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Biomedical subjects

B North

Publications and source records attributed to B North.

16 recordsLinked to original sources

Haplotype association analysis of discrete and continuous traits using mixture of regression models.

We present a regression-based method of haplotype association analysis for quantitative and dichotomous traits in samples consisting of unrelated individuals. The method takes account of uncertain phase by initially estimating haplotype frequencies and obtaining the posterior probabilities of all possible haplotype combinations in each individual, then using these as weights in a finite mixture of regression models. Using this method, different combinations of marker loci can be modeled, to find a parsimonious set of marker loci that are most predictive and therefore most likely to be closely associated with the a quantitative trait locus. The method has the additional advantage of being able to use individuals with some missing genotype data, by considering all possible genotypes at the missing markers. We have implemented this method using the SNPHAP and Mx programs and illustrated its use on published data on idiopathic generalized epilepsy.

Chromosome Mapping↗

Interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in non-ST-elevation acute coronary syndromes.

OBJECTIVES: The goal of this study was to determine the interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in patients admitted with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: An increased incidence of the P1(A2) polymorphism in smokers presenting with ST-elevation acute myocardial infarction (AMI) has recently been reported. We, therefore, postulated that, as a consequence of this interaction, fewer smokers with the P1(A2) polymorphism would present with non-ST-elevation ACS. METHODS: We performed a prospective cohort analysis of 220 white Caucasoid patients admitted with non-ST-elevation ACS fulfilling Braunwald class IIIb criteria for unstable angina who were stratified by smoking status. RESULTS: There were twice as many nonsmokers as smokers. Nonsmokers compared with smokers were older (mean [SD]; 63.9 [11.2] vs. 57.6 [10.3]; p < 0.0001), more likely to have had a previous admission with unstable angina (24.3% vs. 13.2%; p = 0.051) and AMI (45.8% vs. 30.3%; p < 0.026), more likely to have undergone revascularization (24.3% vs. 1.8%; p = 0.028) and were more likely to be on aspirin on admission (60.4% vs. 44.7%; p = 0.026). The proportion of nonsmokers positive for the P1(A2) polymorphism was equivalent to that expected for this population but was significantly reduced in smokers (28.7% vs. 10%; Pearson chi-square = 9.09, p = 0.0026). In a logistic regression model, the odds ratio (OR) for being positive for the P1(A2) polymorphism was significantly reduced by smoking (OR [interquartile range]: 0.26 [0.11 to 0.62]; p = 0.0026). CONCLUSIONS: There is a significant reduction in the P1(A2) polymorphism in smokers admitted with non-ST-elevation ACS compared with nonsmokers, which suggests an interaction between smoking and this polymorphism.

Acute Disease↗

D(n)-symmetrical tertiary templates for the design of tubular proteins.

Antiparallel helical bundles are found in a wide range of proteins. Often, four-helical bundles form tube-like structures, with binding sites for substrates or cofactors near their centers. For example, a transmembrane four-helical bundle in cytochrome bc(1) binds a pair of porphyrins in an elongated central cavity running down the center of the structure. Antiparallel helical barrels with larger diameters are found in the crystal structures of TolC and DSD, which form antiparallel 12-helical and six-helical bundles, respectively. The backbone geometries of the helical bundles of cytochrome bc(1), TolC, and DSD are well described using a simple D(n)-symmetrical model with only eight adjustable parameters. This parameterization provides an excellent starting point for construction of minimal models of these proteins as well as the de novo design of proteins with novel functions.

Bacterial Outer Membrane Proteins↗

The external urethral barrier for stress incontinence: a multicenter trial of safety and efficacy. Miniguard Investigators Group.

