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Biomedical subjects

J Narula

Publications and source records attributed to J Narula.

At least 91 records · Page 5Linked to original sources

Imaging the rejecting heart. In vivo detection of major histocompatibility complex class II antigen induction.

BACKGROUND: Mice with abdominal heterotopic heart transplants were studied to determine whether scintigraphic detection of an increase in major histocompatibility complex (MHC) class II antigen expression could be used as a noninvasive method for diagnosing early rejection. METHODS AND RESULTS: Allografts from C3H/He (H2k) donors were transplanted into BALB/c (H2d) recipients (n = 18). Two of the 18 allografted mice were treated with cyclosporine (15 mg/kg/day), and two isografted mice served as controls. Each mouse was injected intravenously with 100 microCi of 111In-labeled anti-MHC class II monoclonal antibodies (10-2-16 and 14-4-4S) 24 hours before scintigraphy. After imaging, the mice were killed for tissue counting and histopathology. Radiotracer uptake in the grafts reflected the severity of rejection as determined by histopathological criteria. The percent injected dose per gram of tissue in excised grafts was 4.8 +/- 1.8 (mean +/- SD) for normal grafts (n = 8), 11.1 +/- 9.7 for grafts with grade IA rejection (n = 3, NS), 18.0 +/- 3.8 for grafts with grade IIIA rejection (n = 4, p less than 0.001 versus normal), 18.7 +/- 3.2 for grafts with grade IIIB rejection (n = 3, p less than 0.001 versus normal), and 22.6 +/- 5.4 for grafts with severe rejection (grade IV) (n = 3, p less than 0.001 versus normal). Rejecting allografts with lymphocyte infiltration but without significant myocyte necrosis could be identified by this scintigraphic method. In the BALB/c donor-C57BL/6 (H2b, IE-) recipient combination, rejecting allografts were visualized by 14-4-4S (anti-IEk,d,p,r) antibody but not by 10-2-16 (anti-IAk,r,s,f) antibody. This difference shows that class II antigens induced on donor hearts are solely responsible for the antibody uptake in positive scintigrams of rejecting allografts. CONCLUSIONS: We conclude that 111In-labeled anti-MHC class II antigen antibody imaging is a sensitive and noninvasive method for detecting cardiac allograft rejection.

Animals↗

Asymptomatic eosinophilic myocarditis: 2 + 2 = 4 or 5!

A twenty-eight year old man was admitted with a cerebrovascular accident and hypereosinophilia secondary to microfilarial infection. Endomyocardial biopsy revealed focal eosinophilic myocarditis. The intriguing presence of this asymptomatic myocarditis raises interesting possibilities.

Adult↗

Correlation of immunoreactivity and polymer formation to DTPA modification of a monoclonal antibody.

The protocol used for coupling of monoclonal antibodies with mixed anhydride of DTPA for subsequent radiolabeling with indium-111 affects the integrity of the immunoreactivity of the antibody preparations. To analyze the effect of minor methodological variations on coupling characteristics, a two-step addition of DTPA to antimyosin antibody with gentle mixing was compared to a single addition with vigorous stirring. The molar ratios of DTPA to antibody were also varied. The polymer formation was assessed by SDS-PAGE and immunoreactivity was assessed by solid phase radioimmunoassay using human heart myosin as the antigen. The immunoreactivity was significantly decreased in the two-step, gentle-mixing method where polymer formation was evident. The one-step, vigorous-stirring method of DTPA incorporation produced no polymerization and no loss of immunoreactivity.

Antibodies, Monoclonal↗

Histomorphologic characteristics of endomyocardial fibrosis: an endomyocardial biopsy study.

Endomyocardial biopsies from right, left, or both ventricles were performed in 13 angiographically documented cases of endomyocardial fibrosis. The endocardium was appreciably thickened due to acellular hyalinized collagen tissue in all cases. Variable amounts of elastic tissue intimately admixed with fibrous tissue were recognized. A "zonal layering" pattern of the endocardium was absent. Thrombus, inflammatory cells, and granulation tissue at the endomyocardial interphase, and eosinophils within the biopsy were not seen. In addition, lymphomononuclear interstitial inflammatory infiltrates were seen in five cases.

