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Biomedical subjects

P Chopra

Publications and source records attributed to P Chopra.

At least 19 recordsLinked to original sources

The nature and significance of liver cell vacuolation following hepatocellular injury--an analysis based on observations on rats rendered tolerant to hepatotoxic damage.

Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.

Adaptation, Physiological

Phenotypic characterization of cellular components of cardiac myxoma: a light microscopy and immunohistochemistry study.

Cardiac myxoma is the most common primary tumor of the heart. A detailed evaluation of cell types in 41 cardiac myxomas by light microscopy and in 30 cases by immunohistochemistry was made. Reactivity to the various antisera were observed in the surface lining cells, the stromal myxoma cells and the cells in the perivascular location. Factor VIII-related antigen (FVIIIR-Ag) and Ulex europaeus agglutinin (UEA-1), both endothelial markers, were positive in 23 cases each. UEA-1 was found to be a more sensitive marker than factor VIII. Desmin and myoglobin were positive in 16 and 24 cases, respectively. Reactivity for cytokeratin was noted in ten cases, one of which showed glandular differentiation. Vimentin and S-100 positivity was obtained in 16 and 14 cases respectively. Thus, cardiac myxoma appears to arise from multipotent cells which have the potential to differentiate along several mesenchymal cells or epithelial cells and may also concurrently exhibit reactivity for both mesenchymal and epithelial markers.

Adolescent

Assessment of antiretroviral therapy by plasma viral load testing: standard and ICD HIV-1 p24 antigen and viral RNA (QC-PCR) assays compared.

To assess the utility of quantitative competitive-polymerase chain reaction (QC-PCR) measurements of plasma human immunodeficiency virus type 1 (HIV-1) RNA and other viral load markers for assessment of antiretroviral therapy, we used archived cryopreserved specimens from a randomized controlled clinical trial of 135 patients (CD4+ T cell count < or = 500/mm3), comparing zidovudine (500 mg/day) versus the nonnucleoside reverse transcriptase inhibitor L-697, 661 (50, 300, or 1,000 mg daily). We evaluated treatment-associated changes in plasma viral load by standard and immune complex-dissociated (ICD) HIV-1 p24 antigen assays, and, in a representative subset of patients (n = 46), by QC-PCR determination of virion-associated HIV-1 RNA. At baseline, HIV-1 RNA was quantifiable by QC-PCR in all patients tested (100%), whereas standard and ICD HIV-1 p24 antigen tests were positive (> or = 30 pg/ml) in 42% and 56%, respectively. All viral load parameters showed significant decreases from baseline within 1 week of initiation of zidovudine, as measured by standard p24 antigen assay, ICD p24 assay, and QC-PCR. At 1 week, patients treated with either 300 or 1,000 mg/day of L-697,661 showed significant decreases from baseline in plasma standard and ICD p24 antigen and QC-PCR-determined HIV-1 RNA levels. Whereas viral load decreases seen with zidovudine were sustained for the duration of treatment, plasma viral markers often returned to pretreatment levels despite ongoing L-697,661 treatment, with evidence of the emergence of drug-resistant virus. Whereas standard p24, ICD p24, and viral RNA levels changed similarly in response to treatment, the superior sensitivity and available dynamic range of plasma viral RNA assays like QC-PCR analysis provide an advantage for clinical monitoring of plasma viral load, allowing tracking of treatment-related changes even in patients with earlier stage disease and lower levels of viral load.

Antiviral Agents

Endomyocardial biopsy--technical aspects experience and current status. An Indian perspective.

Our study ellucidates the utility of endomyocardial biopsy (EMB) in various cardiac-muscle disorders seen in a tropical country like India. The procedure has been successfully performed in 501 patients (572 procedures) at our centre from April 1985 to December 1992. This included 60 infants and children. The indications were dilated cardiomyopathy (DCM) in 214, non-specific aortoarteritis in 91, rheumatic heart disease in 75, restrictive cardiomyopathy in 45, constrictive pericarditis in 14 and miscellaneous in 62 patients. There was no mortality, however, one patient developed cardiac tamponade and another sustained ventricular tachycardia requiring cardioversion. There was transient atrial fibrillation in six patients and all these had acute rheumatic heart disease. Transient complete heart block occurred in six patients with underlying left-bundle branch-block. Histological examination of EMB revealed myocarditis in 34/214 (15.4%) patients in DCM group and helped in following up these cases on immunosuppressive treatment. In the presence of restrictive haemodynamics it could identify amyloidosis in four patients. It was also helpful in differentiating between endomyocardial fibrosis and chronic constrictive pericarditis. In patients with non-specific aorto-arteritis significant histological changes of inflammatory myocarditis were observed in patients especially in congestive heart failure. Furthermore, it was helpful in identifying the nature of cardiac tumour in one patient. Its utility has also been evaluated in disorders, including rheumatic heart disease, peripartum cardiomyopathy and systemic disorders like systemic lupus erythematosis. Even in the absence of cardiac-transplant programmes at national level we have found EMB to be a useful investigation in a tropical country like India.

