PubMed Health⌕ Search

Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 19 recordsLinked to original sources
PubMed2006

Cell salvage for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood, have prompted reconsideration of the use of allogeneic (blood from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents and the websites of international health technology assessment agencies. The reference lists in identified trials and review articles were also searched, and study authors were contacted to identify additional studies. The searches were updated in January 2004. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed methodological quality. The main outcomes measures were the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction, renal failure), mortality, and length of hospital stay (LOS). MAIN RESULTS: Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (relative risk [RR] = 0.61: 95% confidence interval [CI] 0.52 to 0.71). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 23% (95% CI 16% to 30%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.42 (95% CI 0.32 to 0.54) compared to 0.77 (95% CI 0.68 to 0.87) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.67 units of allogeneic RBC per patient (weighted mean difference was -0.64; 95% CI -0.89 to -0.45). Cell salvage did not appear to impact adversely on clinical outcomes. AUTHORS' CONCLUSIONS: The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective surgery. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients' treatment status biasing the results in favour of cell salvage.

Blood Specimen Collection↗
PubMed2006

Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia.

The deficiency of glucose-6-phosphatase (G6Pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type Ia (GSD-Ia). An adeno-associated virus (AAV) vector encoding G6Pase was pseudotyped as AAV8 and administered to 2-week-old GSD-Ia mice (n = 9). Median survival was prolonged to 7 months following vector administration, in contrast to untreated GSD-Ia mice that survived for only 2 weeks. Although GSD-Ia mice were initially growth-retarded, treated mice increased fourfold in weight to normal size. Blood glucose was partially corrected by 2 weeks following treatment, whereas blood cholesterol normalized. Glucose-6-phosphatase activity was partially corrected to 25% of the normal level at 7 months of age in treated mice, and blood glucose during fasting remained lower in treated, affected mice than in normal mice. Glycogen storage was partially corrected in the liver by 2 weeks following treatment, but reaccumulated to pre-treatment levels by 7 months old (m.o.). Vector genome DNA decreased between 3 days and 3 weeks in the liver following vector administration, mainly through the loss of single-stranded genomes; however, double-stranded vector genomes were more stable. Although CD8+ lymphocytic infiltrates were present in the liver, partial biochemical correction was sustained at 7 m.o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure.

Animals↗
PubMed2006

Microscopic intrarenal particles after pulsatile machine preservation do not adversely affect outcomes after renal transplantation.

INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. RESULTS: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.

Adult↗
PubMed2006

Short term estimates of adult HIV incidence by mode of transmission: Kenya and Thailand as examples.

OBJECTIVE: Patterns of transmission of HIV are different among different regions of the world and change over time within regions. In order to adapt prevention strategies to changing patterns of risk, we need to understand the behaviours that put people at risk of infection and how new infections are distributed among risk groups. METHODS: A model is described to calculate the expected incidence of HIV infections in the adult population by mode of exposure using the current distribution of prevalent infections and the patterns of risk within different populations. For illustration the model is applied to Thailand and Kenya. RESULTS: New infections in Kenya were mainly transmitted through heterosexual contact (90%), while a small but significant number were related to injecting drug use (4.8%) and men who have sex with men (4.5%). In Thailand, the epidemic has spread over time to the sexual partners of vulnerable groups and in 2005 the majority of new infections occurred among the low risk heterosexual population (43%). Men having sex with men accounted for 21% and sex work (including sex workers, clients, and partners of clients) for 18% of new infections. Medical interventions did not contribute significantly to new infections in either Kenya or Thailand. CONCLUSIONS: The model provides a simple tool to inform the planning of effective, appropriately targeted, country specific intervention programmes. However, better surveillance systems are needed in countries to obtain more reliable biological and behavioural data in order to improve the estimates of incidence by risk group.

Adolescent↗
PubMed2006

Improving projections at the country level: the UNAIDS Estimation and Projection Package 2005.

