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Biomedical subjects

R Brown

Publications and source records attributed to R Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

A comparison of the effects of A1 and A2 beta-casein protein variants on blood cholesterol concentrations in New Zealand adults.

Beta-casein is a cow's milk protein that occurs predominantly in two forms, A1 and A2. Epidemiological evidence suggests that per capita consumption of beta-casein A1 is associated with national mortality rates from ischaemic heart disease. A biological mechanism was proposed after rabbits fed diets containing beta-casein A2 had lower serum cholesterol concentrations and less aortic intimal thickening than rabbits fed beta-casein A1. We tested whether beta-casein A1 and A2 variants differentially affect plasma cholesterol concentrations in humans. In a randomised crossover trial of two four-and-a-half week periods without washout, 62 participants replaced all dairy products in their diet with 500 mL of low-fat milk and 28 g of full-fat cheese that differed in the proportion of beta-casein A1 and A2 variants. Duplicate blood samples were taken on non-consecutive days at the end of each treatment period from 55 people who completed the study. Mean (S.D.) plasma total, low-density and high-density lipoprotein cholesterol concentrations were 5.60 (0.77), 3.73 (0.70) and 1.26 (0.34) mmol/L after the A1 diet and 5.63 (0.81), 3.75 (0.75) and 1.27 (0.37) mmol/L after the A2 diets. We found no evidence that dairy products containing beta-casein A1 or A2 exerted differential effects (P > 0.05) on plasma cholesterol concentrations in humans.

Adult↗
PubMed2005

The evolution of Titan's mid-latitude clouds.

Spectra from Cassini's Visual and Infrared Mapping Spectrometer reveal that the horizontal structure, height, and optical depth of Titan's clouds are highly dynamic. Vigorous cloud centers are seen to rise from the middle to the upper troposphere within 30 minutes and dissipate within the next hour. Their development indicates that Titan's clouds evolve convectively; dissipate through rain; and, over the next several hours, waft downwind to achieve their great longitude extents. These and other characteristics suggest that temperate clouds originate from circulation-induced convergence, in addition to a forcing at the surface associated with Saturn's tides, geology, and/or surface composition.

Atmosphere↗
PubMed2005

Characterization of non-neuronal elements within fibronectin mats implanted into the damaged adult rat spinal cord.

Previous studies have shown that mats made from fibronectin (FN) integrate well into spinal cord lesion sites and support extensive axonal growth. Using immunohistochemistry, we have investigated the non-neuronal factors that contribute to these properties. Extensive vascularization was observed in FN mats by 1 week along with heavy macrophage infiltration by 3 days post-implantation. By 1 week post-implantation, laminin tubules had formed and were associated with axons and p75 immunoreactive Schwann cells. By 4 weeks post-implantation, most axons were associated with Schwann cell derived myelin. Few oligodendrocytes were present within the mat, even with an increase in the number of oligodendrocyte precursors around the implant site by 7 days post-implantation. Astrocyte proliferation also occurred in the intact tissue, with a prominent glial scar forming around the implant within 4 weeks. However, by 2 months post-implantation astrocytes were present in the FN implant site and were intermingled with the axons. Axonal ingrowth and integration of the FN mats is probably due to the ability of FN mats to support and organize infiltration of Schwann cells and deposition of laminin. At later time points, myelinated axons remain in the implant site, even after other elements (e.g. macrophages and laminin) have disappeared. Both of these properties are likely to be important in the design of biomaterial bridges for CNS regeneration.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2005

A hypothesis: the conjunction of soldiers, gas, pigs, ducks, geese and horses in northern France during the Great War provided the conditions for the emergence of the "Spanish" influenza pandemic of 1918-1919.