OBJECTIVE: To assess the efficacy and safety of an external urethral barrier for the management of mild to moderate stress urinary incontinence in adult women. METHODS: Four hundred eleven women with the symptom of stress urinary incontinence in 12 United States centers participated. Additional inclusion and exclusion criteria were applied before protocol device use, and ultimately 390 subjects began device use. Outcome measures for efficacy and safety were assessed. Efficacy was evaluated by the number of leakage episodes using a voiding diary, subjective urinary leakage severity, incontinence impact scores, and pad testing. Safety was evaluated by symptom assessment, urinalysis, urine culture, measurement of postvoid residual urine volume, vulvar cytology, vaginal culture, and (n = 81) cystometric testing. RESULTS: Efficacy was indicated by statistically significant reductions in the number of leakage episodes, subjective leakage severity scores, incontinence impact scores, and pad-test loss during device use. The data also indicated that the device was safe, as evidenced by the lack of statistically significant changes in the percentage of subjects with urinary tract infections during device use or in postvoid residual urine volume and cystometric indices. Symptoms of vulvar irritation or lower urinary tract discomfort occurred in a small percentage of subjects but were generally transient, and only three women discontinued using the device. CONCLUSION: The external urethral barrier appears to be a safe nonsurgical alternative to absorbent products for the management of mild to moderate stress urinary incontinence in adult women.

Adolescent↗

A multiyear study of blood cholinesterase activity in urban pesticide applicators.

This article is a review of blood cholinesterase activity in a cohort of urban pesticide applicators ranging from 1680 to over 3800 workers. During the period 1981-1991, 208, 788 blood samples were taken for measurement of cholinesterase activity with an average of 6 samples per year from each worker. A total of 150 workers or 0.44% of the cohort was removed from exposure to cholinesterase-inhibiting insecticides because of decreased cholinesterase activity. No worker required treatment for signs of cholinesterase inhibition.

Adult↗

Risk factors for tumors of the brain and meninges: results from the Adelaide Adult Brain Tumor Study.

A population-based case-control study of incident primary brain tumors in adults was carried out in Adelaide, Australia in the period 1987 through 1990. It included 110 subjects with newly diagnosed primary glioma, 60 subjects with meningioma and 417 controls selected from the Australian Electoral Roll and frequency-matched to cases for age (within 2 years), sex and postal code. Some interesting new associations were found: (1) an increased risk of glioma in women who reported working with cathode-ray tubes (relative risk = 4.1, 95% confidence interval: 1.3-13.2); (2) a decreased risk of glioma in those with a history of allergic diseases (relative risk = 0.5, 95% confidence interval: 0.3-0.9); and (3) an increased risk of meningioma in those exposed to passive smoking from a spouse, especially amongst females (relative risk = 2.7, 95% confidence interval: 1.2-6.1). A pooled analysis of the multi-center group of studies to which the present study belongs should allow more confident claims concerning risk factors for brain tumors.

Adult↗

Amalgam fillings, diagnostic dental x-rays and tumours of the brain and meninges.

A population-based case-control study of incident brain tumours in adults in Adelaide, South Australia considered possible associations of exposures to amalgam fillings and diagnostic dental X-rays with subsequent development of glioma and meningioma. The study, conducted in 1987-1990, recorded data from 110 subjects with glioma, 60 with meningioma and 417 controls. Principal findings were unexplained decreased risks for glioma associated with both exposure to amalgam fillings (age- and sex adjusted relative risk = 0.47, 95% confidence interval: 0.25-0.91; P = 0.02) and to diagnostic dental X-rays (adjusted relative risk = 0.42; 95% confidence interval: 0.24-0.76; P = 0.004), and a possible increased risk for meningioma in males exposed to dental X-rays. The choice of the unexposed comparison group is important in determining if an increased risk is associated with panoramic or full-mouth X-rays in glioma.

Adult↗

Living in a halo.

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Activities of Daily Living↗

Malignant astrocytoma in South Australia: treatment and case survival.