BACKGROUND: UNAIDS has developed the Estimation and Projection Package (EPP) as a tool for national programmes to use for making national estimates and short term projections of HIV prevalence. EPP provides direct input to Spectrum, which produces incidence, deaths, and AIDS impacts. METHODS: The latest version, EPP 2005, includes substantial methodological improvements over the previous version. These include: (1) parallel, but unique, interfaces for generalised and concentrated epidemics; (2) use of maximum likelihood fitting procedures; (3) a new procedure, known as level fits, adjusting for expansion of national surveillance systems into lower prevalence sites; (4) provisions for handling turnover in at-risk populations, including the reassignment of HIV positive former members to lower risk populations; and (5) user-defined calibration to HIV prevalence levels from general population or other epidemiological surveys. RESULTS: Following regional training in mid 2005, this new version has been applied by many national programmes to make their end of 2005 estimates of HIV infections. UNAIDS has combined these national estimates to form the 2005 global HIV and AIDS estimates. CONCLUSION: EPP 2005 is a substantial improvement over previous versions, forming a solid base for the next round of modifications. Proposed modifications for that next version are presented for the reader's information.

Disease Outbreaks↗
PubMed2005

Interventions for preventing obesity in children.

BACKGROUND: Obesity prevention is an international public health priority. The prevalence of obesity and overweight is increasing in child populations throughout the world, impacting on short and long-term health. Obesity prevention strategies for children can change behaviour but efficacy in terms of preventing obesity remains poorly understood. OBJECTIVES: To assess the effectiveness of interventions designed to prevent obesity in childhood through diet, physical activity and/or lifestyle and social support. SEARCH STRATEGY: MEDLINE, PsycINFO, EMBASE, CINAHL and CENTRAL were searched from 1990 to February 2005. Non-English language papers were included and experts contacted. SELECTION CRITERIA: Randomised controlled trials and controlled clinical trials with minimum duration twelve weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Twenty-two studies were included; ten long-term (at least 12 months) and twelve short-term (12 weeks to 12 months). Nineteen were school/preschool-based interventions, one was a community-based intervention targeting low-income families, and two were family-based interventions targeting non-obese children of obese or overweight parents. Six of the ten long-term studies combined dietary education and physical activity interventions; five resulted in no difference in overweight status between groups and one resulted in improvements for girls receiving the intervention, but not boys. Two studies focused on physical activity alone. Of these, a multi-media approach appeared to be effective in preventing obesity. Two studies focused on nutrition education alone, but neither were effective in preventing obesity. Four of the twelve short-term studies focused on interventions to increase physical activity levels, and two of these studies resulted in minor reductions in overweight status in favour of the intervention. The other eight studies combined advice on diet and physical activity, but none had a significant impact. The studies were heterogeneous in terms of study design, quality, target population, theoretical underpinning, and outcome measures, making it impossible to combine study findings using statistical methods. There was an absence of cost-effectiveness data. AUTHORS' CONCLUSIONS: The majority of studies were short-term. Studies that focused on combining dietary and physical activity approaches did not significantly improve BMI, but some studies that focused on dietary or physical activity approaches showed a small but positive impact on BMI status. Nearly all studies included resulted in some improvement in diet or physical activity. Appropriateness of development, design, duration and intensity of interventions to prevent obesity in childhood needs to be reconsidered alongside comprehensive reporting of the intervention scope and process.

Adolescent↗
PubMed2005

Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury.

Extension of a burn wound over the first 24h following injury is recognised clinically, and leads to diagnostic and therapeutic dilemmas. In the central nervous system, a similar spread of damage, beyond the initial injury, can occur via the spread of death signals from injured cells to their healthy neighbours via Connexin43 (Cx43) gap junction channels. In the skin, Cx43 is expressed in the basal epidermis and in fibroblasts and dermal appendages. We have used Cx43 specific antisense oligodeoxynucleotide approach to transiently down-regulate Cx43 protein in the early stages of partial thickness cutaneous burn wound healing. Antisense ODNs reduce the spread of tissue damage and neutrophil infiltration around the wound following injury. Epithelial cell proliferation is increased and the rate of wound closure is accelerated, compared to controls. Resultant scarring is smaller with less granulation tissue and more dermal appendages than controls. These findings suggest that Cx43 antisense treatment speeds partial thickness burn wound healing and reduces scarring. We suggest that this approach may provide an effective adjunct to managing partial thickness burn wounds.

Animals↗
PubMed2005

Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis.

