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Biomedical subjects

K O'Malley

Publications and source records attributed to K O'Malley.

At least 19 recordsLinked to original sources
PubMed1992

The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry.

This cross-sectional study investigated whether the technique of blood pressure measurement used (conventional sphygmomanometry vs. ambulatory monitoring) affects the relation between blood pressure and both age and body mass index. Two independent data sets were analyzed. The first comprised 328 subjects (48% men) drawn from the population of a small Belgian town, and the second comprised 776 Irish bank employees (51% men). Age ranged from 17 years to 81 years, and body mass index (weight (kg)/height (m)2) ranged from 16.6 to 40.2. Twenty-four-hour ambulatory blood pressure was lower than blood pressure measured by a nurse in both the Belgian population sample (118/71 mmHg vs. 122/73 mmHg) and the Irish employees (118/72 mmHg vs. 119/76 mmHg). When blood pressure was measured by an observer, the well-established relations between systolic and diastolic blood pressure and both age and body mass index were evident. When the analyses were repeated using 24-hour measurements, the increment (cross-sectionally assessed) in blood pressure with age was weaker, especially in young and middle-aged subjects (20-60 years), while the increase in blood pressure with body mass index was also reduced. The within-subject differences between the conventional and ambulatory blood pressure measurements increased with older age and greater body mass index. Several other relations with blood pressure as the response variable may require revision in light of the present findings.

Adult↗
PubMed1992

Individual quality of life in patients undergoing hip replacement.

Quality of life (QoL) assessment is becoming increasingly important for measuring the impact of illnesses, diseases, and their treatment and for deciding priorities when allocating resources. We developed a novel method to measure QoL from the perspective of the individual patient. The schedule for the evaluation of individual quality of life (SEIQoL) was devised from the technique known as judgment analysis to measure patients' level of functioning in five self-nominated facets of life and the relative weight or importance attached to these areas. We applied this method, together with traditional measures of health status, in a prospective intervention study of 20 patients undergoing unilateral total hip-replacement surgery with six-month follow-up by comparison with matched, non-patient controls. Health status was significantly improved by hip replacement on the McMaster health index questionnaire (p less than 0.001) and the arthritis impact measurement scales (p less than 0.001). Individually measured QoL was significantly increased after surgery when measured by SEIQoL (p less than 0.02). The individual nature of QoL was reflected in the variety of life areas nominated as important by individual patients, the differences in relative weights attached to these areas, and the complex nature of the changes that occurred postoperatively. Our data not only highlight such individuality but also show that SEIQoL provides a means by which this can be assessed scientifically.

Adult↗
PubMed1992

Management of elderly patients with sustained hypertension.

OBJECTIVE: To assess the clinical benefits of treating hypertension in elderly patients and to derive practical guidelines regarding indications, goals, and forms of treatment. DESIGN: Review of six published randomised trials. RESULTS: Active treatment of hypertension in elderly patients was associated with significant improvements in several indices of cardiovascular morbidity and mortality, particularly the incidence of fatal and non-fatal strokes. On the basis of the trial data, combined systolic and diastolic hypertension was defined as a sustained systolic pressure greater than 160 mmHg and diastolic pressure greater than 90 mmHg. There is convincing evidence that efforts should be made to reduce both systolic and diastolic pressures to below these levels in patients up to the age of 80 years. Isolated systolic hypertension was defined as a systolic pressure greater than 160 mmHg in the presence of a diastolic pressure less than 90 mmHg. Two trials reported benefit from the treatment of isolated systolic hypertension in patients up to the age of 80, and further trials are underway to support or refute this recommendation. Diuretics have an established role in the management of hypertension in elderly patients; beta adrenoceptor antagonists have given variable results, and the benefits are less impressive than with diuretic based regimens. Newer agents show promise in the treatment of elderly patients, particularly in the presence of coexisting disease, but their effects on morbidity and mortality have not been evaluated in large randomised trials. CONCLUSIONS: Diuretics rather than beta blockers are the treatment of choice for patients with uncomplicated hypertension, but combinations of drugs may be required in as many as 50% of patients.

Adrenergic beta-Antagonists↗
PubMed1992

The medical arts.

There were 152 entries for the Medical Arts Society's annual exhibition and all were shown at the Westminster Gallery, London on October 14-19, last year. The show displayed an exhibition of skill in the mediums of painting, printmaking, sculpture and drawing and prizes were awarded on merit.

Art↗
PubMed1992

Twenty-four hour blood pressure monitoring in the Syst-Eur trial.

This article describes the objectives and protocol of a study on ambulatory blood pressure in elderly patients with isolated systolic hypertension. This study constitutes an optional side-project to the Syst-Eur trial. The multicentre Syst-Eur trial investigates whether antihypertensive treatment of elderly patients with isolated systolic hypertension will influence the incidence of stroke. Secondary endpoints include cardiovascular events, such as myocardial infarction. The main objective of the side-project is to investigate whether ambulatory blood pressure monitoring will improve the prediction of cardiovascular complications based on blood pressure measurement in the clinic. The side-project also provides the opportunity to evaluate the diurnal profile of blood pressure in elderly patients with isolated systolic hypertension randomized to placebo or active antihypertensive treatment.

Aged↗
PubMed1992

The effect of in vitro aging on human lung fibroblast beta-adrenergic receptor density, coupling and response.

Age-related changes in regulation of receptor response have been observed in several tissues and include regulation of beta-adrenergic receptor (beta-receptor) responses. The role of cellular aging in age-related changes in receptor response is not clear. We have examined the effect of aging in vitro on human fibroblast beta-receptor function. MRC-5 (embryonic lung) fibroblasts were aged by replication to produce cells of early, middle and late stages corresponding to the following cumulative population doublings: 15-20, 35-45 and greater than 50, respectively. Fibroblast membrane beta-receptor responses to isoproterenol (ISO, 0.1 mM) did not differ between the three stages. Adenylate cyclase responses to prostaglandin E1 (PGE1, 1 microM), guanosine triphosphate (GTP, 0.1 mM) and 5'-guanylimidodiphosphate (Gpp(NH)p, 0.1 mM) were also similar between the stages. Beta-receptor density (Bmax) was unaffected by in vitro aging. Beta-receptor agonist affinity, an indication of the capacity for beta-receptor coupling to the nucleotide binding protein (NS), was also unaffected by cell aging. These findings suggest that cellular aging in fibroblasts alone is not accompanied by changes in beta-receptor function.

Adenylyl Cyclases↗
PubMed1992

The effect of donor age on human fibroblast beta-adrenergic receptor response and agonist-induced desensitization.

Aging has been associated with changes in beta-adrenergic receptor (beta-receptor) function in several tissues. The relative contribution of cellular aging and age-related changes in homeostatic regulation of receptor function is unknown. We have examined beta-receptor function in fibroblasts of young and old donors (young: mean age 31.2 +/- 0.8 years +/- S.E., n = 6; old: mean age 81.8 +/- 0.6 years +/- S.E., n = 6). Beta-receptor responses to isoproterenol (ISO), (1 microM) were similar in the two groups. The concentration of ISO required for 50% maximal beta-receptor-mediated cyclic AMP production (EC50) was similar in both groups. Fibroblast beta-receptor density was also similar in young and old groups. ISO-induced beta-receptor desensitization was both dose- and time-dependent. Submaximal desensitization by acute exposure (30 min) to ISO (1 mM) caused similar levels of beta-receptor desensitization in young (42.5 +/- 2.5%) and old (42.8 +/- 2.8%) groups and a similar increase in ISO EC50. These findings demonstrate that aging in vivo does not cause changes in fibroblast beta-receptor regulation that are retained in culture.

Adult↗
PubMed1992

Effects of aging and hypertension on plasma angiotensin II and platelet angiotensin II receptor density.

Plasma renin activity (PRA) declines with age in normal individuals, but the effect of age on plasma angiotensin II (ANG II) is less clear. A decline in plasma ANG II with age could result in altered platelet ANG II receptor density since plasma hormone levels influence their target organ receptors. To investigate this possibility, PRA, plasma ANG II, and platelet ANG II receptor density were examined in 17 young, 12 middle-aged, and 14 elderly healthy normotensive volunteers. To assess whether hypertension altered receptor density, these variables were also examined in 23 hypertensive patients. In normotensives, there was a negative correlation between age and PRA (r = -0.43, P < .05), no significant change in basal plasma ANG II with age, and a weak positive correlation between age and ANG II receptor density (r = 0.34, P < .05). Multiple regression analysis revealed that the relationship between age and ANG II receptor density was independent of the associated rise in mean arterial pressure with age (P < .05). Platelet ANG II receptor density was not significantly related to PRA or plasma ANG II. ANG II receptor affinity did not change with age. Neither PRA nor ANG II receptor density or affinity differed between hypertensives and normotensives of similar mean age, but plasma ANG II was significantly lower in hypertensives compared with normotensives. We concluded that aging is associated with a decline in supine PRA. The small decrease in plasma ANG II was not significant. Platelet ANG II receptor density increased with age primarily due to a small group of elderly subjects with elevated receptor density. There was no change in ANG II receptor density or affinity in hypertensives despite apparently lower plasma ANG II in these patients.

Adult↗
PubMed1992

The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries.

The evaluation and management of patients with minor head injury (MHI: history of loss of consciousness or posttraumatic amnesia and a GCS score greater than 12) remain controversial. Recommendations vary from routine admission without computed tomographic (CT) scanning to mandatory CT scanning and admission to CT scanning without admission for selected patients. Previous reports examining this issue have included patients with associated non-CNS injuries who confound the interpretation of the data and affect outcome. We hypothesized that patients with MHI and no other reason for admission with normal neurologic examinations and normal CT scans would have a negligible risk of neurologic deterioration requiring surgical intervention. To validate this hypothesis we studied 2766 patients with an isolated MHI admitted to seven trauma centers between January 1, 1988, and December 31, 1991. There were 1898 male patients and 868 female patients; injury was blunt in 99%. A neurologic examination and a CT scan were performed on 2166 patients; 933 patients had normal neurologic examinations and normal CT scans and none required craniotomy; 1170 patients had normal CT scans and none required craniotomy; 2112 patients had normal neurologic examinations and 59 required craniotomy. The sensitivity of the CT scan was 100%, with positive predictive value of 10%, negative predictive value of 100%, and specificity of 51%. The use of CT alone as a diagnostic modality would have saved 3924 hospital days, including 814 ICU days, and $1,509,012 in hospital charges. Based on these data, we believe that CT scanning is essential in the management of patients with MHI and that if the neurologic examination is normal and the scan is negative patients can be safely discharged from the emergency room.

Adolescent↗
PubMed1992

Cumulative sums in quantifying circadian blood pressure patterns.

The plotting of cumulative sums (cusums), a technique of proven value in the detection of trends in data collected at intervals of time, may be modified to analyze circadian blood pressure patterns quantitatively. Mean 24-hour ambulatory blood pressure is taken as the reference value and is subtracted from each pressure value. The products of the remainders and the corresponding time intervals are summed in sequence and are plotted against time to form a modified cusum plot. The slope of the plot over any given time period equals the difference between mean blood pressure during that period and mean 24-hour blood pressure. Crest and trough blood pressures (the mean blood pressures of the 6-hour periods of highest and lowest pressures) may be identified as the 6-hour periods where plot slopes are most steeply ascending and descending, respectively. The magnitude of the circadian blood pressure change, defined as the difference between crest and trough blood pressure, is calculated from the difference between crest and trough plot slopes. The height of the cusum plot, which reflects pressure alteration extent and duration, may also be used as a measure of circadian pattern. The modified cusums technique and cusum-derived statistics are illustrated using ambulatory blood pressure profiles of hypothetical and actual hypertensive subjects. Independence from fixed time periods improves precision and reproducibility. Cusum-derived statistics are simply calculated from raw ambulatory data and should prove useful in the quantitative analysis of circadian blood pressure profiles.

Adult↗
PubMed1992

Clinical pharmacokinetics of calcium antagonists. An update.

The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t 1/2 beta) and may be suitable for twice-daily administration. Amlodipine is an exception with a t 1/2 beta in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced first-pass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs.

Calcium Channel Blockers↗
PubMed1992

The J-shaped curve in elderly hypertensives.

PURPOSE: To review the relationship between mortality and morbidity and achieved blood pressure, after drug treatment in elderly hypertensive patients. CONTENTS: Recent studies have suggested that a reduction in systolic blood pressure, with drug treatment, to levels below about 140 mmHg in elderly patients (greater than 60 years) may increase the risk of stroke. However, a J-shaped relationship between both mortality and morbidity and blood pressure has been reported in the untreated controls of the Hypertension in Elderly Patients in primary care (HEP) study. In the European Working Party on High Blood Pressure in the Elderly trial (EWPHE) there was a U-shaped relationship between total mortality and treated systolic pressure, but a similar U-shaped relationship was observed with diastolic pressure in patients on placebo. In addition, patients with the lowest pressure during treatment showed the greatest falls in body weight and haemoglobin concentrations, suggesting that the increased mortality seen with lower blood pressure levels may have been an expression of a deterioration in general health. Moreover, a U-shaped relationship between blood pressure and mortality has been observed in the very old (aged 80 + years). CONCLUSIONS: While it is premature to conclude, on the basis of present evidence, that reducing blood pressure to the lower part of the normal range is harmful in older patients, it appears prudent, nonetheless, not to lower blood pressure excessively with treatment in this age group.

Aged↗
PubMed1991

Hepatic beta-adrenoceptor adaptation during propranolol administration is impaired in aging rats.

Aging has been associated with changes in beta-adrenoceptor responses and adaptation to prolonged removal of catecholamine stimulation. We have examined the effect of chronic propranolol administration on rat hepatic membrane beta-adrenoceptor density, agonist affinity and response in young (6-7 months) and old (26-7 months) male Wistar rats. Propranolol administration via miniosmotic pumps for 7 days resulted in similar and sustained plasma propranolol levels (approximately 100 ng/ml) in old and young rats. Pretreatment beta-adrenoceptor responses to isoprenaline were significantly higher in old rats. Propranolol administration was associated with significant increases in beta-adrenoceptor response and density (Bmax) in young rats only. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) responses to prostaglandin E1 (PGE1), guanosine triphosphate (GTP), 5'-guanyl-imidodiphosphate (Gpp(NH)p), forskolin and Mn2+ were not significantly different between young and old rats and were not affected by propranolol administration. Neither aging or propranolol administration was associated with a change in beta-adrenoceptor agonist affinity. These findings demonstrate elevated hepatic beta-adrenoceptor response and impaired hepatic beta-adrenoceptor adaptation to beta-adrenoceptor blockade in aging rats.

Adaptation, Physiological↗