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Biomedical subjects

S Rich

Publications and source records attributed to S Rich.

At least 55 records · Page 3Linked to original sources
PubMed1996

Serum nifedipine concentrations and response of patients with pulmonary hypertension.

In patients with primary pulmonary hypertension who respond to nifedipine during acute drug testing, there is a significant linear correlation of serum nifedipine concentration with pulmonary artery pressure and resistance. Although most demonstrate an initial response at readily attainable nifedipine concentrations with conventional dosages, a subset of patients seem to display delayed or incomplete oral absorption; these results may facilitate the clinical use of nifedipine in patients with primary pulmonary hypertension.

Adult↗
PubMed1996

Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study.

BACKGROUND: Ultrafast computed tomography (CT), by acquiring images of the proximal coronary arteries, detects coronary calcifications and has been demonstrated to be highly sensitive for the detection of coronary artery disease in many small studies. The aim of this study was to determine the relationship between ultrafast CT scanning and coronary angiography in a large number of symptomatic patients. METHODS AND RESULTS: The study population consisted of 710 patients from six participating centers. A multivariate logistic regression model was used to evaluate the individual contributions of age, number of calcified vessels, and the calcium score for the probability of angiographically significant disease. Of the 710 patients enrolled, 427 patients had significant angiographic disease, and coronary calcification was detected in 404, yielding a sensitivity of 95%. Of the 23 patients without calcifications, 19 (83%) had single-vessel disease at angiography. Of the 283 patients without angiographically significant disease, 124 had negative ultrafast CT coronary studies, for a specificity of 44%. An increasing number of vessels with calcification present on ultrafast CT was found to increase specificity for the presence of obstructive coronary artery disease in at least one vessel (P < .0001). As the log of the calcium score increases, the probability of multivessel obstructive disease increases (P < .0001). CONCLUSIONS: Ultrafast CT scanning is an noninvasive, non-exercise-dependent test with an excellent sensitivity for the detection of coronary artery disease. The presence of calcifications in multiple vessels and in younger populations correlates with higher specificities for obstructive disease, making ultrafast CT coronary scanning a very useful diagnostic test.

Adult↗
PubMed1996

A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a progressive disease for which no treatment has been shown in a prospective, randomized trial to improve survival. METHODS: We conducted a 12-week prospective, randomized, multicenter open trial comparing the effects of the continuous intravenous infusion of epoprostenol (formerly called prostacyclin) plus conventional therapy with those of conventional therapy alone in 81 patients with severe primary pulmonary hypertension (New York Heart Association functional class III or IV). RESULTS: Exercise capacity was improved in the 41 patients treated with epoprostenol (median distance walked in six minutes, 362 m at 12 weeks vs. 315 m at base line), but it decreased in the 40 patients treated with conventional therapy alone (204 m at 12 weeks vs. 270 m at base line; P < 0.002 for the comparison of the treatment groups). Indexes of the quality of life were improved only in the epoprostenol group (P < 0.01). Hemodynamics improved at 12 weeks in the epoprostenol-treated patients. The changes in mean pulmonary-artery pressure for the epoprostenol and control groups were -8 percent and +3 percent, respectively (difference in mean change, -6.7 mm Hg; 95 percent confidence interval, -10.7 to -2.6 mm Hg; P < 0.002), and the mean changes in pulmonary vascular resistance for the epoprostenol and control groups were -21 percent and +9 percent, respectively (difference in mean change, -4.9 mm Hg/liter/min; 95 percent confidence interval, -7.6 to -2.3 mm Hg/liter/min; P < 0.001). Eight patients died during the study, all of whom had been randomly assigned to conventional therapy (P = 0.003). Serious complications included four episodes of catheter-related sepsis and one thrombotic event. CONCLUSIONS: As compared with conventional therapy, the continuous intravenous infusion of epoprostenol produced symptomatic and hemodynamic improvement, as well as improved survival in patients with severe primary pulmonary hypertension.

