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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 145 records · Page 8Linked to original sources
PubMed1991

Mode of action of chloroquine in patients with non-insulin-dependent diabetes mellitus.

Clinical studies have demonstrated that chloroquine and hydroxychloroquine improve glucose metabolism in patients with insulin-resistant diabetes mellitus. The mechanism of action has not been determined. We undertook a randomized double-blind placebo-controlled trial of 3 days of oral chloroquine phosphate, 250 mg four times daily, in 20 patients with non-insulin-dependent diabetes mellitus controlled by diet. Rates of glucose appearance (Ra) and disappearance (Rd) were evaluated by infusion of stable isotopically labeled D-glucose ([6,6-2H2]glucose) during hyperinsulinemic euglycemic clamps before and after treatment with chloroquine or placebo. Chloroquine significantly improved fasting plasma glucose from 199.8 +/- 8.6 to 165.6 +/- 7.6 mg/dl (P less than 0.01). Total exogenous glucose infusion required to maintain euglycemia significantly increased (1,792.6-2,040.1 mg.kg-1.330 min-1, P less than 0.05) due to an increase in Rd (2,348.0-2,618.9 mg.kg-1.330 min-1, P less than 0.01) without change in Ra. Metabolic clearance rate of insulin decreased by 39% from 14.4 +/- 1.3 to 11.0 +/- 0.6 ml.kg-1.min-1 (P less than 0.01) at plasma insulin levels of 150-200 mU/l but not at levels of 2,000-3,000 mU/l. In addition, chloroquine increased fasting C-peptide secretion by 17% and reduced feedback inhibition of C-peptide by 9.1 and 10.6% during low- and high-dose insulin infusions, respectively.

Blood Glucose↗
PubMed1991

Oral insulin in diabetic dogs.

Bovine crystalline insulin, mixed with an absorption enhancer, was loaded by hand into gelatin capsules, which were then coated with an azopolymer designed to deliver the insulin in the upper colon. In 34 experiments with 14 pancreatectomized mongrel dogs of both sexes, the coated capsules were administered orally after a pre-dose period of 1 h. The dogs had cannulae in the portal vein, hepatic vein and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Insulin and food were withdrawn the day before an experiment. Responses measured were plasma glucose, plasma insulin, hepatic glucose production rate, hepatic plasma flow rate and plasma glucagon-like immunoactivity (GLI). Control experiments, with capsules without insulin, produced small changes from 'pre-dose' values. Insulin-containing capsules, without the azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1.5-2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1.5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

Administration, Oral↗
PubMed1991

Exercise radionuclide angiocardiography predicts cardiac death in patients with coronary artery disease.

The purpose of this investigation was to document the relative importance of three clinical and three radionuclide variables for prediction of cardiac death in a consecutive group of patients evaluated for coronary artery disease. During a 6 1/2-year period, beginning in January 1978, 2,042 consecutive patients underwent radionuclide angiocardiography, with a clinical diagnosis of coronary artery disease, at Duke University Medical Center. A subgroup of 318 patients who underwent surgical myocardial revascularization near the time of initial study were excluded from later analysis. Clinical follow-up information was complete in a group of 1,663 patients who did not undergo interventional therapy. The 141 cardiac deaths in these 1,663 patients were the study end point. Cox proportional hazards models analyzed the prognostic information contained in three clinical variables (pain type, age, and sex) and three radionuclide angiocardiogram variables (exercise ejection fraction, resting end-diastolic volume, and change in heart rate with exercise). One-variable models confirmed the prognostic importance of each of these six variables. A multivariable model in which all six variables were used showed clinical variables to contain only 5% and the radionuclide variables 95% of the prognostic information. The exercise ejection fraction was the single most important variable, which alone contained 85% of the total information in the model. Curves relating probability of no cardiac death to the exercise ejection fraction identified a value of 0.50 as an inflection point. Patients with exercise ejection fractions below 0.50 demonstrate a probability of cardiac death that increases as the ejection fraction decreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1991

Comparison of bicycle and treadmill radionuclide angiocardiography.

