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Biomedical subjects

G L Rubin

Publications and source records attributed to G L Rubin.

At least 19 recordsLinked to original sources

Seasonality of coronary artery deaths in New South Wales, Australia.

BACKGROUND: Complex temporal variations in coronary deaths, including diurnal, weekly, and seasonal trends, have been reported worldwide. OBJECTIVE: To describe the magnitude of seasonal changes in coronary artery deaths in New South Wales, Australia. DESIGN: Hospital morbidity data, mortality statistics, and meteorological data were modelled using time series techniques to determine seasonality of coronary deaths. Data were also analysed to determine whether there was an increase in deaths before or after the Christmas and New Year holidays. RESULTS: A clear seasonality of coronary deaths was shown, with a peak in July. A mean of 2.8 excess coronary deaths per 100 deaths was estimated to occur from June to August each year, with a mean annual excess of 224 winter deaths a year. Mortality data did not show an increase in coronary death ratios before (p = 0.626) or after (p = 0.813) the Christmas and New Year holidays in December. CONCLUSIONS: There is a higher incidence of coronary deaths in winter, which may reflect winter respiratory infections, the direct effect of cold, seasonal changes in lipid concentration, and other factors associated with winter. Hospitals should have contingency plans during the winter months to manage larger numbers of cardiac admissions.

Coronary Artery Disease↗

Appropriateness of red blood cell transfusions in major urban hospitals and effectiveness of an intervention.

OBJECTIVES: To assess the appropriateness of red blood cell (RBC) transfusions and the effectiveness of an intervention to reduce inappropriate RBC transfusions. DESIGN: Medical record audit by hospital staff using a data form, before and after randomly allocated interventions (letter only or letter+visit). Criteria for assessing appropriateness of RBC transfusions were based on a systematic literature review. SETTING: Ten major urban hospitals in Sydney, New South Wales, in 1998 and 1999. SUBJECTS: Medical records of up to 120 patients at each hospital (n=1117). INTERVENTIONS: Letter-only (5 hospitals)--results of first audit at the hospital mailed to chief executive officer of that hospital; letter+visit (5 hospitals) results of first audit at the hospital presented by the research team to a meeting of that hospital's staff, and then mailed to the chief executive officer. MAIN OUTCOME MEASURE: Proportion of RBC transfusions assessed as inappropriate. RESULTS: At first audit, 35% of RBC transfusions were assessed as inappropriate. Small reductions in inappropriate transfusions were found at the second audit, but the change was significant only for the hospitals receiving the letter-only intervention. About 5% of patients received a single RBC unit; 40% of single-unit transfusions were inappropriate. More RBC transfusions were inappropriate in surgical patients than in those treated by other specialties. CONCLUSIONS: About a third of RBC transfusions were assessed as inappropriate. The interventions had only a small effect on transfusion appropriateness.

Aged↗

Folate fortification: potential impact on folate intake in an older population.

OBJECTIVE: To examine the potential impact of different models of folate fortification of Australian foods on the folate intakes of older Australians. DESIGN: Dietary data were collected using a food frequency questionnaire from people attending a population-based health study. SETTING: Two postcode areas west of Sydney, Australia. SUBJECTS: A total of 2895 people aged over 49 y, obtained from a door knock census (79% of 3654 subjects examined). MAIN OUTCOME MEASURES: The folate intake in this population was estimated using four different models: (1) pre-fortification folate values; (2) current voluntary folate fortification in Australia; (3) universal fortification of all foods permitted to add folate, at 25% recommended dietary intake (RDI) per reference serve; and (4) universal fortification of all foods permitted to add folate, at 50% RDI per reference serve. The increased bioavailability of synthetic folic acid (SFA) was included in the analysis. RESULTS: At current voluntary folate fortification, approximately 65% of this population consume 320 microg dietary folate equivalents (DFE) or more per day from diet and supplements, and 0.4% (n=10) consume greater than the recommended upper safety level of 1000 microg from SFA. More than 95% of this older population would be expected to consume more than 320 microg DFE from diet and supplements with universal fortification at 50% of the RDI, and 0.5% (n=14) may consume greater than 1000 microg/day of SFA. CONCLUSIONS: There is unlikely to be a large increase in the proportion of older persons who are likely to consume more than the upper safety level of intake with universal folate fortification. As most of those who currently or are predicted to consume over 1000 microg SFA take supplements containing folic acid, it is highly recommended that vitamin B12 be included in any vitamin supplements containing folate. SPONSORSHIP: This study was supported by the Australian National Health and Medical Research Council (NHMRC).

