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Biomedical subjects

R H Jones

Publications and source records attributed to R H Jones.

At least 19 recordsLinked to original sources
PubMed1992

Performance status and outcome after coronary artery bypass grafting in persons aged 80 to 93 years.

Although coronary artery bypass grafting (CABG) effectively eliminates or diminishes symptoms of myocardial ischemia, the overall performance status and functional outcome in elderly patients undergoing CABG is poorly documented. Therefore, 86 consecutive patients aged 80 to 93 years undergoing isolated CABG were reviewed. Preoperative, intraoperative, and postoperative characteristics and pre- and postoperative performance status (Karnofsky score) were examined. Forty patients (47%) were women, and most patients had highly symptomatic coronary artery disease with class III or IV angina in 94% and unstable angina in 90%. Significant co-morbid disease was present in 49% of patients, and cardiac catheterization revealed left main or 3-vessel disease in 74% of patients. The rate of significant in-hospital complications was 29%, with infection in 14%, stroke in 9%, and respiratory failure in 8% being most frequent. Median performance status (Karnofsky score) improved from 20 to 70% (p = 0.0001) with 89% of hospital survivors being discharged home. Factors associated with failure to achieve a successful functional outcome at discharge were presence of 1 or more preoperative co-morbid conditions (p = 0.048), preoperative myocardial infarction within 7 days of operation (p less than 0.01), and postoperative low cardiac output (p less than 0.01). Survival at 30 days, 6 months, and 3 years were 90, 78, and 64%, respectively. These data demonstrate that CABG can be offered to selected elderly patients with acceptable morbidity and mortality, marked improvement in performance status, and an acceptable quality of life.

Activities of Daily Living↗
PubMed1992

Complex angioplasty: a surgeon's perspective.

Surgeons commonly have reacted with skepticism to the introduction of catheter-based interventional approaches to treating coronary artery disease, prompted apparently, by a desire to protect what had been exclusively their turf. Reasonable surgeons now largely accept the concept of nonoperative mechanical treatment of coronary heart disease, and their constructive criticisms regarding amelioration of coronary anatomy without thoracotomy remains valuable. The value of catheter-based techniques compared with operative or noninterventional treatment has not been defined in many clinical settings. The complexity of evaluating these rival technologies increases as the complexity of cases progresses from simple 1-vessel disease to more extensive coronary artery disease. Ongoing randomized trials may help define indications for these procedures, but patients entering these trials represent a highly select subset. Therefore, applications to broader patient populations will likely require analysis of observational data. Newer catheter-based technologies introduce modes of injury to the coronary arterial system that have not been encountered previously in medical practice. As technologies evolve, decisions about the need for operative intervention become increasingly complex. In the many clinical settings resulting from efforts to improve angioplasty, optimal patient care occurs in environments with good communication and cooperation between all physicians involved in interventional treatment of coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1992

Left ventricular function under stress before and after myocardial revascularization.

To compare left ventricular responses to stress during exercise-induced myocardial ischemia and after myocardial revascularization, 35 patients (mean age 55 +/- 7 years, class III angina) with three-vessel coronary artery disease underwent a rest and exercise initial-transit radionuclide angiocardiography before aortocoronary bypass grafting. Left ventricular ejection fraction decreased during exercise (p less than 0.01), but cardiac output was augmented with an increased heart rate (p less than 0.0001) and left ventricular end-diastolic volume (p less than 0.001). Group A (n = 15) underwent six serial resting studies at different volume loads during the first 24 hours after operation while heart rate and blood pressure were held constant. These data revealed no significant change in left ventricular ejection fraction, but preload varied in all patients because of bleeding and fluid administration, with a mean end-diastolic volume change of 115 to 176 ml. This range of end-diastolic volume was similar to that defined with rest and exercise testing before operation. Group B (n = 20) underwent a repeat rest and exercise test 3 months after operation that demonstrated no change in resting function. However, exercise ejection fraction and peak systolic pressure/end-systolic volume ratio increased (p less than 0.001 and p less than 0.05, respectively) while end-diastolic volume decreased (p less than 0.05) compared with the values before operation. These data indicate that patients with coronary artery disease have chronically adapted cardiac function that makes use of both rapid heart rate and a wide range in preload to augment cardiac function under stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease.