Adolescent↗

Lymphocyte subsets in acute rheumatic fever and rheumatic heart disease.

Lymphocyte subsets in 53 patients with acute rheumatic fever and 78 patients with chronic rheumatic heart disease were compared with 20 normal control subjects and 39 patients suffering from uncomplicated streptococcal pharyngitis to obtain information about the pathogenesis of the disease. Twenty patients with rheumatic fever were followed for 24 weeks to evaluate changes occurring over the course of the disease. Total leukocyte and lymphocyte counts were increased in patients with rheumatic fever and to a lesser extent in those with rheumatic heart disease, when compared with controls. The difference between the two groups was significant. Patients with acute rheumatic fever had an increased number of B cells and a smaller increase in total T and T-helper-inducer (CD-4) cells. The proportion of B cells increased, while that of T-suppressor-cytotoxic (CD-8) cells fell. An increased number and proportion of B cells was also seen in patients with rheumatic heart disease. Total T and T-helper lymphocyte percentages and numbers were significantly higher in patients with rheumatic fever compared with those of patients with rheumatic heart disease. Follow-up studies at 6, 12, and 24 weeks revealed no significant differences from the entry point studies, although there was a trend toward reduction in the degree of derangement from normal values. Patients with uncomplicated streptococcal pharyngitis, however, did not show perturbations in the T-cell and T-subset counts. Our study suggests that the immunoregulatory defect in acute rheumatic fever is characterized by a relative reduction of suppressor T cells with an absolute increase in helper T cells and B cells, resulting in an increased cellular as well as humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Evaluation of spatial R maximum cardiac vector changes in exercise testing: pre-exercise versus post-exercise measurements.

R wave amplitude changes during exercise have been a controversial issue as both increase and decrease in amplitude have been reported in patients with coronary arterial disease. This variability in response is attributed to change in position and heart axis on exercise. In view of this limitation, this study evaluated the change in spatial R maximum amplitude on exercise, which should not be affected by the above factors. Twenty patients with ischaemic heart disease (male 20, age 38-61 years) and 9 control subjects (male 9, age 32-65 years) were studied. Orthogonal leads, X, Y, Z were recorded using corrected Frank lead system on a stereokinematic vectorcardiograph (Tonnies). The magnitude of spatial R maximum cardiac vector increased from 0.1 to 0.6 mV in 8/9 control subjects and decreased or showed no change in 18 of the 20 patients with coronary arterial disease. In the control group, the mean value at the end of exercise (0.98 +/- 0.34 mV) was significantly less (P less than 0.01) as compared to pre-exercise value (1.09 +/- 0.2 mV). Our preliminary observations thus indicate that, with exercise, the magnitude of spatial R maximum cardiac vector decreases or shows no alteration in height in patients with coronary arterial disease whereas it increases in normal subjects.

Adult↗

Unmasking of sinus node dysfunction by ajmaline.

A 75-year-old male with bifascicular block presented with recurrent giddiness and presyncope. Prolonged monitoring of the cardiac rhythm did not reveal any arrhythmia. Electrophysiological evaluation, including an ajmaline stress test, was performed. Ajmaline had an unusual effect. It reproducibly induced sinus arrest and thus unmasked a latent sick sinus syndrome.

Aged↗

HLA-DR/DQ antigens and reactivity to B cell alloantigen D8/17 in Indian patients with rheumatic heart disease.

D8/17, a B cell alloantigen, and its occurrence with DR/DQ antigens was examined in 54 patients with rheumatic heart disease and matched North Indian controls. Thirty-four patients (62.9%) carried D8/17 as compared with a frequency of 12.5% in controls (chi 2 by Yates', 18.75; p less than 0.0001). A marginally increased frequency of human leukocyte antigen (HLA)-DR3 (44.2% vs. 28.8%) and a significantly reduced frequency of HLA-DR2 (21.1% vs. 46.6%; p less than 0.005) was observed in patients as compared with controls. However, the most significant positive association was observed with HLA-DQw2 (63.4% in patients and 31.5% in controls; chi 2 by Yates', 9.85; p less than 0.005). The DQw2 association was significant only in the D8/17-positive patients. These observations suggest that the disease susceptibility gene in rheumatic heart disease may be nearer to the HLA-DQ locus than to the HLA-DR.