Aged↗

Peroxisome proliferator-activated receptor gamma ligands inhibit estrogen biosynthesis in human breast adipose tissue: possible implications for breast cancer therapy.

Estrogen biosynthesis is catalyzed by aromatase cytochrome P-450 (the product of the CYP19 gene). Adipose tissue is the major site of estrogen biosynthesis in postmenopausal women, with the local production of estrogen in breast adipose tissue implicated in the development of breast cancer. In human adipose tissue, aromatase is primarily expressed in the mesenchymal stromal cells and is a marker of the undifferentiated preadipocyte phenotype. Aromatase expression in adipose tissue is regulated via the distal promoter I.4, under the control of glucocorticoids and class I cytokines such as oncostatin M, interleukin 6, and interleukin 11, as well as tumor necrosis factor alpha. These cytokines, which are expressed in adipose, also inhibit adipocyte differentiation. Therefore, we hypothesized that factors which stimulate adipocyte differentiation should inhibit aromatase expression. These factors include synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligands such as thiazolidinediones, e.g., troglitazone and rosiglitazone (BRL49653) and the endogenous PPARgamma ligand 15-deoxy-delta12,14-prostaglandin J2. We have demonstrated by measurement of aromatase activity and by reverse transcription-PCR/Southern blotting that these PPARgamma ligands inhibit aromatase expression in cultured breast adipose stromal cells stimulated with oncostatin M or tumor necrosis factor alpha plus dexamethasone in a concentration-dependent manner, whereas a metabolite of troglitazone that does not activate PPARgamma has no effect. We have also shown that troglitazone inhibits luciferase activity of reporter constructs containing various lengths of the upstream region of promoter I.4 transfected into mouse 3T3-L1 preadipocyte mesenchymal cells, whereas the troglitazone metabolite does not. Because local estrogen production in breast fat is implicated in breast cancer development in postmenopausal women, the actions of PPARgamma ligands suggest that they may have potential therapeutic benefit in the treatment and management of breast cancer.

Adipose Tissue↗

Getting new evidence into medicine.

The rate of transfer of the knowledge gained from health and medical research into evidence-based practice is determined by many factors. Preconditions for the uptake of new evidence are the availability of good evidence, ready access to the evidence, a supportive organisational environment, and effective mechanisms for promoting knowledge uptake. Evidence-based medicine is being promoted in Australia by a body of enthusiastic clinicians, public health practitioners and consumer advocates, supported by initiatives from national, State and local healthcare services and professional bodies. The short to medium term future of evidence-based medicine in Australia is likely to be shaped by three major factors: a reduction in cost and technical barriers which limit access to computerised databases; a trend towards shared decision-making between clinicians and patients; and increased demand for information to fill the gaps in research-based evidence on specific problems.

Australia↗

Sceptical medicine.

Explore the source record for details and available documents.

Attitude of Health Personnel↗

Regulation of sulphotransferase expression in the endometrium during the menstrual cycle, by oral contraceptives and during early pregnancy.

