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Biomedical subjects

K R Bailey

Publications and source records attributed to K R Bailey.

At least 199 records · Page 11Linked to original sources

Signal-averaged electrocardiography: a new noninvasive test to identify patients at risk for ventricular arrhythmias.

Signal-averaged electrocardiography (ECG) is a new noninvasive test for identifying patients at risk for ventricular arrhythmias. This computerized method of analyzing standard ECGs identifies particular microvolt-level signals called late potentials. Late potentials have been correlated with clinical ventricular tachycardia, are predictive of ventricular tachycardia inducibility at the time of electrophysiologic testing, and are predictive of arrhythmic events after myocardial infarction. In this review, we describe late potentials, the method of obtaining and processing the signal-averaged ECG, and clinical studies in various patient groups that have assessed the predictive value of the signal-averaged ECG for identification of patients at risk for subsequent ventricular arrhythmias.

Death, Sudden↗

Blood pressure load--a better determinant of hypertension.

Noninvasive ambulatory blood pressure monitoring was used to evaluate the diagnosis of hypertension in 168 untreated patients with essential hypertension. On the basis of overall office blood pressure--the mean of 12 measurements, 2 in each of three positions (supine, sitting, and standing) on 2 consecutive days--133 patients were diagnosed as having hypertension (diastolic blood pressure of 90 mm Hg or higher) and 35 as having borderline hypertension (diastolic blood pressure of less than 90 mm Hg). The mean blood pressures for those with hypertension and borderline hypertension were 149/99 and 135/87 mm Hg, respectively. The mean ambulatory diastolic blood pressure was 90 mm Hg or higher in 123 patients during awake hours and in 91 patients during 24 hours. The diastolic blood pressure loads (percentage of ambulatory diastolic blood pressures more than 90 mm Hg) in patients with hypertension and borderline hypertension, respectively, were 69% and 43% during awake hours and 59% and 35% during 24 hours. The systolic blood pressure loads (percentage of systolic readings more than 140 mm Hg) during awake and 24 hours were 56% and 48%, respectively, in patients with established hypertension and 31% and 26%, respectively, in those with borderline hypertension. Thus, ambulatory blood pressure monitoring and blood pressure load provide useful information for diagnosing hypertension.

Adult↗

Importance of adequate heparin dosage in arterial angioplasty in a porcine model.

Acute occlusion after a successful angioplasty is a severe complication that has been reported in 2-12% of patients. Therefore, to determine whether there was a relation between the dosage of heparin and the presence of mural thrombosis, we studied in a pig model the relation between the dosage of heparin and acute platelet-thrombus deposition on the site of arterial injury. We retrospectively analyzed the effect of three heparin regimens on platelet deposition in 32 normal pigs (mean weight, 32.7 kg) that underwent bilateral carotid angioplasty and were sacrificed 90 +/- 26 minutes later. Pigs in protocol 1 (n = 7) received an intravenous bolus injection of 4,000 units heparin 10 minutes before angioplasty. Pigs in protocol 2 (n = 11) received two bolus injections of 4,000 units heparin 40 minutes apart; the angioplasty was performed immediately after the second bolus. Pigs in protocol 3 (n = 14) had an initial 4,000-unit bolus injection of heparin followed immediately by an infusion of 4,000 units/hr; angioplasty was performed 20 minutes after starting the infusion. 111In-labeled platelet deposition on deeply injured (torn into the media) arterial segments were 86.3 +/- 68, 56.2 +/- 56.9, and 37.7 +/- 37.7 X 10(6)/cm2 for protocols 1, 2, and 3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis.

