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Biomedical subjects

S Hirst

Publications and source records attributed to S Hirst.

At least 19 recordsLinked to original sources

Regional variation in ICC distribution, pacemaking activity and neural responses in the longitudinal muscle of the murine stomach.

Intramuscular interstitial cells of Cajal (ICC-IM) play a critical role in enteric neural regulation of the circular muscle layer in the stomach, but no studies have been performed on the longitudinal layer. Kit immunohistochemistry was used to examine ICC-IM in the longitudinal muscle layer of the murine corpus and antrum, and it revealed marked heterogeneity in the distribution of ICC-IM in longitudinal muscles. In the corpus, ICC-IM were found along the greater curvature near the fundus. ICC-IM decreased in density in the circumferential axis toward the lesser curvature and in the longitudinal axis toward the antrum. ICC-IM were absent from the longitudinal layer of the antrum. Double labelling with markers for specific classes of enteric motor neurones revealed that cholinergic and nitrergic motor neurones formed close contacts with ICC-IM in the corpus but not in the antrum. Enteric nerve stimulation evoked prominent cholinergic excitatory and nitrergic inhibitory responses in longitudinal muscles of the corpus, but not in the antrum of wild-type animals. Cholinergic and nitrergic nerves were also present in W/W(V) mice, but functional innervation of the longitudinal muscle layer by these nerves in the corpus and antrum were absent. The data show that cholinergic and nitrergic neurotransmission only occurs in the gastric longitudinal layer in regions where ICC-IM are present. In regions, such as the corpus, where ICC-IM are common, robust neural responses are present, but the reduced density of ICC-IM near the lesser curvature and in the distal stomach leads to reduced neural regulation in these gastric regions.

Animals↗

Quality of care for women presenting with benign breast conditions.

The aim of the study was to investigate the management of women with benign breast problems. A consecutive sample of women (n = 194) was assessed who presented to public or private sector providers. The main reasons for referral were breast lumps (62%); 56% of women who attended the public sector did not receive any recommendation compared to 40% who attended the private sector and clinical/general practitioner reviews were recommended to more women in the private sector (54%). Reasons for the discrepancy between public and private patients require further investigation.

Australia↗

Release of biologically active TGF-beta from airway smooth muscle cells induces autocrine synthesis of collagen.

In severe or chronic asthma, there is an increase in airway smooth muscle cell (ASMC) mass as well as an increase in connective tissue proteins in the smooth muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in three isoforms in mammals and is a potent regulator of connective tissue protein synthesis. Using immunohistochemistry, we had previously demonstrated that ASMCs contain large quantities of TGF-beta1-3. In this study, we demonstrate that bovine ASMC-derived TGF-beta associates with the TGF-beta latency binding protein-1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1 localizes TGF-beta extracellularly. Furthermore, plasmin, a serine protease, regulates the secretion of a biologically active form of TGF-beta by ASMCs as well as the release of extracellular TGF-beta. The biologically active TGF-beta released by plasmin induces ASMCs to synthesize collagen I in an autocrine manner. The autocrine induction of collagen expression by ASMCs may contribute to the irreversible fibrosis and remodeling seen in the airways of some asthmatics.

Animals↗

A new name for parasitology today

Parasitology Today is officially the Number One ranked journal in parasitology (impact factor 4.940). Since its launch in 1985, Parasitology Today has been part of the Trends Journal series - the most highly cited group of monthly review journals in the world, that includes Trends in Biochemical Sciences, Trends in Microbiology, Trends in Genetics, Immunology Today and Trends in Cell Biology.

Journal Article↗

Indolocarbazoles: potent and selective inhibitors of platelet-derived growth factor receptor autophosphorylation.

A quantitative assay for measuring the autophosphorylation of platelet-derived growth factor (PDGF) receptors in intact vascular smooth muscle cells has been developed and used to screen for novel tyrosine kinase (TK) inhibitors. Several novel inhibitors of PDGF receptor autophosphorylation have been identified from the indolocarbazole series, including the 3,9 dimethoxy derivative, 3744W (IC50 = 14.5+/-2 nM). Tested against a panel of tyrosine and serine/threonine kinases, 3744W is at least 1,000 fold selective for the PDGF receptor tyrosine kinase and was found to inhibit autophosphorylation of both the alpha and beta isoforms of the PDGF receptor in human smooth muscle cells. PDGF-BB-stimulated DNA synthesis in quiescent cultures of human smooth muscle cells was blocked in a concentration-dependent manner by 3744W, IC50 = 10 nM. Binding studies showed that 3744W did not block the binding of PDGF-BB to cell surface receptors on human airway smooth muscle cells. Furthermore, inhibition of bone marrow stem cell proliferation by 3744W was only observed at concentrations 100-1,000 times greater than those needed to block PDGF-driven DNA synthesis in human smooth muscle cells. 3744W represents a novel, potent and selective inhibitor of PDGF receptor autophosphorylation and a powerful biochemical probe for investigating PDGF-dependent responses in vitro.