Antigens, Differentiation, B-Lymphocyte↗

Quantitative grading of exercise stress test for patients with coronary artery disease using multivariate discriminant analysis.

A group of 111 male patients who had undergone maximal or symptom-limited maximal exercise stress testing for evaluation of coronary artery disease (CAD) were subjected to coronary angiography. Group I comprised 33 patients with normal or single-vessel disease (SVD), while 78 patients with double-vessel disease (DVD) or triple-vessel disease (TVD) formed Group II. On univariate analysis of the exercise test, the following variables were found to be of significance in discriminating between the two groups: age, exercise duration, double product (heart rate X systolic blood pressure) at peak exercise, duration of ST-segment depression, number of leads showing ST depression, ST depression of 1 mm or more, configuration of the depressed ST segment, and diastolic blood pressure response to exercise. Multivariate analysis however revealed that only the following five variables had significant discriminant power: number of leads showing ST depression, exercise duration, double product, diastolic pressure response, and ST-segment configuration. On the basis of their relative importance, a regression equation was developed to give a quantitative score to individual patients. A score of less than zero detected multivessel disease (MVD) with high specificity (94%) and sensitivity (70%), while a score of 15 or more almost excluded MVD (sensitivity 87%). The scoring system as reported here improved the exercise stress test interpretation when compared with the conventional reporting system.

Adult↗

Partial anomalous pulmonary venous drainage and intact atrial septum with mitral stenosis: the paradox of a small shunt.

Clinical, hemodynamic, and angiographic features of 10 patients with partial anomalous pulmonary venous drainage, intact atrial septum, and rheumatic mitral stenosis have been presented. Seventeen patients with this combination of anomalies reported in the literature have also been reviewed. The clinical diagnosis of mitral stenosis was possible in each of our 10 cases. Partial anomalous pulmonary venous drainage and intact atrial septum in addition to mitral stenosis was clinically suspected in only four patients. The findings suggesting additional presence of partial anomalous pulmonary venous drainage and intact atrial septum in a patient with mitral stenosis include: wide variable splitting of the second sound, pulmonary ejection systolic murmur with or without a thrill, and radiological evidence of unilateral increase in pulmonary vascularity or unilateral hilar pulsations. Hemodynamic findings were characterized by a relatively modest left to right shunt (Qp/Qs:2.2 +/- 1.4). Elevated pulmonary vascular resistance was found in the anomalously draining as well as the normally draining lung segments (9.1 +/- 4.9 and 6.5 +/- 3.4 units, respectively, t = 1.32;NS). The mechanism of the unexpected high resistance in the anomalously draining lung segments permitting only a small left to right shunt is discussed.

Adolescent↗

Myocardial involvement and its response to immunosuppressive therapy in nonspecific aortoarteritis (Takayasu's disease)--a study by endomyocardial biopsy.

Myocardial involvement in nonspecific aortoarteritis was evaluated in 16 patients (age 7-37 years, 2 males, 14 females) with the help of endomyocardial biopsy obtained from the right ventricle using the Cordis bioptome introduced from the right femoral vein. Morphological features of myocarditis were present in 8, endocardial thickening in 2, mild to moderate myofibre hypertrophy in 11, and a normal biopsy in 3 patients. Myocarditis was present in 8/11 cases with active disease and in none with inactive disease. Five of the 8 patients with myocarditis presented with congestive cardiac failure with 3 of them having no associated hypertension or valvar involvement to account for it. Immunosuppressive therapy was given to all patients with myocarditis. Serial studies (ongoing) showed clinical, haemodynamic and morphological improvement. Myocarditis appears to occur commonly in nonspecific aortoarteritis during the acute phase of the disease and may precipitate congestive cardiac failure in some patients. Immunosuppressive therapy shows promise and merits further evaluation.

Adolescent↗