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Biomedical subjects

J M Young

Publications and source records attributed to J M Young.

At least 37 records · Page 2Linked to original sources

Histamine H(3) receptor-mediated inhibition of depolarization-induced, dopamine D(1) receptor-dependent release of [(3)H]-gamma-aminobutryic acid from rat striatal slices.

1. A study was made of the regulation of [(3)H]-gamma-aminobutyric acid ([(3)H]-GABA) release from slices of rat striatum by endogenous dopamine and exogenous histamine and a histamine H(3)-agonist. Depolarization-induced release of [(3)H]-GABA was Ca(2+)-dependent and was increased in the presence of the dopamine D(2) receptor family antagonist, sulpiride (10 microM). The sulpiride-potentiated release of [(3)H]-GABA was strongly inhibited by the dopamine D(1) receptor family antagonist, SCH 23390 (1 microM). Neither antagonist altered basal release. 2. The 15 mM K(+)-induced release of [(3)H]-GABA in the presence of sulpiride was inhibited by 100 microM histamine (mean inhibition 78+/-3%) and by the histamine H(3) receptor-selective agonist, immepip, 1 microM (mean inhibition 81+/-5%). The IC(50) values for histamine and immepip were 1.3+/-0.2 microM and 16+/-2 nM, respectively. The inhibitory effects of histamine and immepip were reversed by the H(3) receptor antagonist, thioperamide, 1 microM. 3. The inhibition of 15 mM K(+)-induced [(3)H]-GABA release by immepip was reversed by the H(3) receptor antagonist, clobenpropit, K(d) 0.11+/-0.04 nM. Clobenpropit alone had no effect on basal or stimulated release of [(3)H]-GABA. 4. Elevated K(+) caused little release of [(3)H]-GABA from striatal slices from reserpinized rats, unless the D(1) partial agonist, R(+)-SKF 38393, 1 microM, was also present. The stimulated release in the presence of SKF 38393 was reduced by 1 microM immepip to the level obtained in the absence of SKF 38393. 5. These observations demonstrate that histamine H(3) receptor activation strongly inhibits the dopamine D(1) receptor-dependent release of [(3)H]-GABA from rat striatum; primarily through an interaction at the terminals of GABA neurones.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Evidence-based medicine in general practice: beliefs and barriers among Australian GPs.

If implemented, evidence-based medicine (EBM) in general practice will improve health outcomes for patients. This paper examines the views of 60 Australian general practitioners about EBM. While 57% of respondents had a computer in their surgery, 15% had Internet access and only 3% had access to the Cochrane Library at work. The most commonly cited barrier to EBM was 'patient demand for treatment despite lack of evidence for effectiveness' (45%). The next three most highly rated barriers related to lack of time. For each of three tasks of EBM, namely searching for evidence, appraising evidence and discussing the implications of evidence with patients, lack of time was rated as a 'very important barrier' by significantly more participants than lack of skills (McNemar's tests: chi2(1) = 7.1, P = 0.008, chi2(1) = 14.0, P = 0.001 and chi2(1) = 9.0, P = 0.003, respectively). Preferred resources for EBM included clinical practice guidelines (rated as 'very useful' by 55%) and journals that summarize research evidence, for example Evidence-based Medicine (52%). Systematic reviews were considered 'very useful' by only 15% of respondents, consistent with our finding that 30% did not understand the term 'systematic review'. Furthermore, 43% did not understand 'meta-analysis'. A minority indicated they understood the terms 'relative risk' (23%), 'absolute risk' (28%) and 'number needed to treat' (15%) sufficiently to explain to others. Skills development is crucial to achieve EBM in general practice.

Adult↗

Implementing guidelines for smoking cessation advice in Australian general practice: opinions, current practices, readiness to change and perceived barriers.

