Search

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Nitroglycerin has been shown to cause a downward shift in the left ventricular (LV) pressure-volume relation in patients. To test the hypothesis that this shift is mediated by an alteration in pericardial pressure, 13 patients undergoing diagnostic cardiac catheterization were studied. LV and right ventricular (RV) pressure (micromanometers) and LV diameter (2-dimensional echocardiography) were measured simultaneously before and after sublingual administration of 0.3 to 0.6 mg of nitroglycerin. In the 11 patients with hemodynamic effects from nitroglycerin, mean LV end-diastolic pressure decreased from 12.7 +/- 5 mm Hg (mean +/- standard deviation) to 7.3 +/- 3 mm Hg (p less than 0.002) and mean RV end-diastolic pressure declined from 7.7 +/- 3 mm Hg to 5.0 +/- 1 mm Hg (p less than 0.001). However, nitroglycerin caused only a slight (6%) reduction in LV minor axis diameter, from 52 +/- 8 mm to 49 +/- 9 mm (p less than 0.05). Diastolic pressure-diameter plots constructed from early and late diastolic measurements demonstrated a downward shift in the relation. However, when RV end-diastolic pressure was used as an estimate of pericardial pressure (a procedure validated by studies in our laboratory), the transmural pressure-diameter points before and after administration of nitroglycerin defined a single curve. These observations are in keeping with the conclusions that nitroglycerin did not alter the elastic properties of the myocardium and that the decrease in LV end-diastolic pressure induced by nitroglycerin was primarily attributable to a reduction in external constraint.

Three antigenic fractions were isolated from collagenase-solubilised human glomerular basement membrane utilising affinity columns containing purified human anti-glomerular basement membrane autoantibodies. The three fractions were able to inhibit the binding of sera containing anti-glomerular basement membrane autoantibodies when measured by solid phase radio-immunoassay. Amino acid and carbohydrate analyses revealed differences in the composition of the three fractions and were consistent with them being derived from the non-collagenous components of glomerular basement membrane.

A microculture and radioimmunoassay is described which is capable of generating and detecting very small levels of human anti-DNP antibody. The antibody produced is hapten specific and the response is T-cell dependent. The microculture system described avoids the need for high serum supplements, mitogens, in vivo immunisation or large cell numbers. As this system is simple, sensitive and reproducible it has considerable potential in the study of human immune response regulation and especially the role of lymphokines in human antibody responses.

To assess cardiac status in end-stage renal disease, we compared clinical, ECG, and echocardiographic data from 37 patients on maintenance hemodialysis with data from 42 patients with functioning renal transplants. Cardiovascular symptoms and abnormal cardiovascular findings were more common in dialysis-maintained patients than in those with transplants. Follow-up studies indicated that despite a high prevalence of cardiac symptoms, abnormal physical signs, and dilated left ventricles among patients with end-stage renal disease, systolic left ventricular function was generally well preserved irrespective of renal failure therapy. Compared with maintenance hemodialysis, however, successful renal transplantation is associated with an overall enhancement of cardiac status, the majority of which is probably secondary to transplant-associated improvement in hemoglobin level and control of intravascular volume.

We describe some aspects of the biology of a suppressor factor (SF) secreted by actively metabolizing and dividing alloantigen-primed T cells which functions by regulating human cytotoxic T-lymphocyte (CTL) activation. The SF functions most effectively during the first 24 hr of CTL activation, while it does not function at the CTL effector stage. Both T cells and adherent cells are capable of absorbing out the biological activity from suppressor factor supernatants. Experiments demonstrated that either fresh adherent cells or the addition of interleukin 2 (IL-2) into the test system could reverse the effects of the SF on CTL activation. These data suggest that the SF could be acting by either indirectly restricting IL-2 availability to proliferating CTLs by limiting adherent cell interleukin 1 (IL-1) secretion or, alternatively, SF acting directly on the IL-2-producing T cells.

The soluble material produced from a 96-hour digest of sonicated human glomerular basement membranes with purified collagenase was shown to contain at least 12 components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis with molecular weights ranging from 20×103 to greater than 200 ×103 daltons. Five of these components produced antigenic peaks after two-dimensional immunoelectrophoresis into agar plates containing rabbit antiserum to the solubilised glomerular basement membrane. Two groups of antigenic components were demonstrated in these gels by two-dimensional immunoelectrophoresis autoradiographic techniques utilising 125I-labelled collagenase-digested human glomerular basement membranes reacted with antibodies eluted at acid pH from the kidney of the Goodpasture’s patient. This acid eluate was shown to contain contaminants of α1-antitrypsin and albumin co-eluting with the antibodies bound to the glomerular basement membrane. After removal of these contaminants, the antibodies were linked to cyanogen bromide-activated Sepharose and used to affinity purify four antigenic fractions from the collagenase-digested glomerular basement membrane. These fractions were eluted by 0.2 Mglycine pH 2.8 and with 0.5 Mammonium thiocyanate and had molecular weights of 22–25,43–45,65–70 and 205 ×103 daltons. The smaller molecular weight components were shown to be common to both included and excluded fractions obtained by Ultragel AcA 44 chromatography of the digested material in 10 mM phosphate pH 8. This suggests that the larger molecular weight component would be an aggregate of a smaller component. Preliminary carbohydrate and amino acid analyses indicated that the different elution procedures elicited antigens with different chemical characteristics.

Thirty separate preparations of human Tamm-Horsfall urinary glycoprotein (THP) prepared from pooled urine of normal individuals were assessed for the capacity to stimulate in vitro blast transformation with normal human peripheral blood lymphocytes. Detailed studies were performed on some of these preparations by various biochemical, ultrastructural and in vitro techniques. Heterogeneity amongst the sodium dodecyl sulphate polyacrylamide gel (SDS-PAGE) profiles of several electrophoresis (2D-IEP). Gas liquid chromatographic analysis (GLC) revealed significant amounts of glucose in two of these samples. Ultrastructural studies using direct staining or platinum carbon shadowed specimens confirmed the fibrillar polymeric nature of soluble THP in vitro studies with human peripheral blood lymphocyte populations showed THP to have mitogenic properties towards B cells associated with the production of intracytoplasmic immunoglobulin. THP also stimulated the migration of mouse peritoneal exudate macrophages in a micro macrophages migration assay.

In a prospective study of the results of 5582 consecutive two-dimensional echocardiographic examinations, hypertrophy of a localized region of the basal ventricular septum was identified in 26 patients. Proven diagnoses were coronary disease in five patients, coronary plus valvular disease in three, valvular disease in seven, and miscellaneous in four. Localized septal hypertrophy was the only cardiac diagnosis in seven patients. The ratio of the thickness of the hypertrophied area to that of the adjacent septum was greater than or equal to 1.7 (mean 1.93 +/- 0.19) in all patients. The ration of the length of the hypertrophied portion (mean 0.34 +/- 06) to the length (apex to base) of the septum was less than 0.39 in all but one patient. Although the mitral valve tended to be more anterior than expected in 20, other features of hypertrophic cardiomyopathy were generally lacking. Of four patients undergoing left ventricular angiography, the bulge was identified in only one in whom cranial-caudal angulation was added to the 60-degree left anterior oblique view. An autopsy was performed in one patient; the hypertrophy was identified, although results of microscopic examination showed no fiber disarray. These data suggest that, in most instances, localized septal hypertrophy is an incidental echocardiographic finding. The diagnosis of hypertrophic cardiomyopathy should generally not be made on the basis of this feature alone.