The purpose of this study was to test motion-correction algorithms for initial-transit radionuclide angiocardiograms acquired at rest and during bicycle and treadmill exercise. Treadmill data was spatially reoriented by computer software designed to eliminate motion of a 125I point source simultaneously recorded at a lower energy window. A second algorithm based on left ventricular centroid counts further corrected for motion on all studies. Exercise left ventricular ejection fraction was higher on the treadmill (0.68 +/- 0.07) compared to the bicycle (0.64 +/- 0.08) (p less than 0.0001, r = 0.88). Treadmill exercise also resulted in larger end-diastolic volumes (180 +/- 30 versus 157 +/- 36, p less than 0.0001), stroke volumes (124 +/- 28 versus 101 +/- 29, p less than 0.0001) and cardiac outputs (19.9 +/- 4.6 versus 15.9 +/- 5.0, p less than 0.0001). Similar variances for these hemodynamic measurements suggest that the mean differences observed were physiologic and that error from body motion was effectively corrected by this approach. We conclude that the measurement of left ventricular function during treadmill exercise, when combined with these techniques for correcting motion, is a reasonable alternative to conventional bicycle exercise.

Adult↗
PubMed1991

Determinants of early versus late cardiac death in patients undergoing coronary artery bypass graft surgery.

Most analyses of risk factors affecting survival after coronary artery bypass graft surgery have not differentiated among factors that influence early and late survival. For this reason, a multiphase model was applied to survival data from 2,967 patients undergoing a first coronary artery bypass graft at the Duke University Medical Center between 1969 and 1984. There were 709 deaths during follow-up to 19.6 years. The data were analyzed using a multivariable survival model that separates the underlying hazard function into as much as three different phases, each incorporating separate risk factors. Two distinct phases were detected. One phase dominated early survival (0-1 year), and the second phase dominated late survival (greater than 1 year). Surgery performed earlier in our experience was associated with elevated risk of dying in both phases but with different magnitudes, whereas lower ejection fraction, greater extent of coronary disease, older age, conduction abnormality, and history of hypertension were associated with elevated risk of dying similarly in both phases (p less than 0.05). Severity of angina symptoms and lower weight were associated with an elevated risk of dying only in the early phase (p less than 0.05; because few of the patients were obese, estimates of the relative risk of morbid obesity could not be estimated), whereas vascular disease, diabetes, and extent of myocardial damage were associated with an elevated risk of dying only in the late phase (p less than 0.05). These data illustrate both the differential influence of risk factors over time and the importance of multiphase models.

Cohort Studies↗
PubMed1991

Influence of diabetes and mammary artery grafting on survival after coronary bypass.

The effect of diabetes on survival after coronary bypass surgery is uncertain. Also, although the overall clinical benefits of internal mammary artery (IMA) grafting are well established, the survival benefit attributable to IMA grafting in diabetics is not well characterized. To determine the influence of diabetes and IMA grafting on survival after bypass surgery in the current surgical era, characteristics related to subsequent outcome were analyzed in 5,654 consecutive patients undergoing surgery in the decade of the 1980s. The 1,132 diabetic patients (20%) had more extensive coronary disease, had more left ventricular dysfunction, were older, were more frequently female, received a greater number of grafts (mean, 3.5 versus 3.1), and received more IMA grafts (67% versus 58%) than the 4,522 nondiabetic patients (all p less than 0.001). Overall 5-year survival probability was 0.91 in nondiabetic and 0.80 in diabetic patients (p less than 0.0001). Nondiabetic survival exceeded diabetic survival even in high-risk subgroups such as ejection fraction less than or equal to 0.40 (0.80 versus 0.66, p less than 0.02), age greater than or equal to 65 years (0.85 versus 0.73, p less than 0.0003), and, urgent surgery (0.89 versus 0.76, p less than 0.0001). By multivariate analysis, impairment of left ventricular function, advanced age, failure to use an IMA graft, diabetes, female sex, urgent surgery, number of diseased vessels, and mitral insufficiency were incremental risk factors for cardiac mortality (all p less than 0.006). Failure to use an IMA graft and diabetes were equally strong predictors of outcome. Use of an IMA graft conveyed an independent survival benefit to both nondiabetic (p less than 0.0001) and diabetic (p less than 0.02) patients. The magnitude of the survival benefit attributable to IMA grafting in the two groups did not differ (p = 0.4). Diabetes is an important risk factor for late cardiac mortality after bypass surgery and should be included in analyses of the efficacy of therapies for coronary artery disease. IMA grafting conveys a similar benefit to diabetic and nondiabetic patients but does not negate the adverse effect of diabetes on survival.

