Search PubMed⌕ Search

Biomedical subjects

A Mant

Publications and source records attributed to A Mant.

At least 55 records · Page 3Linked to original sources
PubMed1996

Insomnia in general practice. Results from NSW General Practice Survey 1991-1992.

OBJECTIVE: To assess whether an educational visit to GPs providing information about the non-drug and drug management of anxiety and insomnia can reduce subsequent rates of benzodiazepine prescription. METHOD: A randomised controlled trial of 286 NSW general practitioners conducted during 1991 and 1992. RESULTS: The educational visit was statistically significant in reducing the number of new prescriptions recorded by general practitioners for new diagnoses of insomnia. However, the majority of benzodiazepine prescriptions were for patients continuing treatment for insomnia or anxiety/depression. Overall, benzodiazepines were the sole management of insomnia recorded by the surveyed GPs in most cases (93.5%). In comparison, non-drug management for anxiety and depression was offered to more than a third of patients with anxiety and depression. (Benzodiazepines were the only management of anxiety and depression in just over 50% of cases.) DISCUSSION: This study shows general practitioners can change their management of insomnia and that change is most likely to occur when the problem is new, rather than old. The decreased emphasis on drug treatment in the general practice management of anxiety and depression may reflect the change in psychiatric teaching for these conditions. Further, most of the publicity about benzodiazepines has been in relation to their use for anxiety disorders. Doctors were interested in learning about advances in the understanding of sleep disorders and their non-drug management.

Australia↗
PubMed1995

Sec-dependent thylakoid protein translocation. Delta pH requirement is dictated by passenger protein and ATP concentration.

A Sec-type system is responsible for the translocation of a subset of proteins across the thylakoid membrane in higher plant chloroplasts. Previous studies have suggested that the thylakoidal delta pH plays a minor role in this translocation mechanism, but we show here that it can be essential for the translocation process, depending on the identity of the passenger protein and the concentration of ATP. Studies using chimeric proteins show that, whereas the presequence dictates the translocation pathway, the delta pH requirement is dictated exclusively by the passenger protein; some passenger proteins are virtually delta pH-independent whereas others are absolutely dependent. delta pH requirement is not related to charge characteristics of the passenger proteins, ruling out an electrophoretic effect. Analysis of the 33-kDa photosystem II protein reveals an inverse relationship between delta pH requirement and ATP concentration; import into isolated thylakoids is inhibited 14-fold by nigericin at moderate ATP concentrations, and totally inhibited when the ATP concentration is reduced to 2 microM. The results indicate that the roles of the delta pH and ATP overlap and suggest that the delta pH may be obligatory when the passenger protein is abnormally difficult to translocate, possibly due to the folding of the polypeptide chain. We compare the energetics of this system with those of prokaryotic systems from which the chloroplast system is believed to have evolved.

Adenosine Triphosphate↗
PubMed1995

A new type of signal peptide: central role of a twin-arginine motif in transfer signals for the delta pH-dependent thylakoidal protein translocase.

The delta pH-driven and Sec-related thylakoidal protein translocases recognise distinct types of thylakoid transfer signal, yet all transfer signals resemble bacterial signal peptides in structural terms. Comparison of known transfer signals reveals a single concrete difference: signals for the delta pH-dependent system contain a common twin-arginine motif immediately before the hydrophobic region. We show that this motif is critical for the delta pH-driven translocation process; substitution of the arg-arg by gln-gln or even arg-lys totally blocks translocation across the thylakoid membrane, and replacement by lys-arg reduces the rate of translocation by > 100-fold. The targeting information in this type of signal thus differs fundamentally from that of bacterial signal peptides, where the required positive charge can be supplied by any basic amino acid. Insertion of a twin-arg motif into a Sec-dependent substrate does not alter the pathway followed but reduces translocation efficiency, suggesting that the motif may also repel the Sec-type system. Other information must help to specify the choice of translocation mechanism, but this information is unlikely to reside in the hydrophobic region because substitution by a hydrophobic section from an integral membrane protein does not affect the translocation pathway.

Amino Acid Sequence↗
PubMed1995

A monomeric, tightly folded stromal intermediate on the delta pH-dependent thylakoidal protein transport pathway.

