induced cardiac toxicity is important so that increased cardiac surveillance and drug dose-adjustment or discontinuation may be implemented. Am. J. Hematol. 85:757-759, 2010. © 2010 Wiley-Liss, Inc. [source] Mechanism of Atrial Flutter Occurring Late After Orthotopic Heart Transplantation with Atrio-atrial AnastomosisPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2005JOSEPH E. MARINE Objective: We sought to better define the electrophysiologic mechanism of atrial flutter in patients after heart transplantation. Background: Atrial flutter is a recognized problem in the postcardiac transplant population. The electrophysiologic basis of atrial flutter in this patient population is not completely understood. Methods: Six patients with cardiac allografts and symptoms related to recurrent atrial flutter underwent diagnostic electrophysiologic study with electroanatomic mapping and radiofrequency catheter ablation. Comparison was made with a control nontransplant population of 11 patients with typical counterclockwise right atrial flutter. Results: In each case, mapping showed typical counterclockwise activation of the donor-derived portion of the right atrium, with concealed entrainment shown upon pacing in the cavotricuspid isthmus (CTI). The anastomotic suture line of the atrio-atrial anastomosis formed the posterior barrier of the reentrant circuit. Ablation of the electrically active, donor-derived portion of the CTI was sufficient to terminate atrial flutter and render it noninducible. Comparison with the control population showed that the electrically active portion of the CTI was significantly shorter in patients with transplant-associated flutter and that ablation was accomplished with the same or fewer radiofrequency lesions. Conclusions: Atrial flutter in cardiac transplant recipients is a form of typical counterclockwise, isthmus-dependent flutter in which the atrio-atrial anastomotic suture line forms the posterior barrier of the reentrant circuit. Ablation in the donor-derived portion of the CTI is sufficient to create bidirectional conduction block and eliminate this arrhythmia. Ablation or surgical division of the donor CTI at the time of transplantation could prevent this arrhythmia. [source] Performance of a Rate Responsive Accelerometer-Based Pacemaker with Autocalibration During Standardized Exercise and RecoveryPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2002STEPHANE GARRIGUE GARRIGUE, S., et al.: Performance of a Rate Responsive Accelerometer-Based Pacemaker with Autocal-ibration During Standardized Exercise and Recovery. The rate responsiveness of a single chamber, accelerometer-based pacemaker with an autocalibration function (Opus G VVIR pacemaker, ELA Medical) was studied with a daily life protocol developed to automatically optimize the programming of accelerometer-based sensors. This new sensor was compared with two other body activity sensors that were manually optimized patient by patient. Forty-three pacemaker recipients (mean age 71 ± 11 years), paced > 95% of the time, underwent a daily life protocol consisting of rapid walking for 6 minutes (W), climbing upstairs for 1.5 minutes (U), and downstairs for 1.5 minutes (D), alternated by recovery phases. The results were compared with performances measured in a control population of healthy subjects and in two paced patient populations (one equipped with a Dash Intermedics VVIR pacemaker and the other equipped with a Sensolog III Pacesetter/St. Jude VVIR pacemaker). Sex distribution and mean age between paced patients and control subjects were statistically comparable. The mean heart rate achieved by all paced patients at each time sample was compared with the normograms, assigning acceleration (slope) and rate (rate) scores for exercise and recovery phases. Scores ranged from -10 (hypochronotropic) to +10 (hyperchronotropic). Zero represents exact concordance with the responses of healthy individuals, and values between -2.5 and +2.5 were considered statistically similar to normal. During W, although the overall performances of the Dash, Sensolog, and Opus G did not statistically differ from healthy controls, the scores obtained by the Opus G were significantly closer to controls than those of the two other pacemakers (P = 0.02). For U, the three sensors were hypochronotropic (P = 0.03), though the Opus G was associated with a heart rate response closer to that of healthy controls (P = 0.04). D provided similar mean heart rate scores for the Opus G and the Dash compared with healthy controls, in contrast with the hyperchronotropic behavior of the Sensolog (P = 0.02). Opus G revealed a physiological modulation of the heart rate for W and D tests with a slightly hypochronotropic behavior during U. The Opus G autocalibration function provided daily life performances closer to those of healthy controls than two other pacemakers equipped with a body activity sensor that were manually optimized. [source] Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan anemia: Potential implications for phenotypic heterogeneity,AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2010Aurore Crétien Mutations in the RPS19 gene have been identified in 25% of individuals affected by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia characterized by an aregenerative anemia and a variety of malformations. More than 60 mutations in the five coding exons of RPS19 have been described to date. We previously reported a mutation (c.