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Biomedical subjects

M Walsh

Publications and source records attributed to M Walsh.

At least 73 records · Page 4Linked to original sources

Cost of treating acute myocardial infarction in an Irish teaching hospital.

Recent figures indicate that there are approximately 6,500 patients admitted to hospital following acute myocardial infarction (AMI) in Ireland each year. As hospital admission is frequently the most expensive component of healthcare we determined the costs associated with treatment of AMI in a teaching hospital. The costing evaluation was from the hospital perspective and the strategy used was a micro-costing detailed collection of resources used. The average cost of hospital admission for the treatment of AMI was Pound Sterling 3,976. The average cost per day was calculated at Pound Sterling 501. Approximately 50% of hospital costs were associated with ward costs. Procedures accounted for 35% of costs whereas medications contributed just 7% of total costs.

Aged↗

Are trends in diabetes incidence changing for minority children?

PURPOSE: To contrast incidence rates and time trends of typical type 1 diabetes with non-autoimmune insulin-resistant type 2 diabetes in minority children (Early 2).METHODS: A population based registry of all insulin treated African-American and Hispanic children residing in Chicago, aged 0-17 years at onset, diagnosed between 1985-1994 provided data. Medical records were reviewed and abstracted (N = 739), and a subset of patients were interviewed (n = 195). Based on these data sources, cases were assigned to the early type 2 category if one or more of the following variables were present: notation of "atypical" or "possible type 2" diabetes in the medical record; obesity (defined as BMI >/= 27 (kg/m(2))) or acanthosis nigricans noted at diagnosis; a report by the patient of going off insulin six months after initial diagnosis without developing diabetic ketoacidosis; or reporting the use of oral hypoglycemic agents with or without insulin. The Chi-square test for homogeneity was used to determine differences between proportions of groups. Time trend analysis of incidence was done using regression models with the Poisson distribution.RESULTS: The 10-year average annual incidence rate was 10.3 per 100,000 population for typical type 1 diabetes (n = 565) and 3.2 per 100,000 for those with characteristics of early 2 diabetes (n = 174). Over the ten year interval the incidence rate remained static for typical type 1 diabetes. In the early 2 group there was a 9.0% average annual percent increase over the ten year interval (p < 0.01).CONCLUSIONS: The trends in incidence rates vary between typical type and early 2 diabetes. We hypothesize that this is associated with the increasing rate of obesity and a lack of physical activity in young people.

Journal Article↗

Complete stabilization of neoclassical tearing modes with lower hybrid current drive on COMPASS-D. RF teams.

Lower hybrid current drive (LHCD) with modest powers ( approximately 10% of the total power input) has been used for the first time to completely stabilize performance limiting neoclassical tearing modes in many COMPASS-D tokamak discharges. The stabilizing effect in these experiments is consistent with a reduction in the free energy available in the current profile to drive tearing modes (i.e., the stability index, delta(')) resulting from favorable current gradients (from the LHCD driven current) around the rational surface.

Journal Article↗

Ring-pattern dynamics in smectic-C* and smectic-C*A freely suspended liquid crystal films.

Ring patterns of concentric 2pi solitons in molecular orientation form in freely suspended chiral smectic-C films in response to an in-plane rotating electric field. We present measurements of the driven dynamics of ring formation under conditions of synchronous winding and of the zero-field relaxation of ring patterns, and propose a simple model which enables their quantitative description in low polarization DOBAMBC. In smectic-C*A TFMHPOBC we observe an odd-even layer number effect, with odd layer number films exhibiting order of magnitude slower relaxation rates than even layer films. We show that this rate difference is due to a much larger spontaneous polarization in odd layer number films.

Journal Article↗

Investigation of the role of the carboxyl-terminal tails of the alpha and beta isoforms of the human thromboxane A(2) receptor (TP) in mediating receptor:effector coupling.

