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Biomedical subjects

C Browning

Publications and source records attributed to C Browning.

At least 19 recordsLinked to original sources
PubMed2002

Falls: a comparison of trends in community, hospital and mortality data in older Australians.

BACKGROUND AND AIMS: Falls are major contributors to disability, morbidity and death for older people. Frequently, falls-related data for each of these areas is viewed in isolation. The aim of this study was to establish trends in incidence of falls-related events including: community reporting of falls and falls-related injuries, hospitalizations as a result of accidental falls, and mortality related to accidental falls for older people in two states of Australia (Victoria and South Australia). METHODS: We analysed data sets for falls hospitalizations and mortality rates for the period 1988 to 1997, and from two longitudinal population-based proportional samples during the same time period. RESULTS: Age-standardised falls mortality rates have steadily declined in Victoria, and remained unchanged between 1988 and 1997 in South Australia. In both states, age-standardised falls hospitalization rates have increased significantly (in Victoria, RR=1.32, 95% CI: 1.30-1.34; and South Australia, RR=1.05, 95% CI: 1.03-1.06). In both states, there was a clear age-related effect, with those in the 85-year and older age group having a falls-related mortality rate approximately 40 times that of those aged 65-69 years, and a hospitalization rate 9 times that of those in the 65-69 age group. The community studies indicated that falls rates remain high among older Australians, and that injurious falls occurred in 10% in the first wave of data collection in each of these studies. CONCLUSIONS: The results highlight that various indicators related to falls trends taken in isolation may yield differing conclusions. For a true reflection of the effectiveness of falls prevention programs, falls-related mortality, hospitalization and community data need to be integrated. Increased focus on falls prevention activity in Australia during the 1990's has not reduced the magnitude of this major public health problem.

Accidental Falls↗
PubMed2000

Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors.

We have pharmacologically characterized recombinant human mt(1) and MT(2) receptors, stably expressed in Chinese hamster ovary cells (CHO-mt(1) and CHO-MT(2)), by measurement of [(3)H]-melatonin binding and forskolin-stimulated cyclic AMP (cAMP) production. [3H]-melatonin bound to mt(1) and MT(2) receptors with pK(D) values of 9.89 and 9.56 and B(max) values of 1.20 and 0.82 pmol mg(-1) protein, respectively. Whilst most melatonin receptor agonists had similar affinities for mt(1) and MT(2) receptors, a number of putative antagonists had substantially higher affinities for MT(2) receptors, including luzindole (11 fold), GR128107 (23 fold) and 4-P-PDOT (61 fold). In both CHO-mt(1) and CHO-MT(2) cells, melatonin inhibited forskolin-stimulated accumulation of cyclic AMP in a concentration-dependent manner (pIC(50) 9.53 and 9.74, respectively) causing 83 and 64% inhibition of cyclic AMP production at 100 nM, respectively. The potencies of a range of melatonin receptor agonists were determined. At MT(2) receptors, melatonin, 2-iodomelatonin and 6-chloromelatonin were essentially equipotent, whilst at the mt(1) receptor these agonists gave the rank order of potency of 2-iodomelatonin>melatonin>6-chloromelatonin. In both CHO-mt(1) and CHO-MT(2) cells, melatonin-induced inhibition of forskolin-stimulated cyclic AMP production was antagonized in a concentration-dependent manner by the melatonin receptor antagonist luzindole, with pA(2) values of 5.75 and 7.64, respectively. Melatonin-mediated responses were abolished by pre-treatment of cells with pertussis toxin, consistent with activation of G(i)/G(o) G-proteins. This is the first report of the use of [(3)H]-melatonin for the characterization of recombinant mt(1) and MT(2) receptors. Our results demonstrate that these receptor subtypes have distinct pharmacological profiles.

Animals↗
PubMed1999

Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a comparison of calcium mobilization, inhibition of adenylyl cyclase and stimulation of GTPgammaS binding induced by IL-8 and GROalpha.

