Biomedical subjects
Publications and source records attributed to M Walsh.
This article looks at the challenges facing practice development today and uses key topics in the natural sciences as metaphors to try and stimulate fresh ways of thinking about the way forward. The fundamental challenge we face is one of borders and boundaries, and this is a theme I will keep returning to in this paper.
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Explore the source record for details and available documents.
The following key facts emerge which are relevant to an accident prevention strategy. HIGH RISK TIMES: Just before lunch and late afternoon. HIGH RISK PLACES: Those places which are most familiar to the farmer, his/her own farm, especially the yard and farm buildings. HIGH RISK ACTIVITY: Working at heights (falls) or with moving objects, tractors and cattle. HIGH RISK PEOPLE: Younger men, especially when not working on their own farm or older farmers working with livestock. The majority of these accidents could have been prevented with the correct use of protective clothing or taking more care. Once an accident has happened, the first aid response is likely to be inadequate. The project team are now working on a strategy to persuade farmers that accidents could happen to them personally and of the seriousness of the consequences if they do. This will be coupled with producing accident prevention materials outlining simple precautions that can be taken to prevent accidents. The final stage is to disseminate these materials through a range of channels involving both NHS, farming and school networks. That is the next stage of the project.
This study examined the effect of polymethylmethacrylate (PMMA) on osteocytic necrosis and the role of free radical scavengers in minimizing this damage. Bovine osteoblast cells with a characteristic phenotype were seeded at a density of 4x10(4) cells/cm2 and cultured in a DMEM supplemented with 10% fetal calf serum. A transwell insert with 2 cc of PMMA was suspended above the culture, and a time log response curve was established following elusion of free radicals around the osteoblast media. Chemiluminescence was used to determine quantitative free radical release. Using a Student's two-tailed t test there was a significant difference in the amount of hydroxyl radical released at 1-6 hours compared with controls (P=.028). Using histologic markers, there was a significant correlation between the use of PMMA and osteoblast cell necrosis. Transwell plates were coated with varying concentrations of mannitol, a known hydroxyl radical scavenger. A log dose response curve was established. There was a clear statistical association between a 10% mannitol solution and a reduction in the free radical release from PMMA (P=.03). Similarly, using Trypan blue histologic staining, there was a significant reduction in PMMA-induced cell necrosis when 10% mannitol was used as a scavenger (P=.01). A Rockwell superficial hardness test was used to determine whether mannitol had any effect on the surface hardness of the polymer. No statistical difference could be found between those treated with mannitol and controls at a depth of up to 1 mm. These results demonstrate hydroxyl radical is released from the polymerization reaction of PMMA. These radicals cause cell death in an osteoblast culture medium. This has been addressed using a 10% mannitol solution, which reduced cell necrosis.
Antibiotics are overused in the management of sore throat. Using a scoring system with 108 attenders, we provided feedback on the likelihood of bacterial infection and measured the impact on initial patient expectation for antibiotic therapy. Patient attitudes and beliefs regarding antibiotics were also examined. Of sixty two patients whose score suggested viral infection, 18(29%) opted not to take an antibiotic prescription. The 42(67%) who still wanted an antibiotic, despite being told it was "unlikely or highly unlikely" to help, had a higher mean attendance rate for sore throat (1.63 v 0.83 (p = 0.14)) and other illness (6.53 v 4.22 (p = 0.22)), and a higher mean re-attendance rate following the study (1.68 v 0.50 (p = 0.025)). Qualitative analysis suggests that this subgroup may believe in the analgesic properties of antibiotics.
We have demonstrated previously that the preferential adhesion of prostate cancer cells to human bone marrow endothelial (HBME) cells may contribute to their preferential metastasis to bone. Although a subject of debate, it has been postulated that the endothelial cells of the bone marrow are fenestrated. It is unknown therefore whether prostate cancer cells adhere preferentially to the extracellular matrix (ECM) or the endothelial cells. It has also been demonstrated in other organ systems that the types of cell adhesion molecules on the surface of endothelial cells lining the organ microvasculature are determined, in part, by the ECM of the organ. We investigated how prostate cancer cell adhesion to HBME cells is affected by growing HBME cells on selected organ-derived ECM proteins in vitro. Growth of HBME cells and immortalized human aortic endothelial cells on bone, kidney, and placenta ECM proteins significantly increased their ability to bind PC-3 cells. This increased adhesion was not dose dependent and was not demonstrated with human dermal microvascular endothelial cells. Scanning electron microscopic analysis demonstrated that prostate cancer cells adhered directly to the endothelial cells and not to the underlying substrata. These results suggest that unidentified cell adhesion molecules are expressed or up-regulated on the apical surfaces of human aortic endothelial cells and HBME cells grown on bone, kidney, and placenta ECMs. These results also strongly demonstrate that the adhesion of prostate cancer cells to bone may be initiated by direct binding to endothelial cells rather than direct binding to exposed ECM components.