The Great Influenza Pandemic of 1918-1919 was a cataclysmic outbreak of infection wherein over 50 million people died worldwide within 18 months. The question of the origin is important because most influenza surveillance at present is focussed on S.E. Asia. Two later pandemic viruses in 1957 and 1968 arose in this region. However we present evidence that early outbreaks of a new disease with rapid onset and spreadability, high mortality in young soldiers in the British base camp at Etaples in Northern France in the winter of 1917 is, at least to date, the most likely focus of origin of the pandemic. Pathologists working at Etaples and Aldershot barracks later agreed that these early outbreaks in army camps were the same disease as the infection wave of influenza in 1918. The Etaples camp had the necessary mixture of factors for emergence of pandemic influenza including overcrowding (with 100,000 soldiers daily changing), live pigs, and nearby live geese, duck and chicken markets, horses and an additional factor 24 gases (some of them mutagenic) used in large 100 ton quantities to contaminate soldiers and the landscape. The final trigger for the ensuing pandemic was the return of millions of soldiers to their homelands around the entire world in the autumn of 1918.

Animals↗
PubMed2005

A prospective assessment of mortality in chronic spinal cord injury.

STUDY DESIGN: Prospective mortality study. OBJECTIVE: To assess the relationship between comorbid medical conditions and other health-related factors to mortality in chronic spinal cord injury (SCI). SETTING: Boston, MA, USA. METHODS: Between 1994 and 2000, 361 males >/=1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33-74.4 months) through 12/31/2000 using the National Death Index. RESULTS: At entry, mean (+/-SD) age was 50.6+/-15.0 years (range 23-87) and years since injury was 17.5+/-12.8 years (range 1.0-56.5). Mortality was elevated (observed/expected deaths=37/25.1; SMR=1.47; 95% CI=1.04-2.03) compared to US rates. Risk factors for death were diabetes (RR=2.62; 95% CI=1.19-5.77), heart disease (RR=3.66; 95% CI=1.77-7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390-459) in 40%, and of the respiratory system in 24% (ICD-9 460-519). CONCLUSIONS: These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.

Adult↗
PubMed2005

Gains on 9p are common genomic aberrations in idiopathic myelofibrosis: a comparative genomic hybridization study.

Ideopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder resulting in bone marrow fibrosis as a consequence of growth factor release from clonal haematopoiesis. Conventional cytogenetic analysis identifies abnormalities in approximately a third of cases at diagnosis, although rarely uncovers unique, primary genetic events. We have used comparative genomic hybridization (CGH) to study 25 IMF cases and have compared the results with conventional cytogenetics. Metaphase cells were available for analysis in 13 cases, of which seven showed an abnormal karyotype. CGH chromosomal profiles showed imbalances in 21 of 25 cases. The most frequent aberrations were gains of 9p (12 cases), 2q (seven cases), 3p (seven cases), chromosome 4 (seven cases), 12q (seven cases), 13q (eight cases). The main losses were at 17q and occurred in six cases. The results for CGH and cytogenetics were matched for one case only. Investigation of IMF by CGH suggests that genomic aberrations are much more common than has been previously indicated by conventional cytogenetic analysis and occur in the majority of cases. Gains of 9p were the most frequent finding, occurring in 50% of patients and suggests that genes on 9p may play a crucial role in the pathogenesis of IMF.

Aged↗
PubMed2005

Blurring the boundaries: scenario-based simulation in a clinical setting.

CONTEXT: The ability to perform clinical procedures safely is a key skill for health care professionals. Performing such procedures on conscious patients is challenging and requires a combination of technical and communication skills. We have developed quasi-clinical scenarios, where inanimate models attached to simulated patients provide a convincing learning environment. Procedures are rated by expert observers and by the 'patient' and recorded for subsequent review. This study explores the potential of locating such scenarios within a real clinical setting, allowing participants to experience the challenges of the workplace while ensuring patient safety. An innovative portable digital recording device (the 'Virtual Chaperone') is evaluated for use in clinical settings. METHODS: A qualitative design (observation and interview studies) investigated volunteer medical students undertaking 2 procedure scenarios (insertion of urinary catheter and wound closure with sutures) within the accident unit of a large London hospital. All procedures were observed in real time and recorded digitally (using the Virtual Chaperone). A protocol was used for structured feedback. Observational and interview data was analysed using standard qualitative techniques. RESULTS: Seven sessions with 22 undergraduate medical students took place over 9 months within 1 centre. Data confirmed the feasibility of using a moveable, self-contained training scenario within an authentic clinical setting. Overall, the response from participants was positive. CONCLUSION: Scenario-based teaching within an authentic clinical environment is feasible and perceived by participants to be educationally useful. This approach blurs traditional boundaries between skills laboratory teaching and clinical practice and may offer considerable advantages in training for clinical procedures.

