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Biomedical subjects

S Rich

Publications and source records attributed to S Rich.

At least 91 records · Page 5Linked to original sources
PubMed1990

The effects of phenylephrine on right ventricular performance in patients with pulmonary hypertension.

Pulmonary hypertension causes right ventricular ischemia and failure as a result of increased afterload combined with reduced coronary blood flow. Increasing coronary driving pressure by raising aortic pressure with phenylephrine has been shown to reverse right ventricular ischemia from pulmonary hypertension in animals. Since vasodilators often fail to reduce afterload, we tested whether raising the coronary driving pressure would improve right ventricular function in man. Ten patients with pulmonary hypertension had hemodynamics and right ventricular coronary driving pressure measured before and 10 minutes after a steady state was reached with a phenylephrine infusion titrated to raise aortic pressure by 25 percent. Phenylephrine caused a significant (p less than .01) increase in mean aortic pressure (84 to 108 mm Hg) and right ventricular coronary driving pressure (46 to 69 mm Hg). In response, there was a significant (p less than .01) rise in mean pulmonary artery pressure (58 to 67 mm Hg), right ventricular end-diastolic pressure (10 to 16 mm Hg) and wedge pressure (5 to 9 mm Hg), and an insignificant fall in cardiac output (3.26 to 3.09 L/min) and pulmonary artery O2 saturation (57 to 49 percent). Although phenylephrine increased right ventricular coronary driving pressure, it worsened right ventricular function as manifest by a rise in end-diastolic pressure and fall in cardiac output. Any benefit of raising right ventricular coronary driving pressure may have been offset by alpha vasoconstriction of right ventricular coronary blood flow and/or pulmonary arterial vasoconstriction. Phenylephrine does not appear to be a useful therapy of right ventricular failure from pulmonary hypertension in patients who fail vasodilators.

Adult↗
PubMed1990

Primary pulmonary hypertension: modes of diagnosis and aggressive treatment with vasodilators.

In the last decade we have made great strides in our understanding of the clinical presentation and findings, natural history, and treatment of patients with primary pulmonary hypertension. Recognizing the tendency for in situ thrombosis in many of these patients now gives strong support to the recommendation that anticoagulants be used for patients who are felt to have underlying pulmonary artery thrombosis. Vasodilators in adequate doses can be demonstrated to cause substantial reductions in pulmonary artery pressure and pulmonary vascular resistance which causes regression in right ventricular hypertrophy and marked clinical improvement. There is still much to be accomplished in this field: a major challenge is to diagnose pulmonary hypertension in patients earlier, at a more treatable stage, and to develop effective treatments for patients with severe right ventricular dysfunction refractory to vasodilator treatment.

Cardiac Catheterization↗
PubMed1989

Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy.

Diabetic nephropathy develops in less than half of all patients with diabetes. To study heredity as a possible risk factor for diabetic kidney disease, we examined the concordance rates for diabetic nephropathy in two sets of families in which both probands and siblings had diabetes mellitus. In one set, the probands (n = 11) had no evidence of diabetic nephropathy, with normal creatinine clearance and a urinary albumin excretion rate below 45 mg per day. In the other set, the probands (n = 26) had undergone kidney transplantation because of diabetic nephropathy. Evidence of nephropathy was found in 2 of the 12 diabetic siblings of the probands without nephropathy (17 percent). Of the 29 diabetic siblings of probands with diabetic nephropathy, 24 (83 percent) had evidence of nephropathy (P less than 0.001), including 12 with end-stage renal disease. No significant differences were noted between the sibling groups with respect to the duration of diabetes, blood pressure, glycemic control, or glycosylated hemoglobin levels. Logistic regression analysis found nephropathy in the proband to be the only factor significantly predictive of the renal status of the diabetic sibling. We conclude that diabetic nephropathy occurs in familial clusters. This is consistent with the hypothesis that heredity helps to determine susceptibility to diabetic nephropathy. However, this study cannot rule out the possible influences of environmental factors shared by siblings.

Adolescent↗
PubMed1989

Genetic factors in the electrocardiogram and heart rate of twins reared apart and together.

Important physiologic mechanisms have been thought not to exhibit large amounts of variability, due in part to the assumption that critical biologic functions will have evolved to an evolutionary optimum. The attainment of this optimum would necessarily eliminate individual differences in these variables. Using a sample of monozygotic and dizygotic twins reared apart since birth or early infancy, 12-lead electrocardiographic recordings and vectorcardiograms were obtained. Values of these variables for monozygotic and dizygotic twins reared together were obtained from other studies. Maximum likelihood tests of genetic and environmental components of variation for PR interval, QRS duration, QT interval and ventricular rate indicated a significant contribution of genetic effects (most heritabilities ranged from 30 to 60%), with a negligible contribution from common familial environmental effects.

Electrocardiography↗
PubMed1989

A follow-up study of high-functioning autistic children.

It is well known that IQ is an important prognostic variable in the outcome of autistic children. There are, however, very few data available on the outcome of nonretarded autistic children as adults. We identified 16 such probands from records and followed them up between 11 and 27 years since discharge from a center specializing in the assessment of autistic children. There were 12 males and 4 females, average age was 26, and mean IQ was 92 (range 68-110). Although the majority were functioning poorly in terms of occupational-social outcome and psychiatric symptoms, a surprising number (4) had a very good outcome and might be considered recovered. The severity of early autistic behavior was a poor predictor of outcome, but neuropsychologic measures of nonverbal problem solving were highly correlated with outcomes. The results of the study indicate that a small percentage of nonretarded autistic children can be expected to recover to a substantial degree.

Adolescent↗
PubMed1989

Pulmonary hypertension: a cellular basis for understanding the pathophysiology and treatment.

Much of the understanding of hypertensive pulmonary vascular disease comes from studies of primary pulmonary hypertension. The three subtypes of primary pulmonary hypertension, plexogenic pulmonary arteriopathy, thromboembolic pulmonary hypertension and venoocclusive disease, have served as a basis to understand the mechanisms and to develop treatments of all forms of pulmonary hypertension. However, many inconsistencies regarding presumed pulmonary vasoconstriction and recurrent embolization remain. With newer data on the influence of the endothelium on vascular responsiveness and thrombosis, it appears that older concepts regarding the pathophysiology of pulmonary hypertension need to be revised. Recent studies have shown that plexogenic pulmonary arteriopathy is associated with abnormalities of endothelial structure and function that could result in impaired release of endothelial derived relaxing factors. Thromboembolic pulmonary arteriopathy, or more properly thrombotic pulmonary hypertension, appears to be the result of endothelial cell injury that creates a procoagulant environment in the pulmonary vascular bed with the development of widespread eccentric intimal proliferation and thrombosis in situ. It is possible that the effectiveness of vasodilator or anticoagulant therapy depends on the nature of the endothelial injury. Secondary pulmonary hypertension without endothelial injury, such as that which occurs with hypoxic lung disease or mitral stenosis, appears more satisfactorily treated when the primary cause is reversed.

Humans↗
PubMed1989

Exercise ultrafast computed tomography for the detection of coronary artery disease.

Ultrafast computed tomography permits the assessment of global and regional left ventricular function during exercise. To evaluate the feasibility of using this new technique for the diagnosis of coronary artery disease, 27 patients undergoing cardiac catheterization for diagnosis of chest pain were evaluated. Fifteen patients had significant (greater than 50%) coronary artery stenosis by quantitative coronary angiography. One vessel disease was found in 12 patients and multivessel disease in 3. Fourteen (93%) of the 15 patients with significant coronary stenosis had a decrease in ultrafast computed tomographic ejection fraction during exercise from (mean +/- SD) 65 +/- 7% to 60 +/- 7% (p less than 0.001). The tomographic ejection fraction increased greater than 5% units during exercise in 10 (83%) of the 12 patients with normal coronary arteries. The mean tomographic ejection fraction in this group was 68 +/- 6% at rest and 75 +/- 6% at peak exercise (p less than 0.001). Regional wall motion was quantified by analyzing the segmental ejection fraction of 12 30 degree pie segments at each tomographic level of the left ventricle. A new regional wall motion abnormality developed during exercise in 12 (86%) of 14 patients with coronary artery disease; one patient was excluded because of a technical problem in data storage. Eleven (93%) of the 12 patients with normal coronary arteries had normal wall motion during exercise. In no patient with ischemic heart disease were both variables, ejection fraction response and regional wall motion, normal. Exercise ultrafast computed tomography appears to be a useful technique for the evaluation of coronary artery disease in patients with chest pain and predominant single vessel coronary artery disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. The Multicenter Lisinopril-Captopril Congestive Heart Failure Study Group.

A randomized, parallel, double-blind study was performed with lisinopril, a long-acting angiotensin-converting enzyme inhibitor, versus captopril, a shorter-acting angiotensin-converting enzyme inhibitor, in the treatment of congestive heart failure. All patients were in New York Heart Association class II, III or IV and had remained symptomatic despite therapy with digoxin and diuretics. After a 4 to 14 day placebo baseline period, patients were randomized to receive either lisinopril, 5 mg orally once per day (n = 94), or captopril, 12.5 mg orally three times per day (n = 95), in addition to continuation of digoxin and diuretics. The dose of study drug could be doubled at 4 week intervals for a total of 12 weeks of double-blind therapy. The maximal dose was 20 mg once per day of lisinopril or 50 mg three times per day of captopril. The addition of either lisinopril or captopril to a regimen of diuretics or digoxin, or both, caused an increase in exercise duration as assessed on a motorized treadmill. When protocol violators were excluded, patients receiving lisinopril had a statistically greater increase in exercise duration than that of patients receiving captopril. In patients with renal impairment (serum creatinine greater than 1.6 mg/dl at baseline), lisinopril was superior to captopril in improving exercise duration. Lisinopril, but not captopril, increased left ventricular ejection fraction in patients with moderately to severely (less than 35%) decreased function (p less than 0.05). Improvement in functional capacity and quality of life, as assessed by the Yale Scale dyspnea/fatigue index, was significantly greater for the lisinopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Histopathology of primary pulmonary hypertension. A qualitative and quantitative study of pulmonary blood vessels from 58 patients in the National Heart, Lung, and Blood Institute, Primary Pulmonary Hypertension Registry.

Qualitative and quantitative studies were performed on pulmonary blood vessels in lung tissue obtained by biopsy, pneumonectomy, or autopsy from 58 patients in the Registry of Primary Pulmonary Hypertension sponsored by the Heart, Lung, and Blood Institute of the National Institutes of Health. In 49 patients (84%), the hypertensive vascular disease involved predominantly or exclusively muscular pulmonary arteries and arterioles. In each of these 49 patients, pulmonary artery medial hypertrophy was observed, and in 48 patients, it was also associated with intimal or luminal lesions. On the basis of the predominant histopathologic features, 25 of the 48 patients were classified as having pulmonary arteriopathy with plexiform lesions characterized by a combination of concentric laminar intimal fibrosis, eccentric intimal fibrosis, and plexiform lesions; in nine of these 25, recanalized thrombi were also present. Pulmonary arteriopathy with thrombotic lesions, defined by the presence of both eccentric intimal fibrosis and recanalized thrombi but without plexiform lesions, was observed in 19 patients. Intimal fibrosis, either concentric or eccentric, without plexiform or thrombotic lesions was found in four patients. Among the remaining nine patients in the Registry, pulmonary veno-occlusive disease was present in seven and chronic pulmonary venous hypertension in one. Pulmonary blood vessels were microscopically normal in a lung biopsy specimen from another patient. In general, patients with plexiform lesions and those with veno-occlusive disease had a much poorer prognosis than patients with thrombotic lesions. The present study shows the existence of several distinct histopathologic patterns of pulmonary vascular disease in individuals with primary pulmonary hypertension diagnosed by standardized clinical and laboratory criteria.

Humans↗
PubMed1989

The potential role for ultrafast cardiac computed tomography in patients with stroke.

We studied 40 patients with stroke of potential cardioembolic origin by cardiac ultrafast computed tomography and two-dimensional echocardiography. Cardiac ultrafast computed tomography was more sensitive (positive in eight of 14 instances) than two-dimensional echocardiography (positive in two of 14 instances) for the detection of intracardiac thrombus, which was found in 13 patients. Mitral anular calcification was diagnosed more often by two-dimensional echocardiography (four of five instances) than by cardiac ultrafast computed tomography (one of five instances); this implies a high incidence of false-positives for the former. Cardiac ultrafast computed tomography showed that one half of the patients (21 of 40) had coronary artery calcification, indicating a high incidence of coronary atheroma in this patient population. Future studies comparing brain and cardiac pathology with the findings of cardiac ultrafast computed tomography and patient prognosis are needed to define the significance and utility of this technique in patients with stroke.

Adolescent↗
PubMed1989

The prevalence of pulmonary hypertension in the United States. Adult population estimates obtained from measurements of chest roentgenograms from the NHANES II Survey.

Because a definitive diagnosis of pulmonary hypertension requires cardiac catheterization, there have been no data on the prevalence of pulmonary hypertension in the general population. The diameter of the right descending pulmonary artery, as measured from chest roentgenograms, has been used by clinicians as a noninvasive indicator of pulmonary hypertension. Chest roentgenograms from the Second National Health and Nutrition Examination Survey, a sample survey of the US civilian noninstitutional population, were used in conjunction with estimates of sensitivity and specificity of this technique determined from patients who underwent right heart catheterization to estimate the prevalence of pulmonary hypertension (mean pulmonary artery pressure greater than 20 mm Hg at rest) in the US population aged 25 years and older. The prevalence is estimated to be very low in the population at large, primarily because of the low prevalence in women of all ages. The prevalence in men is 13.4 percent above age 34, and increases to 28.2 percent above age 64. Thus, in elderly men, pulmonary hypertension is relatively common and may have an important impact in the management of this age group.

Adult↗
PubMed1988

Genetic relationships between type I and type II diabetes mellitus.

We propose that at least certain subsets of Type I and Type II diabetes share factor(s) responsible for genetic susceptibility. The data presented here to support this contention include: 1. A significantly increased cumulative risk (CR40) to age 40 for Type I diabetes in sibs of probands in families with a Type II diabetic parent (Type II diabetic parent: CR40-24.7 +/- 10.7%; normal parent: CR40 = 7.5 +/- 2.0%, x2 = 12.8, p less than 0.0005). 2. The relative risk (RR) for HLA DR4 in Type I diabetic probands with a Type II diabetic parent is higher than in probands with normal parents (RR = 2.4). 3. The haptoglobin genotype 2-2 is increased in Type I diabetics with Type II parents and the sharing of both HLA and haptoglobin haplotypes in affected sib pairs is distorted with an excess sharing of both haplotypes.

Age Factors↗
PubMed1988

A rule for the early detection of chronic changes in cystic fibrosis patient status.

A statistical decision-making system has been developed which will predict the clinical status of a patient with cystic fibrosis based on daily self measurements obtained at home. The data for the study were collected from CF patients within 7-12 years of age. Thirty-two participants recorded four daily measurements (weight, vital capacity, breathing rate, and resting pulse) and one weekly measurement (height). In addition to the 4 daily measured values, the clinical status of each patient at his/her most recent previous clinic visit was used as a predictor variable. The measured values were used as the basis for the development of a discriminant rule. The goal of the rule was to determine whether each patient's clinical status was deteriorating, stable, or improving at the time of the most recent set of weekly measurements. Three types of analysis were performed: linear discriminant analysis, quadratic discriminant analysis, and nearest neighbor. Quadratic discriminant analysis provided the best discrimination due to the differences in the covariance matrices among the populations. The rule was able to correctly classify 77% of the 103 cases in the learning set. To further evaluate the rule, both a weighted classification percentage and weighted kappa statistic were calculated for the rule. Bootstrapping was used to predict the performance of the rule on the population with results of 77% correctly classified overall.

Body Weight↗
PubMed1988

Personality similarity in twins reared apart and together.

We administered the Multidimensional Personality Questionnaire (MPQ) to 217 monozygotic and 114 dizygotic reared-together adult twin pairs and 44 monozygotic and 27 dizygotic reared-apart adult twin pairs. A four-parameter biometric model (incorporating genetic, additive versus nonadditive, shared family-environment, and unshared environment components) and five reduced models were fitted through maximum-likelihood techniques to data obtained with the 11 primary MPQ scales and its 3 higher order scales. Solely environmental models did not fit any of the scales. Although the other reduced models, including the simple additive model, did fit many of the scales, only the full model provided a satisfactory fit for all scales. Heritabilities estimated by the full model ranged from .39 to .58. Consistent with previous reports, but contrary to widely held beliefs, the overall contribution of a common family-environment component was small and negligible for all but 2 of the 14 personality measures. Evidence of significant nonadditive genetic effects, possibly emergenic (epistatic) in nature, was obtained for 3 of the measures.

Adult↗
PubMed1988

Pulmonary hypertension from chronic pulmonary thromboembolism.

Pulmonary hypertension may develop whenever chronic obstruction of pulmonary arterial blood flow occurs. Although repeated pulmonary embolism is thought to be the usual underlying cause, there is little clinical evidence to support this theory. Studies of the pulmonary vascular endothelium have shown that perturbations of the normal endothelium can create a procoagulant environment, which could lead to the development of thrombosis in situ at the level of the large or smaller pulmonary vessels. Some patients develop proximal pulmonary thromboemboli, which may be the result of retrograde propagation of thrombus after an initial pulmonary embolus. Others present with unexplained pulmonary hypertension secondary to thrombotic occlusion of the pulmonary microvasculature. A perfusion lung scan will show abnormalities that should lead to correct clinical diagnosis and confirmatory evaluation. Thromboendarterectomy in selected cases provides dramatic clinical improvement in patients with proximal thromboemboli. Vasodilators may be effective in some patients with obstruction at the arteriolar level. Both groups should be treated with chronic warfarin anticoagulant therapy to protect against progression of thromboembolism.

