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Biomedical subjects

J Myers

Publications and source records attributed to J Myers.

At least 19 recordsLinked to original sources
PubMed1992

Four cycles of chemotherapy and regional radiation therapy for clinical early-stage and intermediate-stage Hodgkin's disease.

To achieve a high percentage of durable complete remissions (CR) and prolonged survivals and reduce toxicity in patients with early-stage and intermediate-stage Hodgkin's disease, a randomized trial of four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) versus four cycles of thiotepa, bleomycin, and vinblastine (TBV) combined with regional radiation therapy (RT) was conducted. For MOPP and RT, the CR percentage was 98% (60 of 61), and at 5 years, the percentage of patients in CR was 90%, with freedom from progression of 89% and overall survival of 91%. For TBV and RT, the CR percentage was 93% (55 of 59), with a 5-year duration of CR of 83%, freedom from progression of 81%, and overall survival of 91% (P greater than 0.15). The median follow-up was 65 months (range, 7 to 96 months). For 27 patients with clinical Stage IIIA, the CR percentage for MOPP and RT was 75% (12 of 16), with 1 relapse and 4 deaths. For TBV and RT, the CR percentage for clinical Stage IIIA was 73% (8 of 11) with 2 relapses and 2 deaths. Short-term toxicity except for transient leukopenia was less for TBV and RT than for MOPP and RT. Good results are achievable with combined treatment without excessive toxicity.

Adolescent↗
PubMed1992

Impact of left ventricular hypertrophy on blood pressure responses to exercise.

It is claimed that exaggerated blood pressure (BP) responses to exercise are predictive of future hypertension and may also be indicative of left ventricular (LV) hypertrophy. The relation between LV hypertrophy and maximal exercise BP was examined in 35 normal male volunteers and 65 untreated hypertensive male patients. Multiple stepwise regression analysis revealed that preexercise systolic BP was the major determinant of maximal exercise systolic BP (r = 0.52; p less than or equal to 0.0001), indicating that higher baseline BP predicted higher exercise BP. However, hypertensive patients with LV hypertrophy had the smallest increases in systolic BP with exercise. Accordingly, there was an inverse relation between LV muscle mass and systolic BP responses to exercise in these patients (r = -0.34; p = 0.005). When compared with normotensive subjects, hypertensive patients had lower measures of maximal oxygen uptake and exercise heart rates (p = 0.01). This may indicate lower cardiac performance at maximal exercise and explain the reduced capacity of hypertensive patients with LV hypertrophy to increase systolic BP with exercise. Neither baseline nor exercise BPs correlated with LV mass; instead, the model of regression analysis indicated that body weight was the principal determinant of LV mass. Contrary to previous reports, exaggerated exercise BPs were not associated with LV hypertrophy in hypertensive or normotensive patients.

Adult↗
PubMed1992

High affinity histamine H3 receptors regulate ACTH release by AtT-20 cells.

The distribution of high affinity histamine H3 receptors in various tissues from guinea pig has been determined using [3H]N alpha-methylhistamine binding. In the course of those studies, it was observed that the pituitary gland contains H3 receptors. Using this radioligand, we have now identified and characterized H3 receptors on' the AtT-20 cell line from a murine anterior pituitary tumor. This line has approximately 5000 high affinity (KD = 0.7 nM) H3 binding sites per cell. Competition binding with standard H1, H2 and H3 agents has confirmed that these sites are, indeed, H3 receptors. The H3 receptor specific agonist, (R)-alpha-methylhistamine increased the release of adrenocorticotropic hormone (ACTH) from AtT-20 cells in a dose- and time-dependent manner, while histamine and the H2 agonist dimaprit were significantly less potent. Furthermore, this response was blocked by thioperamide, an H3 receptor specific antagonist, but not by the H1 and H3 antagonists, chlorpeniramine and cimetidine. These results identify, for the first time, a cell line expressing H3 receptors and indicate that the high affinity histamine H3 receptor regulates ACTH release from that cell.

Adrenocorticotropic Hormone↗
PubMed1992

Ventilatory mechanisms of exercise intolerance in chronic heart failure.

