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Biomedical subjects

A Rodgers

Publications and source records attributed to A Rodgers.

At least 55 records · Page 3Linked to original sources
PubMed1997

Regional variation in the incidence of hip fracture in New Zealand.

AIM: To determine the regional incidence of hip fracture among individuals aged 60 years or older in New Zealand. METHODS: New Zealand Health Information Service inpatient morbidity data for the years 1988-92 were examined by area health board region to identify all hip fractures (ICD N820) among individuals aged 60 years or older. RESULTS: Substantial regional variation exists in the incidence of hip fractures among older people in New Zealand. Among both men and women, similar regional variations were observed with the age-standardised rates being consistently highest in the West Coast (790 per 100,000 for women and 360 per 100,000 in men) and lowest in Northland (540 per 100,000 in women and 185 per 100,000 in men). CONCLUSION: These findings have implications for resource allocation, both in terms of targeting prevention initiatives and in providing acute and long term management of hip fracture patients. In addition, they raise questions as to why such variations in hip fracture incidence exist in New Zealand.

Aged↗
PubMed1997

Phase I studies of fluorouracil, doxorubicin and vinorelbine without (FAN) and with (SUPERFAN) folinic acid in patients with advanced breast cancer.

PURPOSE: The Breast Cancer Site Group of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG) undertook two parallel phase I studies to determine the maximum tolerated dose (MTD) and recommended phase II dose of vinorelbine in combination with doxorubicin and fluorouracil (with or without folinic acid) in metastatic breast cancer. METHODS: Cohorts of five patients were to receive: (a) fluorouracil 500 mg/m2 and doxorubicin 50 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on days 1, 8 and 15 every 3 weeks (FAN regimen), or (b) fluorouracil 340 mg/m2 and folinic acid 200 mg/m2 on days 1, 2, 3, 4 and 5, doxorubicin 40 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on day 1 and again on day 5 every 4 weeks (SUPERFAN regimen). Eligibility included measurable or evaluable metastatic breast cancer and having received neither previous chemotherapy for metastatic disease nor anthracycline-containing adjuvant therapy. RESULTS: Of 26 and 12 patients enrolled in the FAN and SUPERFAN regimens, 26 and 12 were evaluable for toxicity and 21 and 9 for response, respectively. Median ages were 60.3 years (41-71 years) and 64.2 years (51-73 years). Both regimens required amendment after the first cohort with an original day- 15 vinorelbine dose omitted from the FAN regimen and more prolonged nadir granulocyte counts allowed. Myelosuppression was dose limiting. MTDs in the FAN and SUPERFAN regimens were vinorelbine 25 mg/m2 and 20 mg/m2. Other toxicities included mucositis, septicemia and febrile neutropenia. Peripheral neuropathy and constipation were mild. Of the 21 FAN patients evaluable for response, 3 (14%) had complete responses and 7 (33%) had partial responses, for an overall response rate of 48%; 9 (43%) had stable disease and 2 (9%) had progressive disease as their best response. Of the nine SUPERFAN patients evaluable for response, none had a complete response. There were two (22%) with partial responses, and six (67%) had stable disease and one (11%) had progressive disease as their best response. CONCLUSIONS: The SUPERFAN regimen was too toxic to pursue even at the lowest dose. The recommended phase II starting dose for the FAN regimen was vinorelbine 20 mg/m2. Although these were phase I studies response rates in evaluable patients were less than expected and toxicity did not allow the use of as much vinorelbine in the combinations as had been anticipated. The limited response data from our study would imply that combining vinorelbine with more toxic agents may not enhance response rates and may defeat the advantage of tolerability, especially in elderly patients.

Adult↗
PubMed1997

Structure and arrangement of the delta subunit in the E. coli ATP synthase (ECF1F0).

F1F0 type ATPases are made up of two parts, an F1, which contains three catalytic sites on beta subunits, and an F0 which contains the proton channel. These two domains have been visualized in electron microscopy as linked by a narrow stalk of around 45 A in length. Biochemical studies have provided clear evidence that the gamma and epsilon subunits are components of this stalk. There is an emerging consensus that the gamma and epsilon subunits rotate relative to the alpha 3 beta 3 domain as part of the cooperativity and energy coupling within the complex. Two other subunits are required to link the F1 to F0 in the E. coli enzyme, and these are the delta and b subunits. The structure of a major part of the delta subunit (residues 1-134) has now been obtained by NMR spectroscopy. The main feature is a six alpha-helix bundle, which provides the N-terminal domain of the delta subunit. This domain interacts with the F1 core via the N-terminal part of the alpha subunit. The C-terminal domain of delta is less well defined. This part is required for binding to the F0 part by direct interaction with the b subunits. It is argued that delta and the two copies of the b subunit are components of a second stalk linking the F1 and F0 parts, which acts as a stator to allow the energy-linked rotational movements of delta and epsilon subunits.