The endometrium plays a key role in reproduction, and this function is tightly regulated by endogenous and xenobiotic steroids. Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is a major deactivating mechanism for steroid hormones and we have investigated the expression and regulation in vivo of SULT in the human endometrium. In the normal cycling endometrium, expression of the phenol sulphotransferases SULT1A1 and SULT1A3 and the oestrogen sulphotransferase SULT1E1 were observed, with SULT1A1 and SULT1E1 expression being higher in the luteal phase than in the follicular phase. No expression of the hydroxysteroid sulphotransferase SULT2A1 was detected at any time in the endometrium. In endometrium from women taking the combined oral contraceptive pill (OCP), SULT1E1 expression was virtually absent, and SULT1A1 expression was substantially reduced. Similarly, in early pregnancy (i.e. first trimester) endometrium, SULT1E1 expression was absent, although SULT1A1 and SULT1A3 expression were unaffected. Our results with normal endometrium support in-vitro data showing that SULT1E1 expression is regulated by progesterone. However, the data obtained from OCP and early pregnancy endometrium suggest that factors other than the concentration of circulating progesterone are involved in the regulation of the expression of this important enzyme in the endometrium.

Adult↗

Design, production and characterization of antibodies discriminating between the phenol- and monoamine-sulphating forms of human phenol sulphotransferase.

1. Phenol sulphotransferases (PSTs) are important enzymes in xenobiotic and endobiotic detoxication, and a key component of the body's chemical defence mechanism. 2. Human phenol-(P-PST) and monoamine-(M-PST) sulphating forms of PST share 93% amino acid sequence identity, and to date the various antibodies produced against PSTs all recognize both enzymes. 3. We have identified two peptides based on the cDNA-derived amino acid sequences of human P-PST and M-PST, which elicited for the first time antibodies capable of discriminating between these highly homologous enzymes. 4. These antibodies represent valuable tools for studying the expression, distribution and function of human phenol sulphotransferases.

Amino Acid Sequence↗

Reduced platelet phenolsulphotransferase activity towards dopamine and 5-hydroxytryptamine in migraine.

OBJECTIVE: The sulphation of the neurotransmitters dopamine and 5-hydroxytryptamine, and of the prototypical xenobiotic 4-nitrophenol, by phenolsulphotransferases was measured in platelet homogenates prepared from a group of migraine sufferers and a group of control subjects. RESULTS: The activity of the M form of phenolsulphotransferase, responsible for the sulphation of dopamine and 5-hydroxytryptamine was significantly reduced in the migraine population, by 28% with dopamine as substrate and by 20% with 5-hydroxytryptamine. The activity of the P form of the enzyme towards 4-nitrophenol was the same in both groups. We also report that the selective inhibition of P form phenolsulphotransferase by red wine is much more potent than previously thought, with a 2000-fold dilution of dealcoholised red wine having the ability to inhibit sulphation by this enzyme by 50%. CONCLUSION: Our findings suggest that a reduced capacity for sulphation and inactivation of biogenic amines and catecholamines may be related to susceptibility to migraine.

Adult↗

Assessing utilisation of health technologies: coronary artery bypass graft surgery in New South Wales.

The New South Wales health system aims to provide the most effective and efficient health care in a context of scarce resources and increasing availability of expensive technologies. The aging of the population and the management of chronic disease place further demands on the health system. Examination of the pattern of provision of services over time and between groups can serve to illustrate trends in clinical management practices which may affect other elements of the health system. In this paper we report an evaluation of the patterns of coronary artery bypass graft surgery (CABG) in New South Wales, within subgroups of the population and over time. The results demonstrate increased utilisation of this procedure in the population over recent years, particularly among the older age groups. We found differences in procedure rates between geographic areas which suggest that there are differences in the management of ischaemic heart disease between population subgroups. These patterns are examined in the context of the available literature on the health outcomes of CABG relative to other management options for ischaemic heart disease.

Adult↗

Diagnostic procedures and health outcomes. Upper gastrointestinal tract investigations in the elderly.