Adult↗
PubMed1996

Predictors of mortality in pulmonary thromboendarterectomy.

BACKGROUND: The operative mortality associated with surgical thromboendarterectomy of the pulmonary arteries has decreased at the University of California in San Diego with the application of new techniques. For universal performance of the procedure, however, those factors that contribute to the high operative mortality must be identified. We analyzed our results in 34 consecutive patients undergoing pulmonary thromboendarterectomy to determine those preoperative factors that contribute to operative mortality. METHODS: Since 1983, 34 patients with severe, surgically correctable chronic thromboembolic pulmonary hypertension who were judged to be operable by pulmonary arteriography underwent pulmonary thromboendarterectomy. No patient was excluded because of right ventricular failure or hemodynamic severity of disease; the mean pulmonary artery pressure (PAP) was 54 mm Hg, the mean pulmonary vascular resistance (PVR) was 1,094 dynes.s.cm-5, and all patients were in New York Heart Association functional class III or IV. RESULTS: Postoperative course was characterized either by swift recovery (mean length of stay, 13 days) or by rapid demise resulting from pulmonary or right ventricular failure, or both (overall operative mortality, 23%). In survivors, the mean PAP, PVR, cardiac output, and New York Heart Association functional class were significantly improved (p < 0.05). Patients who died had a significantly greater mean preoperative PAP than did those who survived (62.1 +/- 1.2 versus 49.5 +/- 2.3 mm Hg; p < 0.01) and significantly higher PVR (1,512 +/- 116 versus 949 +/- 85 dynes.s.cm-5; p < 0.01). In addition, both a PVR of more than 1,100 dynes.s.cm-5 and a mean PAP of more than 50 mm Hg could accurately predict operative mortality: operative mortality was six times greater in patients with a preoperative PVR of greater than 1,100 dynes.s.cm-5 (41% versus 5.85%) and almost five times greater in those with a mean PAP of greater than 50 mm Hg (37% versus 8%). No intraoperative factors, including the use or duration of circulatory arrest, affected outcome. CONCLUSIONS: Patients with severe hemodynamic disease (PVR > 1,100 dynes.s.cm-5 and PAP > 50 mm Hg) have a high likelihood of operative mortality and perhaps should not undergo pulmonary thromboendarterectomy, except at institutions where the operation is performed frequently.

Adult↗
PubMed1995

Pressure and volume loading of the right ventricle have opposite effects on left ventricular ejection fraction.

BACKGROUND: Left ventricular ejection fraction has been reported to be depressed in patients with right ventricular volume overload (RVVO) due to Ebstein's anomaly and uncomplicated atrial septal defect, whereas it is usually preserved in right ventricular pressure overload (RVPO) due to congenital pulmonic stenosis. In the present study, we examined the hypothesis that the differential timing of active displacement of the ventricular septum into the left ventricle in RVPO (end systole) and RVVO (end diastole) results in opposite effects of RVPO and RVVO on left ventricular ejection fraction. METHODS AND RESULTS: Ten patients with severe tricuspid regurgitation after tricuspid valve resection for endocarditis and 10 patients with primary pulmonary hypertension were studied as models of isolated RVVO and RVPO, respectively. Left ventricular ejection fraction, end-diastolic volume, and regional systolic shortening were measured with the use of echocardiographic techniques in these 20 patients and 10 healthy control subjects. In RVPO, despite marked underfilling of the left ventricle relative to the healthy control subjects (end-diastolic volume, 48 +/- 26 versus 77 +/- 20 mL; P < .02), left ventricular ejection fraction was similar to that of the control subjects (56 +/- 5% versus 60 +/- 4%; P = .07) and only 1 of 10 RVPO patients had an ejection fraction of less than 50%. In contrast, in RVVO the left ventricle was volume replete (end-diastolic volume, 84 +/- 26 versus 77 +/- 20 mL; P = NS), but left ventricular ejection fraction was significantly depressed (51 +/- 4% versus 60 +/- 4%, P < .001) compared with the control subjects, and 4 of 10 RVVO patients had an ejection fraction of less than 50%. Analysis of systolic fractional shortening along two perpendicular short-axis diameters and the mutually orthogonal long axis demonstrated isolated augmentation of fractional shortening in the ventricular septal-to-posterolateral free wall dimension in RVPO (47.4 +/- 13.7% versus 34.2 +/- 13.1%, P < .05) and isolated depression of fractional shortening along that same dimension in RVVO (13.7 +/- 11.8% versus 34.2 +/- 13.1%, P < .001) compared with the control subjects. CONCLUSIONS: End-systolic leftward ventricular septal shift in RVPO results in isolated augmentation of systolic shortening in the septal-to-free wall dimension, whereas end-diastolic leftward ventricular septal shift in RVVO results in isolated reduction in systolic shortening in the septal-to-free wall dimension. As a result, despite relative underfilling of the left ventricle in RVPO, resting left ventricular ejection fraction is preserved, whereas ejection fraction is depressed for the volume-replete left ventricle of patients with RVVO.