157 caucasian male patients undergoing vascular surgery for atherosclerosis and a matched control group of patients with high cholesterol levels were screened for antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV1) and type 2 (HSV2), indicative of persistent infection. The prevalence of CMV antibodies was higher in the surgical group than in the control group (90% and 74%, respectively), and a significantly greater percentage (p less than 0.001) of surgical cases than controls had high titres of CMV antibodies (57% and 26%, respectively). Small but not significant differences in antibodies to HSV1 were observed, and there were no differences in HSV2 antibody titres. For each virus there was no correlation between antibody titre and blood levels of total cholesterol or triglycerides. It is suggested that periodically activated virus may have a role in the pathogenesis of atherosclerosis.

Adult↗

Comparison of six pharmacologic regimens for hypercholesterolemia.

Six sequential clinical trials were conducted over 5 years to evaluate the safety and efficacy of different treatment regimens for hypercholesterolemia. Of all the study participants, 11 patients were evaluated in all 6 clinical trials using the following regimens: neomycin, neomycin/niacin, cholestyramine, cholestyramine/neomycin, lovastatin and lovastatin/neomycin. All 6 regimens significantly (p less than 0.05) reduced both total and low-density lipoprotein cholesterol concentrations by 25 to 42% from baseline levels. Only neomycin/niacin, cholestyramine and lovastatin significantly increased the high-density lipoprotein (HDL) cholesterol concentration, reducing the total cholesterol/high-density lipoprotein cholesterol ratio to less than 4.7. Thus, all 6 tested regimens were effective in modifying the plasma lipoprotein concentrations in type II hyperlipoproteinemia, but neomycin/niacin, cholestyramine and lovastatin had the most favorable impact. Only lovastatin treatment was free of adverse effects.

Adult↗

Natural history of candidates for balloon aortic valvuloplasty.

Recently, balloon aortic valvuloplasty has been proposed for the treatment of severe aortic stenosis in elderly patients when aortic valve replacement has been declined or deferred. The natural history of these patients has not been clearly defined. Therefore, to develop a comparison cohort of patients with unoperated aortic stenosis, we reviewed the records of all Mayo Clinic patients in whom severe aortic stenosis had been diagnosed during the period 1978 through 1985 but no surgical procedure had been performed because the patient declined or the physician deferred this option. Among the 50 patients identified (36 men and 14 women; mean age 77 years, range 60 to 89 years), an operation was declined by 28 and deferred in 22. The diagnosis of aortic stenosis was established clinically by a cardiologist in all 50 patients and independently confirmed by echocardiography, Doppler ultrasonography, or catheterization in 47 of the 50. All patients were symptomatic. Follow-up was complete to September 1986 or death in all 50 patients. Actuarial survival at 1, 2, and 3 years was 57, 37, and 25%, respectively. Survival of age- and sex-matched control subjects was 93, 85, and 77%, respectively (P less than 0.0001 at each 1-year interval). At last follow-up, only 13 of the 50 patients (26%) were alive. A cardiac cause was cited for 36 of the 37 deaths. Because of the poor survival in this group of patients, evaluation of alternative nonsurgical therapeutic modalities such as balloon valvuloplasty is imperative when operative intervention is declined or deferred in elderly patients.

Age Factors↗

Cardiac rehabilitation in patients with severe ischemic left ventricular dysfunction.

Twenty patients who had had a myocardial infarction and who had a resting left ventricular ejection fraction of 25% or less participated in an 8-week outpatient supervised exercise and education program. No morbidity or mortality occurred during the program, and most patients achieved a substantial improvement in exercise capacity. During a follow-up interval of a mean of 29.7 +/- 13.0 months, four patients died, an annualized mortality of 8 +/- 4%. The outcome of cardiac rehabilitation was assessed 19.1 +/- 4.4 months after completion of the supervised program. Of the 16 survivors, all of whom had been fully employed before their most recent myocardial infarction, 9 (56%) had returned to full-time work, 6 (38%) were medically disabled, and 1 was retired (age 73 years) but fully active. Of the 16 survivors, 13 (81%) completed a questionnaire about their perceptions of their current quality of life. Of the 13 patients, 12 (92%) had continued to exercise regularly. Four patients (31%) reported the ability to perform all desired activities without symptoms, whereas nine patients (69%) noted some impairment in their functional capacity. Thus, in this group of patients with profound left ventricular dysfunction, the rehabilitation potential, as evidenced by return to productive employment and the ability to perform desired activities-including exercise training-was generally favorable.

Electrocardiography↗

Adrenocortical function in type II hyperlipoproteinemic patients treated with lovastatin (mevinolin).

Lovastatin (Mevinolin), a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, has been used effectively as a hypocholesterolemic agent in man. As an inhibitor of endogenous cholesterol synthesis, a potentially serious side effect of therapy with this drug is interference with adrenocortical function. The effect of lovastatin on adrenal function was evaluated in a 6-month, randomized, double blinded, placebo-controlled, crossover study involving 24 type II hyperlipoproteinemic patients. Despite significant lowering of total and low density lipoprotein (LDL) cholesterol by lovastatin, no statistically or clinically significant differences were seen in free cortisol excretion or in plasma cortisol response to intravenous ACTH infusion between baseline, placebo, and lovastatin-treated patients. We conclude that lovastatin does not adversely affect adrenocortical reserve in patients with heterozygous familial hypercholesterolemia (FH) or non-FH type II hyperlipoproteinemia.

Adrenal Cortex↗

Cardiovascular effects and safety of intravenous and intramuscular pentamidine isethionate.

Intramuscular (im) pentamidine isethionate can cause substantial local pain and inflammation at the injection site. This drug is being used more frequently in recent years to treat Pneumocystis pneumonia, particularly in patients with acquired immunodeficiency syndrome. Clinicians began administering it iv despite warnings that iv administration might cause severe hypotension. We investigated the safety of im and iv pentamidine, monitoring hemodynamics after each dose in 11 patients with intra-arterial lines. Results showed only a small (but statistically significant) fall in mean arterial pressure after both im and slow (60 min) iv administration. A concomitant decrease in pulse occurred, but no change in cardiac output, pulmonary capillary occlusion pressure or systemic vascular resistance was noted. These results suggest that it may be safe to infuse pentamidine slowly intravenously. This route is more comfortable to patients than im administration.

Amidines↗

Effectiveness of mevinolin on plasma lipoprotein concentrations in type II hyperlipoproteinemia.

Patients with low-density lipoprotein (LDL) concentrations in the top 10th percentile of the population (type II hyperlipoproteinemia [HLP]) are at increased risk for premature cardiovascular disease; however, the incidence of myocardial infarction and death can be decreased by LDL cholesterol reduction. Mevinolin, an inhibitor of endogenous cholesterol synthesis, has been shown to reduce LDL cholesterol concentrations in a subset of type II patients with heterozygous familial hypercholesterolemia (FH). Using a double-blind, randomized, crossover, placebo-controlled trial, the safety and efficacy of mevinolin were compared in 24 patients with type II HLP with heterozygous FH (n = 6) or without FH type II HLP (n = 18). Compared with placebo treatment, both apolipoprotein B and LDL cholesterol levels were reduced (p less than 0.01) in both FH and non-FH patients by 28 to 34% with mevinolin treatment. In addition, high-density lipoprotein cholesterol levels were significantly increased (p less than 0.001) in both patients with FH (16%) and those with non-FH type II HLP (14%). Patients had no serious or clinically significant adverse effects. Thus, mevinolin is a useful drug for treatment of most patients with elevated plasma LDL cholesterol concentrations.

Adult↗

The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia.

