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Biomedical subjects

S Rich

Publications and source records attributed to S Rich.

At least 127 records · Page 7Linked to original sources
PubMed1985

The effect of vasodilator therapy on the clinical outcome of patients with primary pulmonary hypertension.

The short- and long-term hemodynamic effects of vasodilators in patients with primary pulmonary hypertension have been studied, but whether they affect survival is unknown. We measured the short-term response to nifedipine and hydralazine in 23 patients with primary pulmonary hypertension and followed their clinical course over 2 years. A favorable drug response, defined as a fall in the pulmonary vascular resistance of 20% or greater, occurred in 18 patients (78%). Half of the patients who exhibited a favorable short-term response were treated with long-term vasodilator therapy. Their clinical course was compared with that of responders who were not treated and with that of the nonresponders. Of the responders who were treated, two improved, four had no change, and three died; of the responders who were not treated, one improved, three had no change, and five died. Using stepwise Cox regression, we evaluated age, sex, functional class on entry, pulmonary arterial pressure, pulmonary vascular resistance, and short-term drug response as predictors of survival and found only functional class and a favorable short-term drug response to be significant predictors (p less than .01); however, there was no difference in survival between the responders who were treated and those who were not. We conclude that the ability to respond to short-term nifedipine or hydralazine therapy predicts longer survival for patients with primary pulmonary hypertension, but placing patients with a favorable short-term response on long-term vasodilator therapy does not affect the overall outcome.

Adolescent↗
PubMed1985

Skeletal muscle basement membrane in maturity-onset diabetes in the young.

We have studied skeletal muscle capillary basement membrane width (CBMW) and intensity of skeletal muscle extracellular basement membrane staining for albumin and IgG in eight families with maturity-onset diabetes in the young (MODY). Ninety-two MODY patients were identified. Sixty-three of these patients, 33 relatives with nondiagnostic oral glucose tolerance studies, and 61 normoglycemic relatives were studied for glucose and insulin. Twenty-six of these MODY patients, 20 normoglycemic relatives, and 16 unrelated normal controls had skeletal muscle capillary morphologic studies. The muscle capillary basement membrane was significantly increased in MODY patients younger than 40 yr when compared with unrelated normal subjects and relatives of the same age (P less than 0.001). However, in these families, the CBMW of MODY patients showed no significant thickening with age (slope = 0.45, P less than 0.14), as expected and seen in the normal subjects and in the normoglycemic relatives of the patients (slope = 1.21, P less than 0.001). The slope derived from the linear regression of age and CBMW in MODY patients (0.45 +/- 0.29) was significantly less (P less than 0.05) than that of the nondiabetic subjects (1.21 +/- 0.19). The mean intensity of skeletal muscle extracellular basement membrane staining for albumin was higher in MODY patients (1.1 +/- 0.15) than in unrelated normal subjects (0.7 +/- 0.1, P less than 0.025) and normal MODY family members (0.6 +/- 0.08, P less than 0.01). The unexpected absence of basement membrane thickening with age in the MODY patients may explain the paucity of vascular complications that have been reported by some.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Complement and HLA. Further definition of high-risk haplotypes in insulin-dependent diabetes.

The families of 41 probands with type I (insulin-dependent) diabetes mellitus (IDDM) were typed for HLA-A, HLA-B, and HLA-DR antigens in addition to the complement polymorphisms C2, C4A, C4B, and Bf. All of these loci are encoded on the short arm of human chromosome 6 in a narrow region. Alleles at HLA-B (8, 15, 18, and 40), HLA-DR (3 and 4), and Bf (F1) have been associated with increased relative risk (RR) for IDDM, while HLA-B7 and HLA-DR2 have been associated with decreased RR for IDDM. This study confirms those significant risks in addition to confirming increased risk for the null (silent) allele for C4A (C4AQ0) and a rare C4B variant (C4B2.9). The significantly associated antigens (alleles) and risks were: HLA-B8 (RR = 3.1), HLA-DR3 (RR = 5.2), HLA-DR4 (RR = 4.3), and BfF1 (RR = 7.1), in addition to C4AQ0 (RR = 2.8) and C4B2.9 (RR = 12.6). Significantly low risk was associated only with HLA-DR2 (RR = 0.1). In a recent study, we defined five high-risk haplotypes that were determined solely by HLA-B, Bf, and HLA-DR (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4). By inclusion of information from the complement polymorphism, we have defined in greater detail three of these five high-risk haplotypes. One previously identified haplotype (B40-BfS-DR4) showed no complement clustering, while the rare high-risk haplotype (B8-BfS-DR4) was seen only once in this smaller sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1984

Suppressor T cell growth and differentiation. Identification of a cofactor required for suppressor T cell function and distinct from interleukin 2.