Adolescent↗
PubMed1995

Transforming growth factor beta 1 costimulated growth and regulatory function of staphylococcal enterotoxin B-responsive CD8+ T cells.

Transforming growth factor beta (TGF-beta) exhibits diverse effects on growth and differentiation of a wide range of cell types. In the immune system, TGF-beta 1 is a potent inhibitor of T cell proliferation and certain T cell effector functions. However, TGF-beta 1 also enhances growth of T cells, predominantly of naive phenotype, and induces their expression of selected cytokines. We have previously demonstrated that TGF-beta 1 costimulates growth of highly purified murine CD8+ T cells activated by immobilized anti-CD3 Ab. TGF-beta 1-costimulated CD8+ T cells rapidly express a memory phenotype, lose lytic function, and express a mixed cytokine pattern with IL-2, IFN-gamma, and appreciable IL-10, as well as TGF-beta 1. The present work examines the possibility that TGF-beta 1 similarly costimulates response of murine CD8+ T cells to the microbial superantigen staphylococcal enterotoxin B (SEB) and characterizes their effector and regulatory functions. TGF-beta 1 significantly enhances CD8+ T cell proliferation to SEB in the presence of MHC class II-positive APC and TGF-beta 1-primed CD8+ T cells are enriched for SEB-reactive V beta 8+ TCR expression. TGF-beta 1 priming also up-regulates a memory-like CD45RBlowCD44highMEL-14low phenotype. TGF-beta 1 priming inhibits development of SEB-specific lytic effector function by more than 90%. However, TGF-beta 1-primed CD8+ effector T cells express elevated levels of IL-10 and TGF-beta 1, variable IFN-gamma, and undetectable IL-4. Additionally, they exhibit growth inhibitory effector function of SEB-induced proliferation of other CD4+ and CD8+ T cells. Growth inhibition by TGF-beta 1-primed CD8+ T cells is reversed in part by anti-IL-10 Ab. Thus, in the context of SEB response, TGF-beta 1 promotes the outgrowth and induces the effector function of CD8+ T cells that have the capacity to impair T cell clonal growth.

Animals↗
PubMed1995

Understanding right and left ventricular systolic function and interactions at rest and with exercise in primary pulmonary hypertension.