Age Factors↗
PubMed1991

Recovery of myocardial function during coronary artery bypass grafting. Intraoperative assessment by pressure-volume loops.

Radionuclide angiocardiography and left ventricular manometry were performed simultaneously in 12 men undergoing elective coronary artery bypass grafting. Pressure-volume loops constructed from these data allow calculation of stroke work and provide a more complete description of global left ventricular function immediately before cardiopulmonary bypass and at a mean of 18 and 34 minutes after termination of ischemic arrest. Early reperfusion was characterized by significant elevation of end-diastolic pressure (p less than 0.01) without a corresponding increase in end-diastolic volume. With continued reperfusion, end-diastolic volume, calculated stroke work, and cardiac output increased significantly with respect to control (p less than 0.05). Heart rate, ejection fraction, mean arterial pressure, stroke work/end-diastolic volume, and maximal dP/dt remained unchanged during the study period. No new focal abnormalities were detected in regional wall motion. These data indicate that minimal residual impairment of diastolic function exists during the acute recovery from cardioplegic arrest and bypass grafting but improves with further reperfusion. Systolic function appears to normalize more rapidly than diastolic function after ischemic arrest.

Adult↗
PubMed1991

Unequally spaced longitudinal data with AR(1) serial correlation.

This paper discusses longitudinal data analysis when each subject is observed at different unequally spaced time points. Observations within subjects are assumed to be either uncorrelated or to have a continuous-time first-order autoregressive structure, possibly with observation error. The random coefficients are assumed to have an arbitrary between-subject covariance matrix. Covariates can be included in the fixed effects part of the model. Exact maximum likelihood estimates of the unknown parameters are computed using the Kalman filter to evaluate the likelihood, which is then maximized with a nonlinear optimization program. An example is presented where a large number of subjects are each observed at a small number of observation times. Hypothesis tests for selecting the best model are carried out using Wald's test on contrasts or likelihood ratio tests based on fitting full and restricted models.

Biometry↗
PubMed1990

Simultaneous measurement of myocardial perfusion and ventricular function during exercise from a single injection of technetium-99m sestamibi in coronary artery disease.

New radiopharmaceuticals permit simultaneous assessment of myocardial perfusion and left ventricular function using a single tracer injection. The purpose of this study was to quantitate the relation between myocardial perfusion and function at rest and during exercise in patients with documented coronary artery disease (CAD). A rest first-pass radionuclide angiocardiogram (RNA) was recorded in 51 patients with CAD during injection of 10 mCi of technetium-99m (Tc-99m) sestamibi, and tomographic perfusion images were obtained 60 minutes later. A treadmill test was then performed, and on attainment of an exercise end point a second first-pass RNA was recorded with 30 mCi of Tc-99m sestamibi. Tomographic images reflecting myocardial perfusion during exercise were obtained 1 hour later. Tomographic perfusion defect size, quantified using modifications of the Cedars-Sinai program, correlated directly with end-systolic volume and inversely with ejection fraction at rest and during exercise. However, perfusion defect size often varied widely in patients with similar left ventricular function. This independence between measurements of perfusion and function suggests that simultaneous assessment of the 2 physiologic variables could improve the diagnostic and prognostic information of radionuclide tests.

Coronary Disease↗
PubMed1990

Early and late changes in left ventricular systolic performance after percutaneous aortic balloon valvuloplasty.

