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Biomedical subjects

P Harvey

Publications and source records attributed to P Harvey.

At least 19 recordsLinked to original sources
PubMed2002

Five year results of a prospective very low calorie diet or conventional weight loss programme in type 2 diabetes.

AIMS: To complete 5-year follow-up of an intensive weight loss programme in established type 2 diabetic subjects. METHODS: Forty-five obese type 2 diabetic subjects, Body mass index (BMI) > 30, expressed interest in an intensive weight loss programme. Group 1 comprised 15 who selected very low calorie diet (VLCD), Group 2, 15 selected intensive conventional diet and exercise (ICD), 15 failed to follow either programme. Group sessions of eight to 15 subjects continued weekly for 6 months, then monthly for 12 months with prospective recording at 3, 6 and 12 months and then annually of quality of life, BMI, waist/hip ratio, blood pressure, fasting blood glucose, serum fructosamine and serum lipids. RESULTS: Weight loss was slower in the intensive conventional diet group than in the VLCD group, but better maintained at 5 years: group 1, 4.8 +/- 6 kg; group 2, 8.9 +/- 4 kg. In the intensive conventional diet group, 5 year high-density lipoprotein cholesterol was increased 1.78 +/- 0.26 mmol L-1 vs. 1.10 +/- 0.32 mmol L-1 at baseline, and diastolic blood pressure reduced 74.5 +/- 13.3 vs. 85.5 +/- 13.3 at baseline, both P < 0.05. CONCLUSIONS: Out-patient VLCD treatment proved safe and effective in overweight diabetic subjects but those who chose conventional diet and exercise had a slower but more sustained weight loss. Diabetic patients willing to attempt VLCD may safely lose sufficient weight to allow major surgery, but weight regain is inevitable. Patients willing to undertake a long-term group programme of conventional diet can sustain significant weight loss for 5 years, but still require antidiabetic medication.

Adult↗
PubMed2001

HGF/SF induces mesothelial cell migration and proliferation by autocrine and paracrine pathways.

Mesothelial repair differs from that of other epithelial-like surfaces as healing does not occur solely by centripetal in-growth of cells as a sheet from the wound margins. Mesothelial cells lose their cell-cell junctions, divide, and adopt a fibroblast-like morphology while scattering across and covering the wound surface. These features are consistent with a cellular response to hepatocyte growth factor/scatter factor (HGF/SF). In this study, we examined the ability of mesothelial cells to secrete HGF/SF and investigated its possible role as an autocrine regulator of mesothelial cell motility and proliferation. We found that human primary mesothelial cells expressed HGF/SF mRNA and secreted active HGF/SF into conditioned medium as determined by ELISA and in a scattering bioassay. These cells also expressed the HGF/SF receptor, Met, as shown by RT-PCR and by Western blot analysis and immunofluorescence. Incubation of mesothelial cells with neutralizing antibodies to HGF/SF decreased cell migration to 25% of controls, whereas addition of HGF/SF disrupted cell-cell junctions and induced scattering and enhanced mesothelial cell migration. Furthermore, HGF/SF showed a small but significant mitogenic effect on all mesothelial cell lines examined. In conclusion, HGF/SF is produced by mesothelial cells and induces both motility and proliferation of these cells. These data are consistent with HGF/SF playing an autocrine role in mesothelial healing.

Antineoplastic Agents↗
PubMed2001

Preventive social health programs: are they Australia's answer to rising health care costs in rural communities?

Although we have good evidence to support the notion that early intervention, prevention and community education programs can mitigate the impact of preventable disease, expanded primary health care is also being promoted by Australian governments as a panacea for reducing growth in demand generally. While preventive programs do reduce acute demand, they may not do so the extent that resources, currently allocated to the acute sector, can be substituted to provide the additional primary care services necessary to reduce acute demand permanently. These developments have particular relevance for rural and isolated communities where access to acute services is already very limited. What appears to be occurring, in rural South Australia at least, is that traditional acute services are being reduced and replaced with lower level care and social intervention programs. This is well and good, but eventually the acute care being provided in rural health units now will still need to be provided by other units elsewhere and probably at much higher cost to the system and to consumers. Where rural communities have previously managed much of their own acute service demand, they may now be forced to send patients to more distant centres for care but at much greater social and economic cost to individuals and the system.