The effort limitation in primary pulmonary hypertension (PPH) is thought to result from an inability to increase cardiac output with exercise. The precise mechanism, however, is unknown. We studied right ventricular (RV) and left ventricular (LV) function and interactions in 16 patients with PPH with electron beam computed tomography (EBCT) at rest and during supine bicycle exercise. RV and LV volumes and masses were measured at systole and diastole, and ejection fraction and cardiac index computed. Resting RV end-diastolic volume (215 +/- 72 ml) and mass (110 +/- 45 g) were increased, whereas stroke volume (65 +/- 26 ml) and ejection fraction (31 +/- 8%) were decreased. LV end-diastolic volume (80 +/- 31 ml) was decreased, whereas ejection fraction remained normal (66 +/- 9%). Cardiac index was at the lower limit of normal (2.26 +/- 0.72 L/min/m2). During exercise, RV end-diastolic volume was unchanged (196 +/- 63 ml, p = NS) but stroke volume (52 +/- 29 ml, p < 0.05) and ejection fraction (26 +/- 10%, p = 0.08) decreased. LV end-diastolic (52 +/- 22 ml, p < 0.001), end-systolic (17 +/- 8 ml, p < 0.001), and stroke volumes (35 +/- 20 ml, p < 0.001) decreased, whereas ejection fraction (65 +/- 15%, p = NS) and cardiac index remained unchanged (2.17 +/- 0.93 L/min/m2, p = NS). the ratio of RV/LV stroke volume at rest (1.21 +/- 1.06) increased with exercise (1.74 +/- 1.13, p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Multimedia computer-assisted instruction in cardiology.

BACKGROUND: Medical education faces problems caused by increasing restraints on resources. A multicenter consortium combined simulation and multimedia computer-assisted instruction (MCAI) to develop unique interactive teaching programs that can address a number of these problems. We describe the consortium, the MCAI system, the programs, and a multicenter evaluation of technical and educational performance. METHODS: The MCAI system uses computer-controlled access to full-screen, full-motion, and full-color laser disc video in combination with digitized sound, images, and graphics stored on removable media. The Socratic teaching method enhances interaction and guides learners through the patient's history, cardiovascular physical examination, laboratory evaluation, and therapy. Self-instruction and instructor-led modes of function are possible. The first five programs, based on simulations of specific cardiology problems, were distributed to four medical centers. Questionnaires evaluated technical function and medical student opinions, while behaviors and scores were automatically tracked and tabulated by program administration software. RESULTS: The MCAI system functioned reliably and accurately in all modes and at all sites. The programs were highly rated. Student ratings, scores, and behaviors were independent of institution and mode of use. CONCLUSION: A multicenter educational consortium developed a system to produce unique, sophisticated MCAI programs in cardiology. Both system and programs functioned reliably at four institutions and were highly rated by fourth-year medical students. With this enthusiastic reception, the economies and strengths associated with MCAI make it an attractive solution to a number of problem areas, and it will likely play an increasingly important role.

Cardiology↗
PubMed1995

Medical treatment of primary pulmonary hypertension: a bridge to transplantation?

Primary pulmonary hypertension is a progressive disease with a mean survival of < 3 years from the time of diagnosis. Recent advances in the medical management have shown that some patients may have an extremely good outcome depending on the response to high doses of calcium antagonists. Anticoagulants are also associated with improved survival, and prostacyclin is showing great promise in patients who are refractory to conventional therapy. At the same time, lung transplantation has developed into a viable treatment option for patients who remain symptomatic and deteriorate on medical management. The role of the various medical treatment modalities, and the ideal timing of lung transplantation, is an issue that is continuing to evolve as improvements in all treatments develop. The cost and availability of the various treatments will likely affect the selection of treatments in individual patients as well.

Anticoagulants↗
PubMed1995

Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography.

OBJECTIVES: This study sought to determine the relation between coronary calcification detected with ultrafast computed tomography and lumen narrowing defined with angiography and evaluated whether this relation is influenced by age and gender. BACKGROUND: Ultrafast computed tomography has been shown to be a sensitive method for detection of coronary calcification associated with atherosclerotic disease, but the relation between the extent of coronary calcification and degree of lumen narrowing and the possible influence of gender or age, or both, on this relation have not been clarified. METHODS: Seventy men and 70 women were studied with ultrafast computed tomography for analysis of coronary calcification and coronary angiography. Coronary atherosclerosis was considered present if any lumen irregularity was noted on angiography, and obstructive coronary artery disease was defined as a lumen diameter narrowing > or = 70%. RESULTS: Coronary calcification had a sensitivity of 88% for identification of patients with atherosclerotic disease and 97% for those with obstructive disease, with corresponding specificities of 55% and 41%, respectively. The sensitivity of coronary calcium for detection of atherosclerotic disease in women < 60 years old was 50%, significantly less than the 97% sensitivity in women > 60 years old and the 87% sensitivity in men < 60 years old (p < 0.05 for each comparison). Logistic regression analysis revealed a 1.81-fold increase in the likelihood of detecting coronary calcification in the atherosclerotic lesions of men compared with those in women (95% confidence interval 1.12 to 2.93, p = 0.016) when controlled for age and severity of coronary disease by angiography. CONCLUSIONS: Atherosclerotic lesions in women are less likely to have coronary calcium than lesions with a similar degree of lumen narrowing in men. Differences in the pattern of coronary calcification between men and women may provide insight into the gender differences observed in the clinical development of symptomatic coronary artery disease.

Aged↗
PubMed1995

Neurohormonal activation in patients with right ventricular failure from pulmonary hypertension: relation to hemodynamic variables and endothelin levels.

OBJECTIVES: This study sought to determine whether neurohormonal activation occurs in isolated right heart failure. BACKGROUND: Neurohormonal activation appears to parallel the severity of left heart failure, but little is known about its role in right heart failure. METHODS: We evaluated neurohormonal activation and endothelin levels in 21 patients with primary pulmonary hypertension at the time of right heart catheterization. RESULTS: Plasma norepinephrine levels correlated significantly with pulmonary artery pressure (r = 0.66, p < 0.01), cardiac index (r = -0.56, p < 0.01) and pulmonary vascular resistance (r = 0.69, p < 0.001). Atrial natriuretic peptide levels were higher in the pulmonary artery than the right atrium and femoral artery and correlated closely with pulmonary artery oxygen saturation (r = -0.73, p < 0.0001). Plasma renin levels were not elevated. Endothelin levels were increased and correlated with right atrial pressure (r = 0.74, p < 0.0001) and pulmonary artery oxygen saturation (r = -0.070, p < 0.0004). CONCLUSIONS: Neurohormonal activation occurs in patients with isolated right ventricular failure and inherently normal left ventricles and appears to be related to the overall severity of cardiopulmonary derangements. The elevation in endothelin levels is consistent with its release in response to pulmonary hypertension.

Adolescent↗
PubMed1995

Comparative acute effects of adenosine and prostacyclin in primary pulmonary hypertension.

Vasodilators have been a main focus of therapy for primary pulmonary hypertension. Adenosine and prostacyclin have been shown to reduce pulmonary vascular resistance acutely in these patients. In order to compare the acute hemodynamic effects of adenosine and prostacyclin, ten patients with severe primary pulmonary hypertension, unresponsive to medical therapy, were studied. After baseline hemodynamics were obtained, an adenosine infusion, 50 to 100 ng/kg/min, was begun and titrated to the maximum tolerated dose. Hemodynamics were allowed to return to baseline, and thereafter, a prostacyclin infusion was begun at 2 ng/kg/min, and titrated to the maximum tolerated dose. Overall, adenosine (200 +/- 53 ng/kg/min) produced a 33 +/- 18% (p < 0.001) fall in pulmonary vascular resistance and a 52 +/- 25% (p < 0.001) increase in cardiac output with no effect on pulmonary or systemic arterial pressures. Prostacyclin (8 +/- 4 ng/kg/min) caused a 22 +/- 18% (p < 0.01) fall in pulmonary vascular resistance and a 25 +/- 26% (p < 0.05) increase in cardiac output with a 14 +/- 6% (p < 0.001) decrease in systemic arterial pressure, but no change in pulmonary arterial pressure. The effects of adenosine and prostacyclin on pulmonary vascular resistance were similar (r = 0.70, r2 = 0.49, p = 0.02). Adenosine and prostacyclin have similar hemodynamic effects acutely in primary pulmonary hypertension. Adenosine may be useful as a test of the potential for long-term prostacyclin therapy in patients with primary pulmonary hypertension.