Two distinct mechanisms have been previously identified for the transport of proteins across the chloroplast thylakoid membrane, one of which is unusual in that neither soluble factors nor ATP are required; the system requires only the transthylakoidal delta pH. We have examined this mechanism by studying the properties of one of its substrates: the extrinsic 23-kDa protein (23K) of photosystem II. Previous work has shown that this protein can be transported into isolated thylakoids as the full-length precursor protein; we show that the stromal import intermediate form of this protein is similarly translocation-competent. Gel filtration tests indicate that the stromal intermediate is probably monomeric. Protease sensitivity tests on both the initial in vitro translation product and the stromal import intermediate show that the presequence is highly susceptible to digestion whereas the mature protein is resistant to high concentrations of trypsin. The mature protein becomes very sensitive to digestion if unfolded in urea, or after heating, and we therefore propose that the natural substrate for this translocation system consists of a relatively unfolded presequence together with a tightly folded passenger protein. The ability of thylakoids to import pre-23K is destroyed by prior treatment of the thylakoids with low concentrations of trypsin, demonstrating the involvement of surface-exposed proteins in the import process. However, we can find no evidence for the binding of pre-23K or i23K to the thylakoid surface, and we therefore propose that the initial interaction of these substrates with the thylakoidal translocase is weak, reversible, and probably delta pH-independent. In the second phase of the translocation mechanism, the delta pH drives either the translocation and unfolding of proteins, or the translocation of a fully folded protein.

Bacterial Proteins↗
PubMed1995

Benzodiazepine prescribing in general practice: dispelling some myths.

The objective was to analyse clinical and non-clinical factors associated with the receipt of a prescription for a benzodiazepine among general practice patients. A survey of 110 consecutive patient encounters (consultations) as recorded by a representative sample of general practitioners in inner urban, outer urban and rural settings was designed. A total of 286 general practitioners took part during 1991-2. 31,256 patients (10,683 male; 34%) were surveyed and the odds of receiving a benzodiazepine script measured. Insomnia, unlike anxiety, was almost routinely managed with a benzodiazepine alone (insomnia 89.6%; anxiety 49.4%), whereas anxiety was more likely to be managed with non-drug management (insomnia 7.2%; anxiety 38.3%). In multiple logistic regression, the variables significantly associated with the prescription of a benzodiazepine included being a female patient, being an older patient and being an established patient, who attends a GP working in a busy practice in an inner urban area. A second regression model was run with the addition of three variables, namely the presenting problems of anxiety and insomnia, and the number of health problems. The only predictors of benzodiazepine prescribing in the full model were these three clinical variables together with patient age. There is a need to educate doctors about the non-drug management of insomnia. The stereotype of the doctor over-prescribing a benzodiazepine without an appropriate problem/diagnosis should be questioned. On the other hand, there is concern that patient age continues to be associated with a prescription of these medications, when all other clinical and non-clinical factors are taken into account.

Adolescent↗
PubMed1995

Four-year follow-up of mortality and sleep-related respiratory disturbance in non-demented seniors.

To ascertain whether sleep-disordered breathing (SDB) in the elderly is associated with increased mortality, a prospective cohort study with 4-year follow-up was conducted at a retirement village complex in Sydney, Australia. The subjects were 163 non-demented retirement village residents. Logistic regression was used to assess SDB and co-morbidity as independent predictors of mortality. Respiratory disturbance index (RDI) was measured in the home; those subjects with RDIs > or = 15 were classified as having SDB. Co-morbidity was measured by an index of Burden of Illness based on the medical history obtained at baseline. At 4 years, 27% (4/15) of those subjects with RDIs > or = 15 and 22% (33/148) of those with RDIs < 15 were dead. RDI had an odds ratio (OR) of 1.00 (95% CI: 0.96, 1.04). Burden of Illness had an OR of 1.90 (95% CI: 1.34, 2.71). Adjustment for age and sex did not alter these findings. Significant predictors of mortality from the illness measure were a history of hypertension, Parkinson's disease and other severe illnesses (usually cancer). RDI was not a predictor of mortality in this population of non-demented seniors, where the prevalence of high levels of RDI was low.