BACKGROUND: A standardized instrument is needed to rate the overall severity of chronic hand dermatitis (CHD), in particular during clinical trials. OBJECTIVES: To design and validate a photographic guide. METHODS: Initially, five experts were asked to grade 50 photographs of CHD, first individually, then as a consensus-building group, in order to select the photographs included in the guide. Then, a validation session with 11 different dermatologists evaluating 28 patients was conducted to assess the interrater reliability and test-retest reproducibility of the assessment of disease severity, relying on the photographic guide, on two consecutive days. Patient order was randomized, and only diseased hands were visible to prevent any bias in evaluation. RESULTS: The experts reached a consensus for development of a photographic guide composed of five severity levels and four photographs per severity level. Results of the validation session showed a high level of interrater reliability and test-retest reproducibility. CONCLUSIONS: The photographic guide is a reliable tool for assessing the morphological severity of hand dermatitis, and can be used as part of a comprehensive evaluation of disease in international multicentre clinical trials.

Adult↗
PubMed2005

Technical note: technique for dissection and analysis of the rumen in young calves.

This paper discusses a technique used to evaluate rumen development in young calves, including removal, dissection, and analysis of tissue. The method allowed for examination of the different sacs of the rumen (dorsal, ventral, cranial, and caudal) using scanning electron microscopy to measure papillae denseness and histology slides to measure papillae length and width. Computer software was used to produce accurate measurements of papillae. The rumens of young calves were dissected, and samples were taken from the cranial, caudal, ventral, and dorsal sections. Calves were part of a nutrition research study, and dietary treatments did have an effect on development measurements such as length, width, and papillae denseness.

Animal Nutritional Physiological Phenomena↗
PubMed2005

[Molecular typing of the Mycobacterium tuberculosis strains circulating in central Russia: efficiency of spoligotyping and VNTR-MIRU].

Current problems of molecular epidemiology of the Mycobacterium tuberculosis strains circulating in Samara Region, Russia are discussed. A total of 190 isolates of Mycobacterium tuberculosis were typed using two PCR-based molecular methods. The cultures were isolated from civil and prison patients with pulmonary tuberculosis recruited from different tuberculosis institutions across the Samara region. The usefulness of spoligotyping and 15-locii VNTR-MIRU was assessed for genotyping of Mycobacterium in population with high prevalence of Beijing strains (67.9%) using statistical analyses that included calculation of Hunter-Gaston index. The VNTR-MIRU method was demonstrated to be more efficient and was characterized by higher discrimination (index 0.747) compare to spoligotyping (index 0.572). VNTR-MIRU loci 10, 26, 31, 39, 40 and ETR-A were mostly polymorphic and therefore recommended for use in screening. It could be performed by manual electrophoresid, provided that automated sequencing is not available.

Bacterial Typing Techniques↗
PubMed2004

Submicron patterning of DNA oligonucleotides on silicon.

The covalent attachment of DNA oligonucleotides onto crystalline silicon (100) surfaces, in patterns with submicron features, in a straightforward, two-step process is presented. UV light exposure of a hydrogen-terminated silicon (100) surface coated with alkenes functionalized with N-hydroxysuccinimide ester groups resulted in the covalent attachment of the alkene as a monolayer on the surface. Submicron-scale patterning of surfaces was achieved by illumination with an interference pattern obtained by the transmission of 248 nm excimer laser light through a phase mask. The N-hydroxysuccinimide ester surface acted as a template for the subsequent covalent attachment of aminohexyl-modified DNA oligonucleotides. Oligonucleotide patterns, with feature sizes of 500 nm, were reliably produced over large areas. The patterned surfaces were characterized with atomic force microscopy, scanning electron microscopy, epifluorescence microscopy and ellipsometry. Complementary oligonucleotides were hybridized to the surface-attached oligonucleotides with a density of 7 x 10(12) DNA oligonucleotides per square centimetre. The method will offer much potential for the creation of nano- and micro-scale DNA biosensor devices in silicon.

Base Pair Mismatch↗
PubMed2004

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers.

BACKGROUND: The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. OBJECTIVES: To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. METHODS: A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. RESULTS: Eighty-four percent of patients were 'poor sleepers' with global sleep scores (GLSc) > 5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc > or = 10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc > 5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. CONCLUSIONS: PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.

Adult↗
PubMed2004

Pushing the envelope in renal preservation; improved results with novel perfusate modifications for pulsatile machine perfusion of cadaver kidneys.

