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Biomedical subjects

R Roberts

Publications and source records attributed to R Roberts.

At least 55 records · Page 3Linked to original sources
PubMed2001

Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration?

AIMS: The aim of this study was to explore whether genetic variation of cytochrome P450 2C9 (CYP2C9) contributes to NSAID-associated gastric ulceration. The hypothesis tested was that CYP2C9 poor metabolizer genotype would predict higher risk of gastric ulceration in patients on NSAIDs that are metabolized by CYP2C9, due to higher plasma NSAID concentrations. METHODS: Peripheral blood DNA samples from 23 people with a history of gastric ulceration attributed to NSAIDs metabolized by CYP2C9, and from 32 people on NSAIDs without gastropathy, were analysed to determine CYP2C9 genotype. RESULTS: The following genotypes were found: *1/*1 (wild type) in 70% of cases and 58% of controls, *1/*2 in 17% of cases and 29% of controls, *1/*3 in 13% of cases and 13% of controls. The difference between case and control nonwild-type genotype frequency was 11.5% (95% CI -14,37%), with the direction of the difference being against the hypothesis. No individuals with homozygote poor metaboliser genotype were identified. The differences in genotype frequencies between the two groups were not significant and the frequencies were similar to those in a large published population study. Ninety-five percent binomial confidence interval analysis confirms that there is no apparent clinically significant relationship between CYP2C9 genotype and risk of gastric ulceration although a small difference in risk in poor metabolizers cannot be excluded. CONCLUSIONS: These results do not support the hypothesis that gastric ulceration resulting from NSAID usage is linked to the poor metabolizing genotypes of CYP2C9.

Adult↗
PubMed2001

How accurate is a CT-based dose calculation on a pencil beam TPS for a patient with a metallic prosthesis?

The accuracy of a CT-based dose calculation on a treatment planning system (TPS) for a radiotherapy patient with a metallic prosthesis has not previously been reported. In this study, the accuracy of the CT-based inhomogeneity correction on a pencil beam TPS (Helax TMS) was determined in a phantom containing a metallic prosthesis. A steel prosthesis phantom and a titanium prosthesis phantom were investigated. The phantoms were CT-scanned and dose plans produced on the TPS, using the CT images to provide density information for the inhomogeneity corrections. Verification measurements were performed on a linear accelerator for 6 and 15 MV x-rays. Measured dose profiles at three different depths were compared to the calculations of the TPS. For the titanium prosthesis and for 6 MV x-rays, the TPS overestimated the beam attenuation by approximately 20% at 15 and 20 cm depths in the phantom. This is due to a limitation in the density allocation of this TPS: any Hounsfield number (HN) above a certain threshold is allocated the density of steel. For the steel prosthesis, the TPS performed the correct mapping of HN to mass density. The dose calculation was within 6% for 6 MV x-rays at 15 and 20 cm depths. However. the accuracy of dose calculation varied with beam energy and depth, with large errors in the region close to the prosthesis. The TPS overestimated the dose by 11% for 6 MV and 15% for 15 MV x-rays at 11 cm depth. 2.5 cm beyond the steel prosthesis. These results highlight the limitations in the density allocation of this TPS and demonstrate shortcomings in the pencil beam dose calculation.

Hip Prosthesis↗
PubMed2001

Modification of a rapid method for the identification of gene-specific polymorphisms in Cryptosporidium parvum and its application to clinical and epidemiological investigations.

The application of genotyping to clinical isolates of Cryptosporidium has increased significantly our knowledge and understanding of the distribution and epidemiology of this parasite. However, some methods can be laborious and demand specialist technical expertise. PCR-restriction fragment length polymorphism (RFLP) techniques represent a more rapid and simple method of genotyping to support epidemiological and clinical investigations than conventional DNA analytical techniques. We describe a nested PCR-RFLP technique that identifies polymorphisms in the C. parvum thrombospondin-related adhesive protein gene locus; this method offers a sensitive and specific tool for the confirmation and investigation of disease associated with C. parvum. The potential of this enhanced method is demonstrated by its application to the confirmation and epidemiological investigation of an outbreak of cryptosporidiosis associated with a school visit to an open farm.

Adult↗
PubMed2001

Dynamic cerebral autoregulation is preserved in neurally mediated syncope.

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80 degrees head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02-0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.

Adult↗
PubMed2001

Depression and substance use in minority middle-school students.