The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.
Loss of heterozygosity (LOH) involving the distal part of the short arm of chromosome 1 occurs frequently in ovarian adenocarcinomas but the tumour suppressor gene(s) targeted by this event is unknown. We have used five microsatellite markers in a panel of 56 ovarian adenocarcinomas to determine which part of 1p34 - 36 is the focus of this LOH. LOH was considerably more common at 1p36 (43%) than at 1p34 - 35 (18%), and 11 tumours showed LOH at 1p36 but not at 1p34 - 35. These data strongly suggest the presence of a tumour suppressor gene inactivated in ovarian adenocarcinoma at 1p36. The p53 homologue, p73, has recently been isolated and mapped to 1p36 and therefore is a candidate for this tumour suppressor gene. However, RT - PCR and Western analyses revealed strong expression of p73 in ovarian adenocarcinoma cell lines but very low or undetectable levels in normal ovarian surface epithelial cells. Immunohistochemical analysis of primary ovarian tumours showed that only 3/22 (14%) contained p73 expressing cells. There was no association between 1p36 LOH and p73 expression in ovarian tumours, nor between p73 and p53 expression. These findings strongly suggest that p73 is not the target of 1p36 LOH in ovarian adenocarcinomas but indicate the presence of an, as yet unidentified, tumour suppressor gene in this region that plays an important role in ovarian tumorigenesis.
1. We report the first simultaneous mechanical reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers of the guinea-pig ileum following mucosal stimulation and distension in vitro. 2. Dissection techniques were used to prevent mechanical interaction between the LM and CM layers both oral and anal to a stimulus site. 3. All graded stimuli produced graded contractions of both the LM and CM orally and anally to the stimulus. Contractions occurred synchronously in the LM and CM and under no circumstances were inhibitory responses recorded in either muscle layer, despite the presence of ongoing cholinergic tone in both the LM and CM. Contractions were abolished by tetrodotoxin (1.6 microM). 4. Local brush stroking of the mucosa evoked a peristaltic wave which readily conducted distally over 13 cm, without the presence of fluid in the lumen. No descending relaxation was observed. 5. Apamin (300 nM) disrupted evoked peristaltic waves and significantly increased the rate-of-rise of the LM and CM contractions anal to a stimulus, and the LM oral to a stimulus. 6. Nomega-nitro-L-arginine (100 microM), a nitric oxide synthesis inhibitor, had no overall significant effect on the characteristics of the LM and CM contractions, although on occasion an enhancement in their peak amplitude was noted. 7. It is suggested that the guinea-pig ileum does not conform to the 'law of the intestine' as postulated by Bayliss & Starling (1899). Rather, local physiological stimulation of the ileum elicits a contraction both orally and anally to a stimulus, which occurs synchronously in both the CM and LM layers. Apamin-sensitive inhibitory neurotransmission modulates the rate-of-rise of the anal contraction of the CM, possibly to generate distal propulsion.
Inflammation is increasingly considered to be involved in the pathogenesis of acute coronary syndromes. We documented persistent elevation in the levels of soluble ICAM-1 and soluble VCAM-1 and a decrease in the levels of soluble E-selectin in the first 72 hours of acute presentation in patients with unstable angina and subendocardial myocardial infarction.