The effect of interleukin-8 (IL-8) and growth-related oncogene alpha (GROalpha) on [35S]-guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding, forskolin-stimulated cyclic AMP accumulation and cytosolic calcium concentration were determined in recombinant CHO cells expressing HA-tagged CXC-chemokine receptors 1 and 2 (CXCR1 and CXCR2). Radioligand binding assays confirmed that the binding profiles of the recombinant receptors were similar to those of the native proteins. IL-8 displaced [125I]-IL-8 binding to CXCR1 and CXCR2 with pKi values of 8.89+/-0.05 and 9.27+/-0.03, respectively. GROalpha, a selective CXCR2 ligand, had a pKi value of 9.66+/-0.39 at CXCR2 but a pKi>8 at CXCR1. Calcium mobilization experiments were also consistent with previous reports on native receptors. Activation of both receptors resulted in stimulation of [35S]GTPgammaS binding and inhibition of adenylyl cyclase. A comparison of the functional data at CXCRI showed that a similar potency order (IL-8> >GROalpha) was obtained in all three assays. However, at CXCR2 whilst the potency orders for calcium mobilization and inhibition of adenylyl cyclase were similar (IL-8 > or = GROalpha), the order was reversed for stimulation of [35S]GTPgammaS binding (GROalpha > IL-8). All of the functional responses at both receptors were inhibited by pertussis toxin (PTX), suggesting coupling to a Gi/Go protein. However, the calcium mobilization induced by IL-8 at CXCR1 was not fully inhibited by PTX, suggesting an interaction with a G-protein of the Gq family. Our results with pertussis toxin also suggested that, in the [35S]GTPgammaS binding assay, CXCR1 displays some constitutive activity. Thus, we have characterized the binding and several functional responses at HA-tagged CXCRs 1 and 2 and have shown that their pharmacology agrees well with that of the native receptors. We also have preliminary evidence that CXCR1 displays constitutive activity in our cell line and that CXCR2 may traffic between different PTX sensitive G-proteins.

Adenylate Cyclase Toxin↗
PubMed1999

The provision of preventive care by general practitioners measured by patient completed questionnaires.

The objective of this study was, by means of patient self-report, to measure the provision of preventive care to patients of a sample of Australian general practitioners. Patient-completed questionnaires from a consecutive sample of Australian general practitioners enrolled in the Quality Assurance and Continuing Medical Education Program of the Royal Australian College of General Practitioners were used. Patients were attendees at Australian general practices. The main outcome measures included the following: the provision of tetanus immunization within the last 10 years; blood pressure measurement within the last 12 months; cholesterol screening within the past 5 years; provision of adequate information to enable patients to stop smoking if they desired; discussion about the benefits of diet and exercise to enhance life, and about alcohol intake; provision of cervical smears in the past 2 years; provision of adequate instruction in breast self-examination and overall satisfaction with service provision. A total of 12,605 questionnaires from 133 general practices were completed. There was wide variability between practices in the reported provision of preventive care items including an average of 86% (range 36-100) of patients reporting the provision of blood pressure checking in the past 12 months, 62% (range 25-97%) reporting the provision of tetanus immunization in the past 10 years, and 63% (range 10-91%) reporting having had a cervical smear in the past 2 years. Patients who were very satisfied were more likely to have reported that they had received blood pressure measurement in the past 12 months, participated in discussions about the benefits of diet and exercise in enhancing life, and participated in discussions about alcohol intake and provision of adequate instruction in the technique of breast self-examination. Patient self-reporting identified variability between practitioners in the provision of preventive care conforming to accepted guidelines. Patients who reported that they were very satisfied or who regularly attend only one general practice reported the provision of more preventive care than those who were not very satisfied or who regularly visited two or more general practitioners.

Adolescent↗
PubMed1999

A patient determined general practice satisfaction questionnaire.