Animals↗

Consulting about priorities for the NHMRC National Breast Cancer Centre: how good is the nominal group technique.

The National Health and Medical Research Council National Breast Cancer Centre was established to improve outcomes for women by reviewing the literature, developing best practice guidelines and resources and developing a national monitoring system. Its broad terms of reference meant that it was important at the outset to identify priorities for action. The Centre used a national consultative process based on nominal groups to identify priorities. Thirteen consultative workshops were held with over 300 participants including women diagnosed with breast cancer, some of their families and health professionals. There was a high level of agreement between workshops in priorities identified, indicating that the nominal group process results in reliable data. A sub-sample of participants surveyed after the workshops reported being highly satisfied with their participation in the process. The findings indicate that the nominal group process can be useful in selecting priorities for action in health.

Academies and Institutes↗

Effect of ethnic media on cervical cancer screening rates.

The effect on cervical screening rates of paid publicity on ethnic radio was evaluated. The radio publicity occurred during three discrete periods between 1992 and 1994. The numbers of women having Pap smears before and after the intervention were compared in postcode areas with high and low percentages of residents of non-English-speaking background. During the second and third publicity periods, when the media coverage was more intense, a larger increase in screening rates was evident in postcode areas with high percentages of women of non-English-speaking background. Across the three intervention periods, the media publicity appeared to generate an additional 6.7 per cent (95 per cent confidence interval 4.4 to 9.2 per cent) increase in screening in areas with a high proportion of women of non-English-speaking-background compared with changes in screening in areas with a low proportion of women of non-English-speaking background. Paid publicity on ethnic radio may be an effective strategy to increase cervical screening rates among women of non-English-speaking background.

Female↗

An evaluation of educational outreach to general practitioners as part of a statewide cervical screening program.

OBJECTIVES: The purpose of this study was to determine the acceptability, effectiveness, and cost of a face-to-face educational outreach intervention in the context of a program aimed at increasing cervical screening in Victoria, Australia. METHODS: All identified general practitioners in a specified intervention area were offered a visit by a general practitioner educator. Practitioners completed a questionnaire evaluating the acceptability of the visit. Odds ratios for a woman being screened in the 3 months following the visits were determined. RESULTS: Fifty-nine general practitioners (69.4%) accepted the offer of a visit. Most found both the process and the content of the intervention to be acceptable. The intervention and nonintervention regions did not differ either before or after the intervention. In both regions, there was a statistically significant increase in number of Pap tests performed. There was no difference in the change in screening between the two regions. Costs were estimated at Au$34 per general practitioner visited. CONCLUSIONS: This strategy cannot be recommended for widespread use in a cervical screening program.

Adult↗

Development and evaluation of a novel patient information system.

A comprehensive patient information datafile of 320 topics has been developed, subserving the domains of medicine, surgery, gynaecology and paediatrics. The system was designed as loose-leaf sheets capable of being photocopied, as well as a computer-based datafile. In a four-practice study, 73% of consecutive general practice attenders could be issued with the relevant disorder or procedure information sheet. With a questionnaire return rate of 79%, 886 patients rated the three criteria of readability, understandability and usefulness of their leaflets as very or quite easy and very or quite useful in more than 94% of instances. This system could be a valuable adjunct to patient education in both general and hospital practice settings.

Family Practice↗

Fetal growth and insulin secretion in adult life.