This report describes a Ts costimulator assay and its use to analyze cofactors required for the expression of suppressor T cell function. Activation of primed MLR-Ts (alloantigen-activated suppressor T cells suppressive of mixed leukocyte reaction) to suppressor T cell factor (TsF) production typically fails in the presence of glutaraldehyde-fixed rather than irradiated allogeneic stimulator cells. However, MLR-TsF production was restored by the addition of 48-h primary MLR supernates; MLR-derived Ts costimulator neither activated primed MLR-Ts in the absence of fixed allogeneic stimulators nor directly suppressed assay MLR. Lack of antigen specificity or genetic restriction and failure to activate unprimed MLR-Ts precursors suggested that Ts costimulator activity differed from previously described Ts inducer functions and was more closely aligned with the lymphocyte- or monocyte-derived interleukins (IL). Three findings distinguished Ts costimulator from IL-2. Depletion of IL-2 activity from MLR supernates by HT2 adsorption failed to affect Ts costimulator function. In addition, MLR supernates prepared in the presence of cyclosporin A contained no IL-2 but expressed Ts costimulator activity. Finally, gel chromatography demonstrated Ts costimulator in peaks of 21,000 and 43,000 mol wt that were largely distinct from the IL-2-containing fractions. Ts costimulator activity was also identified in phorbol myristate acetate (PMA)-induced EL4 supernates and was retained in those supernates after IL-2 depletion by HT2 adsorption. In preliminary functional characterization, MLR supernate-derived Ts costimulator triggered MLR-TsF production from irradiated MLR-Ts in the absence of proliferation. Thus a differentiative rather than proliferative stimulus required for primed MLR-Ts function appears to be provided by this Ts costimulator and has been provisionally termed Ts differentiative factor ( TsDF ). This initial characterization may thus identify one of a possibly distinctive family of interleukins required in the alloantigen-driven activation of suppressor T cells to effector function.

Animals↗
PubMed1984

Characteristics of surviving and nonsurviving patients with primary pulmonary hypertension.

Primary pulmonary hypertension is considered a fatal illness, with survival typically of less than four years, although survival of more than 10 years has been well documented. To assess the characteristics of patients with primary pulmonary hypertension who survive versus those who do not, 12 patients with primary pulmonary hypertension were followed, and their clinical course was documented with serial catheterization. The survivors, four male and three female, had their illness for a mean of 5.2 +/- 2 years from the time of initial catheterization, with six of the seven alive at the end of the follow-up period. The five nonsurvivors, all female, had a mean survival of 0.3 +/- 0.2 years. The nonsurviving group had significantly higher right atrial pressures (17 +/- 6 versus 6 +/- 2 mm Hg), lower cardiac indexes (1.2 +/- 0.1 versus 2.3 +/- 0.5 liters/minute/m2) and stroke volume indexes (12 +/- 7 versus 30 +/- 5 ml/beat/m2), and higher systemic resistances (64 +/- 13 versus 43 +/- 14 units) and pulmonary resistances (57 +/- 31 versus 20 +/- 4 units). The pulmonary artery pressure did not significantly differ between the groups. Using regression analysis, it was found that stroke volume index and right atrial pressure were the best independent predictors of survival, with a coefficient of determination (r2) of 83 and 72, respectively. When the initial and most recent catheterization data were compared among the survivors, no significant differences were found. Determining the stroke volume index and right atrial pressure of patients with primary pulmonary hypertension at the time of their initial presentation should help in predicting their clinical course.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

The pericardial effusion pattern on phase images.

UNLABELLED: The effect of pericardial effusion on phase images of gated studies was investigated. Twenty-six patients with suspected or known pericardial effusion were correlated with echocardiography and/or clinical and other laboratory data to ascertain the presence and size of effusion. The phase image pattern and parameters were compared to the results previously obtained in seven normal patients, and in 26 patients with documented regional wall motion abnormalities but no evidence of pericardial effusion. The phase pattern was graded into five categories: typical (IV) (wide histogram, well defined concentric convex pattern, progressive delay toward the inferolateral area, identifiable also over the right ventricle); less pronounced (III); atypical (II); ill defined changes (I); and normal (0). RESULTS: Group L (large pericardial effusion): four of six had pattern (IV) and the left ventricular histogram showed abnormal parameters. These patients had large free effusions in the pericardial sac and none had regional wall motion abnormalities. Two of six had pattern (III) and (II) but also had ancillary pericardial pathology and/or decreased ejection fraction. Group M (moderate pericardial effusion), S (small pericardial effusion), and A (absent pericardial effusion, but not normal) had variable phase images and numeric parameters. After therapeutic drainage of pericardial fluid two patients changed pattern from IV and III to 0 and a third from III to I. Category IV pattern is 100% specific for pericardial effusion; the combination of category IV or III is 87.5% specific and 61% sensitive for large and moderate pericardial effusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Computed tomography of the heart and great vessels: present and future.

Computed tomography (CT) has emerged as a new imaging method for the diagnosis and evaluation of cardiovascular disease. With CT body scanners and contrast enhancement, evaluation of aortic dissections and aneurysms, coronary bypass graft patency, cardiovascular thrombus, cardiac tumors, and pericardial disease is possible. On occasion, this technique provides clinically useful information that is not available with other imaging methods. Electrocardiographic gating retrospectively or prospectively improves the image resolution of CT scans, but a new ultrafast CT scanner with a scan time of 30 to 50 milliseconds offers the greatest promise for expanding the application of the technology for cardiovascular diagnosis. Accurate measurement of cardiac chamber volume, mass, wall motion, and wall thickening will be feasible. Ultrafast CT scanning also shows great promise for the measurement of myocardial infarct size and regional myocardial blood flow.

Aortic Dissection↗
PubMed1983

Suppressive mechanisms in alloantigen-induced T cell responses.

In this report we examined the possibility that suppression of the mixed lymphocyte response by MLR-TsF results from interference with IL-2 regulation of T cell proliferation. Two distinct processes of inhibition involving both a direct effect on IL-2-driven proliferation of responder T cells, and induction of a second-order suppressor cell (Ts2) were described. Exogenous IL-2 did not abrogate MLR-TsF-induced suppression, and activated responder cells from suppressed cultures expressed functional IL-2 receptors by IL-2 adsorption analysis. Thus, suppression is not due to lack of available IL-2 or to abnormal acquisition of receptors for IL-2 during T cell activation. In contrast, a profound MLR-TsF effect on IL-2-induced proliferation of HT2 cells as well as MLR-activated cells was observed even after presaturation of receptors with excess IL-2. These results differentiated the direct responder cell effect of MLR-TsF from its Ts2 inductive capacity, and localized the defect in responder cell proliferation to events occurring subsequent to IL-2 binding. When analyzed in terms of proposed models for hormone-receptor interactions, characteristic dose-response curves similarly predict a postreceptor defect. Examination of the Ts2 pathway of suppression revealed a late-acting inhibitory effect peaking 72 h after MLR initiation. A minor part of Ts2 activity was susceptible to exogenous IL-2, and may reflect a requirement for IL-2 during Ts2 expansion. However, the most significant component of Ts2-mediated suppression was resistant to excess IL-2, and IL-2 production was normal in Ts2-regulated cultures, thus ruling out limitation of IL-2 for responder cell use as the major mechanism of Ts2 suppression. The complete pathway of Ts2 suppression and its functional relationship to other MLR-TsF inhibitory activities is not yet fully understood. However, these results suggest that the ultimate mechanisms of alloantigen-induced suppression involve late events of the IL-2-dependent lymphokine cascade.

Animals↗
PubMed1983

Comparative actions of hydralazine, nifedipine and amrinone in primary pulmonary hypertension.

The effects of 3 types of vasoactive agents, hydralazine, nifedipine and amrinone, were evaluated in 7 patients with primary pulmonary hypertension (PPH). Hemodynamic values were measured before and after drug administration in every patient. All drugs increased cardiac output and reduced both systemic and pulmonary resistance in the patients studied. Only nifedipine significantly reduced pulmonary artery (PA) pressure (6 +/- 5 mm Hg). In addition, it decreased pulmonary resistance to a greater degree than systemic resistance in 2 of the 7 patients, suggesting that nifedipine can cause selective pulmonary vasodilation in some patients. Hydralazine appeared to increase cardiac output and stroke volume by reducing systemic resistance. There was no evidence of direct pulmonary vasodilating effects; it decreased systemic resistance more than pulmonary resistance in every case. The increase in cardiac output from amrinone was secondary to a decrease in systemic arterial pressure with reflex tachycardia; stroke volume was unchanged. Amrinone had little pulmonary effect in all but 1 patient, in whom it substantially reduced PA pressure and pulmonary resistance. The mechanism of action of these 3 drugs in PPH differs. Nifedipine holds the most promise as an effective pulmonary vasodilator. A study of the effects of long-term administration of nifedipine in PPH is warranted.

Adult↗
PubMed1983

Regulatory mechanisms in cell-mediated immune responses. Role of I-J and I-C determinants in the activation of H-2I and H-2K/D alloantigen-specific suppressor T cells.

The role of individual H-2I subregion determinants in the activation of H-2I alloantigen-primed mixed leukocyte response suppressor T cells (MLR Ts), as well as their possible expression on stimulator cells required to trigger primed H-2K- or D-specific MLR Ts, was addressed in these studies. Both genetic and serologic studies demonstrated that MLR Ts potentially primed to alloantigens encoded by the entire H-2I region were triggered to MLR Ts factor production only by stimulator cells bearing the priming I-J and/or I-C, but not I-A or I-E alloantigens. The relevant I-J and I-C determinants were demonstrated on a single antigen-presenting cell population that is used in common by independent I-J-specific and I-C-specific MLR Ts. Unexpectedly, the stimulator cell population necessary to trigger MLR Ts primed to class I H-2K or D alloantigens expressed not only the priming class I determinant, but in addition, I-C alloantigens syngeneic with the MLR Ts haplotype. Stimulator populations bearing the appropriate H-2K or D alloantigen but serologically depleted of I-C+ cells or genetically constructed to display MLR Ts-disparate I-C determinants were ineffective stimulators of class I antigen-primed MLR Ts. Thus these data suggest that as allogeneic determinants, I-J- and I-C-encoded molecules are together the major triggering elements for MLR Ts primed to disparate H-2I region determinants. In addition, self-I-C molecule recognition appears to constitute an important feature of the triggering, and by implication, priming process of H-2 class I antigen-specific Ts cells.

Animals↗
PubMed1983

Current use of myocardial protection during coronary artery bypass surgery: results of a survey.

The literature suggests that certain methods of myocardial protection employed during coronary artery bypass graft (CABG) surgery may significantly affect postoperative recovery. A retrospective study comparing the use of different cardioplegia solutions during CABG surgery at our institution failed to show significant differences in perioperative ischemic events or in patient survival. A subsequent survey was conducted among 140 surgeons worldwide to determine the influence of myocardial protection on perioperative ischemic events and patient survival.

Journal Article↗
PubMed1982

M-mode echocardiography in left bundle branch block: significance of frontal plane QRS axis.

M-mode echocardiograms were obtained in 48 patients with complete left bundle branch block (LBBB). Of these 48 patients, 28 had LBBB with normal frontal plane QRS axis (-20 degrees to +90 degrees, mean +/- SD 18 degrees +/- 34 degrees), and 20 had LBBB with a left axis deviation (LAD) (-30 degrees to -60 degrees, mean +/- SD -48 degrees +/- 11 degrees). In the group with LBBB and normal axis, 25 patients had typical early mean +/- SD -48 degrees +/- 11 degrees). In the group with LBBB and normal axis, 25 patients had typical early systolic posterior septal motion characteristic of LBBB. Septal motion following early posterior septal motion (through the ejection period) was posterior in 24 patients (86%), anterior (paradoxical) in 2 (7%), and flat in 2 (7%). In the group with LBBB and LAD, 16 patients had the typical early systolic posterior septal motion; subsequent septal motion was posterior in 3 (15%), anterior (paradoxical) in 13 (65%), and flat in 4 (20%). Patients with LBBB and normal axis had a higher frequency of posterior septal motion, and patients with LAD had a higher frequency of anterior septal motion (p less than 0.001). The correlation of abnormal axis and paradoxical septal motion may be explained by the activation pattern producing LAD or by a septal disease process producing both abnormalities of axis and abnormal septal motion.

Adolescent↗
PubMed1982

Determination of left ventricular ejection fraction by visual estimation during real-time two-dimensional echocardiography.

It has been shown that the measured reduction in the cross-sectional area of the left ventricle (LV), as viewed in the short axis, closely approximates its ejection fraction (EF). We assessed the reliability of using two-dimensional echocardiography (2DE) to visually estimate the EF during real-time viewing, without the need of digitizers, planimetry, or calculations. Twenty-five adult hospitalized patients with either suspected or known cardiac disease were evaluated prospectively. Each patient also had gated nuclear angiography during the same admission, and 14 had cardiac catheterization with left ventriculography. The EF was determined by 2DE using a visual estimate of the percent area reduction of the LV cavity in the short-axis view at the level of the papillary muscles. All 2 DE studies were read by two or more blinded reviewers, with a value for the EF to the nearest 2.5% determined by consensus. These values correlated closely to the values determined in all 25 patients with gated nuclear angiography (r = 0.927) and the 14 patients who had left ventriculography (r = 0.935). We believe that this method of visually estimating the LVEF will enable echocardiographers to easily use 2 DE for a reliable and instantaneous assessment of ventricular function, without the need of sophisticated analytical equipment.

Adult↗