OBJECTIVE: The aim of this study was to ascertain opinions, current practices, likely readiness to change and perceived barriers to change among Australian GPs in order to develop a plan to implement national guidelines for smoking cessation advice. METHOD: A postal survey of randomly selected GPs in New South Wales, Australia was carried out. RESULTS: We received 311 returned questionnaires (73% response rate). Only 34% of respondents reported providing cessation advice during every routine consultation with a smoker, in accordance with national guidelines. Specific evidence-based approaches recommended in guidelines were under-utilized, with only 54% 'always' or 'frequently' arranging follow-up, 32% providing written materials and 28% setting a 'quit date'. Respondents were no more likely to advise quitting completely than the less effective method of nicotine fading. More than one in four respondents (28%) indicated readiness to change their behaviour. Respondents rated their patients' lack of motivation and uninterest as the most important barriers to smoking cessation advice in general practice. Neither uncertainty about effective smoking cessation strategies nor lack of reimbursement for smoking cessation advice were identified as barriers. CONCLUSIONS: A multicomponent intervention to address suboptimal behaviour and barriers as revealed by this survey holds considerable potential to plan effective implementation of smoking cessation guidelines in general practice. The use of readiness to change as a tool to 'individualize' strategies for guideline implementation should be explored.

Adult↗

A revision of Rhizobium Frank 1889, with an emended description of the genus, and the inclusion of all species of Agrobacterium Conn 1942 and Allorhizobium undicola de Lajudie et al. 1998 as new combinations: Rhizobium radiobacter, R. rhizogenes, R. rubi, R. undicola and R. vitis.

Rhizobium, Agrobacterium and Allorhizobium are genera within the bacterial family Rhizobiaceae, together with Sinorhizobium. The species of Agrobacterium, Agrobacterium tumefaciens (syn. Agrobacterium radiobacter), Agrobacterium rhizogenes, Agrobacterium rubi and Agrobacterium vitis, together with Allorhizobium undicola, form a monophyletic group with all Rhizobium species, based on comparative 16S rDNA analyses. Agrobacterium is an artificial genus comprising plant-pathogenic species. The monophyletic nature of Agrobacterium, Allorhizobium and Rhizobium and their common phenotypic generic circumscription support their amalgamation into a single genus, Rhizobium. Agrobacterium tumefaciens was conserved as the type species of Agrobacterium, but the epithet radiobacter would take precedence as Rhizobium radiobacter in the revised genus. The proposed new combinations are Rhizobium radiobacter, Rhizobium rhizogenes, Rhizobium rubi, Rhizobium undicola and Rhizobium vitis.

Base Composition↗

Implications of alternative classifications and horizontal gene transfer for bacterial taxonomy.

Following the publication of the Approved Lists, there has been a tendency to regard all subsequent revisions of classification as providing improved nomenclature, to be accepted without question. This takes no account of the fact that such revisions may be based on one of three alternative concepts, phenetic, phylogenetic or polyphasic classification, sometimes leading to different, valid, but incompatible nomenclature, or that some investigations are based only on subsets of relevant taxa and on limited data, leading to incomplete and sometimes confusing revisions of nomenclature. The polyphasic approach to classification has widespread support, although there appears to be a tendency to allow comparative sequence analyses of 16S rDNA to determine classification contrary to the indications of other data. In some cases, classification is based solely on 16S rDNA data. Examples are considered. Consideration is given to the criteria by which taxa are circumscribed, particularly at the level of genus and species. It is suggested that there is a need for reconciliation of the criteria by which taxa at these levels are circumscribed. Recent studies demonstrating the widespread occurrence of horizontal gene transfer suggest that there is a need for caution in monophyletic interpretations, especially when these are based on the analysis of single sequences.

Bacteria↗

Audit and feedback: effects on professional practice and health care outcomes.

BACKGROUND: Audit and feedback has been identified as having the potential to change the practice of health care professionals. OBJECTIVES: To assess the effects of audit and feedback on the practice of health professionals and patient outcomes. SEARCH STRATEGY: We searched MEDLINE up to June 1997, the Research and Development Resource Base in Continuing Medical Education, and reference lists of related systematic reviews and articles. SELECTION CRITERIA: Randomised trials of audit and feedback (defined as any summary of clinical performance of health care over a specified period of time). The participants were health care professionals responsible for patient care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Thirty-seven studies were included, involving more than 4977 physicians. The reporting of study methods was inadequate for almost all studies. In 31 out of 37 studies the randomisation process could not be determined. Information regarding data analysis was also lacking. For example, power calculations were not mentioned in 27 out of 37 studies. A variety of behaviours were targeted including the reduction of diagnostic test ordering, prescribing practices, preventive care, and the general management of a problem, for example hypertension. Twenty-eight studies measured physician performance, one study targeted patient outcomes in diabetes and the remaining eight studies measured both physician performance and patient outcomes. The relative percentage differences ranged from -16% to 152%. The clinical importance of the changes was not always clear. REVIEWER'S CONCLUSIONS: Audit and feedback can sometimes be effective in improving the practice of health care professionals, in particular prescribing and diagnostic test ordering. When it is effective, the effects appear to be small to moderate but potentially worthwhile. Those attempting to enhance professional behaviour should not rely solely on this approach.