OBJECTIVES: This study investigated the association between depression and substance use in a sample of middle-school students. METHODS: The 5721 students (59%-63% Hispanic) completed self-report items on depressive symptoms, recent smoking and binge drinking, and lifetime use of marijuana, cocaine, and inhalants. RESULTS: Symptoms of depression were strongly and positively related to substance use. For every type of use, a stepwise increase was seen between the percentage of students with low symptom frequency and the percentage of students with more symptoms. A sizable number of users reported symptoms indicating major depression. Depression scores showed few clinically meaningful differences among demographic subgroups. Substance use scores, in contrast, showed meaningful intergroup differences for racial/ethnic group and other demographic variables. CONCLUSIONS: Depressive symptoms and substance use were associated in a sample of middle-school students who were largely non-White and predominantly Hispanic. Greater understanding of the nature of this association is needed; this understanding should be used to design prevention programs, and prevention programs should be introduced at least in the middle-school years.

Achievement↗
PubMed2001

Fibrinolytic variables in patients with recurrent venous thrombosis: a prospective cohort study.

To determine whether fibrinolytic testing predicts recurrent venous thrombosis, we have performed a prospective cohort study in which 303 patients with a first episode of venous thromboembolism underwent comprehensive fibrinolytic testing while receiving oral anticoagulants, and after anticoagulants had been discontinued. They were then followed for up to 3 years for recurrent venous thrombosis. No systematic differences in the levels or activity of type 1 plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (tPA) or euglobulin clot lysis times were detected between patients who did, or did not, suffer recurrent thrombosis. There were also no differences in these variables when patients whose initial thrombosis was idiopathic were compared to patients whose thrombosis occurred in the setting of a known thrombotic risk factor. Based on these results, neither measuring fibrinolytic parameters in patients with venous thromboembolism, nor modification of treatment based on the results of such testing, are justified. Our study also confirms that patients with idiopathic venous thromboembolism have a high risk of recurrence.

Anticoagulants↗
PubMed2000

Identification and characterization of a novel gene (C4orf5) located on human chromosome 4q with specific expression in cardiac and skeletal muscle.

The loci of several genes responsible for arrhythmogenic right ventricular dysplasia (ARVD) have been mapped. Since ARVD involves the right ventricle, we sought candidate genes preferentially expressed in the right ventricle utilizing differential display polymerase chain reaction (PCR) on mRNA from the chambers of an adult human heart. PCR products were cloned, sequenced, and used to screen an adult heart cDNA library. A novel 1.3-kb cDNA (HGMW-approved symbol C4orf5) with an open reading frame of 795 bp was identified. A probe designed from the 3' untranslated region of the 1.3-kb cDNA was hybridized to the 1.3-kb transcript and an alternatively spliced 2.5-kb transcript in the heart and skeletal muscle RNA lanes on a multitissue Northern blot. Analysis of a 39-kb partial genomic sequence identified three intronic splice sites in the 1.3-kb transcript. The gene was mapped to human chromosome 4q26-q27. Computer-based analysis indicated that this gene is novel with no known function.

Adolescent↗
PubMed2000

Human protein tyrosine phosphatase-like gene: expression profile, genomic structure, and mutation analysis in families with ARVD.

The mouse protein tyrosine phosphatase-like gene (Ptpla) was recently cloned and data suggested that it plays a role in myogenesis and cardiogenesis. The human homologue (PTPLA) was mapped to chromosome 10p13-14, a region where we have mapped a locus responsible for arrhythmogenic right ventricular dysplasia (ARVD). As a positional candidate gene, we characterized PTPLA by determining its tissue expression, its genomic structure, and we also screened for mutations in the ARVD patients. Northern analysis demonstrated PTPLA is preferentially expressed in both adult and fetal heart. A much lower expression was detected in skeletal and smooth muscle tissues. Virtually no expression was observed in other tissues. The protein-encoding sequences of PTPLA consist of seven exons. A sequence variation (Lys64Gln) was found in all the affecteds in a large ARVD family. However, the same variant was also detected in normal control subjects (three alleles/100 chromosomes). Thus, the variant (Lys64Gln) is not responsible for ARVD in our family and is a benign polymorphism. Nevertheless, its tissue-specific expression in the developing and adult heart suggest PTPLA has a role in regulating cardiac development, differentiation, or other cellular events. The genomic structure and intragenic polymorphism of PTPLA should be useful for further clinical and genetic studies such as gene targeting of PTPLA.