Age Factors↗
PubMed1995

A controlled trial of educational visiting to improve benzodiazepine prescribing in general practice.

A randomised controlled trial studied the effect of an educational visit on benzodiazepine prescribing. An approximately representative sample of 286 general practitioners was allocated to an intervention or a control group. Rates of benzodiazepine prescriptions were derived from two comprehensive self-report surveys seven months apart. Two months after the first survey the intervention group received an educational visit and supporting material from a doctor or pharmacist, ostensibly unconnected with the surveys. The overall benzodiazepine prescribing rate fell by 23.7 per cent from the first to the second surveys, from 4.93 to 3.76 prescriptions per 100 encounters (P < 0.001). Anxiety and insomnia diagnosis rates also declined from 4.68 to 3.76 per 100 encounters (19.7 per cent). After adjusting for confounders, there was a differential downward trend in prescriptions per diagnosis of insomnia but not to a statistical level. The same was true of initial prescriptions per insomnia diagnosis. In a subsidiary analysis selecting only new insomnia diagnoses, the intervention had a strong effect in reducing initial prescriptions (odds ratio 0.18, 95 per cent confidence interval 0.04 to 0.73). No effect was seen on prescribing for anxiety diagnoses. Educational practice visiting for benzodiazepine prescribing in anxiety, as we conducted it, is not justified in an unselected population of general practitioners. Specific education on prescribing for insomnia is probably useful. Our interpretation of the reduction in benzodiazepine prescribing is that probably there was an effect from self-monitoring alone which overwhelmed a main-analysis intervention effect. Retrospective diagnosis may also have obscured a real intervention effect.

Anti-Anxiety Agents↗
PubMed1994

Multiple mechanisms for the targeting of photosystem I subunits F, H, K, L, and N into and across the thylakoid membrane.

The photosystem I (PSI) complex in higher plants contains eight nuclear-encoded subunits, of which two (PSI-F and -N) are synthesized with bipartite presequences containing cleavable thylakoid transfer sequences. Previous studies on four other chloroplast proteins bearing bipartite presequences have shown that they are transported across the thylakoid membrane by two distinct mechanisms. One mechanism is delta pH-dependent and hence sensitive to uncouplers, whereas the other is inhibited by azide. We show that PSI-F is targeted by the latter pathway, since its translocation across the thylakoid membrane is inhibited by azide but not by nigericin. Translocation is furthermore unaffected by the presence of high concentrations of the lumenal 23-kDa photosystem II (PSII) protein, which is known to be transported by the delta pH-dependent pathway. In contrast, translocation of PSI-N across the thylakoid membrane is completely blocked by saturating concentrations of pre-23-kDa protein. Three proteins are now known to be synthesized with thylakoid transfer signals in both higher plants and cyanobacteria (PSI-F, plastocyanin, and the 33-kDa PSII protein), and all three are transported by the azide-sensitive, possibly sec-dependent pathway. In contrast, PSI-N and the 23-kDa and 16-kDa PSII proteins (transported by the delta pH-driven pathway in higher plants) are all absent in cyanobacteria. These data suggest that the delta pH-dependent translocation mechanism for these proteins may also have arisen relatively recently during the evolution of the chloroplast. Three additional PSI proteins (PSI-H, -K, and -L) are synthesized in the cytosol with stroma-targeting presequences and hence integrate into the thylakoid membrane by means of information in the mature proteins. We show that the integration mechanisms are insensitive to azide in each case, and nigericin causes only a slight inhibition of integration in each case. We therefore suggest that these proteins are targeted into the thylakoid membrane by a separate pathway(s).

Azides↗
PubMed1994

Import of barley photosystem I subunit N into the thylakoid lumen is mediated by a bipartite presequence lacking an intermediate processing site. Role of the delta pH in translocation across the thylakoid membrane.