OBJECTIVES: To develop and explore the use of a patient satisfaction questionnaire based on patient perceptions of items which influence satisfaction and to explore patient and practitioner characteristics which influence the results. METHOD: Twenty focus groups identified 39 items which were then assembled into a questionnaire which was evaluated by attendees at 133 Australian general practices. MAIN OUTCOME MEASURES: Overall satisfaction with general practitioner services and the appropriateness of the 39 items identified by focus group participants; socio-demographic characteristics of patients and practitioners and the impact of these characteristics on the results; factor analysis of the relationship of the items to each other and to overall satisfaction. RESULTS: Questionnaires were completed by 12,605 patients of 133 general practices. Seventy-three percent of these patients reported they were overall very satisfied with the care they received and 26% were satisfied. There were five individual items for which an average of more than 10% of patients reported they were not satisfied: waiting time at the surgery (18%); ease of obtaining home visits (17%); ease of seeing the doctor out of normal hours (15%); cost of drugs (12%) and facilities for children in the waiting room (10%). Factors which were more likely to result in a report of patients being very satisfied included: patients being older; if patients had visited recently; if they had attended the practice for a long time; if they visited only one general practice and had more consultations in the past 12 months. Patients of solo practitioners were more likely to report they were satisfied with individual items and patients of practices of three or more practitioners were least likely. No significant differences between practices of different sizes in the level of overall satisfaction were detected. Factor analysis identified three major factors which we have described as containing interaction, technical and accessibility items. These three factors explained 44.4% of the variance in results. CONCLUSION: This project found the items patients identified were similar to those identified by practitioners, and reiterated previous findings that there is substantial variability in the levels of satisfaction reported by patients of Australian general practices.

Adolescent↗
PubMed1998

Health actions and social class among older Australians.

This paper aims to identify aspects of social class that are related to health actions important for older Australians. Data are from the 1994 Health Status of Older People Project baseline survey of 1,000 participants aged 65 and over in Melbourne. Analyses employed logistic regression controlling for age and gender. Physical activity was related to both former occupation and current income; social activity to former occupation; and not smoking to home ownership. Health promotion strategies require a better understanding of the ways in which aspects of social class affect the life course experiences of different birth cohorts. Promotion of physical and social activity in old age needs to take account of the continuing influence of advantages associated with social class.

Age Factors↗
PubMed1998

Preventive care and continuity of attendance. Is there a risk?

OBJECTIVE: To explore whether there are associations between continuity of care and the provision of items of preventive care in Australian general practice. METHOD: Patient completed questionnaires from a 'consecutive' sample of Australian general practitioners enrolled in the Patient Participation Program of the Quality Assurance and Continuing Medical Education Program of the Royal Australian College of General Practitioners. MAIN OUTCOME MEASURES: An association was sought between the length of time patients reported attending their practitioner, whether they regularly attended more than one practice, and whether they were provided with preventive care. RESULTS: Data from 12,605 questionnaires, completed by patients from 133 practices throughout Australia found that patients who reported only visiting one practice on a regular basis were significantly more likely to report the provision of: blood pressure screening within the past 12 months; cholesterol screening in the past 5 years; adequate smoking cessation information if required; to have discussed the benefits of diet and exercise; to have received a cervical smear in the past 2 years; and to have received adequate instruction in the technique of breast self examination. Patients attending the same practices for longer periods were significantly more likely to have received the above items with the exception of adequate information to enable them to stop smoking if they desired; and cervical smears in the past 2 years. Such patients were less likely to report the provision of tetanus immunisation in the past 10 years and cervical smears in the past 2 years. CONCLUSIONS: Patients reporting greater continuity of care measured by only consulting at one practice or visiting the practice for a longer time period reported a greater provision of preventive care than patients who did not report these characteristics.

Australia↗
PubMed1998

GR196429: a nonindolic agonist at high-affinity melatonin receptors.