Adenosine↗
PubMed1994

Education attainment level of caregivers versus readability level of written instructions in a pediatric emergency department.

Our objectives were 1) to determine the education attainment level (EAL) of parents attending the pediatric emergency department (PED); 2) to assess the readability level (RL) of the written instructions available to these parents; and 3) to revise these instruction forms at a level of comprehension based on the EAL of parents. We used a questionnaire of EAL and RL assessment using the SMOG and FOG readability formulas. We then revised the written instructions and used parents in the PED to pretest them. The setting was a PED in a tertiary care hospital (Children's Hospital of Western Ontario). The participants were 1034 parents of children in the PED between 8 AM and 11 PM over a six-month period. Parents were chosen at 30-minute intervals on randomly selected weekdays and weekends. A total of 1022 completed the study. Seven forms commonly used in the PED were assessed for RL. Seven forms were rewritten at grade 6 to 7 RL, and each was pretested in 21 of 24 parents or guardians in the PED using a standardized questionnaire with open-ended questions. Ninety percent of respondents spoke English, and 85% had English as their first language. Forty-nine percent of parents had a grade 13 or lower EAL. This included the following EALs; < grade 12 EAL, 23%; < grade 10 EAL, 15%; and < grade 8 EAL, 4%. Of the seven forms tested, five were written at a college RL. Pretesting of revised forms elicited the following responses from parents: easy to understand (100%), understood everything (96-100%), worth remembering (77-96%), liked the form (67-100%), found it informative (52-85%), and thought it was applicable to all people (82-100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Differential activation of CD8+ T cells by transforming growth factor-beta 1.

Transforming growth factor-beta (TGF-beta) is a highly conserved multifunctional factor that broadly regulates cell growth and differentiation, and exhibits diverse regulatory roles in the immune system. In contrast to other studies describing TGF-beta as a potent inhibitor of lymphocyte growth, we have shown previously that TGF-beta 1 can also costimulate proliferation of murine splenic T cells activated by immobilized anti-CD3 antibody. In the present studies, we further investigate the subsets of T cells that are responsive to TGF-beta 1 costimulation. T cells were isolated into CD45RBhi/lo or CD4+/8+ populations, and their responses to TGF-beta 1 were examined. Sorted CD45RBhi cells were highly responsive to TGF-beta 1 costimulation, and proliferated to a level similar to that of unsorted T cells in response to TGF-beta 1. TGF-beta 1 also costimulated proliferation in the CD45RBlo population that was distinguished by low response and delayed kinetics. In contrast, sorted CD4+ and CD8+ T cells showed a striking differential response. Anti-CD3-stimulated proliferation of sorted CD8+ or CD4- T cells was substantially enhanced by TGF-beta 1, whereas sorted CD4+ or CD8- T cells were unresponsive. TGF-beta 1 also down-regulated CD45RB and increased CD44 expression on responsive CD8+ and CD45RBhi T cells, thereby leading to a population of T cells enriched in mature phenotype. Generation of anti-CD3-redirected lytic activity by these TGF-beta 1-costimulated CD8+ cells was strongly suppressed. However, these CD8+ T cells exhibited cytotoxic activity after restimulation in the absence of TGF-beta. TGF-beta 1 precultured CD8+ T cells also had heightened IL-2 and IFN-gamma secretion upon restimulation in comparison to cells activated initially without TGF-beta. CD8+ T cells precultured with anti-CD3 and TGF-beta remained responsive to growth enhancement by TGF-beta, although re-exposure to TGF-beta depressed other functions of these cells. Thus, TGF-beta 1 demonstrates important costimulatory roles in both growth and maturation of CD8+ T cells.

Animals↗