Australia↗
PubMed2001

The impact of coordinated care: Eyre region, South Australia 1997-1999.

The SA HealthPlus Coordinated Care Trial in the Eyre Region began in fortuitous circumstances. First, it coincided with the completion of the Eyre Regional Health Service (ERHS) needs assessment in 1996, which highlighted outstanding health service needs and community concerns in relation to health care across the region. Second, although conceived as a formal trial, using standard research techniques, scientific processes and formal control groups to test significant differences between intervention and control groups, the trial did not conform strictly to the rules of social science or pure science and became more an exercise in action research. More significantly still, the Eyre Region became involved in the process, not so much as a way of proving a concept (the SA Health Plus hypotheses around utilisation, funding and health outcomes), but as a way of creating opportunities for change in the regional health system. If nothing else, the region stood to benefit from the implementation of the trial and involvement in the trial process. The present paper outlines the impact of the Eyre Coordinated Care Trial, not in terms of hypotheses and data analysis, but in terms of the impact of the trial processes on systems change and the evolution of an outcome-based health system. Such a system has the potential to deliver improved health outcomes to communities within existing financial resources and make much more effective use of resources by integrating care delivery and encouraging collaboration between health providers. In addition, the success of the change process in Eyre also supports the notion that change is not necessarily predicated upon scientific processes and research outcomes alone, but also upon the human and social structures associated with such endeavours. This perspective also contributes to the debate about the nature and role of science in the advancement of knowledge.

Chronic Disease↗
PubMed2001

Phenotypic and genotypic characterization of macrolide-resistant group A Streptococcus strains in the province of Quebec, Canada.

Resistance to macrolides among group A streptococci is an increasing problem worldwide. We examined 496 strains phenotypically and genotypically for resistance to erythromycin and clindamycin. Strains were isolated in five different geographical areas representing about 45% of the total Quebec population. The overall resistance rate was 4.6% but varied from 0% in rural areas to 9.4% in Montreal. Of the 23 strains showing resistance to erythromycin, 15 (65%) had an identical pulsed-field gel electrophoresis pattern, were of serotype M28T28 and harboured the erm(TR) gene, suggesting the spread of a single clone. Of the remaining eight strains, two strains had the erm(B) gene, five had the mef gene and one with a different serotype also had the erm(TR) gene.

Anti-Bacterial Agents↗
PubMed2000

Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases.

The identification of 8-ethyl-2-phenylamino-8H-pyrido[2, 3-d]pyrimidin-7-one (1) as an inhibitor of Cdk4 led to the initiation of a program to evaluate related pyrido[2, 3-d]pyrimidin-7-ones for inhibition of cyclin-dependent kinases (Cdks). Analysis of more than 60 analogues has identified some clear SAR trends that may be exploited in the design of more potent Cdk inhibitors. The most potent Cdk4 inhibitors reported in this study inhibit Cdk4 with IC(50) = 0.004 microM ([ATP] = 25 microM). X-ray crystallographic analysis of representative compounds bound to the related kinase, Cdk2, reveals that they occupy the ATP binding site. Modest selectivity between Cdks is exhibited by some compounds, and Cdk4-selective inhibitors block pRb(+) cells in the G(1)-phase of the cell division cycle.

Adenosine Triphosphate↗
PubMed2000

Use of the local lymph node assay for the estimation of relative contact allergenic potency.

