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Biomedical subjects

Paul Brown

Publications and source records attributed to Paul Brown.

At least 19 recordsLinked to original sources
PubMed2006

Incidence of stroke in women in Auckland, New Zealand. Ethnic trends over two decades: 1981-2003.

BACKGROUND AND PURPOSE: Although women have a greater lifetime risk of stroke than men, along with other gender differences in stroke, there is lack of reliable data on long-term trends in stroke in women. This paper presents the results of three population-based registers in Auckland (1981-1982, 1991-1992, and 2002-2003) which aimed to determine the trends in the incidence of stroke in New Zealand. This paper reports on the burden of stroke in women across different ethnic groups over the study period from 1981 to 2003. METHODS: Three studies using similar methodology and overlapping case finding methods have been conducted in New Zealand to estimate trends in the incidence and outcome of stroke. The studies are recognised as meeting the 'ideal' criteria for stroke incidence and identify all first-ever and recurrent strokes in residents (aged greater than and equal to 15 years) the population of Auckland, New Zealand in the 12-month periods from 1981-1982, 1991-1992, and 2002-2003. There were totals of 307,578 strokes among women in 1981, 372,642 in 1991, and 470,727 in 2001, according to each Census representing over 50% of the population at each period (51%-54%). The WHO standard world population was used for direct age standardisation of annual rates (per 100,000 population), reported with 95% confidence intervals (CI). RESULTS: The proportion of women who have experienced a stroke did not change markedly over the study period but there were ethnic differences emerging which were related to population changes within the New Zealand population. Standardised stroke incidence in women was relatively stable across the three study periods (1981-1982), 133 [95% CI 118-151]; (1991-1992), 143 [95% CI 116-241]; and (2002-2003), 124 [95% CI 115-134]). However, a significant decline of 14% (95% CI 2%-29%) in rates of first-ever stroke was found between 1991-1992 and 2002-2003 in women. In contrast to the significant declines in event rates in European women over two decades (Rate ratio 0.84, 95% CI 0.73-0.96), increasing trends in event rates in Pacific women were observed (2.71 95% CI 1.00-7.29). The rate of stroke for Maori women did not change significantly over time. Over half of the women who had a stroke event reported that they had high blood pressure; one in four reported that they had diabetes. The proportion of women who smoked declined over time but increases in body mass index (BMI) indicated weight gains in women over time. These trends were consistent across ethnic groups. Women's survival after 1 month following their stroke has improved by 39% (p<0.0001) over the 20-year period. Favourable changes in early survival were most pronounced in European women. CONCLUSIONS: There was a modest decline in stroke incidence in women (overall and for New Zealand European women in particular) in Auckland over the past 20 years but there also was a trend towards increasing stroke incidence in Maori, Pacific, and Asian women. These divergent trends are likely to be associated with different trends in the prevalence of risk factors in these ethnic populations. Targeted stroke prevention programmes are needed in New Zealand to meet the needs of specific ethnic groups as well as the needs of providing ongoing care and support to women following their stroke.

Adolescent↗
PubMed2006

Increased PC-1 phosphodiesterase activity and inhibition of glucose uptake in adipocytes of type 2 diabetic rats.

This study was designed to understand the cellular mechanisms responsible for defects in the insulin-stimulated signal transduction pathway in a type 2 diabetic animal model. We examined the in vitro PC-1 phosphodiesterase activity and glucose uptake in adipose tissue of streptozotocin (STZ)-induced type 2 diabetic rats. The PC-1 activity was significantly increased in adipose tissue of diabetic rats (0.54 +/- 0.08 nmol PNTP hydrolyzed/mg protein/min) compared with controls (0.29 +/- 0.05 nmol PNTP hydrolyzed/mg protein/min, p < 0.05). Upon insulin stimulation (100 nM), glucose uptake in the adipose tissue of the controls (4.17 +/- 1.28 x 10(-8) micromol/mg/min) was significantly higher than that in the diabetic rats (1.26 +/- 0.35 x 10(-8); p < 0.05). These results suggest that elevated PC-1 phosphodiesterase activity and decreased glucose uptake in adipose tissues may be acquired characteristics contributing to the development of type 2 diabetes mellitus.