Clinical Competence↗
PubMed2005

School attendance in children with Type 1 diabetes.

AIMS: To determine whether children with Type 1 diabetes mellitus (DM) miss more school than their non-DM siblings and peers and to identify factors associated with school absenteeism in children with DM. METHODS: School absenteeism data for the 2000-01 school year were obtained for 78 children with DM, 38 non-DM siblings and 118,269 age-matched peers in Toronto, Ontario. Questionnaires and hospital records were utilized to evaluate child-, family- and diabetes-related factors associated with school absenteeism in children with DM. RESULTS: Children with DM missed only slightly, albeit significantly more school than both their non-DM siblings (mean +/-sd: 10.9 +/- 8.9 vs. 8.1 +/- 8.1 days, P < 0.001) and peers (median: 8.8 vs. 5.5 days, P = 0.0005). A multiple regression analysis indicated that school absenteeism in children with DM was associated with their parents' attitudes towards school attendance (P = 0.002), poorer metabolic control (P = 0.006), shorter disease duration (P = 0.006) and a lack of aggressive behaviour (P = 0.02). CONCLUSIONS: With current management strategies, near normal school attendance is a reasonable goal for all children with DM and should be strongly encouraged by parents, educators and health care professionals.

Absenteeism↗
PubMed2005

Lethal cardiomyopathy in epidermolysis bullosa associated with amitriptyline.

There are previous reports of dilated cardiomyopathy (DCM) in recessive dystrophic epidermolysis bullosa (RDEB), a debilitating blistering skin disorder. The pathogenesis of DCM in RDEB remains uncertain, although dietary deficiency of selenium and carnitine have been implicated. A 6 year old girl with RDEB who died of DCM is reported; attention is drawn to the possible role of two potentially cardiotoxic drugs, amitriptyline and cisapride.

Amitriptyline↗
PubMed2005

Abdominal pain and dysuria in pregnancy: urinary tract infection or life threatening haemorrhage?

This report describes the case of a 27 year old woman presenting at 19 weeks' gestation with epigastric pain and dysuria. Initially diagnosed with a urinary tract infection, she re-presented 10 days later with acute abdominal pain and haemoperitoneum. The diagnosis of placenta percreta was not made until laparotomy. This case highlights placenta percreta as a rare but serious complication of pregnancy that may become increasingly frequent as the rates of caesarean delivery rise. Early diagnosis, close monitoring, and prompt surgical management are essential as massive blood loss can occur. This can be challenging, as clinical presentation can be unusual.

Abdominal Pain↗
PubMed2005

Heterogeneity of IgG glycosylation in adult periodontal disease.

Periodontal disease is a chronic inflammatory disease of bacterial etiology. In many other chronic inflammatory diseases, IgG glycans are galactose-deficient and thus capable of complement activation through the lectin pathway. In this study, we examined whether IgG in serum and gingival crevicular fluid, and IgG locally produced by plasma cells in gingiva of periodontal disease patients, display altered glycosylation. We developed a lectin-ELISA to measure levels of galactose-deficient IgG in the fluids and immunofluorescence staining to detect galactose-deficient IgG-producing cells in gingiva. Our results indicated higher levels of galactose-deficient IgG in sera and gingival crevicular fluid from periodontal disease patients, compared with levels in healthy controls. Furthermore, gingivae from periodontal disease patients exhibited infiltration of IgG-producing plasma cells; many of them contained galactose-deficient IgG in the cytoplasm. Analysis of our data suggests that IgG secreted by B-cells was aberrantly glycosylated, which resulted in the production of pro-inflammatory galactose-deficient IgG.