Education, Medical, Continuing↗

The interaction of U-73122 with the histamine H1 receptor: implications for the use of U-73122 in defining H1 receptor-coupled signalling pathways.

U-73122, an N-aminosteroid homologue of N-ethylmaleimide (NEM), widely used as an inhibitor of phospholipase C, was found to be a potent inhibitor (IC50 5.5+/-0.5 microM) of the binding of [3H]mepyramine to guinea-pig cerebellar membranes. The succinimido analogue, U-73343, also inhibited the binding of [3H]mepyramine (estimated IC50 24+/-1 microM), but NEM was only a weak inhibitor, even at 10 mM. The interaction of U-73122 and U-73343 with the H1 receptor was effectively irreversible, on the time-scale of the experiment. There is no indication that reaction with a receptor thiol residue is involved in the binding of U-73122, since preincubation of membranes with 2 mM NEM did not significantly increase the IC50 for the inhibition of [3H]mepyramine binding by U-73122. We conclude that U-73122 binds to the histamine H1 receptor in the concentration range in which it acts as an inhibitor or PLC. This compromises the use of U-73122 to provide evidence that an H1 agonist action is mediated via PLC. The tight binding of U-73343 to the receptor appears to be primarily a function of the hydrophobic nature of the compound.

Animals↗

Characteristics of the Ca(2+)-dependent inhibition of cyclic AMP accumulation by histamine and thapsigargin in human U373 MG astrocytoma cells.

1. Histamine, acting on H(1)-receptors, caused a Ca(2+)-dependent inhibition of forskolin- and isoprenaline-induced cyclic AMP accumulation in monolayers of human U373 MG cells (IC(50) 1.3+/-0.3 microM, maximum inhibition 66+/-3%). The inhibition was not reversed by the protein kinase inhibitor K-252A. 2. Thapsigargin also inhibited cyclic AMP accumulation (IC(50) 6.0+/-0.3 nM, maximum inhibition 72+/-1%). In the absence of extracellular Ca(2+) 5 microM thapsigargin caused only a 12+/-2% inhibition of cyclic AMP accumulation. 3. The inhibitory effect of 100 nM thapsigargin on forskolin-stimulated cyclic AMP accumulation was blocked by La(3+) (best-fit maximum inhibition 81+/-4%, IC(50) 125+/-8 nM). In contrast, the inhibitory action of 10 microM histamine was much less sensitive to reversal by 1 microM La(3+) (33+/-5% reversal, compared with 78+/-6% reversal of the inhibition by thapsigargin measured concurrently). However, in the presence of both thapsigargin and histamine the inhibition of cyclic AMP accumulation was reversed by 1 microM La(3+) to the same extent as the inhibition by thapsigargin alone. 4.++Thapsigargin (5 microM)+1 microM La(3+) caused only a 20+/-1% inhibition of histamine-stimulated phosphoinositide hydrolysis. 5. There was no indication from measurement of intracellular Ca(2+) of any persistent La(3+)-insensitive Ca(2+) entry component activated by histamine. 6. The results provide evidence that Ca(2+) entry is required for the inhibition by histamine and thapsigargin of drug-induced cyclic AMP accumulation in U373 MG astrocytoma cells. The differential sensitivity of the inhibitory action of the two agents to block by La(3+) suggests that more than one pathway of Ca(2+) entry is involved.

Adenylyl Cyclase Inhibitors↗

Postpartum headache after epidural blood patch: investigation and diagnosis.