OBJECTIVES: To examine the use of upper gastrointestinal endoscopy in people 65 years of age and over in New South Wales, and compare its use between geographic areas, sex and age groups. Also, to investigate the relationship between endoscopy use and peptic ulcer mortality. DESIGN: A retrospective review of upper gastrointestinal tract (GIT) endoscopy hospital separation data for NSW from 1986 to 1989-1990 and peptic ulcer mortality data from 1979 to 1989. MAIN OUTCOME MEASURES: Rates per 1000 population aged 65 years and over were calculated for upper GIT endoscopy for each of the four-year age groups and by sex. Peptic ulcer and other digestive system disease rates for endoscopy patients were determined. Correlations between hospital standardised separation rates for endoscopy and standardised mortality rates for gastric cancer and peptic ulcers were calculated. Age and sex standardised death rates were calculated for each year between 1979 and 1989, and changes in death rates over time were determined by regression analysis. RESULTS: The rate of endoscopies increased significantly (P < 0.001) over the period 1986 to 1989-1990, with the highest rate and greatest increase occurring in patients aged 70 years and over. Men had significantly higher endoscopy rates than women (P < 0.001). Geographic variations in the use of endoscopy were found and were not explained by geographic differences in the proportion of peptic ulcers diagnosed, deaths from peptic ulcers or malignant neoplasms. Despite the increase in endoscopies performed, there was no corresponding significant increase in the rate of peptic ulcers detected. Between 1979 and 1989 peptic ulcer mortality rates for women over 74 years of age increased significantly (P < 0.05); the rate for men did not change. CONCLUSION: Many endoscopies are performed in people aged 65 years and over in NSW and there has been a substantial increase in endoscopy rates in recent years. While the increase in upper GIT endoscopy may have resulted in a number of health benefits, it does not appear to have resulted in a reduction in peptic ulcer related mortality.

Aged↗

Variation in selected childhood surgical procedures: the case of tonsillectomy and management of middle ear disease.

We examined rates of the most common ear, nose and throat (ENT) surgical procedures among NSW residents under 15 years of age, against a background of concern for the relevance of differences in clinical practice to cost and quality of health care. We found significant (P < 0.01) increases in the rate of procedures involving myringotomy (from 5.8/1000 to 7.6/1000) or adenoidectomy (from 5.6/1000 to 6.3/1000) between 1986 and 1989/90. Over this period the proportion of ENT procedures which involved myringotomy also increased significantly (P < 0.01) from 53 to 60%. We found significant (P < 0.01) differences in procedural rates between health areas when aggregated into inner and outer metropolitan and rural groups with the mean rate of procedures involving myringotomy highest in the outer metropolitan group in both years. The difference was not due to variation in patient insurance status, per capita hospital bed or staff numbers. We found no evidence that the National Health and Medical Research Council Tonsillectomy and Adenoidectomy Guidelines (first published in 1982) have been effective in influencing clinical practice. The rate of tonsillectomy had been declining in NSW since the late 1970s but has remained stable in recent years. Surgical intervention for middle ear disease is increasing.

Adenoidectomy↗

An outbreak of Norwalk-like gastroenteritis associated with contaminated drinking water at a caravan park.

During the 1989 Christmas holiday period, a large outbreak of gastroenteritis occurred among persons staying at a caravan park in southern New South Wales. Review of local hospital records found that 77 per cent of patients presenting with infective diarrhoea between 29 December and 3 January had stayed at the caravan park. In a retrospective cohort study we compared rates of illness among caravan park patrons exposed to different water sources. Stools were tested for pathogens and convalescent sera for viral antibodies. Rain and reticulated river water sampled from the caravan park were tested for bacteria and viruses. Of 351 persons interviewed at the caravan park, 305 (87 per cent) reported an illness characterised by diarrhoea, vomiting and abdominal pain. Of 196 persons who used reticulated river water for drinking or ablutions, 175 (89 per cent) became ill compared with 47 of 72 persons (65 per cent) who did not use this water (relative risk 1.4, 95 per cent confidence interval 1.2 to 1.6). The outbreak was probably caused by a 27-28 nm small round structured virus found in the stool from one ill person. High levels of faecal coliforms in the reticulated river water and enterovirus in sediment samples suggest that the outbreak was caused by sewage contaminating the reticulated river water through a break in the pipe directly over the underground water tanks. To prevent such outbreaks, poor water and sewerage system layouts should be avoided and nonpotable water should be clearly labelled. Where feasible, all camping-ground water should stem from town supplies.