Amino Acid Sequence↗
PubMed1997

Effects of beta-blocker therapy on mortality in patients with heart failure. A systematic overview of randomized controlled trials.

AIMS: Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. METHODS AND RESULTS: Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2P = 0.0035), representing an absolute reduction in mean annual mortality from 9.7% to 7.5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were non-significantly greater (2P = 0.09) than those of standard agents (18% reduction SD 15), principally metoprolol. CONCLUSIONS: Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Administration, Oral↗
PubMed1997

Paracetamol poisoning in the north east of England: presentation, early management and outcome.

1. Paracetamol is increasingly involved in self-poisoning in the United Kingdom and remains a common cause of fatal poisoning. 2. To document the epidemiology and early management of paracetamol poisoning data were collected on consecutive patients with suspected paracetamol poisoning presenting to 6 hospitals in the North East of England over 12 weeks in 1994. 3. There were 400 presentations (attendance rate 1.14/10(3) population/yr) involving 343 persons (45% male). Paracetamol concentrations at 4 h correlated weakly with reported paracetamol dose (R = 0.49, P < 0.0001) and were similar comparing those treated and not treated by gastric decontamination. 4. In 38 (9%) cases paracetamol concentrations were above the appropriate nomogram treatment line, including 3% and 20% of patients who reported ingesting less than and more than 12 g respectively. In 21 patients acetylcysteine treatment was deferred until admission to the ward, the mean delay involved was 2.8 h. 5. One patient died, from arrhythmias caused by co-ingested dothiepin. 6. Paracetamol poisoning is common. Most cases do not have potentially toxic plasma paracetamol concentrations, but those who do often present late and antidotal treatment may be delayed inappropriately.

Acetaminophen↗
PubMed1996

Forty years of randomised trials in the New Zealand Medical Journal.

AIM: To identify all randomised trials published in the New Zealand Medical Journal, to document the basic characteristics of these trials and to count the number that were detectable on medline. METHODS: All issues of the New Zealand Medical Journal between 1943 and 1995 were systematically hand-searched. All trials identified were characterised and compared against the trials identified using an optimal medline search strategy. RESULTS: The handsearch identified 152 randomised controlled trials, the first published in 1955. Half the trials recruited less than 34 participants and more than 90% were of pharmaceutical interventions. Only 18% of studies reported on the method of randomisation and 13% provided evidence that final analyses were conducted on an intention to treat basis. Fifty one percent of trials employed a placebo control group and 28% involved a crossover design. Since 1966, when Medline became available, 143 trials were published of which 89 (62%) were identified by the Medline search. CONCLUSIONS: Two of the major difficulties that face those preparing systematic reviews were illustrated by this survey. First, important information on design and analysis is often missing from reports of trials. Second, a large proportion of published randomised trials are not identifiable on Medline. Standard formats for reporting the results of trials and inclusion of trials identified by hand-searching on the Cochrane Collaboration's International Register of Randomised Controlled Trials of Health Care will facilitate the future production of reliable systematic reviews.

Data Interpretation, Statistical↗
PubMed1996

Blood pressure lowering in patients with cerebrovascular disease: results of the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) pilot phase.