OBJECTIVES: This collaborative project between two community hospitals, a Metropolitan Home Care Program and the University, was designed to quantify the applicability (who is eligible for) and acceptability (who will likely comply with) Home Care services, provided through a Quick Response Program (QRP) initiative as compared to usual hospital care services, to patients, families and physicians. METHODS: During a 6 week period of sampling (5 days per week, 8 hours per day) in two Emergency Departments (ED) in moderately sized community hospitals in a major metropolitan city, all patients triaged to the urgent category were assessed for eligibility for QRP services by on-site Home Care Coordinators using specific criteria. Patients meeting the criteria initially were reviewed by the ED physician for approval for QRP services and then randomized to experimental and control conditions. Patients not meeting the eligibility criteria were managed by the usual ED services procedures. Demographic and clinical data were obtained on all urgent category patients at presentation to the ED. Additionally, the nature and cost of all health care services used by the ED patients during the ED event and 10 days follow up, were obtained through hospital and Home Care record abstraction and compared among the different sample groups. RESULTS: The QRP Initiative was applicable to 2% of the total ED patient population and 5% of the urgent category of patients triaged in the ED. It was acceptable to 97% of this eligible group. One hundred and fifty-five patients who initially qualified for QRP were excluded from eligibility at a subsequent assessment. Ninety of these patients were admitted to hospital and 65 were discharged home. In the total "exclusion" group, 37 refused Home Care services including the QRP. HEALTH CARE PRACTICE IMPLICATIONS: The sampling results raise important questions about broader system issues concerning the role of the hospital and community in providing health care services and the social value or utility that guides the allocation of health care funds. What level of applicability and acceptability would justify priority services for certain target groups. In the future, policy makers will need to be able to show that it is in the best interest of patients and society to prioritize mixtures of services to certain target groups.
Few prospective studies have examined associations of lifestyle factors or variables in the insulin resistance syndrome (syndrome X) with incidence of elevated blood pressure (BP) in black subjects and women. This report estimates the 10-year incidence of high blood pressure (HBP) and high normal blood pressure (HNBP) in the biracial cohort of the Coronary Artery Risk Development in (Young) Adults Study (CARDIA), and examines lifestyle factors and four syndrome X variables, measured at baseline, as predictors. CARDIA examined 5115 black and white men and women aged 18-30 years in 1985-1986, and re-examined them at 2, 5, 7, and 10 years. The 10-year incidence of HBP was 16.4% in black men, 7.8% in white men, 13.1% in black women, and 3.2% in white women, while the 10-year incidence of HBP or HNBP was 29.5%, 16.2%, 19.2%, and 6.3%, respectively, in the four sex-race subgroups. Predictors included body mass index, waist circumference, physical activity, alcohol intake, pulse rate, cigarette smoking, education, fasting insulin, triglycerides, uric acid, and high-density lipoprotein cholesterol, as well as age and systolic BP. In univariate analyses, each of these variables was significantly related to incidence in at least one of the four sex-race groups. In multivariate analyses that included control for age and systolic pressure, independent predictors included fasting insulin in white men and women, triglycerides in white men, uric acid and pulse rate in black men, waist circumference in white men and black women, and education (inverse) in white men and black and white women. These results suggest that lower socioeconomic status, as assessed by education level, and one or more syndrome X variables, ie, fasting insulin, triglycerides, uric acid, may be associated with development of elevated BP in young adults.
Patient satisfaction with care has frequently been used as a measurement of quality, especially in attempts to demonstrate the benefits of changes in nursing practice. Unfortunately such attempts have frequently failed as patient satisfaction ratings have lacked sensitivity, consistently achieving very high scores. They have also failed to isolate the nursing component from the whole health care experience. The Newcastle Satisfaction with Nursing Scale (NSNS) has been developed after extensive research work as an attempt to establish reliable and valid measures of patients' experiences of and satisfaction with nursing care. This study evaluated the use of the NSNS in practice and found that it was readily understood by patients and easily administered by clinical staff. However, several lessons were learnt which could help its administration. The results demonstrated a very high degree of satisfaction with nursing care which left the discriminatory ability of the scale open to question, although its potential benefits in standard setting were demonstrated. Further evaluative studies are needed if the potential benefits of the NSNS are to be fully realised.
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Depression is a common cause of illness with significant social, vocational, and economic consequences. As one of the most treatable forms of mental illness, depression often is underrecognized and undertreated. The annual cost of depression to the United States economy is approximately $43.7 billion, with 55 percent (or $23.8 billion) accounting for missed work and lowered productivity. The prevalence rate of depression is estimated at 12-20 percent. The depressed patient utilizes two to three times more health services. There is little in the literature to demonstrate the care of the depressed person across the continuum in an integrated health care system. This article reviews the development and implementation of the treatment of depression care across multiple sites along the continuum. The care management depression team utilized the principles of performance improvement; Plan, Do, Check, Act framework for the initiative.
BACKGROUND: 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatelite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). AIMS: To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. METHODS: A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and beta catenin immunohistochemistry was determined in the three groups. RESULTS: MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and beta catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant beta catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). CONCLUSIONS: MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp.