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Biomedical subjects

J J McNeil

Publications and source records attributed to J J McNeil.

At least 19 recordsLinked to original sources
PubMed1992

Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension.

The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Survey of drug-related deaths in Victoria.

OBJECTIVE: To audit drug-related deaths to determine the types of agents causing death in Victoria and to identify possible strategies for prevention of deaths in future. DESIGN: Retrospective audit of Coroner's case records. SUBJECTS: All deaths reported to the Coroner during 14 months from 1 July 1989 to 31 August 1990 in Victoria in which toxicological investigation was undertaken and drugs or poisons were detected and were believed to be a major cause of death. RESULTS: Of the 231 people who had drug-related deaths, 156 were males, 75 were females and the average age was 35.5 +/- 14 years. Heroin and morphine were judged to be the primary cause of death in 35% of subjects and methadone in a further 4.8%. Tricyclic antidepressants were responsible for 14% of deaths, with no deaths due solely to mianserin. Benzodiazepines were the prime cause of death in 6.5% of subjects, but were identified in 40%. Poisons and chemicals were involved in only 3% of deaths. Prescription drugs were primarily responsible for 47% of deaths. Forty-eight per cent of deaths occurred in known injecting drug users and 42% of all subjects had a clear history of antecedent depression. Only one drug-related death was clearly accidental, that of a two-year-old child taking his parents' medications, but the mode of most deaths was not clear, and may not have been suicide. Most deaths occurred outside hospital, only 25 subjects reaching hospital alive. CONCLUSIONS: Barbiturates and chloral hydrate are no longer major causes of drug-related deaths, probably because of decreased availability. Some drug-related deaths, especially those related to tricyclic antidepressants, may be prevented if deaths and hospitalisations due to toxic substances are monitored and the availability and scheduling of toxic substances are regularly reviewed.

Adolescent↗
PubMed1992

Haematological profile of healthy elderly Australians.

OBJECTIVE: To determine normal values for haematological parameters in healthy elderly persons, and document any changes in these over a 12 month period. DESIGN: The study was conducted as part of a randomised controlled trial of low-dose aspirin for primary prevention of cardiovascular disease in the elderly. All participants (380) had a full blood examination performed at entry, which was repeated after 12 months. The baseline results for all patients and the 12 month findings in a cohort of 162 persons allocated placebo were used in the present study. SETTING: Community-based (general practices and residential retirement villages). SUBJECTS: Persons aged 70 years and over (53% females) who were ambulatory, living independently, and volunteered to participate. None had significant vascular disease, peptic ulceration, haemorrhagic symptoms or were currently taking non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Full blood examination (excluding white cell differential counts) performed with a Technicon H1 analyser. RESULTS: The mean haemoglobin level +/- standard deviation (SD) was 14.69 +/- 1.10 g/dL (for men) and 13.72 +/- 1.05 g/dL (for women). Significant differences (P less than 0.001) in packed cell volume, red cell and platelet counts were observed between the two sexes. No clinically significant change was observed in any of the parameters over a 12 month period. CONCLUSIONS: Haematological reference values for healthy elderly Australians are consistent with normal values reported in younger populations for both sexes. As a result recommendations are provided for normal reference values among this group in an Australian setting.

Aged↗
PubMed1992

Monitoring chemical exposure using breast milk: a methodological review.

Retrospective exposure assessments are often a major weakness in environmental epidemiologic studies. Many environmentally important chemicals are persistent lipophilic compounds which partition into fat and breast milk. The analysis of these chemicals in breast milk provides a noninvasive means of collecting large volumes of a biologic fluid that correlates well with body burden. This may provide an integrated measure of cumulative absorption over several years which can be used to assess exposure in several different epidemiologic study designs. However, consideration of toxicokinetic principles in the study design is important in order to allow for maternal and other factors unrelated to exposure which may influence breast milk concentrations. These factors include maternal age, parity, maternal body weight, time of sampling during the lactation period, and fat content of the breast milk. Failure to use standardized entrance criteria and to allow for the above factors in the analysis and interpretation of the study results may lead to invalid conclusions regarding past exposures. Allowance must also be made for the restrictions on the sampling frame available in any epidemiologic study using breast milk analysis. Published studies to date often have had several methodological deficiencies. With the introduction of biologic specimen banks, breast milk collection and analysis should play an important role in future epidemiologic studies, especially those investigating health outcomes in infants.

Body Weight↗
PubMed1992

Linking prescription and patient-identifying data: a pilot study.

OBJECTIVE: To link a Pharmaceutical Benefits Scheme (PBS) prescription data set with patient-identifying data held by the Health Insurance Commission (HIC) and to then determine the prevalence of prescribing of cardiovascular drugs, non-steroidal anti-inflammatory drugs, hypnotics and minor tranquillizers, and diuretics (prescribed without other cardiovascular drugs) by age and sex in two defined populations. DESIGN: Prescription data for a three-month period in 1985 were matched with patient-identifying information to obtain a database which included the patient's age, sex and an identifying number, for each prescription record. The percentages of the population taking a drug from each of the drug categories mentioned above were then determined and the effect of age, sex and region of residence on prescribing prevalence was investigated using logistic regression analysis. SETTING: Two rural regions of Australia with a total population of 65,087 residents. MEASUREMENTS AND MAIN RESULTS: Of the 101,383 prescriptions dispensed over the period 96% could be matched with HIC information. In the two regions combined, the percentages of the population taking a cardiovascular drug, non-steroidal anti-inflammatory drug, hypnotic or minor tranquilizer, or diuretic (without other cardiovascular drugs) were 10.4%, 5.8%, 3.5% and 2.5%, respectively. Prescribing rates were higher for females than males, increased with age and varied between the two regions. Approximately 5% of women aged 30-39 years were taking diuretics without other cardiovascular drugs, compared with only 0.2% of men in the same age group. CONCLUSIONS: This pilot study illustrates the use of a patient-identified prescription database for drug utilisation review, therapeutic audit and hypothesis generation.

Adult↗
PubMed1992

Drug overdose--reducing the load.

OBJECTIVE: To review available information about various methods for reducing gastrointestinal absorption of a poison or drug. DATA SOURCES: Articles on overdose and accidental poisoning generated by the Australian Medlars Service and concentrating on the period between 1985 and 1990 were surveyed. Earlier studies were included if relevant. STUDY SELECTION AND DATA EXTRACTION: English language articles with an emphasis on studies using objective methods to measure individual and comparative efficacy of gastrointestinal decontamination techniques were selected. A total of 65 articles were reviewed. DATA SYNTHESIS: Gastric emptying procedures (gastric lavage or emesis caused by syrup of ipecac) are only effective if performed within one hour of drug ingestion. Gastric lavage is superior to syrup of ipecac. Oral administration of activated charcoal is more effective than either gastric emptying procedure, and is recommended for most cases of poisoning. Cathartics (sorbitol) can be used with activated charcoal. Whole bowel lavage with polyethylene glycol is indicated in selected cases of potentially lethal overdose where the toxic substance cannot be absorbed by charcoal and has passed the pylorus. CONCLUSIONS: Children--syrup of ipecac can be given at home to children older than 12 months. Most children who reach hospital can be treated by charcoal alone. ADULTS--Most patients are managed with supportive care and, in the absence of contraindications, a single dose of activated charcoal if seen within four hours of ingestion of the poison or drug. Gastric lavage is used if the patient presents within one hour of ingestion and has clinical features of toxicity.

Adult↗
PubMed1992

Epidemiologic aspects of isolated systolic hypertension and implications for future research.