Mechanisms that have been suggested to underlie the abnormal ventilatory response to exercise in patients with chronic congestive heart failure (CHF) include high pulmonary pressures, ventilation-perfusion mismatching, early metabolic acidosis, and abnormal respiratory control. To evaluate the role that ventilation and gas exchange play in limiting exercise capacity in patients with CHF, data from 33 patients with CHF and 34 normal subjects of similar age who underwent maximal exercise testing were analyzed. Maximal oxygen uptake was higher among normal subjects (31.7 +/- 6 ml/kg/min) than among patients with CHF (17.7 +/- 4 ml/kg/min; p less than 0.001). The ventilatory equivalent for oxygen, expressed as a percentage of maximal oxygen uptake, was 25% to 35% higher among patients with CHF compared with normal subjects throughout exercise (p less than 0.01). A steeper component effect of ventilation on maximal oxygen uptake was observed among normal subjects compared with patients with CHF, which suggests that a significant portion of ventilation in CHF is wasted. Maximal oxygen uptake was inversely related to the ratio of maximal estimated ventilatory dead space to maximal tidal volume (VD/VT) in both groups (r = -0.73, p less than 0.001). Any given oxygen uptake at high levels of exercise among patients with CHF was accompanied by a higher VD/VT, lower tidal volume, and higher respiratory rate compared with normal subjects (p less than 0.01). Relative hyperventilation in patients with CHF started at the beginning of exercise and was observed both below and above the ventilatory threshold, which suggests that the excess ventilation was not directly related to earlier than normal metabolic acidosis. Thus abnormal ventilatory mechanisms contribute to exercise intolerance in CHF, and excess ventilation is associated with both a higher physiologic dead space and an abnormal breathing pattern. The high dead space is most likely due to ventilation-perfusion mismatching in the lungs, which is related to poor cardiac output, and the abnormal breathing pattern appears to be an effort to reduce the elevated work of breathing that is caused by high pulmonary pressures and poor lung compliance.

Adult↗
PubMed1992

Role of balloon atrial septostomy before early arterial switch repair of transposition of the great arteries.

Preoperative balloon atrial septostomy is the standard therapy for babies with uncomplicated cyanotic dextrotransposition of the great arteries despite the effectiveness of prostaglandin E1 infusion in alleviating systemic hypoxemia and the reported success of arterial switch repair during the 1st weeks after birth. The clinical records and echocardiographic findings of 23 infants (mean birth weight +/- SD 3.3 +/- 0.5 kg) with uncomplicated transposition of the great arteries were analyzed. Fifteen infants (Group I) did not undergo septostomy, and 8 (Group II) underwent septostomy. Before prostaglandin infusion, mean arterial oxygen tension (Po2) in Group I (26 mm Hg) did not differ from that in Group II. After prostaglandin infusion, Po2 increased significantly in Group I (43 +/- 8 mm Hg, p less than 0.001) but not in Group II despite a widely patent ductus and predominant left to right ductal shunt in all. After septostomy, Po2 increased significantly (43 +/- 4 mm Hg, p less than 0.03), and did not differ from that in Group I. Echocardiographic features generally demonstrated a nonrestrictive foramen ovale in Group I and a restrictive foramen ovale in Group II. The latter was associated with persistent hypoxemia after prostaglandin. Thus, the diameter of the foramen ovale was the primary factor influencing arterial oxygenation during prostaglandin infusion. Babies underwent the arterial switch operation at a mean age of 70 +/- 65 h with an overall survival rate of 96%; there was only one postoperative death (Group II). Absence of septostomy had no negative influence on any postoperative variable, including duration of ventilatory and inotropic support, time to discharge, or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗
PubMed1992

Individualized ramp treadmill. Observations on a new protocol.

The many different approaches to exercise testing have hindered the consistent interpretation of hemodynamic, electrocardiographic, and ventilatory gas exchange responses. One of the most influential approaches is the choice of the exercise protocol. Recent data suggest that the protocol can have an important impact on test sensitivity, the reason for test termination, the ST/HR slope calculation, the interpretation of gas exchange responses, and the accuracy with which oxygen uptake is predicted from work rate. Recent recommendations for optimizing the test have focused on the test duration, reducing the increments in work rate, and individualizing the test relative to the purpose of the test and the subject tested. We describe a treadmill test which considers these recommendations for optimizing exercise testing.

Adult↗
PubMed1991

Hemodynamic determinants of exercise capacity in chronic heart failure.

PURPOSE: To synthesize information on hemodynamic determinants of exercise capacity in patients with chronic heart failure. DATA IDENTIFICATION: Relevant studies published from the mid-1960s to the present were identified by a manual search of the English-language literature and by bibliographic review of pertinent articles. STUDY SELECTION: Both controlled and observational studies that reported measures of either exercise time or oxygen uptake and hemodynamic variables in patients with heart failure were reviewed for quality and included when relevant to the discussion. DATA EXTRACTION: Key conclusions or data, or both, were extracted from each article and described. DATA SYNTHESIS: Exercise intolerance is a hallmark of chronic congestive heart failure. Studies have emphasized central factors and indices of systolic ventricular function, but poor relations have been consistently found between these measurements and exercise capacity. Recent data suggest that diastolic function (that is, ventricular filling and compliance) is an important factor affecting the ability to increase cardiac output and determining exercise capacity, but this issue needs further study. A clearer picture of histologic and biochemical abnormalities in skeletal muscle has recently emerged; patients with heart failure show greater glycolysis, reduced oxidative phosphorylation, and reduced oxidative enzyme activity. Vasodilatory abnormalities in heart failure were first described more than 20 years ago, and such abnormalities may underlie recently reported reductions in skeletal muscle blood flow during exercise. Relative hyperventilation is commonly observed during exercise in patients with heart failure and is related to ventilation-perfusion mismatching in the lung due to a higher-than-normal fraction of physiologic dead space. Neurohumoral abnormalities include reductions in beta-receptor density and sensitivity and contribute to reduced inotropic and chronotropic responses to exercise. CONCLUSIONS: Systolic function and exercise capacity are unrelated in patients with chronic heart failure, but many hemodynamic abnormalities (including those in the heart, lung, and skeletal muscle) overlap, which leads to exercise intolerance in these patients.