The reduction of elevated low density lipoprotein (LDL) cholesterol concentrations in patients with Type II hyperlipoproteinemia leads to improved cardiovascular morbidity and mortality. Two agents which may be of value in treating hypercholesterolemia are mevinolin and neomycin. Since these drugs lower cholesterol levels through complementary mechanisms, we evaluated the effects of mevinolin and combined mevinolin-neomycin treatment on plasma lipoprotein concentrations in 21 type II hyperlipoproteinemic patients. Mevinolin reduced total and LDL cholesterol concentrations by 24% and 31% respectively (P less than 0.001) and 81% of the patients reduced their LDL cholesterol levels to less than 200 mg/dl. Although the addition of neomycin to mevinolin treatment further lowered total (5%) and LDL (4%) cholesterol concentrations, it also reduced HDL cholesterol levels (19%) (P less than 0.05). Therefore mevinolin normalizes the plasma lipid concentrations in patients with type II hyperlipoproteinemia and combined mevinolin and neomycin treatment offers no advantage over mevinolin-only therapy. In addition, these findings emphasize the importance of determining the HDL cholesterol level to fully evaluate the effects of hypolipidemic therapy.

Cholesterol, HDL↗

The effect of neomycin on plasma alpha tocopherol levels in type II hyperlipoproteinemia.

Use of oral neomycin as a hypocholesterolemic agent was found to decrease plasma alpha tocopherol levels during a 9-month, randomized, crossover placebo-controlled clinical trial with controlled diet. Pooled data from each treatment sequence showed a placebo alpha-tocopherol level of 1,896 +/- 643 micrograms/dl, and a neomycin alpha-tocopherol concentration of 1,449 +/- 451 micrograms/dl (p less than .01). When all subjects were on neomycin simultaneously, the level increased to 1,665 +/- 614 micrograms/dl (p less than .05 from placebo). Normal plasma alpha-tocopherol ranges from 400-1,000 micrograms/dl. Neomycin treatment reduces but does not normalize elevated levels of alpha-tocopherol found in Type II hyperlipoproteinemia.

Cholesterol, LDL↗

Effects of combination cholestyramine-neomycin treatment on plasma lipoprotein concentrations in type II hyperlipoproteinemia.

Recent prospective clinical trials have established that cholesterol reduction in patients with elevated (upper 90th percentile) concentrations of low-density lipoproteins (LDL) reduces the incidence of myocardial infarction and sudden death. Because the level of protection from these cardiovascular sequelae is directly related to the degree of LDL reduction, combination therapy using different hypolipidemic agents has been used in patients with type II hyperlipoproteinemia (HLP). Neomycin is as effective as cholestyramine in reducing LDL levels and combination neomycin-niacin treatment normalizes the plasma lipoproteins in 92% of patients with type II HLP. Because neomycin could theoretically ameliorate some of the gastrointestinal side effects of cholestyramine in addition to further affecting cholesterol levels, the effects of combination cholestyramine-neomycin treatment on the plasma lipoprotein were assessed in 18 patients with type II HLP in a 9-month clinical trial. Compared with diet-only treatment, cholestyramine reduced total and LDL cholesterol levels by 77 mg/dl (22%) and 78 mg/dl (31%), respectively. In addition to relieving cholestyramine-induced constipation, neomycin further reduced the total cholesterol level by 20 mg/dl (6%). However, this further reduction in total cholesterol concentration was the result of a decrease in the concentration of high-density lipoprotein cholesterol. These findings indicate that combination therapy does not have an additive LDL cholesterol-lowering effect and that neomycin and cholestyramine is not a useful drug combination. In addition, these results illustrate the importance of determining the high-density lipoprotein cholesterol concentration to fully interpret the effects of hypolipidemic treatment.

Cholesterol, HDL↗

Drinking water source and mortality in US cities.

An apparent excess risk of all-cancer mortality among 473 of the largest US cities was found in relation to surface drinking water supplies. The increased risk for 100% surface water versus 100% ground water use was slight, about 2%, but statistically significant. This finding agrees with reports from several earlier studies in smaller geographical regions of the US, Great Britain and Canada. A relationship was further supported by the replication of this association within the larger of the 11 independent regions studied. Our data suggest that the association with surface water may be specific to cancer mortality. The increased risk would be expected to be greater than 2% if analyses were restricted to cancers of sites previously related to the use of surface drinking water.