We have investigated the functional coupling of alpha and beta isoforms of the human thromboxane A(2) receptor (TP) to Galpha(16) and Galpha(12) members of the G(q) and G(12) families of heterotrimeric G proteins in human embryonic kidney (HEK) 293 cell lines HEK.alpha10 or HEK.beta3, stably over-expressing TPalpha and TPbeta, respectively. Moreover, using HEK.TP(Delta328) cells which over-express a variant of TP truncated at the point of divergence of TPalpha and TPbeta, we investigated the requirement of the C-tail per se in mediating G protein coupling and effector activation. Both TPalpha and TPbeta couple similarly to Galpha(16) to affect increases in inositol 1,4,5-trisphosphate (IP(3)) and mobilisation of intracellular calcium ([Ca(2+)](i)) in response to the TP agonist U46619. Whilst both TP isoforms mediated [Ca(2+)](i) mobilisation in cells co-transfected with Galpha(12), neither receptor generated corresponding increases in IP(3), indicating that the Galpha(12)-mediated increases in [Ca(2+)](i) do not involve PLC activation. Verapamil, an inhibitor of voltage dependent Ca(2+) channels, reduced [Ca(2+)](i) mobilisation in TPalpha and TPbeta cells co-transfected with Galpha(12) to approximately 40% of that mobilised in its absence, whereas [8-(N,N-diethylamino)-octyl-3,4, 5-trimethoxybenzoate, hydrochloride] (TMB-8), an antagonist of intracellular Ca(2+) release, had no effect on [Ca(2+)](i) mobilisation by either receptor isoform co-transfected with Galpha(12). Despite the lack of differential coupling specificity by TPalpha and TPbeta, TP(Delta328) signalled more efficiently in the absence of a co-transfected G protein compared to the wild type receptors but, on the other hand, displayed an impaired ability to couple to co-transfected Galpha(11), Galpha(12) or Galpha(16) subunits. In studies investigating the role of the C-tail in influencing coupling to the effector adenylyl cyclase, similar to TPalpha but not TPbeta, TP(Delta328) coupled to Galpha(s), leading to increased adenosine 3',5'-cyclic monophosphate (cAMP), rather than to Galpha(i). Whereas TP(Delta328) signalled more efficiently in the absence of co-transfected G protein compared to the wild type TPalpha, co-transfection of Galpha(s) did not augment cAMP generation by TP(Delta328). Hence, from these studies involving the wild type TPalpha, TPbeta and TP(Delta328), we conclude that the C-tail sequences of TP are not a major determinant of G protein coupling specificity to Galpha(11) and Galpha(16) members of the G(q) family or to Galpha(12); it may play a role in determining G(s) versus G(i) coupling and may act as a determinant of coupling efficiency.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Purinergic and cholinergic neuro-neuronal transmission underlying reflexes activated by mucosal stimulation in the isolated guinea-pig ileum.

1. We present evidence that adenosine triphosphate (ATP) plays a major role in excitatory neuro-neuronal transmission in ascending and descending reflex pathways to the longitudinal (LM) and circular muscle (CM). 2. A partitioned bath was used for the pharmacological isolation of a segment of guinea-pig ileum ( approximately 6 cm in length), allowing drugs to be selectively applied to an intermediate region between the region where mucosal stimulation was applied and that where mechanical recordings were made. 3. Brush stroking the mucosa (3 strokes) elicited a synchronous contraction of the LM and CM both above (ascending excitation) and below (descending excitation) the site of stimulation. All reflexes were abolished when tetrodotoxin (1 microM) was applied to the intermediate chamber. 4. Hexamethonium (300 microM) added to the intermediate chamber abolished the ascending contraction in 15 % of oral preparations (from 26 preparations, 18 animals) and the descending contraction in 13% of anal preparations studied (from 53 preparations, 48 animals). In the remaining 85% of oral preparations, hexamethonium usually attenuated the oral contraction of the LM and CM. However, in the remaining 87% of anal preparations, hexamethonium had no effect on the anal contraction of the LM and CM. 5. Oral and anal reflexes that were hexamethonium resistant were either abolished or attenuated by the further addition of the P2 purinergic receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 10 microM) or alpha,beta-methylene ATP (50-100 microM) to the intermediate chamber. 6. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP, 20 microM) or alpha,beta-methylene ATP (50-100 microM) stimulated both ascending and descending excitatory pathways, when applied to the intermediate chamber. 7. In conclusion, ascending and descending neuro-neuronal transmission in excitatory nervous pathways to the LM and CM is complex and clearly involves neurotransmitter(s) other than acetylcholine (ACh). We suggest mucosal stimulation releases ACh and ATP in both ascending and descending excitatory reflex pathways that synapse with excitatory motoneurons to the LM and CM.