Kernohan grade III and IV astrocytomas are usually fetal and in the past have had a case survival rate of only about 10% two years from diagnosis. Data on 285 cases registered at the Royal Adelaide Hospital in 1977-1986 showed a median survival of approximately six months. The survival rate was 25% at one year and 15% at two years. Survival reduced markedly with increase in age at diagnosis from a two-year rate of 53% for patients under 40 years of age to 5% for patients aged 70 years or more. This may have been due in part to the more frequent treatment of younger patients by decompression and radiotherapy. Apart from age and treatment mode, factors related to extended survival included a longer duration of symptoms before diagnosis and location of the tumour in the frontal lobes. Notwithstanding prospects for an increase in short-term survival from the use of radiotherapy as an adjunct to surgery, long-term outcomes for these neoplasms are still very poor.

Adult↗

Comparison among three methods of intracranial pressure recording.

Fluid-coupled recording systems are the most popular method of recording intracranial pressure (ICP), but they can be prone to blockage and infection. A series of 378 recordings of ICP was analyzed to identify complications and cases in which recording had to be discontinued prematurely because of catheter blockage. Three different methods of ICP recording were used: a ventricular catheter, a Richmond screw, and a subdural catheter. Richmond screws became blocked more often (16%) than subdural catheters (2.7%) or ventricular catheters (2.5%). Complications of infection and intracerebral hemorrhage were observed mostly in the ventricular catheter patients. Of these three methods, a subdural catheter is the preferred method of recording ICP.

Catheterization↗

Neurological injuries in South Australia: the influence of distance on management and outcome.

It has been shown that in at least two Australian states (New South Wales and South Australia), there is a disproportionately high incidence of lethal neurological injuries in country areas. To determine whether any of this increased rural mortality results from geographical remoteness from specialized hospital services, we have studied prospectively a consecutive series of 153 patients with head injuries (140) or spinal injuries (13), who were transferred to Adelaide, South Australia from country centres during a six month period. Distance appeared to be an occasional cause of delay in instituting expert primary treatment. Of 13 deaths, three resulted from potentially remediable causes (intracranial bleeding, airway obstruction), and in two others difficulties in early supportive care may have contributed to death. First aid sometimes had to be administered by lay persons, and appeared to have been occasionally inadequate. Undesirable delay in transfer from accident site to country hospital was recorded in a few cases; in some of these, private transport was used. Distance was an important cause of delay in transferring patients to Adelaide, since 77% of patients had to travel in excess of 50 km. Thirty patients were brought to Adelaide by medical retrieval teams. These teams, which are centrally co-ordinated, have been useful in extending to country areas the specialized techniques of emergency intensive care and less frequently of operative neurosurgery.

Adolescent↗

Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and stromal cells.

Histone deacetylases (HDACs) represent a large family of enzymes identified as key regulators of nucleosomal histone acetylation, a major epigenetic event that controls eukaryotic gene transcription. Inappropriate deacetylation mediated by HDACs has been associated with profound alterations in cellular biology. We have thus hypothesized that an altered HDAC expression may favor cancer development/progression. To test this possibility, we have sought to screen the expression profiles of several class I and class II HDACs (HDAC1-8) in DU-145, PC-3 and LNCaP human prostate cancer cell lines as well as in matched malignant and non-malignant prostate tissues by use of real time RT-PCR, immunoblot and immunohistochemistry. All HDAC transcripts tested were detected at various levels in all prostate cancer cell lines and tissue samples analyzed. In prostate tissues, the abundance of HDAC1 protein, which was exclusively expressed in the cell nucleus, was similar in normal and malignant epithelial cells, but was usually lower in stromal cells. Unexpectedly, HDAC8, another class I HDAC, was not detected in epithelial cells but was uniquely expressed in the cytoplasm of stromal cells. HDAC5, a class II HDAC involved in myogenesis, was not detected in the tissues. Altogether, our findings indicate that epithelial and stromal cells exhibit distinct class I HDAC expression profiles, and the abundance of HDAC1 is not altered in human prostate cancer. In addition, our observations are the first to demonstrate the prominently cytosolic distribution of a class I HDAC, HDAC8.

Cell Line, Tumor↗