Autosomal-dominant polycystic kidney disease results in renal failure at a varying age from childhood to old age. We postulated that factors other than the culprit gene alone contribute to the course of progression of the renal failure. We studied 580 subjects with autosomal-dominant polycystic kidney disease and 194 unaffected family members. We calculated survival curves to end-stage renal failure or death and developed a linear model for testing the effects of single or multiple variables on the progression of renal failure as estimated from the reciprocal of serum creatinine. Fifty-two subjects died and 94 reached end-stage renal failure during the period of observation, yielding functional survivals of 71% at age 50 years, 53% at 58 years and 23% at 70 years. The following variables were independently associated with worse mean renal function at a given age (P value less than 0.01): the PKD1 gene, younger age at diagnosis, male gender, hypertension, increased left ventricular mass, hepatic cysts in women, three or more pregnancies, gross hematuria, urinary tract infections in men and renal size expressed as renal volume. The following were not associated significantly with the course of renal function: gender of affected parent, mitral valve prolapse, intracranial aneurysms, any pregnancy, hepatic cysts in men and urinary tract infections in women. The identification of unalterable maleficent factors such as the PKD1 gene and male gender permit more informed counseling while the identification of alterable factors such as hypertension, number of pregnancies and recurrent urinary tract infections provides the clinician with the opportunity to modify these factors and improve the management of patients with autosomal-dominant polycystic kidney disease.

Adult↗
PubMed1992

Incomplete suppression of hepatic glucose production in non-insulin dependent diabetes mellitus measured with [6,6-2H2]glucose enriched glucose infusion during hyperinsulinaemic euglycaemic clamps.

We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6-2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non-insulin-dependent diabetes mellitus during low (1 mU kg-1 min-1) and high (8 mU kg-1 min-1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 +/- 0.8 mumol kg-1 min-1. This suppressed by only 68% to 4.6 +/- 0.8 mumol kg-1 min-1 during the low-dose insulin infusion (plasma insulin 0.85 +/- 0.05 nmol l-1) and did not suppress further during the high-dose insulin infusion (plasma insulin 14.55 +/- 0.83 nmol l-1). Hepatic glucose production was significantly higher than zero throughout the study. Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1992

Microsurgical repair of nerves injured during third molar surgery.

The inferior dental and lingual nerves are in close proximity to the mandibular third molar. In approximately 5 per cent of cases of the surgical removal of this tooth one or other of these nerves may be injured. In most cases the injury is reversible but in 1 per cent a distressing dysaesthesia may occur. The diagnosis of the sensory deficit is made by repeated sensory testing. If there is no improvement by six to nine months then complete spontaneous recovery will not occur. These irreversible nerve injuries can be successfully treated microsurgically.

Humans↗
PubMed1992

Intraperitoneal insulin is more potent than subcutaneous insulin at restoring hepatic insulin-like growth factor-I mRNA levels in the diabetic rat: a functional role for the portal vascular link.