To evaluate early and late hemodynamics after aortic valvuloplasty, 17 patients underwent first-pass radionuclide angiocardiography with simultaneous high-fidelity micromanometer pressure before, 10 minutes after and 6 months after aortic valvuloplasty. Pressure-volume and stress data were assessed. Immediately after the procedure, no significant change was observed in heart rate, systemic blood pressure, cardiac output or aortic insufficiency (as measured by visual or quantitative aortography). The mean and peak transvalvular gradient decreased from 64 to 36 mm Hg (p less than 0.001) and 76 to 38 mm Hg (p less than 0.001), respectively. The mean aortic valve area increased from 0.5 to 0.8 cm2 (p less than 0.001). Using echocardiography, meridional end-systolic wall stress decreased from 81 to 63 x 10(3) dynes/cm2 (p less than 0.001). Left ventricular ejection fraction increased from 0.48 to 0.54 (p less than 0.01), end-diastolic volume decreased from 161 to 143 ml (p less than 0.001) and end-diastolic pressure decreased from 18 to 13 mm Hg (p less than 0.01). Left ventricular stroke work (the area of the pressure-volume loop) also decreased from 17.5 to 14.7 x 10(6) ergs (p less than 0.001). The loop shifted to the left and downward. At the 6-month study, the mean and peak aortic valve gradient increased from 36 to 56 mm Hg (p less than 0.001) and 38 to 61 mm Hg (p less than 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Changes in left ventricular systolic performance immediately after percutaneous aortic balloon valvuloplasty.

To evaluate the acute changes in left ventricular (LV) performance before and immediately after percutaneous aortic valvuloplasty, 25 patients underwent first-pass radionuclide angiocardiography for construction of pressure-volume loops. Simultaneously, high-fidelity micromanometric aortic and LV pressures were recorded. Echocardiographic wall thickness was used to define wall stress. After valvuloplasty, no acute changes were observed in the heart rate, aortic systolic pressure, cardiac output or degree of aortic insufficiency. Valvuloplasty decreased the peak aortic valve gradient from 73 to 40 mm Hg (p less than 0.001) and the mean gradient from 61 to 30 mm Hg (p less than 0.001); aortic valve area increased from 0.55 to 0.80 cm2 (p less than 0.001). Meridional end-systolic wall stress decreased from 83 to 55 X 10(3) dynes/cm2 (p less than 0.01). LV ejection fraction increased from 0.41 to 0.48 (p less than 0.01). LV end-diastolic volume decreased from 186 to 160 ml (p less than 0.001), end-systolic volume decreased from 115 to 87 ml (p less than 0.001) and end-diastolic pressure decreased from 22 to 17 mm Hg (p less than 0.01). LV stroke work decreased from 16.0 to 14.0 X 10(6) erg (p less than 0.001). No change was observed in peak positive LV dP/dt or the end-systolic pressure-volume ratio. This study documents variable and complex changes in the measures of cardiac function after aortic valvuloplasty. A decrease in the amount of LV outflow obstruction with maintenance of the cardiac output at a decreased level of LV filling occurs.

Aged↗
PubMed1990

Effects of standard mitral valve replacement on left ventricular function.

Recent studies have suggested that excision of the mitral valve apparatus during mitral valve replacement impairs left ventricular performance. However, functional measurements in humans have been difficult to obtain in a load-independent fashion. To investigate this concept, 12 patients (mean age, 65 +/- 8 years; mean New York Heart Association functional class, 3.3 +/- 0.7) with 4+ mitral regurgitation (n = 8) or mitral stenosis (valve area, 1.2 +/- 0.2 cm2) (n = 4) underwent prosthetic valve replacement using crystalloid cardioplegia. No patient required therapeutic inotropic support, every patient had at least the anterior mitral leaflet excised, and paced heart rate was maintained constant throughout. Left ventricular volume was measured with radionuclide angiocardiography, left ventricular pressure with a 3F micromanometer, and left ventricular wall volume with two-dimensional transesophageal echocardiography. Left ventricular preload was varied over a mean end-diastolic pressure range of 9 to 20 mm Hg and an end-diastolic volume range of 134 to 170 mL to generate four to five steady-state pressure-volume loops before and ten minutes after cardiopulmonary bypass. Left ventricular performance was estimated with the stroke work/end-diastolic volume relationship, which is insensitive to load. After bypass, no significant change (p greater than 0.1) was noted in wall volume for patients with mitral regurgitation or mitral stenosis (175 +/- 68 to 189 +/- 63 mL/m2 and 130 +/- 22 to 127 +/- 19 mL/m2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Serial evaluation of ventricular function after percutaneous aortic balloon valvuloplasty.