Isolated systolic hypertension represents an important public health issue in the 1990s because of its prevalence in the elderly and its importance as a risk factor for cardiovascular morbidity and mortality. Methodologic differences may account for the wide variation between prevalence rates in studies reported. With the advent of newer methods of blood pressure (BP) assessment, such as noninvasive ambulatory BP monitoring, it may be possible to define more accurately the true population at risk. Recent data from the Systolic Hypertension in the Elderly Program has indicated a clear benefit of treatment with a reduction in total stroke of 36%, and a reduction of 25 and 32% in the combined end points of coronary heart disease and cardiovascular disease, respectively. Further studies are now required to elucidate what treatment regimens are most effective in preferentially reducing both systolic BP, without producing undesirable effects such as diastolic hypotension, and fatal and nonfatal events. One such trial is underway in Europe using a drug regimen different from that in the Systolic Hypertension in the Elderly Program. The cost implications associated with treating the population at risk are potentially large but these are now based on firm scientific evidence.

Aged↗
PubMed1992

Risk factors for cardiovascular disease in chronic spinal cord injury patients.

To establish whether the reported increased cardiovascular (CV) morbidity in spinal cord injury (SCI) patients is due to increased levels of established CV risk factors, we assessed overall CV risk in 102 consecutive patients aged 25-64 by calculation of a 'risk factor score' (RFS) derived from the MRFIT study (age, diastolic blood pressure (DBP), total cholesterol (TC) level, cigarettes/day, sex), obtaining a percentile position amongst an age and sex matched peer group from the 1983 Australian Risk Factor Prevalence Study. Chronic SCI patients had a very low overall percentile position of risk of 26.03 + 15.06 (mean +/- S.D.) and those patients with SCI for greater than 10 years had only a slightly higher risk position of 33.16 +/- 29.66. The low relative risk in SCI patients was due mainly to significantly lower DBP levels (67 +/- 13 mm hg), as TC levels (5.38 +/- 1.60 mmol/L) and cigarette consumption (31% smokers, mode 11-20/day) were similar to the control population (83 +/- 12 mmHg, 5.68 +/- 1.2 mmol/L, 28% smokers, mode 11-20/day, respectively). As other known risk factors such as lipoprotein cholesterol fractions were not included in the RFS index, these were measured in 327 consecutive SCI patients. HDL cholesterol levels, which are negatively correlated with CV risk, were significantly lower in SCI patients (1.12 +/- 0.30 mmol/L) compared to controls (1.35 +/- 0.35 mmol/L) and those patients more than 10 years post SCI had still lower levels (1.02 +/- 0.40). These data suggest that the reported increased incidence of CV disease in SCI patients is unexplained by increases in BP, TC or smoking. However, low HDL levels may contribute to CV risk and the role of other risk factors such as increased vascular reactivity remain to be established.

Adult↗
PubMed1992

Components of blood pressure variability in the elderly and effects on sample size calculations for clinical trials.

This study investigated components of blood pressure variability in the elderly using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different design scenarios in the elderly. Twenty-six elderly subjects not receiving antihypertensive medication were recruited from general practices and seen on four occasions at weekly intervals. On each occasion of blood pressure was measured in the clinic using a standard mercury sphygmomanometer and then for 24 h using a noninvasive ambulatory monitoring device. The between subject and between subject/within occasion components of blood pressure variability were determined by analysis of variance and used to calculate to sample size requirements for parallel and crossover trials respectively. The between subject variance of mean blood pressure was 1/3 greater with clinic readings, except within a subgroup of subjects who had isolated systolic hypertension (ISH). Increasing the number of readings or occasions on which measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was small. With crossover designs, the between subject component of variance is eliminated resulting in substantial reduction in sample size. Whereas 60 subjects with ISH would be required to detect a 10 mm Hg difference in systolic blood pressure between two treatments in a parallel design using casual readings, only 18 are required with a crossover trial. If ABPM is used the number of subjects required are 54 and 14, respectively. Reducing variability with ABPM involves a trade-off between the increased number of readings available with the technique against the highly uniform and standardized conditions used to determine clinic blood pressures. ABPM appears most useful as a strategy for reducing sample size in parallel group trials involving small numbers of subjects measured on one occasion.

Aged↗
PubMed1992

Tampons: a novel patient-administered method for the assessment of genital human papillomavirus infection.