The effective toxicological evaluation of skin sensitization demands that potential contact allergens are identified and that the likely risks of sensitization among exposed populations assessed. By definition, chemicals which possess the toxicological property of skin sensitization potentially are capable of causing allergic contact dermatitis (ACD) in humans. However, this hazard is not an all-or-none phenomenon; clear dose-response relationships can be discerned and thresholds identified for both the induction of sensitization and the elicitation of contact dermatitis. Commonly, these parameters are grouped under the heading of potency, determination of which is vital for risk assessment. In the present investigation, the local lymph node assay (LLNA) has been employed to determine the relative potency of a range of 20 chemicals. The parameter used is the estimated concentration required to produce a 3-fold increase in draining lymph-node cell proliferative activity, the EC3 value. These measurements have been compared with an assessment of the human sensitizing potency of the 20 selected chemicals, each being assigned to 1 of 5 classes based on their human sensitizing potency. The EC3 value, derived from LLNA work carried out in acetone/ olive oil vehicle, correlated well with the human classification, with the strongest sensitizers having low EC3 values (<O.1%), weaker sensitizers having EC3 values generally in the 1-10% range, and non-sensitizing chemicals having EC3 values in excess of 100%. In conclusion, the derivation of the EC3 for a chemical provides an objective and quantitative estimate of potency that is of considerable utility for skin sensitization risk assessment.

Allergens↗
PubMed2000

Immunoreactivity for cadherins, HGF/SF, met, and erbB-2 in pleural malignant mesotheliomas.

AIMS: To assess the immunoreactivity of malignant mesotheliomas for N- and E-cadherins, hepatocyte growth factor/scatter factor (HGF/SF) and the tyrosine kinase receptors, met and erbB-2. METHODS AND RESULTS: Pleural malignant mesotheliomas were stained using a standard indirect immunoperoxidase method applied to paraffin sections. Malignant mesotheliomas were immunoreactive for N-cadherin (26/29; 90%), met (29/29; 100%) and erbB-2 (28/29; 97%). Focal immunoreactivity was present for E-cadherin in epithelioid or mixed tumours (14/25; 56%), and for HGF/SF (9/24; 38%). CONCLUSIONS: Expression of N-cadherin supports the diagnosis of malignant mesothelioma and use of appropriate antibodies would be a useful addition to a diagnostic antibody panel. Focal staining for E-cadherin does not exclude mesothelioma. Signalling pathways mediated via met and erbB-2 may play a role in the growth and spread of malignant mesotheliomas.

Adenocarcinoma↗
PubMed2000

Hepatocyte growth factor/scatter factor enhances the invasion of mesothelioma cell lines and the expression of matrix metalloproteinases.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional factor involved both in development and tissue repair, as well as pathological processes such as cancer and metastasis. It has been identified in vivo in many types of tumours together with its tyrosine kinase receptor, Met. We show here that exogenous HGF/SF acts as a strong chemoattractant for human mesothelioma cell lines. The factor also enhanced cell adhesion to and invasion into Matrigel. The mesothelioma cell lines synthesized a panel of matrix metalloproteinases critical for tumour progression such as MMP-1, 2, 3, 9 and membrane-bound MT1-MMP. HGF/SF stimulated the expression of MMP-1, 9 and MT1-MMP and had a slight effect on expression of the MMP inhibitor TIMP-1 but not TIMP-2. However, there was no simple correlation between the levels of MMPs and TIMPs of the cell lines and their different invasion properties or between HGF/SF stimulatory effects on MMP expression and invasion. In addition, effects of protease inhibitors on invasion suggested that serine proteases were also expressed in human mesothelioma cell lines and were involved in HGF/SF-induced invasion. The results show a predominant role for HGF/SF in mesothelioma cell invasion, stimulating simultaneously adhesion, motility, invasion and regulation of MMP and TIMP levels.

Cell Adhesion↗
PubMed2000

Prevalence of non-diabetic renal disease among African-American patients with type II diabetes mellitus.