Acetylcholine↗

Expression of p53 in arsenic-related and sporadic basal cell carcinoma.

BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear, although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia. CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). The more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.

Adult↗

Health effects of depleted uranium on exposed Gulf War veterans.

A small group of Gulf War veterans possess retained fragments of depleted uranium (DU) shrapnel, the long-term health consequences of which are undetermined. We evaluated the clinical health effects of DU exposure in Gulf War veterans compared with nonexposed Gulf War veterans. History and follow-up medical examination were performed on 29 exposed veterans and 38 nonexposed veterans. Outcome measures employed were urinary uranium determinations, clinical laboratory values, and psychiatric and neurocognitive assessment. DU-exposed Gulf War veterans with retained metal shrapnel fragments are excreting elevated levels of urinary uranium 7 years after first exposure (range 0.01-30.7 microg/g creatinine vs 0.01- 0.05 microg/g creatinine in the nonexposed). The persistence of the elevated urine uranium suggests on-going mobilization from a storage depot which results in a chronic systemic exposure. Adverse effects in the kidney, a presumed target organ, are not present at this time, though other effects are observed. Neurocognitive examinations demonstrated a statistical relationship between urine uranium levels and lowered performance on computerized tests assessing performance efficiency. Elevated urinary uranium was statistically related to a high prolactin level (>1.6 ng/ml; P=0.04). More than 7 years after first exposure, DU-exposed Gulf War veterans with retained metal fragments continue to excrete elevated concentrations of urinary uranium. Effects related to this are subtle perturbations in the reproductive and central nervous systems.

Adult↗

Evidence of prolonged inflammation in unstable angina and non-Q wave myocardial infarction.

OBJECTIVES: This study was designed to document the inflammatory response up to one year after acute presentation with unstable angina (UA) and non-Q wave infarction (NQMI) as reflected by the expression of soluble cell adhesion molecules (CAMs). BACKGROUND: Coronary plaque inflammation is a key component in the pathogenesis of acute coronary syndromes. Cell adhesion molecules are critical mediators of the inflammatory process. Soluble forms of these molecules are detectable in serum and are elevated acutely in patients with UA and NQMI. METHODS: Patients presenting with UA and NQMI had serum samples taken at presentation and then after three, six and 12 months. A control group of similar age and gender distribution was used for comparison. Levels of soluble inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-selectin and platelet-selectin were measured using an ELISA technique. RESULTS: We studied 91 patients (M/F = 73/18, mean age 62 +/- 11 years, 56 UA and 35 NQMI) and 24 controls (M/F = 18/6, mean age 56 +/- 12 years). Levels of all four soluble CAMs were significantly elevated in both UA and NQMI patients at presentation, three and six months in comparison with controls. Levels in UA and NQMI groups fell between six and 12 months after initial presentation. CONCLUSIONS: The results suggest that the inflammatory stimulus triggering expression of CAMs is sustained for up to six months after presentation with either UA or NQMI and then returns toward control values over the following six months.

Angina, Unstable↗

Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement.

OBJECTIVES: We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. BACKGROUND: Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. METHODS: Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. RESULTS: The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). CONCLUSIONS: Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.

Aged↗

Leg length discrepancy--an experimental study of compensatory changes in three dimensions using gait analysis.