Heart Failure↗
PubMed1991

The ventilatory threshold: method, protocol, and evaluator agreement.

To evaluate the effects of different methods of detection, exercise modes, protocols, and reviewers on oxygen uptake (VO2) at the ventilatory threshold (ATge), 17 men with heart disease (mean age 59 +/- 6 years) and six healthy men (mean age 60 +/- 11 years) underwent six exercise tests on different days. Each subject performed three treadmill tests (Bruce, Balke, and ramp) and three bicycle ergometer tests (50 W/stage, 25 W/stage, and ramp) in random order. The ventilatory threshold was determined for each of the six exercise tests by three independent, blinded reviewers by means of graphic plots of three commonly used methods of determination: (1) changes in the ventilatory equivalents for VO2 and VCO2, (2) changes in end-tidal oxygen and carbon dioxide pressures, and (3) the intersection of the slope of VCO2 and VO2 (V slope). The largest variability in the ATge was observed with changes in the exercise protocol. The greatest absolute (ml/min) and percentage differences in oxygen uptake at the ATge as a result of changes in protocol, method of determination, and observers were 336 (36%), 125 (12%), and 70 (7%), respectively. The overall intraclass correlation coefficient for VO2 at the ATge among the three reviewers was 0.60 and among the three protocols was 0.85 (p less than 0.01). The V slope method of detection had consistently good agreement among reviewers and was least affected by the protocol. The variance in the ATge (excluding intersubject and error variance) accounted for by differences in protocol, method, and reviewer was 82%, 14%, and 4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold↗
PubMed1991

Comparison of the ramp versus standard exercise protocols.

To compare the hemodynamic and gas exchange responses of ramp treadmill and cycle ergometer tests with standard exercise protocols used clinically, 10 patients with chronic heart failure, 10 with coronary artery disease who were asymptomatic during exercise, 11 with coronary artery disease who were limited by angina during exercise and 10 age-matched normal subjects performed maximal exercise using six different exercise protocols. Gas exchange data were collected continuously during each of the following protocols, performed on separate days in randomized order: Bruce, Balke and an individualized ramp treadmill; 25 W/stage, 50 W/stage and an individualized ramp cycle ergometer test. Maximal oxygen uptake was 16% greater on the treadmill protocols combined (21.4 +/- 8 ml/kg per min) versus the cycle ergometer protocols combined (18.1 +/- 7 ml/kg per min) (p less than 0.01), although no differences were observed in maximal heart rate (131 +/- 24 versus 126 +/- 24 beats/min for the treadmill and cycle ergometer protocols, respectively). No major differences were observed in maximal heart rate or maximal oxygen uptake among the various treadmill protocols or among the various cycle ergometer protocols. The ratio of oxygen uptake to work rate, expressed as a slope, was highest for the ramp tests (slope +/- SEE ml/kg per min = 0.80 +/- 2.5 and 0.78 +/- 1.7 for ramp treadmill and ramp cycle ergometer, respectively). The slopes were poorest for the tests with the largest increments in work (0.62 +/- 4.0 and 0.59 +/- 2.8 for the Bruce treadmill and 50 W/stage cycle ergometer, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations.

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.

Actuarial Analysis↗
PubMed1990

Childhood near-drowning--a 12-year retrospective review.

The epidemiological findings in 107 patients admitted to Red Cross War Memorial Children's Hospital, Cape Town, between 1976 and 1987 with a diagnosis of near-drowning are reported. Of these patients, 77% were less than 5 years of age (ratio of boys to girls 2.1:1) and 46% of accidents occurred in swimming pools, 18% in buckets and only 9% in the sea. The high percentage of bucket near-drownings is unique in published medical reports; this appears prevalent in socially disadvantaged communities. Seventy-six per cent of the children were normal on discharge from hospital, 12% died and 6% had neurological damage. In 6% the final outcome was not known. These results are in keeping with other hospital-based studies. Preventive strategies are discussed and the need for further research highlighted.

Adolescent↗
PubMed1990

Characterization and tissue distribution of H3 histamine receptors in guinea pigs by N alpha-methylhistamine.

We have used [3H]N alpha-methylhistamine to characterize H3-binding in the guinea pig brain and to study its tissue distribution. Kinetic and equilibrium binding experiments indicate a single class of high affinity sites in membranes isolated from guinea pig brain tissue (Kd = 0.4 nM, Bmax = 41 fmol/mg of protein). Competition binding experiments have confirmed that this ligand associates with H3-receptors and, under the conditions used in these experiments, does not bind to H1- or H2-receptors. Although there was some binding in the ileum and large intestine, H3-binding was found primarily in the central nervous system.

Animals↗