Abdominal Pain↗

The health effects of swimming at Sydney beaches. The Sydney Beach Users Study Advisory Group.

OBJECTIVES: The purpose of the study was to determine the health risks of swimming at ocean beaches in Sydney, Australia. METHODS: From people attending 12 Sydney beaches in the period from December 5, 1989 to February 26, 1990, we recruited a cohort of 8413 adults who agreed to participate in this study. Of these, 4424 were excluded either because they had been swimming in the previous 5 days or because they reported a current illness. Of the remainder, 2839 successfully completed a follow-up telephone interview conducted within 10 days after recruitment. We recorded reported respiratory, gastrointestinal, eye, and ear symptoms and fever that occurred within the 10 days between initial interview on the beach and the follow-up interview. RESULTS: A total of 683 participants (24.0%) reported experiencing symptoms in the 10 days following initial interview. Of these, 435 (63.7%) reported respiratory symptoms. Swimmers were almost twice as likely as nonswimmers to report symptoms. There was a linear relationship between water pollution and all reported symptoms with the exception of gastrointestinal complaints. CONCLUSIONS: Swimmers at Sydney ocean beaches are more likely to report respiratory, ear, and eye symptoms than beachgoers who do not swim. The incidence of these symptoms increases slightly with increasing levels of pollution.

Adolescent↗

Mycobacterial disease and AIDS in New South Wales.

OBJECTIVE: To determine the coincidence of mycobacterial disease and acquired immunodeficiency syndrome (AIDS), and whether persons with mycobacterial disease and human immunodeficiency virus (HIV) infection differ from those with mycobacterial disease alone, by age, sex and country of birth. DESIGN: A descriptive study. PARTICIPANTS: Persons on the NSW Tuberculosis Register in 1989 and those on the NSW AIDS database in 1982-1989. MAIN OUTCOME MEASURE: Coincident appearance on the Tuberculosis Register and the AIDS database. RESULTS: People with atypical mycobacterial infection and HIV infection were younger and more likely to be male compared with those with mycobacterial disease alone. There was a strong association between mycobacterial disease and HIV infection. Of 438 patients newly diagnosed with mycobacterial disease in 1989, 75 (17.1%) had HIV infection. Of 318 tuberculosis patients, 8 (2.5%) had HIV infection, and of 120 patients with atypical mycobacterial infection, 67 (55.8%) had HIV infection. CONCLUSION: Close monitoring of HIV patients for mycobacterial infection, and chemoprophylaxis for persons infected with HIV who have positive Mantoux test results will assist in the control of mycobacterial disease. HIV testing and counselling should be considered for all persons with mycobacterial disease.

Acquired Immunodeficiency Syndrome↗

Rabies case in New South Wales, 1990: public health aspects.

OBJECTIVES: To identify the source of rabies in the recent case in New South Wales, and to determine the need for post-exposure rabies prophylaxis among contacts of the patient. DESIGN: Information was obtained by face-to-face interview of the dead girl's family and face-to-face and telephone interviews using a questionnaire of health care workers. Other information was gathered from overseas and local sources through telephone and facsimile contact. RESULTS: The girl had migrated from Vietnam in 1984 to Hong Kong, and from there in 1986 to Australia. No evidence of contact with a rabid animal in Australia or Hong Kong was found. There had also been no organ donations from the girl. Four health care workers were given post-exposure rabies prophylaxis. CONCLUSIONS: Because of the lack of evidence of animal contact in Australia and the fact that extremely long incubation periods for rabies have been documented, it was considered that the most likely source of the rabies virus was North Vietnam. Genetic studies of the virus also supported a South-East Asian source. Nevertheless the presumed incubation period--at least six years and four months--is one of the longest recorded.

Animals↗