Assessment of human papillomavirus (HPV) infection usually requires a speculum examination to collect genital specimens. A technique using tampons as a patient-administered method for the collection of specimens was studied by dot blot hybridization (HPV types 6, 11, 16, 18, 31, and 33) and polymerase chain reaction (PCR). Tampons and cervical scrapes were collected from 48 consecutive women attending a dysplasia clinic. Tampons provided a significantly larger pellet volume (P less than .002) and more DNA (P less than .01) than scrapes. There was a close correlation when samples were analyzed for the presence of HPV DNA. Using dot blot hybridization, 8 cervical scrapes (17%) and 9 tampons (19%) were positive for HPV DNA (90% correlation). By PCR, 35 cervical scrapes (73%) and 33 tampons (69%) were positive for HPV DNA (88% correlation). Thus, tampon specimens are an easy method for assessment of genital HPV infection.

Cervix Uteri↗
PubMed1992

Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects.

In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in less than or equal to 2 h after dosing with an elimination t1/2 of 1-2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5-8 h after dosing, and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2-8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in predose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5-7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose.

Aged↗
PubMed1992

Is isolated systolic hypertension a 'white coat' phenomenon in the elderly?

1. Repeated clinic blood pressure measurement was compared with non-invasive ambulatory blood pressure (ABP) monitoring in 10 elderly subjects with isolated systolic hypertension (ISH) and 11 normotensive controls (NT). 2. Subjects were assessed on four occasions at weekly intervals. None was receiving antihypertensive or vasoactive medication. 3. Mean clinic blood pressure was consistently higher than mean daytime ABP in both clinical groups. This effect was greater for systolic (SBP) than diastolic blood pressure (DBP) and in the ISH group compared with the NT group. The reproducibility of the clinic minus ABP difference was high in both groups; the mean +/- s.d. of the differences was 26 +/- 15/9 +/- 2 mmHg in the ISH group and 7 +/- 18/8 +/- 9 mmHg in the controls. 4. ABP readings were normally distributed for both SBP and DBP in both groups. In the ISH group, the frequency distribution of SBP readings was shifted to the right whilst the distribution of DBP readings overlapped that of the NT subjects. 5. These results suggest a pressor response may largely account for the elevated SBP seen in elderly subjects with sustained ISH based on casual readings.

Aged↗
PubMed1992

Sample size requirements for clinical trials of isolated systolic hypertension.

1. This study investigated components of blood pressure variability in elderly subjects with isolated systolic hypertension (ISH) using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different designs. 2. Eleven elderly subjects not receiving antihypertensive medication were seen on four occasions at weekly intervals. On each occasion blood pressure was measured in the clinic and then for 24 h using a non-invasive ABPM device. Nested analysis of variance was used to calculate the 'between subject' and 'between subject within occasion' components of blood pressure variability. 3. Increasing the number of readings or occasions where measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was less than 50. Use of a cross-over design substantially reduced the sample size required. 4. ABPM appears most useful as a strategy for reducing sample size in parallel group trials in ISH involving small numbers of subjects measured on one occasion.

Aged↗
PubMed1991

Cardiac risk factor management. Experience of an outpatient hypertension clinic.

OBJECTIVE: To describe the outcome of the management of cardiovascular risk factors in the hypertension clinic of a teaching hospital over a five-year period. DESIGN: Retrospective analysis of risk factor data (blood pressure, plasma cholesterol level, body weight, smoking and drinking habits) obtained from computerised hypertension clinic progress report forms. SETTING: Public teaching hospital. PATIENTS: One hundred and thirty-one patients referred to the clinic from both general practice and from within the hospital who attended the clinic regularly during the five-year study period. INTERVENTION: Long term management of hypertension and coexisting coronary risk factors by dietary, medical and lifestyle intervention. RESULTS: There was a significant improvement in diastolic blood pressure control in 1990 versus 1986 in both men and women, while systolic blood pressure improved in women only. The number of patients controlled with monotherapy increased from 38% in 1986 to 45% in 1990. Eighty-nine per cent of the men and 85% of women remained above their maximum desirable weight. Reported levels of alcohol consumption were low and the proportion of smokers was below that of the general population. A significant decline in plasma total cholesterol levels was observed in the women. Despite dietary advice and a limited use of lipid lowering drugs, 53.2% of the men and 66.1% of the women continued to have total plasma cholesterol levels above 5.5 mmol/L in 1990. High density lipoprotein levels increased significantly in the women only. CONCLUSION: A high proportion of our clinic patients have well controlled hypertension, but the clinic program produced little evidence of improvement in risk factors in men stabilised by long term therapy. More intensive methods of achieving lifestyle modification and a wider use of lipid lowering drugs may be needed if we are to achieve satisfactory body weights and lipid profiles in hypertensive patients.