Adipose Tissue↗
PubMed2006

Iatrogenic Creutzfeldt-Jakob disease: the waning of an era.

The outbreaks of iatrogenic Creutzfeldt-Jakob disease (CJD) from cadaveric human growth hormone and dura mater are winding down and, like the only other environmentally acquired form of CJD (variant CJD due to infection with the agent of bovine spongiform encephalopathy), iatrogenic disease seems to have reached its high water mark during the 1990s. The total number of cases has reached 405, and the diminishing number of new cases is due to extremely long incubation periods from infections acquired before 1985 (up to 23 years for dura mater and 36 years for growth hormone). Although no cases associated with surgical or other invasive procedures have been identified during the past several decades, the recent discovery of three transfusion-associated variant CJD infections has provoked new concerns about the possibility of further secondary transmissions from operative procedures as well as blood and tissue donations. Therefore, at least in those countries in which variant CJD has occurred, precautionary measures must continue for the indefinite future.

Animals↗
PubMed2006

Whole-brain radiotherapy in the management of brain metastasis.

Brain metastases are an important cause of morbidity and mortality, afflicting nearly 170,000 Americans annually. The prognosis for these patients is poor, with median survival times measured in months. In this review article, we present the standard treatment approach of whole-brain radiotherapy and discuss new directions, including the role of chemical modifiers and the management and prevention of neurocognitive deficits.

Brain Neoplasms↗
PubMed2006

Inactivation of transmissible spongiform encephalopathy agents in food products by ultra high pressure-temperature treatment.

Bovine spongiform encephalopathy (BSE) contamination of the human food chain most likely resulted from nervous system tissue in mechanically recovered meat used in the manufacture of processed meats. The availability of effective decontamination methods for products considered at risk for BSE or other transmissible spongiform encephalopathies (TSEs) would be an attractive safeguard to human health, but neither of the two proven inactivating methods, autoclaving or exposure to strong alkali or bleach, are applicable to foodstuffs. Ultra high pressure-temperature treatment of foods is an effective decontamination method that can reduce the pathogen load while keeping unaltered the nutritional and organoleptic properties of the product. The application of different combinations of high pressure-temperature pulses to meat products 'spiked' with the agents of TSEs can reduce the level of infectivity by 10(3) to 10(6) mean lethal doses (LD(50)) per gram of tissue. These data indicate that the high pressure-temperature treatment is a ready-to-use and feasible strategy to reduce the risk of TSEs transmission via contaminated meat products.

Animals↗
PubMed2006

Impacting quality of life for patients with advanced cancer with a structured multidisciplinary intervention: a randomized controlled trial.

PURPOSE: The primary goal of this study was to evaluate the feasibility and effectiveness of a structured, multidisciplinary intervention targeted to maintain the overall quality of life (QOL), which is more comprehensive than psychosocial distress, of patients undergoing radiation therapy for advanced-stage cancer. PATIENTS AND METHODS: Radiation therapy patients with advanced cancer and an estimated 5-year survival rate of 0% to 50% were randomly assigned to either an eight-session structured multidisciplinary intervention arm or a standard care arm. The eight 90-minute sessions addressed the five domains of QOL including cognitive, physical, emotional, spiritual, and social functioning. The primary end point of maintaining overall QOL was assessed by a single-item linear analog scale (Linear Analog Scale of Assessment or modified Spitzer Uniscale). QOL was assessed at baseline, week 4 (end of multidisciplinary intervention), week 8, and week 27. RESULTS: Of the 103 participants, overall QOL at week 4 was maintained by the patients in the intervention (n = 49), whereas QOL at week 4 significantly decreased for patients in the control group (n = 54). This change reflected a 3-point increase from baseline in the intervention group and a 9-point decrease from baseline in the control group (P = .009). Intervention participants maintained their QOL, and controls gradually returned to baseline by the end of the 6-month follow-up period. CONCLUSION: Although intervention participants maintained and actually improved their QOL during radiation therapy, control participants experienced a significant decrease in their QOL. Thus, a structured multidisciplinary intervention can help maintain or even improve QOL in patients with advanced cancer who are undergoing cancer treatment.