-1 + 26G>T) and an insertion at ,631 upstream of ATG (c.-147_-146insGCCA) in the noncoding region. Because DBA phenotype is extremely heterogeneous from silent to severe and because haploinsufficiency seems to play a role in this process, it is likely that genetic variations in the noncoding regions affecting translation of RPS19 can modulate the phenotypic expression of DBA. However, to date, very few studies have addressed this question comprehensively. In this study, we performed detailed sequence analysis of the RPS19 gene in 239 patients with DBA and 110 of their relatives. We found that 6.2% of the patients with DBA carried allelic variations upstream of ATG: 3.3% with c.-1 + 26G>T; 2.5% with c.-147_-146insGCCA; and 0.4% with c.-174G>A. Interestingly, the c.-147_-146insGCCA, which has been found in a black American and French Caribbean control population, was not found in 500 Caucasian control chromosomes we studied. However, it was found in association with the same haplotype distribution of four intronic polymorphisms in our patients with DBA. Although a polymorphism, the frequency of this variant in the patients with DBA and its association with the same haplotype raises the possibility that this polymorphism and the other genetic variations in the noncoding region could play a role in DBA pathogenesis. Am. J. Hematol., 2010. © 2009 Wiley-Liss, Inc. [source] Outcome of 122 pregnancies in essential thrombocythemia patients: A report from the Italian registryAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Lorella Melillo Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P < 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%, P = 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%, P = 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013,0.846, P = 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%, P = 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17,32.61; P = 0.038). No outcome concordance between first and second pregnancies was found (P = 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: A report from the Children's Oncology Group,PEDIATRIC BLOOD & CANCER, Issue 2 2010Christine L. Phillips MD Abstract Background The variant polymorphism in the gene MDM2, SNP309, leads to increased level of mdm2 protein and subsequent downregulation of p53 tumor suppressor pathway. Presence of this single nucleotide polymorphism (SNP) has been associated with earlier tumorigenesis in patients with Li,Fraumeni syndrome, as well as decreased survival in patients with CLL. In addition, cells homozygous (G/G) for SNP 309 were found to have 10-fold increase resistance to topoisomerase II inhibitors in vitro. Procedure We genotyped children (n,=,575) with de novo acute myeloid leukemia (AML) treated on three Children's Oncology Group protocols (CCG 2941/2961/AAML 03P1) for the presence of SNP309. Healthy blood donors were genotyped as control population. Results The variant G/G genotype was associated with an increased susceptibility to AML (OR 1.5; P,=,0.049). However, the presence of the variant allele at SNP309 did not modify disease response or toxicity in children treated on CCG protocols 2941/2961. Conclusions The variant SNP 309 influences susceptibility to pediatric AML, but does not impact overall response to therapy. Pediatr Blood Cancer. 2010;55:248,253. © 2010 Wiley,Liss, Inc. [source] MDM2 SNP309 genotype influences survival of metastatic but not of localized neuroblastoma,PEDIATRIC BLOOD & CANCER, Issue 4 2009Chiara Perfumo PhD Abstract Background MDM2 is a major negative regulator of p53 function and is directly regulated by MYCN in neuroblastoma (NB) cells. MDM2 SNP309, a T-to-G substitution in the MDM2 promoter associated with higher gene expression compared to wild-type, may attenuate the p53 pathway in NB, in which p53 mutations are rare. We investigated its impact on NB development and survival in relation with major clinical and biological characteristics. Procedure A consecutive cohort of 497 NB children, diagnosed in Italy between 1995 and 2005, and a healthy control population of 471 adults were genotyped for MDM2 SNP309. NB patients were followed up until June 30, 2008. Results Patients and controls showed similar distribution of MDM2 SNP309 genotypes. In patients, the polymorphism was not associated with any characteristic at diagnosis. In localized stages no effect of the polymorphism on survival was evident. In stage 4 patients overall survival (OS), event free survival (EFS) and survival after relapse (SAR) were significantly poorer for TG/GG than for TT patients (P,=,0.008; P,=,0.013; P,=,0.046, respectively). In this group, such an effect was more evident in patients with MYCN amplification (OS: P,<,0.001; EFS: P,=,0.028; SAR: P,<,0.001). Conclusions While MDM2 SNP309 status does not affect the risk of developing NB nor disease outcome for localized cancer cases, it significantly correlates with survival in stage 4 NB patients, particularly in the presence of MYCN amplification. The impact of small molecule inhibitors of MDM2 activity in the management of such patients could be usefully considered. Pediatr Blood Cancer 2009;53:576,583. © 2009 Wiley-Liss, Inc. [source] Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantationPEDIATRIC TRANSPLANTATION, Issue 6 2005Lavjay Butani Abstract:, Hyperlipidemia is common after renal transplantation (Tx) and contributes to the increased cardiovascular