1. Among patients with cerebrovascular disease, there is a direct and continuous association between blood pressure and the risk of stroke, but previous trials of blood pressure lowering in this patient group have been inconclusive. 2. PROGRESS (Perindopril Protection Against Recurrent Stroke Study) is a multicentre, randomized, placebo-controlled trial that aims to determine reliably the effect of angiotensin converting enzyme (ACE) inhibitor-based blood pressure lowering on stroke risk in patients with a history of cerebrovascular disease. If a 4 week run-in period on active perindopril is well tolerated, participants are randomized to either perindopril (4 mg) +/- indapamide (2.5 mg) or matching placebo(s). The primary study outcome is stroke and follow-up is for a minimum of 4 years. 3. For the pilot study nearly 5000 medical records were screened and 60 patients with recent cerebrovascular events were approached directly in hospital or at a clinic visit. Sixty-seven patients entered the run-in phase (52 from retrospective screening and 15 by prospective approach) and 60 patients proceeded to randomization. Treatment with perindopril was well tolerated; only three patients were withdrawn due to side effects and four were withdrawn for other reasons. The mean age of randomized patients was 68 years; 70% were male and 55% were 'non-hypertensive'. The mean entry blood pressure was 142/83 mmHg and following pre-randomization treatment this was reduced by 7/4 mmHg. 4. Most patients were identified by retrospective review of medical records, but this was less efficient than prospective methods. Blood pressure lowering was well tolerated by both hypertensive and non-hypertensive patients with cerebrovascular disease. The small numbers of patients and the non-randomized nature of the data reported limit the conclusions that can be drawn, but the results confirm the feasibility of the main study.

Antihypertensive Agents↗
PubMed1996

Attitudes and practices of New Zealand anaesthetists with regard to epidural and subarachnoid anaesthesia.

A survey was conducted among 259 New Zealand specialist anaesthetists to assess attitudes and practices with regard to epidural or subarachnoid anaesthesia (ESA). Ninety-four per cent replied and virtually all of the respondents indicated that they performed ESA at some time. ESA was used by most anaesthetists for most patients undergoing major hip or knee surgery, abdomino-perineal resection, cystectomy, caesarean section or transurethral resection of the prostate, ESA was used is about half of patients undergoing abdominal aortic aneurysm repair, femoro-popliteal bypass or thoracotomy and there was marked variation between anaesthetists in the frequency of using ESA for these procedures. There was broad consensus about the importance of a number of factors that might influence the decision to employ ESA; in particular that systemic sepsis and prolonged bleeding time were important contraindications and that patient preference and chronic lung disease were important indications. However respondents were equally divided as to whether they felt that recent myocardial infarction or congestive heart failure constituted indications or contraindications to ESA.

Anesthesia, Epidural↗
PubMed1996

Presentation of poisoned patients to accident and emergency departments in the north of England.

1. A 12 week prospective survey of all patients of any age with confirmed or suspected poisoning presenting to six accident and emergency departments in the North East of England was performed to establish the local incidence and patterns of presentation of poisoning. 2. 945 episodes of poisoning involving 852 patients were recorded representing approximately 1.2% of all A&E presentations and suggesting an annual attendance rate of 2.7 per 1000 persons per year. 3. Attendance rates varied threefold between hospitals and were similar in males and females overall; between the ages of five and 14 attendances were more common in females (1.9 vs 0.6/10(3)/y) while between 0 and 4 y (3.1 vs 2.4) and 25 and 34 y (3.9 vs 2.9/10(3)/y) they were more common in males. 4. The median interval between poisoning and presentation was 2 h (mean 4.1 h) and only 19% of cases presented within 1 h. Presentation was most common between Friday evening and Tuesday morning and in the late afternoon and evening. 5. 6% of the patients presented more than once with poisoning during the study period and 37% had a past history of deliberate self-harm. The most common poisons involved were paracetamol (43%), opioids (15%) and benzodiazepines (15%). 6. The study illustrates the frequency of presentations of poisoning to A&E departments. The high rate of poisoning in young men and the increasing use of paracetamol are particular causes for concern.

Acetaminophen↗
PubMed1996

Factors affecting hospital admission and length of stay of poisoned patients in the north east of England.

1. Poisoning is a common reason for presentation to hospital and hospital admission but there is no agreed policy for managing these patients. This study examined the management of patients presenting with poisoning and the factors affecting the probability of hospital admission and prolonged stay. 2. Data on all cases of poisoning presenting to six Accident and Emergency departments in the North East of England over 12 weeks in 1994 was collected prospectively from A&E notes. Length of stay and outcome were recorded from hospital computer records. 3. Overall, 73% of patients were admitted to a medical ward. Probability of admission was not independently affected by age or gender but was increased in those with intentional poisoning (Odds Ratio (OR) 3.3 [95% CI 1.8, 6.1]), a history of self harm (OR 1.7, [1.0, 2.9]) or potentially hazardous poisoning (OR 3.7 [2.1, 6.6]). There were significant variations between hospitals (50-80%) which could not be attributed to case mix. 4. Prolonged stay (> 2 nights) was more common in patients over 65 years (OR 6.8 [2.9, 16.1]), those with intentional poisoning (OR 2.7 [1.1, 6.6]) and those with potentially hazardous poisoning (OR 2.6 [1.4, 4.9]). Mean hospital stay was 1.5 days and varied significantly between hospitals from 0.8 to 2.1 days and this was independent of case mix. 5. There are appreciable variations in the management of poisoning between hospitals which are not explained by patient characteristics. Savings would occur if rates of admission and duration of stay were reduced by those hospitals where admission is more frequent or hospital stay is longer. However, the impact of this on long term morbidity is unknown.