Activities of Daily Living↗
PubMed2006

Micro-scale open-tube capillary separations of functional proteins.

This article describes a novel technique whereby fully functional proteins or multiprotein complexes are efficiently extracted from biological samples to chemically derivatized walls of fused-silica open-tube capillary columns. Proteins are eluted with very high yields into elution volumes that are smaller in volume than the internal volume of the open-tube capillary column itself, thereby achieving 100-fold increases in target protein concentrations from starting samples of less than 1 ml. The open-tube capillary columns are designed for single use; combined with the physical and chemical characteristics of the open-tube capillary column, this provides exceptional purity to the eluted proteins. Affinity-based open-tube capillary columns are demonstrated here to purify, enrich, and maintain functionality for a monomeric and dimeric enzyme, a low-abundance HeLa nuclear complex, and a light-harvesting octadecameric membrane protein complex. The design of the open-tube capillary column allows for facile direction of the processed protein sample to any number of final detection techniques and is capable of generating final protein concentrations required for many structural biology experiments. The open-tube capillary columns are also characterized by exceptional ease of use. Current designs allow for up to 10 open-tube capillary columns to be applied simultaneously with no fundamental impediments to even greater parallel operation.

Bacterial Proteins↗
PubMed2006

Modulation of glucose uptake in adipose tissue by nitric oxide-generating compounds.

There is increasing evidence that endogenous nitric oxide (NO) influences adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated the effect of NO released from S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) on basal and insulin-stimulated glucose uptake in adipocytes of normoglycaemic and streptozotocin (STZ)-induced diabetic rats. GSNO and SNAP at 0.2,0.5, and 1 mM brought about a concentration-dependent increase in basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes of normoglycaemic and STZ-induced diabetic rats. SNAP at 1.0 mM significantly elevated basal 2-deoxyglucose uptake (115.8+/-10.4% compared with GSNO at the same concentration (116.1+/-9.4%; P less than 0.05) in STZ-induced diabetic rats. Conversely, SNAP at concentrations of 10 mM and 20 mM significantly decreased basal 2-deoxyglucose uptake by 50.0+/-4.5% and 61.5+/-7.2% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). GSNO at concentrations of 10 mM and 20 mM also significantly decreased basal 2-deoxyglucose uptake by 50.8+/-6.4% and 55.2+/-7.8% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). These observations indicate that NO released from GSNO and SNAP at 1 mM or less stimulates basal and insulin-stimulated glucose uptake,and at concentrations of 10 mM and 20 mM inhibits basal glucose uptake. The additive effect of GSNO or SNAP, and insulin observed in this study could be due to different mechanisms and warrants further investigation.

Adipocytes↗
PubMed2006

Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?

BACKGROUND: Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment. METHODS: Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS). RESULTS: There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels. CONCLUSIONS: Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.

Adult↗
PubMed2006

Pathological prion protein in muscles of hamsters and mice infected with rodent-adapted BSE or vCJD.

Recently, pathological prion protein (PrP(TSE)) was detected in muscle from sheep infected with scrapie, the archetype of transmissible spongiform encephalopathies (TSEs). This finding has highlighted the question of whether mammalian muscle may potentially also provide a reservoir for TSE agents related to bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob Disease (vCJD). Here, results are reported from studies in hamsters and mice that provide direct experimental evidence, for the first time, of BSE- and vCJD-associated PrP(TSE) deposition in muscles. Our findings emphasize the need for further assessment of possible public-health risks from TSE involvement of skeletal muscle.

Animals↗
PubMed2006

Infectious agent of sheep scrapie may persist in the environment for at least 16 years.

