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Biomedical subjects

K K Sethi

Publications and source records attributed to K K Sethi.

At least 19 recordsLinked to original sources

Multiplication of human-derived Pneumocystis carinii in severe combined immunodeficient (SCID) mice.

Clinically healthy SCID mice were infected intratracheally with Pneumocystis carinii (PC) of human origin. The data obtained provides unambiguous evidence that progressive multiplication of PC organisms of human origin takes place in the lungs of experimentally infected animals. SCID mice that were infected with human-derived PC also revealed a markedly greater number of mouse PC organisms in their lungs than the controls. All the SCID recipients of human PC died by day 65 post infection, whereas the controls, housed under identical conditions, started dying significantly later due to severe mouse pneumocystosis. This animal model could be used for the maintenance and propagation of human PC, and for evaluating strategies for treating human pneumocystosis.

Animals

Balloon angioplasty of native coarctation of the aorta in adolescents and young adults.

Balloon angioplasty of native coarctation of the aorta was performed in 35 consecutive adolescents and young adults, aged 14 to 37 years (mean 22.6 +/- 7.1). Twenty-eight (80%) patients had isolated discrete coarctation, six (17.1%) had tubular hypoplasia of the aortic isthmus, and one (2.9%) had hypoplasia of the post-coarctation aorta. The peak systolic pressure gradient decreased from 78.5 +/- 23.9 to 15.7 +/- 11.6 mm Hg (p less than 0.001), and the mean coarctation diameter increased from 4.7 +/- 2.4 to 13.1 +/- 2.7 mm (p less than 0.001) immediately after angioplasty. Patients with discrete-type coarctation had significantly less residual gradient than patients with long-segment tubular coarctation (12.3 +/- 10.7 vs 27.2 +/- 6.6 mm Hg, p less than 0.01). On recatheterization and angiography in 26 patients at 12.6 +/- 1.5 months after dilatation, there was no significant change in gradient (15.5 +/- 13.3 mm Hg) and diameter (13.1 +/- 1.8 mm) from the immediate post-angioplasty results. However, two patients had an increase in gradient and three had small aortic aneurysms with no change in appearance on restudy after 2 years. After 3 to 67 months' (mean 32.7 +/- 19.2) follow-up, all patients showed continued clinical improvement. Hypertension was relieved in 37.5% (12/32) and improved in 59.4% (19/32). Our experience suggests that balloon angioplasty of native aortic coarctation in adolescents and young adults is safe and highly effective with sustained improvement on intermediate-term follow-up.

Adolescent

Balloon angioplasty of the aorta in Takayasu's arteritis: initial and long-term results.

Percutaneous transluminal balloon angioplasty for stenosis of the aorta was performed in 36 patients with Takayasu's arteritis (age range, 8 to 36 years; mean, 19.1 +/- 7.7 years). Balloon dilatation was successful in 34 patients and resulted in a decrease in the mean peak systolic pressure gradient (PSG) from 75.2 +/- 29.1 mm Hg to 24.8 +/- 19 mm Hg (p less than 0.001) and a mean increase in the diameter of the stenosed segments from 4.5 +/- 2.2 mm to 9.6 +/- 3.8 mm (p less than 0.001). Hemodynamic and angiographic restudy, which was performed in 20 patients at a mean follow-up period of 7.7 +/- 4.1 months (range, 3 to 24 months), showed a further decrease in PSG (greater than or equal to 15 mm Hg) in seven patients (from 40.0 +/- 11.2 mm Hg to 15.7 +/- 10.2 mm Hg; p less than 0.01), no significant change in PSG in 12 patients (17.1 +/- 13.6 mm Hg vs 16.6 +/- 12.7 mm Hg; p = NS), and an increase in PSG from 15 mm Hg to 85 mm Hg in one patient. The patient who showed restenosis underwent successful redilatation. Six patients who underwent late recatheterization and angiography at 36 to 60 months (mean, 43 +/- 9.4 months) show continued relief of stenosis (mean PSG, 8.8 +/- 7.8 mm Hg). Patients with short-segment (less than 4 cm) stenosis experience more relief than patients with long-segment (greater than or equal to 4 cm) stenosis (residual PSG, 18.6 +/- 8.2 mm Hg vs 40 +/- 16 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Peripartum cardiomyopathy: prognostic variables at initial evaluation.