OBJECTIVE: This study aimed to characterize the prevalence of non-diabetic renal disease among African-Americans (AA) with type II diabetes mellitus based on a biopsy series. No previous study has investigated the nature of renal lesions in AA with type II DM. MATERIAL AND METHODS: Thirty AA patients with type II DM who were being managed at an inner-city hospital had kidney biopsies to evaluate suspected non-diabetic renal disease (NDRD) between 1994 and 1998. The demographic, clinical and histopathological data on these patients were analysed retrospectively. Kidney biopsies were reviewed by light microscopy, immunofluorescence and electron microscopy. RESULTS AND CONCLUSIONS: Three patterns of glomerular disease were observed. Diabetic nephropathy alone was seen in 13 patients (41.9%), diabetic nephropathy coexisted with glomerulonephritis in 12 patients (38.7%), while NDRD was seen in six patients (19.4%).

Adult↗
PubMed1999

Preferences for different sources of information about cancer.

A wide range of cancer information resources is available to patients and their relatives, who are increasingly acting as independent learners. In order to examine preferences for different types of information and to establish the appropriateness of providing a Web-based cancer information resource (CancerHelp UK) a questionnaire survey was undertaken. Of 258 questionnaires distributed to patients attending for oncology outpatient or general practice appointments, 205 (80%) were suitable for analysis. 74% (95% confidence interval 68% to 80%) of participants wanted as much information as possible. All participants cited people most frequently as a future source of cancer information. All participants frequently cited television as a source of both general and cancer-specific information. Despite a lack of computer experience patients were significantly more likely than other groups to say that they would like to use the Web-based resource. It is suggested that such resources are likely to be increasingly well used, particularly by cancer patients, given the growth in health information on the Web and developments in delivery of digital information into the home via television.

Adult↗
PubMed1999

Oestrogen and vascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in postmenopausal women. Epidemiological studies consistently suggest that oestrogen administered to postmenopausal women confers an estimated 30-50% reduction in risk of development and progression of CVD. The long term effect on the cardiovascular system of the addition of a progestogen to the replacement regimen is currently unknown. In addition, it may be argued that it remains to be proven whether the magnitude of the oestrogen-induced cardioprotective effect demonstrated in these observational studies is a real biological phenomenon. No prospective, randomised, controlled studies examining the effect of oestrogen on primary and secondary prevention of CVD have been completed. However, a large number of biologically plausible mechanisms have been identified which provide evidence to support the proposed oestrogen-induced cardioprotection. These include oestrogen mediated favourable changes in metabolic profile, in particular changes in lipid metabolism, insulin resistance and the fibrinolytic system. In addition, recent data have shown that oestrogen may affect vascular structure and function by a variety of mechanisms. It has been shown that oestrogen may induce acute and chronic coronary and cerebral vasodilation through both direct (vascular smooth muscle) and indirect (endothelium dependent) mechanisms. Oestrogen also has recently been shown to have complex anti-atherogenic and antioxidant properties. Much less is known of the vascular effects of progestogens. Progestogens currently in clinical use have androgenic properties and may attenuate the beneficial effects of oestrogen by neutralising or opposing the lipid lowering, vasodilatory and anti-atherogenic actions of oestrogen. Thus further studies are required to elucidate the effects on arterial physiology and CVD outcome of the oestrogens and progestogens of different types, doses and routes of administration which are collectively referred to as postmenopausal 'hormone replacement therapy'.

Blood Pressure↗
PubMed1999

Survival after massive ethylene glycol poisoning: role of an ethanol enriched, bicarbonate-based dialysate.

A 38-year old man presented with drowsiness 14 hours after ingesting about 1200 mls (40 ounces) of antifreeze in a suicide attempt. He was successfully treated with an ethanol enriched, bicarbonate based-dialysate. With a concomitant peripheral intravenous infusion of ethanol, this enrichment of the dialysate helped maintain the intradialytic ethanol concentration between 97-135 mg/dl over an 8 hour dialysis session. The patient developed acute tubular necrosis and required further dialysis. He made a complete recovery after three weeks and was discharged with a serum creatinine of 1.4 mg/dl.

Adult↗