N-[2-[2,3,7,8-tetrahydro-1H-furo(2,3-g)indol-1-yl]ethyl]acetamide (GR196429) is a novel, nonindolic melatonin receptor agonist. GR196429 had high affinity for human mt1 (pKi 9.9) and MT2 (pKi 9.8) receptors expressed in Chinese hamster ovary cells and for 2-[125I]-iodomelatonin binding sites in human cerebellum, guinea pig superior colliculus and hypothalamus and chicken retina and tectum (pKi 8.8-9.5). GR196429 was inactive at a wide range of other hormone and neurotransmitter receptors. In Chinese hamster ovary cells expressing human mt1 or MT2 receptors, both melatonin and GR196429 dose-dependently inhibited forskolin-stimulated cAMP accumulation. In rabbit isolated retina, GR196429 inhibited calcium-dependent [3H]-dopamine release with potency (IC50 30 pM) and maximum effect (76 +/- 5% at 1 nM) similar to those of melatonin. The response was antagonized by the melatonin receptor antagonist luzindole (1 microM). In slices of rat brain suprachiasmatic nucleus, perfusion (1 h) with GR196429 at zeitgeber time 10 phase advanced the circadian peak in neuronal activity measured on the following day, with a maximum phase advance of 2.7 +/- 0.3 h at 10 pM and an EC50 of 0.6 pM, results that indicated a melatonin-like action on the phase of the circadian clock. CNS penetration and duration of receptor occupancy was determined in an ex vivo radioligand binding assay. In membranes of guinea pig superior colliculus prepared 30 min after administration of GR196429 (s.c.), 2-[125I]-iodomelatonin binding was inhibited with an ED50 of 0.04 mg/kg. After a dose of 1 mg/kg, binding was significantly inhibited for at least 3 h. Thus GR196429 is a potent and selective agonist at high-affinity melatonin receptors, which modulates circadian rhythms in an in vitro model of the circadian clock and which readily penetrates the CNS.

Animals↗
PubMed1997

The sequence and structure of the 3' arm of the first stem-loop of the human immunodeficiency virus type 2 trans-activation responsive region mediate Tat-2 transactivation.

Human immunodeficiency virus type 2 (HIV-2) causes AIDS, but generally after a much longer asymptomatic period than that which follows infection with HIV-1. At the molecular level, HIV-2 is much more closely related to the simian immunodeficiency viruses than to HIV-1 and our previous studies have demonstrated that HIV-2 and HIV-1 enhancer stimulation is mediated by different sets of cellular proteins following T-cell activation. Similar to HIV-1, HIV-2 encodes a transactivating protein, Tat, which appears to be necessary for viral replication and stimulates viral transcriptional initiation and/or elongation. While Tat-1 binds to the RNA of the trans-activation responsive (TAR) region of HIV-1 and HIV-2, cellular factors that bind to the RNA transcript are also necessary for Tat to function in vivo. Since almost all previous investigations of cellular cofactors for Tat had focused on HIV-1, we undertook studies aimed at understanding the interaction between the TAR RNA region of the HIV-2 promoter (TAR-2) and cellular proteins. By using extension inhibition analysis (toeprinting) and RNA electrophoretic mobility shift assays, we demonstrated binding of a nuclear factor(s) in T cells to the base of the promoter-proximal stem-loop structure. Mutational analysis of this region revealed that both the sequence of the 3' arm and the stem structure itself are important for activation of the promoter by Tat-2. In contrast, the structure is necessary for activation of TAR-2 by Tat-1 but the sequence is less important. These results suggest that a cellular factor interacts with the 3' arm of the proximal stem-loop structure of TAR-2 and mediates Tat-2-induced increases in the level of HIV-2 transcripts.

Base Sequence↗
PubMed1996

The relevance of hearing a crack in ankle injuries.