Adolescent

Clinical profile of biopsy proven idiopathic myocarditis.

We studied 20 patients in detail (age: 27 months to 45 years, mean 22 years; 15 males, 5 females) of idiopathic myocarditis histologically confirmed by endomyocardial biopsy. None of these patients had evidence of active or previous rheumatic fever. The commonest mode of presentation was congestive heart failure (16 patients) followed by arrhythmias (seven patients--five of whom had associated congestive heart failure) and chest pain resembling myocardial infarction (two patients). Ten patients had a history of preceding upper respiratory infection. Only one of these patients had a significant rising serum titre for Coxsackie B3 virus. Throat and rectal swabs for virus culture were negative in all patients. The electrocardiogram was abnormal in all patients, with a prolonged corrected QT-interval being the commonest abnormality (14 patients). Serial electrocardiographic patterns of evolving myocardial infarction occurred in three patients. Echocardiographic left ventricular end diastolic dimension (4.15 +/- 1.01 cm/m2) and end systolic dimension (3.37 +/- 1.03 cm/m2) were increased in 15 of the 18 patients studied. Pericardial involvement occurred in only one patient. Radionuclide ventriculography showed a reduced left ventricular ejection fraction (< 50%) in 17 patients, global hypokinesia in 12 patients and regional wall motion abnormalities in five patients. Left ventricular and right ventricular end diastolic pressures were elevated in 15 and 11 patients, respectively.

Adolescent

An enzyme linked immunosorbent assay for detection of anti-aorta antibodies in Takayasu arteritis patients.

Thirty cases of clinically and angiographically proven non-specific aortoarteritis with appropriate controls were studied. Antiaorta antibody titres were estimated using enzyme linked immunosorbent assay (ELISA) method. The controls included patients of vascular diseases other than non-specific aortoarteritis, autoimmune diseases (rheumatoid arthritis and systemic lupus erythematosis), and normal healthy individuals. An absorbance value at 492 nm at a dilution of 1:500 of patients' sera was expressed as the antiaorta antibody titre. There was a significant difference (P < 0.005) between the mean value of the antibody titre of non-specific aortoarteritis patients (0.471 +/- 0.073) and patients of other vascular diseases (0.209 +/- 0.056), autoimmune disease patients (0.143 +/- 0.024) and controls (0.108 +/- 0.012). Collagenase treatment of the aorta resulted in the fall of the antibody titre of aortitis patients (0.162 +/- 0.036) suggesting that the collagen might be one of the components responsible for autoantigenecity of the aorta resulting in aortitis. The precise nature of the antigen needs to be identified.

Adolescent

Non-specific aortoarteritis: long-term follow-up on immunosuppressive therapy.

Thirteen patients with non-specific aortoarteritis and endomyocardial biopsy evidence of myocarditis were followed-up on immunosuppressive therapy comprising of prednisolone and cyclophosphamide in addition to conventional treatment for hypertension and/or congestive heart failure. Serial determinations of erythrocyte sedimentation rate, chest roentgenogram, radionuclide ventriculogram and hemodynamic study including endomyocardial biopsy were carried out at 12, 24 and 52 weeks of therapy. Arterial lesions were also assessed by digital subtraction angiography at 0 and 52 weeks of immunosuppressive therapy. At the end of a year of treatment all patients with congestive heart failure (10/13) showed symptomatic improvement by at least one New York Heart Association (NYHA) class. There was a significant fall in erythrocyte sedimentation rate (48 +/- 12 mm/1st h to 31 +/- 12 mm/1st h, P < 0.05), pulmonary artery pressure (32 +/- 14 mmHg to 20 +/- 9 mmHg, P < 0.05), left ventricular filling pressure (20 +/- 11 mmHg to 11 +/- 7 mmHg, P < 0.05) and increase in left ventricle ejection fraction (39 +/- 16% to 51 +/- 14%, P < 0.05) associated with resolution of morphological changes on endomyocardial biopsy. Arterial lesions remained static with neither progression nor appearance of new lesions. No significant complications of therapy were noticed in any patient. Our uncontrolled observations suggest that immunosuppressive therapy is safe and results in clinical, hemodynamic and myocardial morphological improvement in a subset of patients with non-specific aortoarteritis and associated myocarditis.