Translocation across the thylakoid membrane of the recently identified photosystem I polypeptide, PSI-N, has been analyzed in pea (Pisum sativum) and barley (Hordeum vulgare). PSI-N from barley is synthesized in the cytosol with a bipartite presequence similar in structural terms to those of other cytosolically synthesized proteins routed to the thylakoid lumen. In vitro reconstitution assays demonstrate that translocation into thylakoids is absolutely dependent on the transthylakoidal delta pH, but that nucleotide triphosphates are not required; the translocation mechanism is thus similar in these respects to those utilized by the 23- and 16-kDa proteins of the oxygen-evolving complex. The translocation of PSI-N is unique in that the presequence of PSI-N does not contain an intermediate cleavage site for the stromal processing peptidase; important experiments using intact chloroplasts depleted of a delta pH by nigericin treatment demonstrate the accumulation of the full precursor protein in the stroma. Translocation across the thylakoid membrane can take place in the absence of stromal factors, although the presence of stromal extracts leads to a consistent but slight enhancement of translocation efficiency. We also show that efficient translocation of the 33-kDa protein of the oxygen-evolving complex can take place in the complete absence of a delta pH, in apparent contradiction with earlier findings; the translocation of this protein is thus similar in several respects to that of plastocyanin. The data indicate the operation of two very different types of translocation mechanism, with PSI-N exhibiting additional separate characteristics.

Chloroplasts↗
PubMed1994

General practice and dementia. A national survey of Australian GPs.

OBJECTIVE: To find out what difficulties general practitioners (GPs) experience with diagnosing and managing dementia. DESIGN: Postal questionnaire to a random stratified sample of one in seven active Australian GPs (2182 of 14,932). RESULTS: 1473 GPs (67.5%) responded to the questionnaire. The results indicated reasonable knowledge about diagnostic features of dementia and good insight into common issues facing family carers. Even so, GPs had difficulties with diagnosis and management of dementia and wanted assessment protocols and educational programs. A minority of GPs regularly screened elderly patients for cognitive impairment but the majority relied on passive means of diagnosing dementia. Although generally positive about Aged Care Assessment Teams (ACATs) and Aged Care Community Services (ACCS), GPs expressed some concerns about these services. CONCLUSIONS: Recommendations arising from the survey were: development of an assessment protocol and a screening instrument, regular cognitive check-ups for patients over 75 years, educational programs, improved coordination with Aged Care Assessment Teams and Community Services, inventories and registers of local community services and residential facilities, and appropriate Medicare rebates.

Australia↗
PubMed1994

Educational visiting and hypnosedative prescribing in general practice.

Public concern about the prescription of hypnosedative drugs (mostly benzodiazepines) led to a controlled trial of an educational intervention to promote rational prescribing by general practitioners (GPs). This paper describes the educational intervention and its process evaluation. In urban and rural New South Wales 137 GPs were visited in office hours by a GP or pharmacist who had undergone communication skills training. Material offered to GPs included relaxation tapes and a booklet of problem-orientated management guidelines. The interview had three stages: rapport was established, then educational material was introduced and finally the visitor sought the doctor's agreement to review five patients on long-term benzodiazepines. The visits were well received. Several measures were composed to reflect doctors' motivation and interest in non-drug management; there was virtually no correlation between any of these process measures and the trial outcome: a change in prescribing behaviour. Self-rating of benzodiazepine prescribing greatly underestimated actual self-reported incidents of prescribing. We interpret this as a reminder that we do not always do what we mean to do, and that we do not always do what we think we do.

Anti-Anxiety Agents↗
PubMed1994

General practitioner diagnosis of depression and dementia in the elderly: can academic detailing make a difference?

The objective was to improve the ability of general practitioners (GPs) to diagnose depression and dementia compared with standard screening measures. The setting was a retirement village on the outskirts of Sydney, Australia. The study used a prepost design with a 6 month follow-up. The intervention involved a visit to the GP by an academic detailer who spent 15 minutes discussing the diagnosis of depression and dementia. Ratings of depression and dementia on two occasions by GPs, and by independent interviews were made using the Geriatric Depression Scale, Mini-mental State Examination and Canberra Interview for the Elderly. In the case of depression, the level of agreement (Kappa) between the GPs and all instruments increased significantly by a factor of between 2.3 and 3.3. The doctors did not significantly improve in their agreement with the instruments on the diagnosis of dementia. An academic detailing approach to improving GPs' abilities in the diagnosis of depression can be effective. A controlled trial would be justified to confirm this finding.

Aged↗