Adult↗
PubMed2005

Maxillary incisor palatal erosion: no correlation with dietary variables?

The objectives of the study were to examine a relationship between tooth erosion affecting the palatal aspects of permanent maxillary central incisors with dietary, behavioral and medical variables. The methods included, 251 schoolchildren aged 11 to 13 years were recruited to participate. Each subject had dental impressions of the palatal aspects of both upper central incisors recorded at baseline, 9 and 18 months intervals. From these, electroconductive replicas were fabricated, mapped and compared using a surface matching technique. At the end of the study all participants underwent a structured interview that sought to assay the level of potential erosive dietary, behavioral and medical risk factors. Correlation analyses of the responses given in the final structured interview with the degrees of palatal tooth substance loss (both previous and measured) were under taken. The results showed: (1) The degree of previous erosion did not predict the level of measured ongoing erosion. (2) Brushing the teeth more frequently with fluoridated toothpaste correlated significantly with lower levels of ongoing erosion (P = 0 011). It was concluded that: (1) Evidence of previous palatal erosion did not predict future erosion. (2) The application of topical fluoride as a by-product of tooth brushing may provide an element of protection against palatal erosion. (3) In view of the lack of correlation between exposure to potential risk factors and the level of ongoing palatal tooth surface loss in this study, other factors (such as an individual's susceptibility and salivary buffering power) may well be more important predictors. The clinical relevance included: Preventive advice to patients with dental erosion should not only include the use of topical fluoride, in the form of toothpaste, but recognize individual susceptibility to this condition.

Adolescent↗
PubMed2004

Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display.

OBJECTIVE: To identify differentially expressed genes in synovial fibroblasts and examine the effect on gene expression of exposure to TNF-alpha and IL-1beta. METHODS: Restriction fragment differential display was used to isolate genes using degenerate primers complementary to the lysophosphatidic acid acyl transferase gene family. Differential gene expression was confirmed by reverse transcription-polymerase chain reaction and immunohistochemistry using a variety of synovial fibroblasts, including cells from patients with osteoarthritis and self-limiting parvovirus arthritis. RESULTS: Irrespective of disease process, synovial fibroblasts constitutively produced higher levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) (CCL2) than skin fibroblasts. Seven genes were differentially expressed in synovial fibroblasts compared with skin fibroblasts. Of these genes, four [tissue factor pathway inhibitor 2 (TFPI2), growth regulatory oncogene beta (GRObeta), manganese superoxide dismutase (MnSOD) and granulocyte chemotactic protein 2 (GCP-2)] were all found to be constitutively overexpressed in synoviocytes derived from patients with osteoarthritis. These four genes were only weakly expressed in other synovial fibroblasts (rheumatoid and self-limiting parvovirus infection). However, expression in all types of fibroblasts was increased after stimulation with TNF-alpha and IL-1beta. Three other genes (aggrecan, biglycan and caldesmon) were expressed at higher levels in all types of synovial fibroblasts compared with skin fibroblasts even after stimulation with TNF-alpha and IL-1. CONCLUSIONS: Seven genes have been identified with differential expression patterns in terms of disease process (osteoarthritis vs rheumatoid arthritis), state of activation (resting vs cytokine activation) and anatomical location (synovium vs skin). Four of these genes, TFPI2, GRObeta (CXCL2), MnSOD and GCP-2 (CXCL6), were selectively overexpressed in osteoarthritis fibroblasts rather than rheumatoid fibroblasts. While these differences may represent differential behaviour of synovial fibroblasts in in vitro culture, these observations suggest that TFPI2, GRObeta (CXCL2), MnSOD and GCP-2 (CXCL6) may represent new targets for treatments specifically tailored to osteoarthritis.