Use of an epidural blood patch to treat spinal headache after accidental dural puncture is well recognized. The high success rate associated with this practice has been questioned and it is not uncommon for patients to suffer recurring headaches after a supposedly successful blood patch. We describe a patient in labour who suffered accidental dural puncture, and whose headache was treated twice with an epidural blood patch. Despite this, the headache persisted. The case highlights the difficulty in the diagnosis of headache in the postnatal period in patients who have had regional analgesia and the importance of considering an alternative pathology, even if epidural blood patching has been successful. In this case, a diagnosis of cortical vein thrombosis was made. The incidence, presentation, aetiology and treatment of this rare condition is described.

Adult↗

General practitioners' use of evidence databases.

OBJECTIVE: To determine the awareness and use of the Cochrane Library and access to the Internet by general practitioners in New South Wales. DESIGN: Cross-sectional postal survey in September 1997. PARTICIPANTS: 311 of 428 (73% response rate) randomly selected general practitioners in New South Wales. MAIN OUTCOME MEASURES: Proportion of respondents with access to the Internet at home or at work; proportion of respondents aware of, with access to, and ever using the Cochrane Library; independent predictors of awareness of the Cochrane Library. RESULTS: 134 respondents (43%) had access to the Internet either at home or at work; 42 (14%) were "on line" at their workplace. Seventy (22%) were aware of the Cochrane Library, although only 20 (6%) had access to it and 13 (4%) had ever used it. Those in group practice and members of Divisions were independently more likely to be aware of the Cochrane Library. CONCLUSIONS: As patient outcomes will improve with systematic implementation of evidence-based treatments, these low rates of access to useful evidence databases raise issues regarding the best ways to support general practitioners with information technology.

Adult↗

Characterisation of alpha1B-adrenoceptors linked to inositol phosphate formation and calcium mobilisation in human astrocytoma U373 MG cells.

The human U373 MG astrocytoma cell line has been widely used as a model system for the investigation of astrocyte function. The aim of this study was to establish which alpha1-adrenoceptors are present on these cells. The specific binding of [3H]prazosin to membranes of U373 MG cells (Bmax 32+/-3 fmol mg(-1) protein, Kd 0.27+/-0.03 nM) was inhibited in a monophasic manner by alpha1-antagonists that have different affinities for alpha1A-, alpha1B- and alpha1D-adrenoceptors. Estimates for pKi values were: prazosin 9.69+/-0.06, 5-methylurapidil 7.10+/-0.21; (+)-niguldipine 7.06+/-0.26; WB 4101 8.26+/-0.16; and BMY 7378 6.60+/-0.21. The specific binding of [3H]prazosin was reduced to low levels by pretreatment of cells with 10 microM chloroethylclonidine for 15 min. In the presence of 30 mM LiCl, 100 microM noradrenaline stimulated [3H]inositol phosphate accumulation by 2.1+/-0.1-fold of basal after 30-min incubation. The EC50 for the accumulation of [3H]IP1, the major product detected (85+/-2% of total [3H]IP1 + [3H]IP2 + [3H]IP3), was 0.38+/-0.05 microM. Noradrenaline-induced [3H]IP1 accumulation was also inhibited by alpha1-antagonists. Estimates for pKi values were: 5-methylurapidil 6.95+/-0.01; WB 4101 8.31+/-0.07; and BMY 7378 6.71+/-0.28. The accumulation of [3H]IP1 in response to 100 microM noradrenaline was not significantly affected by raising the extracellular Ca2+ concentration from 1.3 to 4 mM. Noradrenaline (100 microM) also produced an increase in intracellular Ca2+ (mean peak 86+/-5 nM above basal). Pretreatment with chloroethylclonidine (10 microM, 15 min) abolished noradrenaline-induced [3H]IP1 accumulation and Ca2+ mobilisation. Activation of the alpha1B-adrenoceptors by 10 microM phenylephrine increased [3H]thymidine uptake to 140+/-5% of control uptake. Taken together, these results indicate that U373 MG cells express a single class of alpha1-adrenoceptors, the alpha1B-subtype, which are coupled to phosphoinositide hydrolysis and calcium mobilisation, and which mediate a mitogenic response to alpha1-agonists.

Adrenergic alpha-Antagonists↗

A unique role: the peer mentor on the spinal cord team at G.F. Strong Rehab Centre.