INTRODUCTION: Novel preservation techniques may diminish ischemia/reperfusion (I/R) injury. Our preservation laboratory has modified Belzer MPS for machine perfusion (MP) with prostaglandin E1 (PGE 1), nitroglycerin (NTG), and polyethylene glycol-superoxide dismutase (PEG-SOD) to attenuate I/R injury. We reviewed our recent experience using this novel formulation (NF) compared with standard perfusates. RESULTS: Between January 1998 and March 2000, 1060 consecutive kidneys were preserved in our laboratory. One hundred forty-eight kidneys (14%) were discarded. Fifty-eight percent of kidneys during this time period underwent MP (n = 532). En bloc kidney pairs were randomly assigned to pulsatile MP using Waters RM3 or MOX-100 perfusion systems using 1 of 3 perfusates; NF (NF; n = 119), Belzer MPS (MPS; n = 201), or Belzer II albumin gluconate (ALB; n = 212) Significant improvements in delayed graft function (DGF) rate were seen with NF versus other perfusates (8% vs 14% vs 19%, respectively; P =.03). At 6 months, graft survival was significantly improved with NF compared with MPS and ALB (96% vs 90% vs 87%, respectively; P =.03). NF also produced a significantly higher percentage of recipients with a serum creatinine level < or = 1.5 mg/dL. CONCLUSIONS: Novel modifications of standard MP perfusate improved outcomes after renal transplantation. Preservation-based interventions targeted to ameliorate I/R injury can improve outcomes and may allow expansion of the donor pool.

Adult↗
PubMed2004

Strategies for prevention: occupational contact dermatitis.

The economic consequence of occupational contact dermatitis (OCD) is considerable and impacts on an individual's quality of life. There are a range of prevention strategies, which include: elimination or substitution of harmful exposures; technical control measures; personal protection; identification of susceptible individuals; and education, training and health surveillance. Each one has been shown to have varying degrees of success in reducing OCD, but further work is required to evaluate the effectiveness of preventive measures in the workplace. OCD is not considered a high priority in most affected industries and therefore the development of health and safety policies to reduce its prevalence should be encouraged, although guidance and assistance would be required, because all employees are entitled to a safe working environment.

Dermatitis, Occupational↗
PubMed2004

Detection of mutations associated with isoniazid and rifampin resistance in Mycobacterium tuberculosis isolates from Samara Region, Russian Federation.

High incidence rates of isoniazid-, rifampin-, and multiple-drug-resistant tuberculosis have been reported in countries of the former Soviet Union (FSU). Genotypic (unlike phenotypic) drug resistance assays do not require viable cultures but require accurate knowledge of both the target gene and the mutations associated with resistance. For these assays to be clinically useful, they must be able to detect the range of mutations seen in isolates from the population of tuberculosis patients to which they are applied. Two novel macroarrays were applied to detect mutations associated with rifampin (rpoB) and isoniazid (katG and inhA) resistance. In a sample of 233 isolates from patients in Samara, central Russia, 46.5% of isolates possessed mutations in both the rpoB and the katG (or inhA) genes. Combined results from the macroarrays demonstrated concordance in 95.4 and 90.4% of phenotypically defined rifampin- and isoniazid-resistant isolates, respectively. The contribution of different mutations to resistance was comparable to that reported previously for non-FSU countries, with 90% of rifampin-resistant isolates and 93% of isoniazid resistant isolates due to rpoB531 and katG315 mutations, respectively. The percentage of phenotypically resistant rifampin isolates with no mutations in the rpoB codons 509 to 536 was 4.2%, which was similar to previous reports. Novel macroarrays offer a rapid, accurate, and relatively cheap system for the identification of rifampin-, isoniazid-, and multiple-drug-resistant Mycobacterium tuberculosis isolates.

Antitubercular Agents↗
PubMed2004

Emergency physicians in critical care: a consultant's experience.

There is a growing interest in the interface between emergency medicine and critical care medicine. Previous articles in this journal have looked at the opportunities and advantages of training in critical care medicine for emergency medicine trainees. In the UK there are a small number of emergency physicians who also have a commitment to critical care medicine. This article describes a personal experience of such a job, looking at the advantages and disadvantages. Depending upon future developments in the role of emergency medicine in the UK, together with the proposed expansion in critical care medicine, such posts may become more common.

Attitude of Health Personnel↗