Adult↗
PubMed2004

Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene.

Over 50% of human genes are associated with CpG islands and DNA methylation within such CpG islands has been clearly correlated with inhibition of expression. Whereas changes in DNA methylation play a key role in a number of human diseases, in particular cancer, in normal DNA CpG islands are nearly always methylation free, regardless of the expression status of the associated gene. Only limited evidence supports a role for DNA methylation in controlling tissue-specific expression in adult somatic tissue. Loss of expression of the MCJ gene has previously been linked to increased chemotherapeutic drug resistance in ovarian cancer. We report that loss of expression of MCJ in drug-resistant ovarian cancer cell lines depends on methylation of a CpG island within its first exon, but is independent of methylation within the promoter region. Furthermore, cell type-specific expression of the MCJ gene in normal cells also depends on the methylation status of the CpG island within its first exon. The MCJ CpG island is methylated and the gene is not expressed in cells of epithelial origin, but unmethylated and expressed in cells of lymphocyte or fibroblast origin. Chromatin immunoprecipitation assays determined that MCJ CpG island methylation was associated with loss of histone acetylation in ovarian epithelial cells compared with unmethylated fibroblast cells. Reduced acetylation was observed not only within the CpG island, but also within the promoter region, suggesting that CpG island methylation may direct alterations in chromatin structure within the promoter region, leading to gene inactivation.

Acetylation↗
PubMed2004

Outcomes of adults with acute myelogenous leukemia in remission given 550 cGy of single-exposure total body irradiation, cyclophosphamide, and unrelated donor bone marrow transplants.

On the basis of observations from dog models and human studies, we hypothesized that a low-dose (550 cGy), single-exposure total body irradiation (TBI)-based regimen would result in improved survival when given to adult patients with acute myelogenous leukemia (AML) who were undergoing unrelated donor bone marrow transplantation in complete remission (CR). The regimen consisted of single exposure (550 cGy) of TBI given at a high dose rate (30 cGy/min) and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine, methotrexate, and corticosteroids. Thirty-two consecutive adult patients (median age, 47 years) with AML in CR (15 in CR 1 and 17 in CR > or =2) were treated. Sixteen patients (50%) were alive and in remission at last follow-up (median, 2.2 years; range, 0.6-4.0 years). Kaplan-Meier estimates of overall and leukemia-free survival at 3 years were 55% +/- 14% (mean +/- SE) and 57% +/- 14% in CR 1 patients and were both 39% +/- 12% in CR > or =2 patients. Transplant-related mortality was 13% for patients in CR 1 and 41% for those in CR > or =2. Only 1 patient (3%) experienced fatal regimen-related organ toxicity, and only 1 had grade III or IV acute graft-versus-host disease. Graft failure was not observed. Relapse occurred in 22% of patients. This low-dose (550 cGy), single-exposure TBI-based regimen resulted in good survival and a low risk of fatal regimen-related organ toxicity in adult patients with AML who underwent unrelated donor bone marrow transplantation in CR.

Adult↗
PubMed2004

Histological criteria for the identification of acute cellular rejection in human small bowel allografts: results of the pathology workshop at the VIII International Small Bowel Transplant Symposium.

Acute cellular rejection remains a serious and frequent complication during the posttransplant course of small bowel allograft recipients. Currently, small bowel biopsies are the optimal method to identify this form of rejection. The morphological criteria for this diagnosis have been known for some time; however, no consensus study has classified these changes. To address issues in bowel transplant pathology, several pathologists experienced in this particular subdiscipline participated in a Pathology Workshop preceding the VIIIth International Small Bowel Transplant Symposium in Miami, Florida. Among the results of this workshop was the development a standardized grading scheme for acute cellular rejection in small bowel transplants.

Biopsy↗