Twenty patients with peripartum cardiomyopathy were followed up for a period ranging from 6-14 months (mean 6 +/- 2 months). At initial evaluation, 16 patients were in New York Heart Association Class IV and the remainder in Class III. During follow up, 12 patients improved to Class I, 7 patients either failed to improve or deteriorated and one patient died. Certain variables at initial evaluation were related to prognosis. The patients who deteriorated, as compared to those who improved, were significantly older (30 +/- 6.8 vs 24 +/- 3 years, P less than 0.01), of higher parity (3 +/- 1 pregnancies vs 1.5 +/- 5 pregnancies, P less than 0.001) and had later onset of symptoms after delivery (7.6 +/- 4 weeks vs 3 +/- 1.3 weeks, P less than 0.001). They also had higher echocardiographic left ventricular end diastolic dimensions (7.0 +/- 8.4 cm vs 3.0 +/- 0.8 cm, P less than 0.001) and higher mean pulmonary arterial (38 +/- 4 mmHg vs 28 +/- 6 mmHg, P less than 0.001) and pulmonary arterial wedge pressures (24 +/- 2 mmHg vs 20 +/- 2 mmHg, P less than 0.001) at cardiac catheterization. Conduction defects were present on the surface electrocardiogram in all the patients who deteriorated, as compared to 4 patients who improved. In conclusion, certain variables at initial evaluation can help in identifying high risk subsets with peripartum cardiomyopathy.

Adult

Assessment of mitral valvar stenosis by echocardiography: utility of various methods before and after mitral valvotomy.

Cross-sectional and Doppler echocardiography are currently the most important non-invasive tests for the evaluation of mitral stenosis. Recent experience has, however, shown that parameters that are reliable before mitral valvotomy may not be valid after the procedure. We have studied the validity of estimation of the area of the mitral valve by echo-planimetry, by Doppler pressure half time and the transmitral end-diastolic pressure gradient calculated by continuous wave Doppler in 100 patients (aged 10-30 years) before and after balloon mitral valvoplasty (n = 70) or surgical closed mitral valvotomy (n = 30). These patients underwent cardiac catheterisation and echocardiographic studies before, immediately after and 8-12 (9.3 +/- 2.2) weeks following balloon valvoplasty or closed valvotomy. The area as estimated echocardiographically correlated well with that obtained by the Gorlin formula before (r = 0.80), but not immediately after (r = 0.67) or on follow up after mitral valvotomy. There was good correlation between Doppler pressure half time and the area as estimated by the Gorlin formula before (r = 0.89) and on follow up after valvotomy (r = 0.82), but the correlation was not as good in the immediate period after valvotomy (r = 0.60). The end-diastolic pressure gradients obtained by Doppler examination and at cardiac catheterisation correlated well with each other before (r = 0.94), immediately after valvotomy (r = 0.92) and on follow up (r = 0.94). Hence, the reliability of estimation of the area of the mitral valve by echo-planimetry and by Doppler pressure half time varies according to the time at which the examination is performed following commissurotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Contribution of atrial contraction to left ventricular filling in patients with sick sinus syndrome on AAI pacing.

Doppler echocardiographic evaluation of the contribution of atrial contraction to left ventricular filling, its determinants and relationship with early diastolic filling was studied in 20 patients with sick sinus syndrome without structural heart disease on AAI pacing over a wide range of physiological atrioventricular delays (PR intervals). The results were compared with 20 normal controls matched for age, sex and heart rate. Left ventricular filling pattern, and the contribution of left atrial contraction to diastolic filling, were similar in the two groups. AAI pacing restores the physiological dynamics of left ventricular filling in patients with sick sinus syndrome without organic heart disease.

Cardiac Pacing, Artificial

Oral metoprolol therapy in dilated cardiomyopathy: hemodynamic evidence for improved diastolic function accompanying amelioration of symptoms.

Twenty patients with dilated cardiomyopathy (11 males and 9 females) aged from 14 to 54 (37.3 +/- 10.5) years were treated orally with metoprolol (dose 37.5 mg-100 mg/day, mean 91 +/- 18.6 mg/day) after a baseline hemodynamic study. On follow-up, all patients showed improvement in symptomatic status by at least one NYHA class within 2 to 4 weeks of the initiation of therapy. Repeat right heart study and left ventricular angiography (venous digital subtraction angiography) afer 3 to 6 months of treatment in 10 patients showed a fall in the mean pulmonary arterial wedge pressure from 24.4 +/- 9.6 to 12.8 +/- 7.7 mm Hg (P = 0.025), right ventricular end-diastolic pressure from 8.8 +/- 4.7 mm Hg to 4.5 +/- 1.9 mm Hg (P = 0.025) and mean pulmonary arterial pressure from 34.2 +/- 12.4 mm Hg to 25.9 +/- 10.9 mm Hg (P less than 0.01). There was no significant change in the left ventricular ejection fraction (18.7 +/- 1.6% vs. 22 +/- 0.48%, P = NS) or cardiac index (2.2 +/- 0.48 l/m/m2 to 2.12 +/- 0.68 l/m/m2, P = NS). These hemodynamic results indicate that the improvement in symptoms and congestive cardiac failure produced by treatment with metoprolol in patients having dilated cardiomyopathy is related to improvement in diastolic function of the myocardium.