Arrhythmogenic Right Ventricular Dysplasia↗
PubMed2000

Tissue Doppler imaging consistently detects myocardial contraction and relaxation abnormalities, irrespective of cardiac hypertrophy, in a transgenic rabbit model of human hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is diagnosed clinically by the presence of left ventricular hypertrophy (LVH). However, LVH is absent in a significant number of genotype-positive patients. Because myocyte dysfunction and disarray are the primary abnormalities in HCM, we reasoned that tissue Doppler imaging could identify contraction and relaxation abnormalities, irrespective of hypertrophy, in a transgenic rabbit model of human HCM. METHODS AND RESULTS: M-mode, 2D, Doppler echocardiography and tissue Doppler imaging were performed in nontransgenic (n=24), wild-type beta-myosin heavy chain-arginine(403) (n=14), and mutant beta-myosin heavy chain-glutamic acid(403) (n=24) transgenic rabbits. Mean septal thicknesses were 2.0+/-0.3, 2.0+/-0.25, and 2.75+/-0.3 mm in the 3 groups, respectively (P:=0.001). LVH was absent in 9 of the 24 mutant rabbits. Left ventricular dimensions, systolic function, heart rate, mitral inflow velocities, and time intervals were similar in the groups. However, the difference between atrial reversal and transmitral A wave duration was increased in the mutant rabbits (P:<0.001). More importantly, systolic and early diastolic tissue Doppler velocities were significantly lower in all mutant rabbits (7.45+/-2.2 versus 10.8+/-2.3 cm/s in nontransgenic and 9. 0+/-0.76 cm/s in wild-type; P:<0.001), including the 9 without LVH. A systolic velocity <8.5 cm/s had an 86% sensitivity and 100% specificity in identifying the mutant transgenic rabbits. CONCLUSIONS: Myocardial contraction and relaxation were reduced in the mutant beta-myosin heavy chain-glutamic acid(403) transgenic rabbit model of human HCM, irrespective of the presence or absence of LVH. In addition, tissue Doppler imaging is more sensitive than conventional echocardiography for HCM screening.

Analysis of Variance↗
PubMed2000

Molecular cloning, expression analysis, and chromosome mapping of WDR6, a novel human WD-repeat gene.

The WD-repeat proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as signal transduction, transcription, and proliferation. Here we report on the cloning and characterization of a novel human WD-repeat gene, WDR6, which encodes a protein of 1121 amino acids and contains 11 WD-repeat units. WDR6 is unique since its 11 WD repeats are clustered into two distinct groups separated by a putative transmembrane domain. The WDR6 gene was mapped to chromosome 15q21 by fluorescence in situ hybridization. Northern analysis demonstrated that WDR6 is ubiquitously expressed in human adult and fetal tissues. WDR6 is not homologous to any previously identified human WD-repeat genes including WDR1 through WDR5. However, it was found to have significant sequence similarity with Arabidopsis thaliana hypothetical protein T7B11.12, yeast putative elongation factor G, and probable membrane protein YPL183c. All of them have been defined as WD-repeat proteins. Therefore, WDR6 is a novel protein and probably belongs to a highly conserved subfamily of WD-repeat proteins in which T7B11.12 and YPL183c are its distantly related members.

Amino Acid Sequence↗
PubMed2000

Identification of patients most likely to benefit from implantable cardioverter-defibrillator therapy: the Canadian Implantable Defibrillator Study.

BACKGROUND: Patients with resuscitated ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation) benefit from implantable cardioverter-defibrillators (ICDs) compared with medical therapy. We hypothesized that the patients who benefit most from an ICD are those at greatest risk of death. METHODS AND RESULTS: In the Canadian Implantable Defibrillator Study (CIDS), 659 patients with resuscitated ventricular tachyarrhythmias were randomly assigned to receive an ICD or amiodarone and were then followed for a mean of 3 years. There were 98 and 83 deaths in the amiodarone and ICD groups, respectively. We used multivariate Cox analysis to assess the impact of baseline parameters on the mortality in the amiodarone group. Reduced left ventricular ejection fraction, advanced age, and poor NYHA status identified high-risk patients (P=0.0001 to 0.0009). Quartiles of risk were constructed, and the mortality reduction associated with ICD treatment in each quartile was assessed. There was a significant interaction between risk quartile and the ICD treatment effect (P=0.011). In the highest risk quartile, there was a 50% relative risk reduction (95% CI 21% to 68%) of death in the ICD group, whereas in the 3 lower quartiles, there was no benefit. Patients who are most likely to benefit from an ICD can be identified with a simple risk score (>/=2 of the following factors: age >/=70 years, left ventricular ejection fraction </=35%, and NYHA class III or IV). Thirteen of 15 deaths that were prevented by the ICD occurred in patients with >/=2 risk factors. CONCLUSIONS: In CIDS, patients at highest risk of death benefited most from ICD therapy. These can be identified easily on the basis of age, poor ventricular function, and poor functional status.

Aged↗