Recent studies suggest that NIDDM is linked with reduced fetal and infant growth. Observations on malnourished infants and studies of experimental animals exposed to protein energy or protein deficiency in fetal or early neonatal life suggest that the basis of this link could lie in the detrimental effects of poor early nutrition on the development of the beta cells of the islets of Langerhans. To test this hypothesis we have measured insulin secretion following an IVGTT in a sample of 82 normoglycaemic and 23 glucose intolerant subjects who were born in Preston, England, and whose birthweight and body size had been recorded at birth. The subjects with impaired glucose tolerance had lower first phase insulin secretion than the normoglycaemic subjects (mean plasma insulin concentrations 3 min after intravenous glucose 416 vs 564 pmol/l, p = 0.04). Insulin secretion was higher in men than women (601 vs 457 pmol/l, p = 0.02) and correlated with fasting insulin level (p = 0.04). However, there was no relationship between insulin secretion and the measurements of prenatal growth in either the normoglycaemic or glucose intolerant subjects. These results argue against a major role for defective insulin secretion as a cause of glucose intolerance in adults who were growth retarded in prenatal life.

Blood Glucose↗

Thinness at birth and insulin resistance in adult life.

Type 2 (non-insulin-dependent) diabetes mellitus may originate through impaired development in fetal life. Both insulin deficiency and resistance to the action of insulin are thought to be important in its pathogenesis. Although there is evidence that impaired fetal development may result in insulin deficiency, it is not known whether insulin resistance could also be a consequence of reduced early growth. Insulin resistance was therefore measured in 81 normoglycaemic subjects, and 22 subjects with impaired glucose tolerance, who were born in Preston, UK, between 1935 and 1943. Their birth measurements had been recorded in detail. Insulin resistance was measured by the insulin tolerance test which uses the rate of fall in blood glucose concentrations after intravenous injection of insulin as an index of insulin resistance. Men and women who were thin at birth, as measured by a low ponderal index, were more insulin resistant. The association was statistically significant (p = 0.01) and independent of duration of gestation, adult body mass index and waist to hip ratio and of confounding variables including social class at birth or currently. Thinness at birth and in adult life has opposing effects such that resistance fell with increasing ponderal index at birth but rose with increasing adult body mass index. It is concluded that insulin resistance is associated with impaired development in fetal life.

Adult↗

Reproducibility of the short insulin tolerance test.

The short insulin tolerance test is a simple method of estimating insulin resistance by measuring the rate of fall of blood glucose following the intravenous administration of insulin. To determine its reproducibility, 18 healthy subjects underwent duplicate insulin tolerance tests separated by at least 1 week. Intravenous insulin (0.05 units kg-1) was administered into an antecubital vein and arterialized venous samples were obtained from a retrogradely cannulated vein on the dorsum of the hand on the same side. The test was terminated with an intravenous glucose injection 15 min after the administration of insulin. The mean whole blood glucose concentration fell from 4.6 mmol l-1 to 2.8 mmol l-1 while plasma insulin concentrations rose to supraphysiological levels and declined exponentially. The glucose disappearance rate (Kitt) calculated from the slope of the fall in log transformed blood glucose between 3 and 15 min after insulin injection ranged from 2.1 to 6.5 (mean 4.4) % min-1 during the first visit and 1.7 to 7.4 (mean 4.4) % min-1 during the second. The ratio of the within-subject to between-subject variance of the test was 0.24, the within-subject coefficient of variation was 13% and the between-subject coefficient of variation 26%. The short insulin tolerance test is reproducible and could be used to measure insulin resistance in large-scale epidemiological studies.

Adult↗

Barriers to cervical screening in older women.

OBJECTIVE: To explore the reasons why some older women do not have regular Papanicolaou smear tests. SETTING: The Ballarat region of Victoria. DESIGN AND METHOD: Cross-sectional survey administered by telephone interview. SAMPLE: Three hundred and forty-seven women aged 40 to 70. RESULTS: 1. 41% of women had not had a Papanicolaou smear test within the preceding 2 years. 2. Women who agreed with the statement that healthy women do not need to have Papanicolaou tests were six times more likely to be overdue for a Papanicolaou test than women who did not agree. 3. Being over 60 significantly increased the likelihood that a woman would be overdue for a Papanicolaou test, compared with younger women. 4. Women who thought that the test is only needed at intervals of 3 years or more were over six times more likely to be overdue than women who believed the interval to be 2 years or less. 5. Women who perceived themselves as being too embarrassed were nearly seven times more likely to be overdue than women who claimed no embarrassment. 6. Women who saw themselves as being too busy to have the test were three times more likely to be overdue than women who did not see themselves this way. 7. Women with a spouse were less likely to be overdue than other women. 8. Women who knew to start having Papanicolaou tests when they were sexually active were less likely to be overdue than women who did not know this. CONCLUSION: Many of these barriers can be overcome by the clinician in routine practice.