To evaluate the serial changes in right and left ventricular performance after percutaneous aortic balloon valvuloplasty, 15 patients, mean age 75 +/- 18 years, and in New York Heart Association (NYHA) class III, were studied with first-pass radionuclide angiocardiography (RNA) immediately before, then 5 minutes, 2 hours, 4 hours, 6 hours, and 3 days after valvuloplasty. No change was observed in heart rate, aortic root systolic pressure, Fick, or RNA cardiac output, amount of aortic insufficiency measured either angiographically or with the regurgitant fraction determination immediately after valvuloplasty. However, significant changes were observed in the peak-to-peak aortic valve gradient (63 to 35 mm Hg; p less than 0.001), mean aortic valve gradient (54 to 33 mm Hg; p less than 0.001), aortic valve area (0.60 to 0.90 cm2; p less than 0.001), and meridional wall stress (79 to 50 10(3) dynes/cm2; p less than 0.01) immediately following valvuloplasty. In addition, left ventricular end-diastolic volume decreased from 186 to 153 ml (p less than 0.001), end-systolic volume decreased from 114 to 86 ml (p less than 0.001), micromanometric left ventricular end-diastolic pressure decreased from 20 to 14 mm Hg (p less than 0.02), and left ventricular ejection fraction increased from 0.39 to 0.45 (p less than 0.001). Peak positive left ventricular dP/dt and end-systolic pressure-volume ratio did not change after valvuloplasty (1700 to 1550 mm Hg/sec, 2.1 to 2.5 mm Hg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Estimation of left ventricular volume and ejection fraction by two-dimensional transoesophageal echocardiography: comparison of short axis imaging and simultaneous radionuclide angiography.

We have compared short axis images of the left ventricle (LV) obtained with transoesophageal echocardiography (TOE) to assess LV size and function with those obtained by radionuclide angiography (RNA). Simultaneous TOE and RNA images were attempted in 14 patients and results obtained in 12 patients undergoing repair of abdominal aortic aneurysms. The area of the LV cavity seen in the short axis images at a mid-papillary muscle level at end-systole (ESA) and end-diastole (EDA) were compared with volumes measured by RNA at end-systole (ESV) and end-diastole (EDV). An area ejection fraction (AEF) calculated from the TOE images (AEF = EDA-ESA/EDA) was compared with the RNA ejection fraction (EF) where EF = EDV-ESV/EDV. Good correlations were found between TOE log EDA and RNA log EDV (r = 0.86), TOE log ESA and RNA log ESV (r = 0.92) and TOE AEF and RNA EF (r = 0.96). This suggests that TOE short axis imaging at a mid-papillary muscle level is generally adequate for monitoring LV function during operation.

Echocardiography↗
PubMed1990

Isolation of arboviruses from Culicoides midges (Diptera: Ceratopogonidae) in Colorado during an epizootic of vesicular stomatitis New Jersey.

An arbovirus survey was conducted in Colorado and Utah during an epizootic of vesicular stomatitis New Jersey (VSNJ) that occurred in the western United States in 1982-1983. From 120,422 insect specimens assayed, 106 viruses were isolated. Four were rhabdoviruses (VSNJ), three were orbiviruses (bluetongue serotype-11), 92 were Bunyamwera group (65 Main Drain and 27 Lokern), and seven were Simbu group (Buttonwillow) bunyaviruses. Culicoides spp. accounted for 105 viral isolates (C. (Selfia) spp., C. variipennis (Coquillett), C. stellifer (Coquillett), and C. cockerellii (Coquillett], and one was from Simulium bivittatum Malloch. C. (Selfia) spp. accounted for 59% of all pooled specimens and was the source of 89.6% (95) of the isolates. Insects from two sites accounted for 44% (52,802) of all pooled specimens and 67% (71) of the viral isolates. The isolations of VSNJ, Main Drain, Lokern, and Buttonwillow viruses from C. (Selfia) spp. are the first arbovirus isolations reported for this subgenus; this is the first time these viruses have been isolated from Culicoides species other than C. variipennis.

Animals↗