Adolescent

Does endomyocardial biopsy aid in the diagnosis of active rheumatic carditis?

BACKGROUND: Carditis is the only component of rheumatic fever that leads to permanent disability. The diagnosis of carditis is presently made by using composite clinical criteria based on the revised Jones' criteria. Since myocardial involvement is an important component of rheumatic carditis, right ventricular endomyocardial biopsies were performed in 54 patients with clinical acute rheumatic fever and quiescent rheumatic heart disease to evaluate the role of biopsy for the diagnosis of rheumatic carditis. METHODS AND RESULTS: In 11 of the 54 patients, clinical consensus was certain about rheumatic fever and carditis based on the revised Jones' criteria (group 1). Histomorphological abnormalities in these patients were scarce. The diagnostic features of rheumatic myocarditis including Aschoff nodules or histiocytic aggregates were encountered in 3 patients (27%). Lymphocytic infiltration was sparse. A majority of patients demonstrated myocyte degeneration, interstitial degeneration, or occasional interstitial mononuclear cell infiltration, but since these histopathological lesions may occur in other conditions also, they were considered nondiagnostic. In 33 of the 54 patients with preexisting rheumatic heart disease, the diagnosis of carditis was suspected based on varied clinical presentations. Since previous cardiac findings were not available in these patients, the clinical diagnosis of carditis could not be made without equivocation (group 2). Twenty-three patients presented with unexplained acute onset of congestive heart failure and evidence of recent streptococcal infection (group 2A). While 13 of them had one or more other major manifestations, 10 patients had only minor manifestations. Mimetic carditis was suspected in the remaining 10 of 33 patients based on carditis having occurred in previous episodes of rheumatic fever (group 2B). The endomyocardial biopsy provided confirmatory evidence of rheumatic myocarditis in 9 patients of group 2A but in none of the 10 patients with suspected mimetic carditis. Nondiagnostic myocyte or interstitial alterations were frequently observed in group 2. Ten of the 54 patients had no clinical evidence of active carditis (group 3). No histological alterations diagnostic of rheumatic carditis were noted in these patients. Twenty-two follow-up biopsies were performed in the first 10 consecutive patients. Diagnostic histiocytic aggregates or Aschoff nodules were observed in initial biopsies in 4 of 10 patients, and nonspecific myocyte or interstitial alterations were observed in 9. All patients with diagnostic changes in initial biopsy demonstrated fibrohistiocytic nodules in 6- or 12-week biopsy samples. Nondiagnostic alterations, similar to those seen in acute cases, were present in 5 of 8 patients at 6 weeks, 5 of 8 patients at 12 weeks, and 3 of the 6 patients at 24 weeks despite the presumed adequate immunosuppressive therapy. No complications related to biopsy were encountered. CONCLUSIONS: The present study highlights the low frequency of diagnostic features in the biopsy specimens of patients with definite clinical rheumatic carditis. Although such alterations are not observed in patients with chronic rheumatic heart disease, endomyocardial biopsy does not appear to provide additional diagnostic information where clinical consensus is certain about diagnosis of rheumatic carditis. Our study, however, substantiates the concept of carditis underlying unexplained congestive heart failure of acute onset in patients with preexisting rheumatic heart disease and elevated antistreptolysin-O titers.

Acute Disease

Amlodipine in mild and moderate hypertension: initial Indian experience.

In an open, non-comparative, variable-dose study, 20 outpatients with mild to moderate essential hypertension were treated with 5-10 mg amlodipine once daily for 4 weeks, after their blood pressures had stabilized on placebo. Amlodipine produced a significant decrease in blood pressure (P < 0.05) from the initial mean of 162/100 mm Hg to 139/85 mm Hg at 4 weeks. 80% of the patients reached the goal diastolic blood pressure of < or = 90 mm Hg with a once-daily dose of 5 mg amlodipine within 2 weeks. The remaining 20% also attained the goal diastolic blood pressure within 4 weeks, with a one-step increase in the dose to 10 mg at 2 weeks. Amlodipine maintained blood pressure reduction throughout the 24-hours dosing interval with a once-daily dose. Notably, no side effects were observed; pulse rate, electrocardiogram, and laboratory parameters were not significantly altered with therapy. Amlodipine in a single daily dose of 5-10 mg is effective and well tolerated in the treatment of patients with mild to moderate hypertension.