morbidity seen in the post-transplant period. Limited data are available on the utility of the statins in children after renal Tx. This 12-month prospective study was undertaken to determine the efficacy of pravastatin in reducing dyslipidemia after renal Tx in children and to determine predictors of dyslipidemia after Tx. From August 2001 to April 2004, all 17 newly transplanted pediatric renal transplant recipients at our center were preemptively treated with pravastatin from the immediate post-transplant period. Fasting lipid profiles were obtained at 1, 3, 6 and 12 months after Tx. Trends in the lipid profile were analyzed using the repeated measures general linear model (GLM). A historical cohort of pediatric renal-transplant recipients not treated with pravastatin was used as the control population. The mixed effects GLM was used for multivariable logistic regression analyses to determine the independent effect of age, pretransplant cholesterol (Chol), body mass index (BMI), creatinine clearance (CrCl), and corticosteroid and tacrolimus doses on the development of dyslipidemia. The mean age of the children at Tx was 8.7 yr. The GLM analysis showed that with time, there was a significant decline in the total Chol, serum triglyceride (TG), LDL and also HDL-Chol (p-value <0.05 for each). Compared with the controls, the mean serum Chol was lower at all time points post-transplant in the treated patients. However, despite treatment, the prevalence of hypercholesterolemia increased from 31% pretransplant to 53% at 1-month, but declined thereafter to 6% at 3 and 6 months and 0% at 1 yr. Multivariable regression analyses showed the prednisone dose, pretransplant Chol and age to be the most important risk factors for the development of dyslipidemia. No child developed complications related to therapy. In summary, pravastatin is safe in the post-transplant period in children and reduces serum Chol, LDL-Chol and TG. An unexpected finding in our study was the decline in HDL-Chol after Tx. Whether the preemptive use of the statins will result in lower cardiovascular morbidity, especially considering the concomitant reduction in HDL-Chol remains to be determined. [source] Effects of theatrical smokes and fogs on respiratory health in the entertainment industryAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 5 2005Sunil Varughese MSc Abstract Background Theatrical fogs (glycol or mineral oil aerosols) are widely used in the entertainment industry to create special effects and make lighting visible. Methods We studied 101 employees at 19 sites using fogs and measured personal fog exposures, across work shift lung function, and acute and chronic symptoms. Results were also compared to an external control population, studied previously. Results Chronic work-related wheezing and chest tightness were significantly associated with increased cumulative exposure to fogs (mineral oil and glycols) over the previous 2 years. Acute cough and dry throat were associated with acute exposure to glycol-based fogs; increased acute upper airway symptoms were associated with increased fog aerosol overall. Lung function was significantly lower among those working closest to the fog source. Conclusions Mineral oil- and glycol-based fogs are associated with acute and chronic adverse effects on respiratory health among employees. Reducing exposure, through controls, substitution, and elimination where possible, is likely to reduce these effects. Am. J. Ind. Med. 47:411,418, 2005. © 2005 Wiley-Liss, Inc. [source] Respiratory effects of exposure to low levels of concrete dust containing crystalline silicaAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2001E. Meijer MD Abstract Background Dusts containing crystalline silica are generated in mining, construction, glass, granite and concrete production industries. The association between exposure to low levels of concrete dust containing crystalline silica and reduction in lung function, was evaluated in a cross-sectional study. Methods The study was carried out among 144 concrete workers, from two factories, with exposure assessment of respirable dust and silica by personal samplers. Results of respiratory questionnaires and standardized measurements of lung function were compared with the results in a control population. Multiple linear regression analysis was used in selecting factors that predict (age and standing height standardized residual) lung function. Results The average concentration of respirable dust in both factories was 0.8 mg/m3 and 0.06 mg/m3 for respirable silica. The average silica content of the dust was 9%. The average cumulative dust exposure was 7.0 mg/m3 year and cumulative silica exposure was 0.6 mg/m3 year. Significant associations between exposure to concrete dust and a small lung function (FEV1/FVC ratio, MMEF) loss were found, independent of smoking habits and of a history of allergy. Conclusions Our results indicate that, concrete workers with chronic obstructive pulmonary symptoms and/or work-related lower respiratory symptoms are at risk of having a reduction in lung function (FEV&1/FVC ratio) outside the 5th percentile of the external reference population, and therefore, of mild chronic obstructive pulmonary disease, at respirable concrete dust levels below 1 mg/m3 with a respirable crystalline silica content of 10% (TWA, 8 hr). Am. J. Ind. Med. 40:133,140, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||