There is evidence that the hormonal control of hepatic IGF-I production is mediated by GH and insulin. To elucidate the role of these hormones further we administered s.c. or i.p. insulin (at 2.5 and 5.0 IU/day) and/or GH (0.8 IU/day) to rats made diabetic with streptozotocin 16 days previously. Hepatic IGF-I production was then assessed by quantifying hepatic IGF-I mRNA levels by autoradiography of Northern blots. Diabetes resulted in a fivefold reduction in hepatic IGF-I mRNA levels (optical density (OD) of the 0.7-1.1 kb band: controls, 1.3 +/- 0.09; diabetics, 0.28 +/- 0.08; P < 0.01), which was not significantly changed by treatment with s.c. insulin (OD: low dose, 0.55 +/- 0.05; high dose, 0.58 +/- 0.05) or low dose i.p. insulin (OD: 0.40 +/- 0.03). High dose i.p. insulin enhanced hepatic IGF-I mRNA levels (OD: 0.93 +/- 0.23) compared with diabetic rats (P < 0.01) and those given high dose s.c. insulin (P < 0.04), despite the blood glucose values being similar in the treated groups (i.p., 4.72 +/- 0.29 mmol/l; s.c., 3.32 +/- 0.03 mmol/l). Administration of GH alone partially restored the hepatic IGF-I mRNA level (OD: GH-treated, 1.00 +/- 0.05; diabetic, 0.28 +/- 0.08; P < 0.01), whilst having no effect on blood glucose values (diabetic, 36.35 +/- 0.45 mmol/l; GH-treated, 38.65 +/- 2.39 mmol/l). Additional administration of s.c. insulin completely restored IGF-I mRNA levels to those of controls (OD: low dose, 1.35 +/- 0.14; high dose, 1.27 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Anti-oxidant status in an in vitro model for hyperglycaemic lens cataract formation: competition for available nicotinamide adenine dinucleotide phosphate between glutathione reduction and the polyol pathway.

The level of NADPH, total glutathione and sorbitol have been measured in a normal (5mM) and hyperglycaemic (35mM glucose) in vitro rat lens model. In hyperglycaemic conditions, these intermediates are 50%, 84% and 3628% of the normal level. When oxidatively stressed with H2O2 (0.1mM-1.0mM) a gradation in the NADPH and total glutathione decrease is seen, at both glucose levels. This effect is most pronounced in lenses incubated in 35mM glucose, with levels already decreased, the NADPH falls to 15% of the normal lens. Sorbitol levels are correspondingly lower when the lens is oxidatively stressed. The inclusion of the ethyl ester of glutathione alleviates the disruption in anti-oxidant status caused by H2O2 but is unable to restore the NADPH level depleted by hyperglycaemia. These results are discussed in relation to the competitive requirements for NADPH between anti-oxidant preservation and sorbitol formation, as a mechanism for lens opacification in diabetes.

Animals↗
PubMed1992

Observational comparison of event-free survival with medical and surgical therapy in patients with coronary artery disease. 20 years of follow-up.

BACKGROUND: The purpose of this study was to describe the long-term event-free survival patterns of patients with significant coronary artery disease treated medically versus patterns of those treated surgically and to evaluate the factors associated with improved event-free survival. METHODS AND RESULTS: We studied the results of 5,824 patients undergoing medical and surgical therapy for ischemic heart disease from 1969 to 1984, with follow-up to 1991. Events considered for this evaluation were nonfatal myocardial infarction or cardiovascular death. The Cox proportional hazards model was used to determine factors differentially affecting surgical event-free survival. The survival benefits previously reported for bypass surgery in this population were largely preserved when event-free survival was examined. The two factors associated with significant event-free survival benefits for surgically treated patients were more severe coronary artery disease and a more recent surgery data. Patients with more severe coronary obstruction had a greater relative improvement with surgery in event-free survival than did patients with less severe anatomic disease. Event-free survival with surgery progressively improved over the period of the study and, by 1984, was significantly better than medical therapy for most patient subgroups. Patients with poor prognosis because of risk factors such as older age, severe angina, or left ventricular dysfunction had a risk reduction with surgery proportional to their overall risk under medical therapy. CONCLUSIONS: Higher-risk patients with more severe disease (due to either coronary disease or other risk factors and age) should be considered for coronary revascularization because it is in these patients that coronary artery bypass graft surgery has the greatest impact in reducing future cardiovascular events.

Cardiac Catheterization↗
PubMed1991

Prediction of death and myocardial infarction by radionuclide angiocardiography in patients with suspected coronary artery disease.