Carcinogens, Environmental↗

Framingham Disability Study: relationship of disability to cardiovascular risk factors among persons free of diagnosed cardiovascular disease.

The relationship between physical disability and cardiovascular risk factors among persons free of diagnosed cardiovascular disease was examined. Between 1948 and 1951, a cohort of adult, Framingham, Massachusetts, residents was assembled for a longitudinal examination of cardiovascular disease. Twenty-seven years after the participants' initial examination (between 1976 and 1978), members of the cohort who were still participating in the Framingham Heart Study were interviewed to ascertain their self-assessed ability to perform various physical activities. A score on the cumulative disability index was assigned to 2,021 persons free of diagnosed cardiovascular disease. Analyses controlled for noncardiovascular health conditions which were identified as related to disability. Among women, both long-term and current hypertension and body mass index, as well as diabetes, were associated with disability. Among men, long-term hypertension was related to disability. Age-specific analyses indicated that, for women, current hypertension was statistically significantly related to disability in the middle and oldest age groups; long-term hypertension was related to disability in the middle age group. Both long-term and current measures of diabetes in the oldest age group and long-term measure of cigarette use in the middle age group of women were also related to disability. Age-specific analyses among men indicated that the only statistically significant risk factor was long-term hypertension in the youngest age group. Cholesterol was not related to disability. Results suggest that certain cardiovascular risk factors should be considered in efforts to understand further the development of disability.

Age Factors↗

Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models.

The Animal Models for Protecting Ischemic Myocardium Study was undertaken for the purpose of developing reproducible animal models that could be used to assess interventions designed to limit infarct size. This paper describes the results obtained in an unconscious dog model and in a conscious dog model, developed in three participating laboratories. The unconscious dog model, involving reperfusion after 3 hours of ischemia in open-chest dogs, was intended to determine whether therapy followed by early reperfusion would limit infarct size more than reperfusion alone. The conscious dog model used chronically instrumented dogs and permanent coronary occlusion to better mimic myocardial infarction in man. In both models, the proximal circumflex artery was occluded, and the primary experimental endpoint was infarct size, as measured by histological techniques 3 days after the initial occlusion. Infarct size was analyzed in relation to baseline variables including the anatomic area at risk, collateral blood flow to the subepicardial zone of ischemia and hemodynamic determinants of myocardial metabolic demand. Most of the variation in infarct size in control dogs could be related to variation in the area at risk, collateral blood flow, and rate pressure product. Using multivariate analysis and groups of 15 dogs, an intervention that limited infarct size by 10-13% of the area at risk would have been detected 50% of the time. Larger treatment effects would be detected more readily, and smaller effects often would be missed, unless group sizes were larger. Two drugs, verapamil and ibuprofen, were evaluated in both models, with experimental group sizes averaging 13 and 20 dogs, in the unconscious and conscious models, respectively. Three of 15 verapamil-treated dogs in the unconscious model study had much smaller infarcts than expected from baseline parameters. With these exceptions, neither drug limited infarct size in either model.

Anesthesia↗

Assessment of interaction between carcinogens in long-term factorially designed animal experiments.

Two substances interact if the combined action results in an effect which is greater than, or less than, that of the sum of the effects produced separately by the substances. Finney (1971, Probit Analysis, 3rd ed. Cambridge: Cambridge University Press) proposed a probabilistic model for simple independent action of two substances for the case of dichotomous outcomes. Using Finney's underlying model, we examine tests for interaction between carcinogens or toxic substances for data from long-term 2 x 2 and 2 x 2 x 2 factorially designed animal experiments. The outcome of interest is the occurrence or not of a certain event (for example, the appearance of a tumor) and the time at which the event occurred. The proposed tests are based on the proportional hazards model. We discuss some simple methods for checking the appropriateness of the proportional hazards assumption. Applications of the tests are made to data from a 2 x 2 and a 2 x 2 x 2 experiment.

Animals↗