Adolescent

Application of immunoblotting to detect soluble Pneumocystis carinii antigen(s) in bronchoalveolar lavage of patients with Pneumocystis pneumonia and AIDS.

The technique of immunoblotting for detecting soluble Pneumocystis carinii antigen(s) in bronchoalveolar lavage fluid specimens from patients with AIDS and Pneumocystis pneumonia was evaluated. A soluble 67 kilodalton polypeptide that was immunoreactive with an anti-P carinii monoclonal antibody (2G2) was found in the supernatants of 26 lavage samples from patients with pneumocystosis. Intact organisms in lavage sediments were detected by methenamine silver or immunofluorescence staining procedures. The diagnostic use of this technique was shown in four cases in which lavage sediments proved negative for intact Pneumocystis carinii organisms on first examination; 2G2 reactive soluble antigen, however, was identified in the immunoblots of the supernatants from the same samples. It is concluded that immunoblotting of bronchoalveolar lavage specimens using 2G2 monoclonal antibody as a detection probe may be a useful adjunct to the morphological demonstration of organisms by special staining procedures.

Acquired Immunodeficiency Syndrome

Immunoblot analysis of the serological response in Hantavirus infections.

Sera from patients with nephropathia epidemica (NE) or Korean hemorrhagic fever (KHF) were tested for specific antibody response to antigens of Hällnäs virus and Hantaan virus strain 76-118. A Vero E6 derived cell line persistently infected with Hällnäs virus strain B1, and Vero E6 cells freshly infected with Hantaan virus type strain 76-118 were used as antigens in the immunofluorescence assay (IFA) and the immunoblot. Blots were prepared from whole cell lysates. The convalescent-phase sera of NE patients tested in this study regularly revealed a marked reaction with a 52 kilodalton (Kd) protein of Hällnäs virus and a 50 Kd protein of Hantaan virus. A convalescent serum from a patient with Korean hemorrhagic fever and a rat antiserum against Hantaan virus could recognize the 50 Kd band of Hantaan virus but showed no apparent reactivity with the 52 Kd component of Hällnäs virus in the standard dilutions. Some sera could additionally identify minor bands in the 55 Kd and/or 67 Kd region of the blots. A one-way cross reactivity between Hantaan and Hällnäs viruses was also evident from the results of the immunofluorescence assays in that NE convalescent sera reacted with both viruses, whereas KHF convalescent or anti-Hantaan sera gave strongly positive results with Hantaan virus but only faint reaction with Hällnäs virus.

Antibodies, Viral

Percutaneous balloon mitral valvuloplasty in children and young adults with rheumatic mitral stenosis.

Twenty-eight patients with mitral stenosis, 17 females and 11 males, underwent percutaneous balloon mitral valvuloplasty (BMV). The age range was 10 to 30 (mean 17.8 +/- 6.7) years and all were symptomatic (New York Heart Association [NYHA] class III, 12 patients; class IV, 16 patients). BMV was done with a single balloon in 10 patients and double balloon in 16 patients. Following BMV, there was a significant reduction in transmitral end-diastolic pressure gradient from 23.1 +/- 5.8 to 7.6 +/- 4.2 mm Hg (p less than 0.001) and a significant increase in mitral valve area from 1.06 +/- 0.29 to 2.64 +/- 1.35 cm2 (p less than 0.001), along with an increase in cardiac index from 3.40 +/- 1.18 to 4.26 +/- 1.46 L/min/m2 (p less than 0.01). Improvement in symptomatic status by at least one NYHA class was seen in all patients. Mild mitral regurgitation developed in four and moderate mitral regurgitation developed in one patient. Angiographic evidence of atrial septal defect was present in one patient. Follow-up at 8 to 12 weeks in 12 patients has shown sustained hemodynamic improvement. These short-term results indicate that BMV is an effective nonsurgical procedure for the management of patients with rheumatic mitral stenosis.

Adolescent

Clinical, haemodynamic and echocardiographic study in chronic cor pulmonale.