Adult

Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview.

Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject.

Adrenal Glands

Immunosuppressive therapy in inflammatory myocarditis: long-term follow-up.

Sixteen patients (12 male and 4 female, age 2-46 years) with endomyocardial biopsy-proven myocarditis were prospectively evaluated with immunosuppressive therapy including azathioprine and prednisolone in addition to other standard measures. Patients were either in NYHA class IV (n = 12) or class III (n = 4). Twelve patients showed improvement and the remaining 4 continued to deteriorate: 2 died at 1 and 2 months after therapy and the other 2 were lost to follow-up after 4-6 weeks of therapy. Three of the 12 patients who showed significant improvement, after sudden omission of therapy (at 8 weeks, 6 and 8 months) worsened and died. One patient who showed significant improvement died suddenly after 9 months of therapy while playing football. The remaining patients have shown significant clinical and haemodynamic improvement with normalization of myocardial morphology. Serial haemodynamic studies revealed a significant fall in cardiothoracic ratio (before: 62.3 +/- 4.7%; 3 months: 55.1 +/- 3.1%, P less than 0.0001; 6-12 months: 50.6 +/- 1.5%, P less than 0.0001), mean pulmonary artery pressure (before: 34.3 +/- 13.05 mm; 3 months: 20.4 +/- 8.71 mm, P less than 0.01; 6-12 months: 20.0 +/- 2.75 mm, P less than 0.01) and mean pulmonary artery wedge pressure (before: 26.0 +/- 9.07 mm; 3 months 14.0 +/- 5.63 mm, P less than 0.001; 6-12 months: 13.2 +/- 4.57 mm, P less than 0.001). The left ventricular ejection fraction improved from 24.3 +/- 8.36% to 35.8 +/- 9.72% (P less than 0.001) at 3 months and 49.8 +/- 18.2% (P less than 0.0001) at 6-12 months of therapy. Two patients have been subsequently lost to follow-up whereas the remaining 6 patients are on follow-up for 1-4 years after therapy and are doing fine. Our uncontrolled observations suggest that immunosuppressive therapy may be useful in patients with inflammatory myocarditis.

Adolescent

Immunohistochemical and histochemical profile of Aschoff bodies in rheumatic carditis in excised left atrial appendages: an immunoperoxidase study in fresh and paraffin-embedded tissue.

We have evaluated the nature of Aschoff cells within Aschoff bodies seen in 35 of 100 excised left atrial appendages from cases of rheumatic mitral stenosis who underwent closed mitral valvotomy. These were tested using a panel of monoclonal and polyclonal antisera by the indirect immunoperoxidase staining for leucocyte common antigen, macrophage, desmin, vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, lysozyme, acid phosphatase and nonspecific esterase. The Aschoff cell gave strong reactivity with monoclonal antisera to vimentin, macrophage and variable reaction with polyclonal antisera known to recognise macrophages/histiocytes in tissues, namely alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. These were also strongly positive for acid phosphatase and nonspecific esterase. The Aschoff cell lacked affinity for desmin and only an occasional cell in 4 out of 20 and 6 out of 35 cases showed a weak reaction with myoglobin and leucocyte common antigen, respectively. Intense consistent reactivity with several histiocytic markers affirms the genesis of these cells from macrophages/histiocytes and not muscle cells; a controversy which must be laid to rest!

Antibodies, Monoclonal

Chronic rheumatic heart disease in India: a reappraisal of pathologic changes.