The prognostic value of radionuclide angiocardiography was examined in patients with suspected coronary artery disease. Nine hundred and eight patients who underwent rest and exercise radionuclide angiocardiography without subsequent cardiac catheterization were followed for a median of 4.6 years. Fifty-two cardiovascular deaths and 28 nonfatal myocardial infarctions occurred during the follow-up period. Thirty-nine radionuclide angiocardiographic and clinical variables were analyzed in association with the end points of cardiovascular death, total cardiac events and death from all causes using the Cox proportional hazards model and Kaplan-Meier survival estimates. Univariable analysis identified the exercise ejection fraction as the best predictor of cardiovascular death (chi-square = 82), total cardiac events (chi-square = 84) and death from all causes (chi-square = 66). A small subset of patients (n = 45) with an exercise ejection fraction less than 0.35 were at high risk for future cardiac events, whereas most patients (n = 776) had an exercise ejection fraction greater than or equal to 0.50 and a low probability of a subsequent event. Three variables--the exercise ejection fraction, the exercise change in heart rate, and gender--contained independent prognostic information determined by multivariable analysis. The exercise ejection fraction was the strongest independent predictor (p less than 0.0001) for every end point. The measurement of ventricular function during exercise provides important independent prognostic information in patients with suspected coronary artery disease. Radionuclide angiocardiography successfully identifies patients requiring invasive assessment, and the low probability of cardiac events in patients with good exercise ventricular function obviates the need for interventional therapy.

Adult↗
PubMed1991

Combined exercise radionuclide angiocardiography and single photon emission computed tomography perfusion studies for assessment of coronary artery disease.

Although there is widespread use of exercise thallium 201 scintigraphy and radionuclide angiocardiography in patients with coronary artery disease (CAD), little is known about the independence, concordance, or relative importance of these studies in the diagnosis, prognosis, and assessment of the outcome of therapy. The use of both tests in the same patient has been impractical because of the logistic considerations imposed by two exercise tests on separate days, and excessive radiation exposure. New technetium 99m-labeled radiopharmaceuticals with high myocardial extraction now permit the simultaneous assessment of myocardial perfusion (single photon emission computed tomography [SPECT]) and ventricular function (radionuclide angiocardiography [RNA]) during treadmill exercise (exercise tolerance test [ETT]). The ability to perform all three tests during a single exercise session offers a very attractive technique to evaluate patients with CAD. The investigators studied 86 patients with chronic CAD using the same-day perfusion and function protocol combined with treadmill exercise. The results demonstrate good concordance between myocardial perfusion and ventricular function as indicated by a significant correlation between tomographic perfusion defect size and ejection fraction (P less than .0001, R = 0.75 at rest and P less than .0001, R = 0.76 during exercise). Stepwise logistic regression was used to model ETT, RNA, and SPECT variables against the presence of one or more 60% stenoses by quantitative angiography, an end point present in 47 patients. Univariable analysis showed all three tests (ETT, RNA, and SPECT) to be significant predictors of the end points (lambda 2 = 5.1, P less than .05; lambda 2 = 12.5, P less than .001; and lambda 2 = 16.1, P less than .001, respectively). Multivariable analysis demonstrated that SPECT provided more diagnostic information than ETT and RNA (Lambda 2 = 16.1, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1991

Construct validity of practical questionnaires for assessing disability of low-back pain.

Four practical questionnaires used for assessing disability associated with chronic low-back pain were investigated. Comparison of findings among 93 patients disclosed a moderate level of agreement (r = 0.44-0.63) between the scales, providing limited evidence that a single construct is being measured by each. The questionnaires were more strongly related to each other than to psychosocial scales, which suggests that findings are distinguishable from distress. However, higher distress was significantly associated with greater reports of disability. This was most discernible in the form of more enduring characteristics that may reflect neuroticism. These findings allow modest support for the construct validity of the four questionnaires and suggest a need for caution with their use because persistently negative affect may be a biasing factor.

Adult↗
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↗