The peer mentor is a full time paid staff member of the G. F. Strong Rehab Centre Spinal Cord Program. To qualify for the position, an individual with a high lesion spinal cord injury must live a self-managed life in the community. The peer mentor's role bridges professional, lay, and client perspectives, and is a voice for both clients and staff unlike any other team member. This report focuses on the peer mentor's facilitation of communication between clients and staff and on two initiatives that promote clients' perspectives.

British Columbia↗

Laryngeal mask airway use in children with acute burns: intraoperative airway management.

Paediatric patients with acute burns often require many operative procedures in short succession; yet due to inhalation injury or recent extubation their airways may be susceptible to tracheal tube induced damage. We proposed the laryngeal mask airway (LMA) as a useful airway management tool in this setting. In this prospective study, 80 eight (88) patients with mean age (+/- SD) of 7.8 +/- 4.7 years and average percentage total body surface area burned (%TBSA) of 21 +/- 18% had their airways managed with an LMA while in the operating room for 141 procedures. Twenty-five patients (28.4%) had been previously intubated for burn management and 19 (21.6%) had evidence of inhalation injury. During each procedure, the patient was evaluated for airway obstruction, laryngospasm, inability to ventilate, hypoxaemia, evidence of aspiration/regurgitation or any situation which required intraoperative manipulation/removal of the LMA. Of the 141 procedures, 122 were without airway problems. Of the remaining 19, nine required only a simple reseating of the LMA for correction. The other 10 events include arterial desaturation (n = 3), partial laryngospasm (5), airway obstruction (1) and regurgitation without aspiration (1). In each case, corrective action led to resolution of the problem with no patient morbidity. This series demonstrates the LMA is a safe and efficacious airway management device in the paediatric burn population.

Acute Disease↗

Strategies to improve cancer screening in general practice: are guidelines the answer?

BACKGROUND: GPs are ideally placed to recommend appropriate cancer screening for their patients. However, opportunities to discuss screening are often missed and screening procedures are not always recommended in accordance with national policy. The development of clinical practice guidelines represents one strategy for improving cancer screening in general practice. OBJECTIVE: We aimed to ascertain Australian GPs' ratings of current clinical practice guidelines and their views of the likely usefulness of 18 strategies to improve cancer screening in general practice. METHOD: A self-administered questionnaire was mailed to a national random sample of 1271 GPs in May 1996. Responders rated the usefulness of each of eight clinical practice guidelines current at the time of the survey. They then rated the usefulness of each of 18 strategies for support of cancer screening. RESULTS: We received 855 completed questionnaires (a 67% response rate). There was greatest support for guidelines already available on breast and cervical cancer. The most popular strategy to improve cancer screening was seminars with experts in preventive care, rated as 'very useful' by 658 (77%), followed by NHMRC guidelines (597, 70%) and pamphlets for patients (587, 69%). There was less support for more innovative strategies including assessment and feedback (35%), case finding by nurse practitioners (11%) and academic detailing (10%). CONCLUSION: Responders indicated that strategies involving passive dissemination of information would be most useful for improving cancer screening in general practice. Identification of an effective combination of acceptable initiatives is needed.

Attitude of Health Personnel↗

Population-based cancer control: where is the greatest benefit from proven strategies to 'regain' years of life lost prematurely?

OBJECTIVE: To apply a 'health gain' approach to population-based cancer control. METHOD: We calculated the potential years of life otherwise lost prematurely which could be 'regained' through implementation of cancer control programs for which Level I or Level II evidence already exists for population outcomes. RESULTS: More potential years of life lost (PYLLs) would be 'regained' by enforcing a 'smoke-free' Australia than by any other possible scenario based on proven effectiveness. Even achievable scenarios for tobacco control (17% or 20% prevalence) would 'regain' more PYLL than either mammographic screening according to national policy or faecal occult blood testing (FOBT) of both men and women over 50 years for colorectal cancer. CONCLUSIONS: As few commentators remain optimistic that more money will be allocated to health, strategic thinking for health gain needs to re-appraise resource allocation for population-based cancer control in Australia. IMPLICATIONS: We recommend wider debate in response to our finding that, on the basis of best available evidence, the greatest potential for health gain lies less in cancer screening than fully funded tobacco control.

Aged↗