Adult↗

Cervical cancer screening: a comparison of recruitment strategies among older women.

OBJECTIVE: To compare the effectiveness of different recruitment strategies in encouraging older women to have a Papanicolaou (Pap) test. DESIGN: A 2 x 2 factorial study. SETTING: Two rural areas of Victoria, Australia. PARTICIPANTS: A total of 10,620 persons aged between 40 and 69 years and designated as female on electoral lists. INTERVENTIONS: A personal letter of invitation and a community-based campaign of 4 weeks' duration alone and in combination. A control group received no active intervention. OUTCOME MEASURE: The proportion of eligible women having a Pap test report issued by the Victorian Cytology Service during the 12 weeks after the intervention compared with the 12 weeks before the intervention, with an intervening two-week washout period. RESULTS: The odds ratio of an eligible woman being screened during the intervention period relative to the pre-intervention period was 3.00 for women who were exposed to the campaign and sent the letter of invitation (95% confidence interval, 2.38-3.77, P less than 0.001), 1.86 for women who were exposed to the campaign (95% confidence interval, 1.49-2.33, P less than 0.001), 1.61 for women who were sent the letter of invitation (95% confidence interval, 1.34-1.92, P less than 0.001). The baseline was a control group who received no active intervention. CONCLUSIONS: Both personal invitation letters and community-based campaigns are effective in recruiting women for Pap test screening. Combined strategies are more effective than single strategies.

Adult↗

Demographic characteristics and knowledge of BSE of women electing to attend a BSE training program in Victoria, Australia.

Participants in the Mammacheck breast self-examination (BSE) training program were surveyed to assess the characteristics of women choosing to attend BSE training sessions, as well as to assess the factors that related to their BSE practice prior to attending the session. In all, 5,673 women completed questionnaires. In comparison with the general population, women who attended Mammacheck tended to be younger, married, and more highly educated, but did not differ in relation to prior experience of breast problems. Previous BSE practice related predominantly to the amount of knowledge about BSE the women reported that they had acquired before attending a training session. The findings highlight the importance of education and raised the important question of how to teach women with lower education levels and little or no knowledge about BSE. Recommendations are made.

Adult↗

Increasing cervical screening in women of more than 40 years of age: an intervention in general practice.

An intervention that was aimed at increasing cervical screening in women of more than 40 years of age was undertaken, with general practitioners as the primary point of contact. The intervention consisted of the practice receptionist giving female patients pamphlets about Papanicolaou smear-tests and the general practitioner offering a Papanicolaou smear-test. Nineteen general practitioners and their female patients (n = 466) of more than 40 years of age who presented for consultation over a 10-day period were involved in this study. Each woman in the study was asked when she had last undergone a Papanicolaou smear-test. All women who were found to be "at risk", that is, who had not undergone a Papanicolaou smear-test in the previous two years (57% of those women who were asked) were offered cervical screening. Over-all about 50% of the women who were found to be "at risk" underwent a Papanicolaou smear-test at the general practitioner initiated request, either at the same consultation (26% of those "at risk") or on their return at a later date (23% of those "at risk"). Therefore, the intervention appears to have been effective in encouraging a relatively high-risk group of patients to undergo Papanicolaou smear-tests. However, the strategy was differentially effective depending on age: more women of less than 65 years of age underwent a Papanicolaou smear-test than did women of more than 65 years of age. The feasibility of using the intervention in everyday general practice depends on the willingness of medical practitioners to ask female patients to undergo a Papanicolaou smear-test, the ability to take a Papanicolaou smear during the consultation or soon after, and the acceptance of the invitation by women as based on an understanding of the need.

Adult↗

An evaluation of a campaign to increase cervical cancer screening in rural Victoria.

This paper reports on the second of four regionally-based campaigns co-ordinated in rural Victoria by the Anti-Cancer Council of Victoria. The campaign encompassed community-based activities, general practitioner involvement and screening clinics. The impact of the campaign on Pap test rates and on the profile of women whose tests were reported by the Victorian Cytology Gynaecological Service is examined. We conclude that the campaign was successful in achieving its primary objective of attracting older and relatively underscreened women into having a Pap test. The special screening clinics were considered particularly effective in reaching women in the target audience. As a result of this campaign, new initiatives, were incorporated into subsequent programs.

Adult↗