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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 325 records · Page 18Linked to original sources

Projection structure of an invertebrate rhodopsin.

Rhodopsin is the G-protein-coupled membrane receptor that initiates the visual transduction cascade in retinal photoreceptors. In the present study rhodopsin from the dark-adapted retinas of squid (Loligo forbesi) was detergent-extracted, purified, and reconstituted into native squid photoreceptor lipids following proteolytic cleavage of its prolinerich C-terminus. Two-dimensional crystals of C-terminally truncated rhodopsin reconstituted from octyl glucoside solution formed in a p222(1) lattice (a = 44 A, b = 131 A). Electron micrographs of frozen-hydrated crystals were processed and a projection structure to 8 A resolution was calculated. The projection map obtained is very similar to maps previously determined for bovine and frog rhodopsins although the crystal packing of the molecules is quite different. Comparison of the maps shows that the arrangement of alpha-helices in the proteins is very similar despite their great phylogenetic distance; this structure is likely to be present in the whole superfamily of G-protein-coupled receptors. Invertebrate rhodopsins have a large insertion in the helix 5-helix 6 loop. Assignment of an additional density in the squid rhodopsin map to this region supports a previously proposed helix assignment and identifies the end-to-end contacts as helices 1 and 5.

Animals↗

Does the Kensey catheter keep a coaxial position inside the arterial lumen? An in-vitro angioscopic study.

Angioscopy was used to evaluate the "self-centering" ability of three Kensey catheters (KC) with different flexibility: one 8Fr "peripheral" and two 5Fr "coronary" (I & II). Angioscopic observations were made inside arteries, 5-18 mm in diameter. There was a good correlation between flexibility and self-centering of the KC [r = 0.83, p less than 0.05]. Increasing the flow rate of rinsing solution from 18 to 60 ml/min prolonged coaxial position from 8.9 +/- 3.3 to 36 +/- 2.2 sec/min of activation [p less than 0.001]. A smaller effect on coaxial position was exerted by increasing cam speed from 5.2 +/- 0.7 to 19.2 +/- 1.6 sec/min (p less than 0.001). In conclusion, angioscopy showed that the KC has a limited ability to maintain a coaxial position inside the arterial lumen and operators cannot rely on its self-centering property.

Angioplasty, Balloon, Coronary↗

Risperidone versus haloperidol: I. Meta-analysis of efficacy and safety.

Haloperidol is widely considered a reference standard in antipsychotic therapy and is commonly used in comparative studies of the efficacy and safety of antipsychotic medication. Comparative clinical trials have shown that the novel antipsychotic agent risperidone tends to have greater efficacy (i.e., clinical response defined as a > or = 20% reduction in total scores on the Positive and Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and Laird's random-effects model to analyze pooled patient data from available randomized, double-masked, comparative trials of risperidone and haloperidol in patients with schizophrenia treated for at least 4 weeks at recommended doses. The purpose of the analysis was to determine whether there are significant overall differences in the rates of patient clinical response, prescription of anticholinergic agents, and treatment dropout. Six of the nine trials revealed in a literature search met all criteria for inclusion in the meta-analysis. The meta-analysis showed that in patients with chronic schizophrenia, risperidone therapy is associated with significantly higher response rates, significantly less prescribing of anticholinergic medication, and significantly lower treatment dropout rates than haloperidol. These results demonstrate the greater treatment efficacy associated with risperidone compared with haloperidol and suggest both a lower incidence of EPS and improved treatment compliance.

Antipsychotic Agents↗

Risperidone versus haloperidol: II. Cost-effectiveness.

Australia and Canada are currently the only Western nations with government guidelines for analyzing the cost-effectiveness of drugs. We used guidelines issued by the Australian Pharmaceutical Benefits Advisory Committee to construct a model for comparing the cost-effectiveness of risperidone and haloperidol over a 2-year period in patients with chronic schizophrenia. Use of clozapine was also included in the analysis as an alternative treatment given to patients who proved unresponsive to therapy with haloperidol or risperidone. Results are expressed in Australian dollars. Cost-effectiveness was determined by using decision-analytic modeling to compare clinical outcomes and costs. The analytic model contained a decision tree for each of the compared agents that tracked the distribution of patients between treatment outcome pathways (i.e., scenarios). Distributions were based on probabilities derived from our meta-analysis results reported elsewhere and from other sources. Each scenario had an associated monetary cost that included all significant direct costs (i.e., hospital costs; outpatient costs; and the cost of drugs, the services of health care professionals, and government-subsidized hostel accommodation). The cost for a given outcome was the sum of costs for all scenarios leading to that outcome. Cost-effectiveness was expressed as the total cost per favorable outcome. The definition of a favorable outcome was one in which the patient was in a response phase at the end of the 2-year period. The probability of a patient experiencing a favorable outcome at the end of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for haloperidol. The expected cost per favorable outcome was $19,709.00 for risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective than haloperidol and therefore was "dominant" in pharmacoeconomic terms because it produced a higher proportion of favorable outcomes at lower cost. Sensitivity analysis showed that the difference in clinical response rate was a key determinant of cost-effectiveness.