Ambulatory Care Facilities↗
PubMed1991

Hypertension in the elderly: epidemiology and pathophysiology.

In all but a few remote and unacculturated tribes, blood pressure rises with advancing age. By the time Western adult males or females reach their 70s their probability of being hypertensive (BP greater than 140/90 mmHg) exceeds 50%. Unlike various other risk factors for vascular disease, hypertension retains its predictive power as age increases, but since the baseline risk is higher, the number of cases of disease attributable to hypertension is much higher in the elderly than in the young. The reason for the rise in blood pressure with aging is not well established, although a high lifetime intake of sodium may be a contributing factor. It now appears that the major hemodynamic abnormality is an increased peripheral resistance. It is possible that an accentuation of changes that take place with normal aging might be responsible for this phenomenon. They include a reduction in renal function, decreased baroreceptor sensitivity, or increased sympathetic activity. Up until the present time studies have been unable to isolate the mechanisms involved.

Age Factors↗
PubMed1991

Comparison of recruitment strategies for a large-scale clinical trial in the elderly.

Formal evaluation of recruitment strategies for clinical trials conducted in the community setting, rather than in hospitals, is limited despite recruitment rates and costs having significant implications for the planning of large trials. As part of the development of a large-scale primary prevention trial of low-dose aspirin in 15,000 elderly persons (aged 70 years and above) to be undertaken in a community setting, a pilot study involving 400 participants was carried out to evaluate different recruitment strategies. Three techniques were compared: recruiting from the electoral roll (by individual invitation using direct mail), local community approach (through retirement villages, local media, elderly community groups), and using general/family practice (identifying persons over 70 within a practice and direct mail invitation to participate). Screening of potential participants was carried out by a trained trial nurse with limited involvement only of medical practitioners. The target recruitment figure was achieved in 4 months using the equivalent of 1.5 full-time nurses. General practice was the most effective method utilized, with a yield of one participant recruited per six approached at an estimated cost of A$48.36 per recruited participant. This compares with yield rates of 1 per 29 (for the local community approach) and 1 per 17 for the electoral roll, and costs per participant of A$42.54 and A$59.37 respectively. Other less tangible benefits of general practice include the greater cooperation of primary care practitioners in patient follow-up and end-point ascertainment.

Aged↗
PubMed1991

Rationale for a primary prevention study using low-dose aspirin to prevent coronary and cerebrovascular disease in the elderly.

The benefits of prophylactic aspirin therapy to prevent cardiovascular and cerebrovascular disease in asymptomatic individuals remains unclear. The rationale for developing a multicentered, double-blind, placebo-controlled clinical trial to determine whether low-dose aspirin (100 mg daily) prevents cardiovascular and cerebrovascular morbidity and mortality in persons aged 70 years and over with no evidence of pre-existing cardiovascular or cerebrovascular disease is described. Sample size calculations have indicated that 15,000 subjects would be required over a 4-year follow-up period in order to demonstrate a 20% reduction in overall cardiovascular mortality at the 0.01 level with a power of 0.8. Such a large-scale community-based clinical trial has never been conducted in Australia in this age group. Therefore the PACE (prevention by low-dose aspirin of cardiovascular disease in the elderly) pilot study has been developed to test recruitment strategies and methods and ascertaining disease end-points.

Adult↗