Angiography↗
PubMed1987

Suppressor T cell growth and differentiation: evidence for induced receptors on suppressor T cells that bind a suppressor T cell differentiation factor.

T suppressor cell differentiation factor (TsDF) induces the differentiation of alloantigen-primed suppressor T cells (MLR-Ts) to expression of their effector function, i.e., to active TsF production. The initial activation stimulus to Ts is provided by alloantigen binding; after this binding, Ts are functionally responsive only for a period of hours to the additional stimulus provided by TsDF. The present studies addressed the possibility that MLR-Ts responsiveness to TsDF reflects the induced and transient display of TsDF-binding receptors. TsDF receptor expression was investigated by determining the capacity of TsDF-responsive MLR-Ts to adsorb TsDF activity and to respond to that TsDF pulse by TsF production. Primed Ts populations that were alloantigen restimulated for 8 hr adsorbed TsDF in a cell dose-dependent fashion and produced TsF in response to that adsorption, whereas alloantigen-stimulated naive cells or primed but nonrestimulated cells neither responded to nor bound TsDF. Primed and restimulated L3T4-Ly-2+ but not L3T4+-Ly-2--enriched T cells bound TsDF. TsDF adsorption was saturable and time and temperature dependent. Glutaraldehyde fixation did not prevent TsDF adsorption by restimulated MLR-Ts, whereas pronase treatment abolished their TsDF-binding capacity. Kinetic analyses demonstrated that the capacity to bind TsDF developed rapidly after alloantigen reexposure, with maximal binding within 8 hr, followed by rapid decay with loss of TsDF binding by 36 hr. The kinetics of TsDF-induced TsF production correlated precisely with those of TsDF binding. These observations provide strong evidence that TsDF affects primed alloantigen-reactive Ts by interaction with antigen-induced and transiently expressed cell surface receptors. TsDF-receptor binding is then the stimulus for expression of Ts effector function.

Animals↗
PubMed1987

Suppressor T cell growth and differentiation: production of suppressor T cell differentiation factor by the murine thymoma BW5147.

Previous studies have identified a lymphokine, termed Ts differentiation factor (TsDF), in primary MLR supernatants that induces effector function of alloantigen-primed MLR-Ts. The present report describes constitutive production of TsDF by the murine thymoma BW5147, and its use to analyze alloantigen and TsDF requirements for MLR-Ts activation to TsF production. Serum-free supernatants of BW5147 restored the capacity of MLR-TsF production to alloantigen-primed MLR-Ts cultured with glutaraldehyde-fixed allogeneic stimulator cells, and were not themselves directly suppressive in the MLR assay. BW5147 supernatant induced MLR-TsF production from primed L3T4-Ly2+ MLR-Ts in the absence of concomitant proliferation, suggesting that the function of BW5147 supernatant, like that of MLR-derived TsDF, is a differentiative rather than a proliferative one, and is required for the synthesis or release of TsF. The differentiative activity of BW5147 supernatant was associated with a molecular species of approximately 14,500 m.w. by HPLC fractionation and was expressed independently of detectable IL 2, IL 3, IFN-gamma, and IL 1. The functional activity of BW5147 supernatant has therefore been provisionally designated BW5147-derived Ts differentiative factor, or BW-TsDF. By using BW-TsDF, it was demonstrated that MLR-Ts fail to respond to TsDF in the absence of, or preceding, reexposure to priming alloantigen. Instead, alloantigen binding by primed MLR-Ts appears to create a transient state of TsDF responsiveness. Primed MLR-Ts were fully sensitive to delayed addition of TsDF for approximately 12 hr after reexposure to alloantigen, but became TsDF-unresponsive within 24 to 36 hr. MLR-Ts cultured alone for 36 hr were fully responsive to the combined addition of TsDF and alloantigen. Thus, MLR-Ts activation to TsF release requires the sequential events of specific alloantigen binding, which induces a TsDF-responsive state, followed by interaction with TsDF. The transience of induced TsDF responsiveness suggests a precise mechanism for control of antigen-initiated Ts activation to effector function.

Animals↗