Adolescent↗
PubMed1995

Blood pressure lowering for the primary and secondary prevention of coronary and cerebrovascular disease.

An overview of the 17 completed randomised trials of antihypertensive treatment demonstrates that a 5-6 mm Hg reduction in DBP reduced stroke risk by 38% (SD 4) and CHD risk by 16% (SD 4). These results indicate that a few years' treatment with diuretic- or beta-blocker-based therapy produces most or all of the long-term stroke avoidance and much of the long-term CHD avoidance that would be predicted from observational epidemiological studies, given the blood pressure reductions that were achieved in the trials. The relative risk reductions were similar in trials of older and younger patients, although the absolute reduction in events was more than twice as great in the trials in older patients. From these results it can be estimated that in fully compliant patients at similar risk of vascular disease to those included in the trials, antihypertensive treatment for 5 years would prevent one major vascular event among every 20 older patients and one major vascular event among every 60 younger patients. Obviously the benefits of treatment will be greater among those at higher risk than the patients included in the previous trials. The greatest benefits are likely to be achieved in those with a history of vascular disease since their risk of future events is particularly high. Among such patients it is possible that blood pressure reduction will confer worthwhile benefits in those without hypertension, as well as those with hypertension. It is also possible that the benefits of treatment will be determined by the size of the blood pressure reduction and by the choice of the anti-hypertensive agent. However, each of these possibilities requires confirmation in large scale randomised controlled trials.

Adult↗
PubMed1995

Determination of urinary calcium oxalate crystallization mechanisms and kinetics using flow cytometry.

This paper describes the application of flow cytometry to the determination of calcium oxalate crystallization kinetics and mechanisms in real urine. The technique has the unique advantage of simultaneously providing quantitative particle number-size distributions and qualitative data concerning particle structure and morphology. Twenty-four-hour urines from 10 healthy male subjects were treated with sodium oxalate and the ensuing crystallization of calcium oxalate was monitored by flow cytometry. In 7 specimens crystallization was accompanied by increasing size and by a fundamental change in particle morphology. This suggests that nucleation and aggregation occurred in these specimens. In the remaining 3 samples, increasing particle numbers occurred without any changes in size or morphology, indicating that nucleation was the sole mechanism in these specimens. These results demonstrate that flow cytometry is able to differentiate between nucleation, growth and aggregation mechanisms thereby making it an extremely useful analytical tool for stone researchers.

Adult↗
PubMed1995

Immunization with class I human histocompatibility leukocyte antigen can protect macaques against challenge infection with SIVmac-32H.

OBJECTIVE: To evaluate the efficacy of immunopurified class I human histocompatibility leukocyte antigen (HLA) to protect against SIV infection. METHODS: HLA class I antigens were immunopurified from a human B-lymphoblastoid cell line. Groups of four macaques were vaccinated subcutaneously with four doses of the immunogen in adjuvant, or with adjuvant alone and subsequently challenged intravenously with 10 median monkey infectious doses of cell-free SIVmac-32H. Infection was determined by polymerase chain reaction for SIVmac proviral DNA and by virus isolation. Antigen-specific humoral and cellular immune responses were monitored. RESULTS: Macaques immunized with the HLA molecules produced anti-HLA class I antibodies that inhibited SIV replication in vitro and downregulated autologous T-cell proliferation against irradiated C8166 cells. They were partially protected (two out of four) from virus infection for at least 33 weeks when challenged with SIV grown in human cells. All four control animals were infected. CONCLUSIONS: This demonstration of partial protection, together with our previous work reporting that vaccination with allogenic cynomolgus lymphocytes can protect against challenge infection with SIV grown in simian cells, suggests that allogenic immune response induced before or during establishment of HIV infection may have important implications for AIDS disease progression.

Animals↗