Antipsychotic Agents↗

Prospective randomized trial to assess caloric and protein needs of critically Ill, anuric, ventilated patients requiring continuous renal replacement therapy.

OBJECTIVES: We measured the energy and protein needs in 50 sequential, critically ill, ventilated patients requiring continuous renal replacement therapy (CRRT) for renal failure by using indirect calorimetry and three sequential isocaloric protein-feeding regimes of 1.5, 2.0, and 2.5 g. kg(-1). d(-1). We also assessed the compliance of actual feeding with target feeding and correlated the predictive energy requirements of the formulae with the actual energy expenditure (EE) measured by indirect calorimetry. We also determined whether these feeding regimes affected patient outcome. METHODS: The energy and protein needs of 50 consecutive, critically ill patients (31 male; age 53.3 +/- 17.4 y; Acute Physiology and Chronic Health Evaluation (APACHE II) score: 26.0 +/- 8.0; Acute Physiology and Chronic Health Evaluation score predicted risk of death: 50.0 +/- 25.0%) were assessed by using indirect calorimetry and ultrafiltrate nitrogen loss. Entry into this study was on commencement of CRRT. To eliminate any beneficial effect from the passage of time on nitrogen balance, 10 of the 50 patients were randomized to receive 2.0 g. kg(-1). d(-1) throughout the study, and the others received an escalating isocaloric feeding regime (1.5, 2.0, and 2.5 g. kg(-1). d(-1)) at 48-h intervals. Enteral feeding was preferred, but if this was not tolerated or unable to meet target, it was supplemented or replaced by a continuous infusion of total parenteral nutrition. Energy was given to meet caloric requirements as predicted by the Schofield equation corrected by stress factors or based on the metabolic cart readings of EE and was kept constant for all patients throughout the trial. Patients were stabilized on each feeding regime for at least 24 h before samples of dialysate were taken for nitrogen analysis at 8-h intervals on the second day. CRRT was performed by using a blood pump with a blood flow of 100 to 175 mL/min. Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h. A biocompatible polyacrylonitrile hemofilter was used in all cases. RESULTS: EE was 2153 +/- 380 cal/d and increased by 56 +/- 24 cal/d (P < 0.0001) throughout the 6-d study period to 2431 +/- 498 cal/d. At study entry, the mean predicted (Schofield) caloric requirement was 2101 +/- 410. Patients received 99% of the predicted energy requirements. However, the mean EE was 11% higher at 2336 +/- 482 calories. This difference was not uniform. If the predicted caloric requirement was less than 2500, the EE exceeded the predicted by an average of 19%. If the predicted caloric requirement was greater than 2500, the EE on average was 6% less than predicted. This relation was significant (P = 0.025) and has not been described previously. Nitrogen balance was inversely related to EE (P = 0.05), positively related to protein intake (P = 0.0075), and more likely to be attained with protein intakes larger than 2 g. kg(-1). d(-1) (P = 0.0001). Nitrogen balance became positive in trial patients over time but were negative in control patients over time (P = 0.0001). Nitrogen balance was directly associated with hospital outcome (P = 0.03) and intensive care unit outcome (P = 0.02). For every 1-g/d increase in nitrogen balance, the probability of survival increased by 21% (P = 0.03; odds ratio, 1.211; 95% confidence limits, 1.017,1.443). Further, although enterally and parenterally fed patients had lower mortalities than predicted, the presence of enteral feeding, even after adjusting for predicted risk of death, had a statistically significant benefit to patient outcome (P = 0.04). CONCLUSIONS: This study found that a metabolic cart can improve the accuracy of energy provision and that a protein intake of 2.5 g. kg(-1). d(-1) in these patients increases the likelihood of achieving a positive nitrogen balance and improving survival. Enteral feeding is preferable, but if this is not possible or does not achieve the target, then it should be supplemented by parenteral feeding.

APACHE↗

Predicting the criminal antecedents of a stranger rapist from his offence behaviour.

Approximately 85% of stranger rapists have criminal records, which usually contain a mixture of crime types. This study was designed to ascertain if inferences about such records could be made from aspects of offence behaviour, as described by the rape victims, focusing on both non-sexual behaviours and traits more obviously associated with previous criminality. The statistical technique used was logistic regression. The results demonstrated that it was very possible to obtain indications of a rapist's criminal antecedents from his offence behaviour. The three most promising models were those that predicted whether or not the offender had convictions for burglary, whether or not he had convictions for violent offences, and whether the offence was an apparent 'one-off' occurrence rather than the work of an experienced rapist.

Behavior↗