OBJECTIVE: To examine the predictive value of a crack noise or sensation in the history of injury in the diagnosis of ankle fracture. METHODS: A short questionnaire was filled in on 464 patients with isolated ankle injuries attending the accident and emergency department in a three month period from July to September. These patients were seen in the usual way in the department and the need for x ray assessed according to clinical judgement and existing departmental guidelines. Cases which subsequently proved to be other than ankle injuries, for example, fractured calcaneus, were excluded from the study. RESULTS: A positive history of hearing or feeling a crack did not indicate the need for an x ray or increase the possibility of a fracture; indeed the history of a crack made the presence of a fracture less likely. The clinical diagnosis of absence of fracture without radiological examination may require careful explanation to the patient. CONCLUSIONS: Hearing a crack in the ankle does not suggest a fracture.

Ankle Injuries↗
PubMed1994

Injury patterns in cyclists attending an accident and emergency department: a comparison of helmet wearers and non-wearers.

OBJECTIVES: To study circumstances of bicycle accidents and nature of injuries sustained and to determine effect of safety helmets on pattern of injuries. DESIGN: Prospective study of patients with cycle related injuries. SETTING: Accident and emergency department of teaching hospital. SUBJECTS: 1040 patients with complete data presenting to the department in one year with cycle related injuries, of whom 114 had worn cycle helmets when accident occurred. MAIN OUTCOME MEASURES: Type of accident and nature and distribution of injuries among patients with and without safety helmets. RESULTS: There were no significant differences between the two groups with respect to type of accident or nature and distribution of injuries other than those to the head. Head injury was sustained by 4/114 (4%) of helmet wearers compared with 100/928 (11%) of non-wearers (P = 0.023). Significantly more children wore helmets (50/309 (16%)) than did adults (64/731 (9%)) (P < 0.001). The incidence of head injuries sustained in accidents involving motor vehicles (52/288 (18%)) was significantly higher than in those not involving motor vehicles (52/754 (7%)) (chi 2 = 28.9, P < 0.0001). Multiple logistic regression analysis of probability of sustaining a head injury showed that only two variables were significant: helmet use and involvement of a motor vehicle. Mutually adjusted odds ratios showed a risk factor of 2.95 (95% confidence interval 1.95 to 4.47, P < 0.0001) for accidents involving a motor vehicle and a protective factor of 3.25 (1.17 to 9.06, P = 0.024) for wearing a helmet. CONCLUSION: The findings suggest an increased risk of sustaining head injury in a bicycle accident when a motor vehicle is involved and confirm protective effect of helmet wearing for any bicycle accident.

Accidents, Traffic↗
PubMed1990

Prolonged anorectal manometry and external anal sphincter electromyography in ambulant human subjects.

We have developed a method for prolonged combined anorectal manometry and electromyography (EMG) of the external anal sphincter in ambulant subjects. Fourteen healthy volunteers were studied for a total of 284 hr (mean of 20.3 hr/subject). Anorectal manometry was performed using a probe with twin pressure sensors. EMG was recorded by one indifferent and two differential silver-silver chloride surface electrodes positioned 0.5-0.75 cm from the anus on either side. The sampling reflex occurred frequently and was significantly (P less than 0.001) more common during wakefulness than during sleep and also following meals than during fasting (P less than 0.01). The passage of flatus was associated with transient relaxation of the anal canal in 19% of episodes. In contrast, there was a contractile episode with no preceding relaxation in 75% of episodes. The anal sphincter had significantly (P less than 0.05) more action potentials (APs) during the day (12.8 +/- 3.2 APs/10 min) than at night (1.6 +/- 1.3 APs/10 min). During micturition, anal canal pressure rose (mean 15 mm Hg) in association with powerful external anal sphincter contractions. Our data show that, normally, contractile activity both in the anal canal and external anal sphincter maintains fecal continence during micturition and the passage of flatus. The technique should lead to a better understanding of the normal mechanisms of fecal continence during waking and sleep and of the pathophysiology of disorders of anorectal function.

Action Potentials↗