Thirty patients of chronic cor pulmonale were studied clinically and by chest skiagram, electrocardiography, echocardiography, pulmonary function tests, arterial blood gas analysis and, wherever possible by right heart catheterization. Pulmonary arterial pressures (PAP) correlated significantly only with cardiomegaly on skiagram and with arterial oxygen tension (PaO2). There was no significant correlation between mean PA pressures and prominent pulmonary conus on RVH by ECG, FEV1, PaCO2 or right ventricular outflow tract dimensions by echocardiography. Left ventricular function, as assessed by pulmonary capillary wedge pressure on cardiac catheterization, by LV ejection fraction and fractional shortening on echocardiography was normal in all cases except two (6.67%). There was significant increase in left ventricular posterior wall thickness in the patients studied.

Adult

Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones.

A variety of clinical syndromes, including AIDS and neurological disorders, may follow as a consequence of infection with the human immunodeficiency virus type 1 (HIV-1). It is not yet clear, however, to what extent the destruction of lymphocytes and neural cells associated with these conditions is caused by adverse immune responses to HIV-1 or how much is due to cytopathic effects of the virus itself. Here we document the existence of HLA-restricted, HIV-1-specific cytotoxic T lymphocytes in the cerebrospinal fluid of two AIDS patients manifesting neurologic disorders. These cytotoxic T lymphocytes showed dual specificity, recognizing target cells coated with purified HIV-1 envelope glycoprotein (gp 120) or inactivated HIV-1 in the context of HLA antigens. Cytotoxic T-cell clones derived from one of the AIDS patients revealed restriction specificities representing both HLA class I and HLA class II antigens. Considerable phenotypic heterogeneity was observed amongst these clones, some expressing conventional combinations of cytotoxic T-cell surface markers, and others displaying unusual phenotypes. The presence of HIV-specific cytotoxic T lymphocytes in AIDS patients, and in particular in their cerebrospinal fluid, suggests that these cytotoxic effectors may participate in the lymphoid cell and/or neurologic damage observed in such patients.

Acquired Immunodeficiency Syndrome

Evaluation of non-radioactive in situ hybridisation method to detect Chlamydia trachomatis in cell culture.

A DNA probe combined with a non-radioactive stain was used to detect inclusions of Chlamydia trachomatis in cell culture. Of 39 positive cultures detected by monoclonal antibodies in combination with direct immunofluorescence, 35 were positive by the DNA hybridisation method, the sensitivity being 89.7%. Staining with iodine showed a sensitivity of 87.2%, corresponding to 34 positive cultures. The specificity of DNA hybridisation method was 100%, as all 162 cultures that were negative by the immunofluorescence method were also negative when assessed by the DNA hybridisation method.

Cells, Cultured

Production and characterization of monoclonal antibodies specific for pathogenic serogroups O:3, O:8, and O:9 of Yersinia enterocolitica.

A panel of 7 murine hybridoma derived monoclonal antibodies (MAbs) to Yersinia enterocolitica were produced and characterized by indirect fluorescence assay (IFA) and agglutination reactions. One MAb designated 2D8 (IgG 3) showed specific reactivity both in the IFA and agglutination assays with 70 of the 70 strains belonging to serogroup O:3 of Y. enterocolitica. Three MAbs, 8E9 (IgG 3b), 10G11 (IgG3) and 11G2 (IgG 3), gave unequivocal positive reactions in the IFA and agglutination tests with all the strains representing serogroup O:9 (56/56), but not with serogroup O:3 or O:8 strains. Another MAb coded 1G2 (IgG 1) reacted specially in the IFA test (but not in the agglutination test) with all the strains representing serogroup O:3 (70/70) and O:9 (56/56) indicating that this antibody recognizes an immunodeterminant shared by serogroups O:3 and O:9. Finally, 2 MAbs 4C2 (IgM) and 6G5 (IgM), showed reactivity both in IFA and agglutination assays with "esculin negative" biogroups 1 (pathogenic American strains) strains of serogroup O:8 (12/12), whereas the strains assigned to "esculin positive" biogroup 1 (nonpathogenic) failed to react (6/6). However, 4C2 and 6G5 exhibited narrow cross reactivity with type strains assigned to serogroups O:18, O:20, and O:22. The results of absorption tests and the clear out cell wall immunofluorescence imply that the antigenic molecule(s) recognized by these MAbs are exposed on the bacterial cell surfaces. Some of the MAbs described in this report are useful reagents for precise serotyping of clinical isolates of Y. enterocolitica by simple and rapid slide agglutination assay. They may also allow the development of specific and sensitive tests for probing the presence of pathogenic Y. enterocolitica organism in clinical and food materials.

Agglutination Tests

Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.

Blood Pressure