Rheumatic heart disease contributes to significant cardiac morbidity and mortality in India. The disease predominantly affects the valvular endocardium culminating in crippling valvular deformities, preferentially involving the mitral valve which may be severely affected in children and young adults. This appears to be unique to India and has been termed juvenile mitral stenosis. It is characterized by cardiomegaly, refractory congestive heart failure, and marked by elevated pulmonary vascular pressures and a progressive, fulminant clinical course. Autopsies of patients dying of rheumatic heart disease revealed that the mitral valve was most commonly afflicted either alone or in combination with the aortic and tricuspid valves in 31.6% and 52.8%, respectively. Organic involvement of the tricuspid valve was documented in 38.4% of cases. The extent and severity of the disease process was most marked in the mitral valve, followed by the aortic and tricuspid valves. Mitral valves showed various degrees of calcification, moderate or severe calcification being observed in 36.4%. Chronic inflammatory cell infiltration was observed in both calcified and non-calcified valves. The phenotypic profile of the inflammatory cells by immunohistochemical staining revealed a significant number to be T-helper/inducer lymphocytes. Lungs from cases of mitral stenosis exhibited prominent vascular and parenchymal changes. Pulmonary vessels revealed moderate to marked medial hypertrophy of the medium sized branches of the pulmonary artery. Dilatation lesions were also seen in a few cases. The most striking parenchymal change was the prominent smooth muscle in the bronchoalveolar walls. The extent and severity of the vascular and parenchymal changes were more marked in juvenile patients. The presence of inflammatory cells in cases of chronic heart disease reflects a possible ongoing insult/injury to some persistent antigenic stimulus by beta hemolytic streptococcal antigens that have primed the various target tissues. Further study of surface characteristics of various mesenchymal cells may help in understanding the nature and pathogenesis of this serious cardiac problem.

Adolescent

Peritoneal tuberculosis: laparoscopic patterns and its diagnostic accuracy.

We report laparoscopic findings in 38 proven cases of peritoneal tuberculosis. The laparoscopic appearances can be classified into three types: thickened peritoneum with miliary yellowish white tubercles with or without adhesions (n = 25), only thickened peritoneum with or without adhesions (n = 8), and fibroadhesive pattern (n = 5). Biopsies were avoided from fibroadhesive lesions due to risk of complications. Visual diagnosis was accurate in 95% of patients. In comparison, in 27 (82%) of 33 patients, the examination enabled a histologic diagnosis to be made on the basis of typical granulomas. The combined use of guinea pig inoculation and culture isolated Mycobacterium tuberculosis in six (37.5%) of 16 patients. Mycobacteria were scarcely (3%) seen on histological sections. We conclude that, although target biopsy is an effective method of obtaining an early diagnosis of peritoneal tuberculosis, chemotherapy may be started on the basis of visual laparoscopic appearances alone.

Adult

Cardiac involvement in nonspecific aortoarteritis (Takayasu's arteritis).

Fifty-four patients (18 males and 36 females, ages 2 to 37 years) with nonspecific aortoarteritis (NSAA) were studied. Evaluation revealed hypertension in 35, congestive heart failure (CHF) in 24, mild to moderate mitral regurgitation in six, and mild aortic regurgitation in two. Erythrocyte sedimentation rate was raised (greater than 35 mm in the first hour) in 38 patients. The arterial lesions included type I in seven, type II in eight, and type III in 34. Pulmonary artery involvement was present in 4 (type IV) of the 20 patients in whom it was studied. Selective coronary angiography was done in 11 patients and revealed 90% left main stenosis in one patient. Hemodynamic data revealed raised (greater than 7 mm Hg) mean right atrial pressure in nine, raised mean pulmonary artery pressure (greater than 20 mm Hg) in 29, and raised left ventricular filling pressure (greater than 12 mm Hg) in 27 patients. Radionuclide ventriculography revealed reduced (less than 45%) left ventricular ejection fraction (LVEF) in 27 patients. The myocardial morphology as evaluated on right ventricular endomyocardial biopsy revealed normal histology in nine, features of inflammatory myocarditis in 24, and nonspecific changes suggestive of dilated cardiomyopathy in six patients. Marked right ventricular endocardial thickening was present in three. All patients with CHF had some histologic abnormality. We emphasize that myocardial involvement including myocarditis is common in NSAA and may precipitate CHF in these patients.

Adolescent

Scanning electron microscope features of rheumatic vegetations in acute rheumatic carditis.

We have studied four cases of acute rheumatic carditis at autopsy in which the cardiac valves revealed rheumatic vegetations. The features of these vegetations were investigated by scanning electron microscopy. There was a loss of the normal mosaic arrangement of endothelial cells and marked architectural modifications of the valvar collagen. These features explain well the pathologic processes of rheumatic valvitis and the infective complications, if any, thereof. To the best of our knowledge, this is the first time that an analysis has been made of the structure of the surface of rheumatic vegetations.

Acute Disease