Patients with leg length discrepancy (LLD) develop compensatory mechanisms, which result in kinematic alterations in the lower limbs and pelvis. We investigated these compensatory mechanisms. Seven normal subjects underwent three-dimensional (3-D) gait analysis using a CODA MPX 30(R) analyser. The subjects were fitted with raises of varying heights to one lower limb and then analysed in static and dynamic modes. Pelvic obliquity was the most common mechanism used to compensate for small degrees of leg length discrepancy up to 2.2 cm, particularly in static standing. With larger degrees of discrepancy, the subjects developed flexion of the knee of the longer leg. Compensatory mechanisms during walking were more complex and included a combination of kinematic changes at the pelvis, knee and ankle. We developed mathematical models for the compensatory mechanisms at all the three levels. We conclude that 3-D gait analysis is a useful tool in the assessment of patients with functional and structural leg length discrepancies.

Adaptation, Physiological↗

Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using thromboelastography.

Amide local anaesthetics inhibit platelet function. We hypothesized that residual anaesthetic in the epidural space could decrease efficacy of an epidural blood patch in preventing postdural puncture headache. Levobupivacaine has recently been approved for epidural anaesthesia. Its effects on coagulation have not previously been studied. The aim of this study was to determine the effects of levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG analyser. Whole blood, a 50% saline control and two levobupivacaine solutions (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former reproduces that produced in the epidural space by blood (20 mL for an epidural blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P < 0.05 was considered significant. Maximum amplitude (MA), a measure of clot strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural blood patch.

Adult↗

A nurse practitioner-led farmers' health service: setting up and evaluating a UK project.

The farming community in the UK have significant unmet health-care needs that have traditionally remained invisible. The project that is the subject of this paper is an attempt to improve access to health care for farmers and make their needs visible. It is based in an upland area of England and involves two nurse practitioners (NPs) and two support workers who provide health care for the farming community. The main targets of the project are farm accidents, mental health and occupational diseases. The NPs visit farms, on request, for consultations and also attend auction marts, agricultural shows and other farmers' meetings. Evaluation is by a telephone follow-up interview with a sample of clients seen by the NP, who will be compared with a group from a similar area who do not receive the service. A farm accident survey is underway, case notes are being audited and the NPs are keeping a reflective diary as further sources of data.

Accidents, Occupational↗

Funding issues for Victorian hospitals: the risk-adjusted vision beyond casemix funding.

This paper discusses casemix funding issues in Victoria impacting on teaching hospitals. For casemix payments to be acceptable, the average price and cost weights must be set at an appropriate standard. The average price is based on a normative, policy basis rather than benchmarking. The 'averaging principle' inherent in cost weights has resulted in some AN-DRG weights being too low for teaching hospitals that are key State-wide providers of high complexity services such as neurosurgery and trauma. Casemix data have been analysed using international risk adjustment methodologies to successfully negotiate with the Victorian State Government for specified grants for several high complexity AN-DRGs. A risk-adjusted capitation funding model has also been developed for cystic fibrosis patients treated by The Alfred, called an Australian Health Maintenance Organisation (AHMO). This will facilitate the development of similar models by both the Victorian and Federal governments.

Benchmarking↗

A perspective of pesticide residue variability and acute dietary risk assessment.

The question of the variability of pesticide residues and acute risk assessment has arisen in the context of the work of the European Commission's Scientific Committee for Plants (SCP). A brief outline is presented of European Community legislation on pesticide residues and the authorization of plant protection products. It is stated that although chronic risk assessment is systematically carried out in connection with the fixing of Community MRLs, the same has not applied for acute risk assessment. The reasons for this situation have been the absence of an agreed methodology, acute reference dose (RfD) and adequate dietary and residue data. It is stated that in the opinion of the Scientific Committee for Plants an acute risk assessment should be considered on a routine basis and that steps should be taken to ensure the availability of the necessary data. Possible implications for risk communication and the authorization of plant protection products in the EC are also discussed.

Consumer Product Safety↗

Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting.

BACKGROUND: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. DESIGN: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. RESULTS: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P: < 0.0001) and women (r = 0.84, P: < 0.0001). FFM(BIA) and FFM(DXA) were significantly different (P: < 0.01 in men and P: < 0.0001 in women). The difference between FFM(DXA) and FFM(BIA) was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P: = 0.001 for weight; r = -0.60, P: < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. CONCLUSIONS: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting. BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting.

Absorptiometry, Photon↗