In 1978, a rigorous programme was implemented to stop the spread of, and subsequently eradicate, sheep scrapie in Iceland. Affected flocks were culled, premises were disinfected and, after 2-3 years, restocked with lambs from scrapie-free areas. Between 1978 and 2004, scrapie recurred on 33 farms. Nine of these recurrences occurred 14-21 years after culling, apparently as the result of environmental contamination, but outside entry could not always be absolutely excluded. Of special interest was one farm with a small, completely self-contained flock where scrapie recurred 18 years after culling, 2 years after some lambs had been housed in an old sheep-house that had never been disinfected. Epidemiological investigation established with near certitude that the disease had not been introduced from the outside and it is concluded that the agent may have persisted in the old sheep-house for at least 16 years.

Animals↗
PubMed2006

Workgroup report: Review of genomics data based on experience with mock submissions--view of the CDER Pharmacology Toxicology Nonclinical Pharmacogenomics Subcommittee.

Over the past few years, both the U.S. Food and Drug Administration (FDA) and the pharmaceutical industry have recognized the potential importance of pharmacogenomics and toxicogenomics to drug development. To resolve the uncertainties surrounding the use of microarray technology and the presentation of genomics data for regulatory purposes, several pharmaceutical companies and genomics technology providers have provided the FDA with reports of genomics studies that included supporting toxicology data (e.g., serum chemistry, histopathology). These studies were not associated with any active drug application and were exploratory or hypothesis generating in nature. For training purposes, these reports were reviewed by the Nonclinical Pharmacogenomics Subcommittee consisting of the Center for Drug Evaluation and Research pharmacology and toxicology researchers and reviewers. In this article, we describe some of these submissions and report on our assessment of data content, format, and quality control metrics that were useful for evaluating these nonclinical genomics submissions, specifically in relation to the proposed MIAME/MINTox (minimum information about a microarray experiment/minimum information needed for a toxicology experiment) recommendations. These genomics submissions allowed both researchers and regulators to gain experience in the process of reviewing and analyzing toxicogenomics data. The experience will allow development of recommendations for the submission and review of these data as the state of the science evolves.

Animals↗
PubMed2006

Republicans accused of witch-hunt against climate-change scientists.

Some of America's leading scientists have accused Republican politicians of intimidating climate-change experts by placing them under unprecedented scrutiny. A far-reaching inquiry into the careers of three of the U.S.'s most senior climate specialists has been launched by Joe Barton, chairman of the House of Representatives committee on energy and commerce. He has demanded details of all their sources of funding, methods, and everything they have ever published. The inquiry has sent shockwaves through the U.S. scientific establishment, already under pressure from the Bush administration, which links funding to policy objectives.

Climate↗
PubMed2005

Experimental validation of the docking orientation of Cdc25 with its Cdk2-CycA protein substrate.

Cdc25 phosphatases are key activators of the eukaryotic cell cycle and compelling anticancer targets because their overexpression has been associated with numerous cancers. However, drug discovery targeting these phosphatases has been hampered by the lack of structural information about how Cdc25s interact with their native protein substrates, the cyclin-dependent kinases. Herein, we predict a docked orientation for Cdc25B with its Cdk2-pTpY-CycA protein substrate by a rigid-body docking method and refine the docked models with full-scale molecular dynamics simulations and minimization. We validate the stable ensemble structure experimentally by a variety of in vitro and in vivo techniques. Specifically, we compare our model with a crystal structure of the substrate-trapping mutant of Cdc25B. We identify and validate in vivo a novel hot-spot residue on Cdc25B (Arg492) that plays a central role in protein substrate recognition. We identify a hot-spot residue on the substrate Cdk2 (Asp206) and confirm its interaction with hot-spot residues on Cdc25 using hot-spot swapping and double mutant cycles to derive interaction energies. Our experimentally validated model is consistent with previous studies of Cdk2 and its interaction partners and initiates the opportunity for drug discovery of inhibitors that target the remote binding sites of this protein-protein interaction.

Binding Sites↗
PubMed2005

Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats.

BACKGROUND: The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released from its donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), on glucose uptake in skeletal muscle of normoglyceamic and type 2 diabetic rats. MATERIAL/METHODS: Skeletal muscle strips of type 2 diabetic and normoglycaemic Sprague-Dawley rats were incubated with or without various concentrations (200 microM, 500 microM, 1000 microM, 10 mM & 20 mM) of SNAP or GSNO in the presence or absence of insulin (100 nM or 10 microM). The associated radioactivity was determined by liquid scintillation counting in a Beckman LS6000 scintillation counter programmed for dual-channel counting. RESULTS: SNAP and GSNO at 1000 microM significantly elevated basal and insulin-stimulated 2-deoxyglucose uptake (P<0.05) in normoglycaemic and diabetic rats. Millimolar concentrations (10 & 20 mM) of GSNO and SNAP significantly decreased basal and insulin-stimulated glucose uptake in skeletal muscle strips of normoglycaemic and type 2 diabetic rats in a concentration-dependent manner (P<0.05). The inhibition of insulin-stimulated glucose uptake was greater in the diabetic rats using both NO donors compared with normoglycaemic rats (P<0.05). CONCLUSIONS: The stimulatory effect of micromolar concentrations of GSNO and SNAP enhances basal and insulin-stimulated glucose uptake in normoglycaemic and type 2 diabetic rats, however higher concentrations elicited an inhibitory effect in normoglycaemic and diabetic rats. This highlights the NO-glucose uptake mechanism as a possible potential therapeutic target in the treatment of type 2 diabetes.

Animals↗
PubMed2005

Dollars and sense. Is there a better way to determine private surgical fees in New Zealand?

In New Zealand, private insurers reimburse surgeons on a fee-for-service basis. Ideally, the level of reimbursements should reflect competitive market prices. Due to concerns such a market does not exist, other countries have adopted Relative Value Scales (RVS) to estimate a fair reimbursement level for different procedures. No such scale exists in New Zealand for surgeons, but it does for anaesthetists. This study compares reimbursements to surgeons and anaesthetists from private insurers using data from 3186 procedures performed between 1996 and 2002. We calculate an implicit hourly rate of reimbursement and compare the level of reimbursement between procedures and the variance of reimbursements within procedures for surgeons and anaesthetists. The results suggest that there are significantly greater deviations in average reimbursements between procedures for surgeons than for anaesthetists. Furthermore, the variability of reimbursements is greater for reimbursements to surgeons within specific procedures. While the results do not necessarily imply that surgical reimbursements are inconsistent with underlying market rates, the results are consistent with the hypothesis that anaesthetist's fees show greater stability because of the existence of a RVS. We conclude by discussing what would be required to implement a RVS for surgical fees in New Zealand.

Anesthesiology↗
PubMed2005

Individual socio-economic status, community socio-economic status and stroke in New Zealand: a case control study.

There is considerable debate about the association between individual socio-economic status, community socio-economic status and health. The current study examines individual data from a case-control study of stroke (n = 3489) conducted in Auckland, New Zealand. The study sought to identify whether individual socio-economic status (as measured by income from lifetime occupation) and community socio-economic status (measured in a number of ways) predicts the onset of stroke both independently and after controlling for individual risk factors (e.g., smoking, obesity and hypertension). Logistic regression results show that individual socio-economic status and all of the community socio-economic status measures predict the onset of stroke before controlling for individual risk factors. However, there is a high correlation between the various measures of community socio-economic status. Stepwise regression results suggest that average household income is the measure of community-level socio-economic status with the greatest predictive power. The results suggest that individual income and average household income are significant predictors of onset of stroke both independently and after controlling for behavioural and medical risk factors. Logistic regression analysis of the pathway suggests that individual income is a significant predictor of smoking and obesity, and that community socio-economic status is a significant predictor of heart disease, heavy drinking, diabetes, smoking and obesity.

Adult↗