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Biomedical subjects

D Gupta

Publications and source records attributed to D Gupta.

At least 91 records · Page 5Linked to original sources

Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage.

Twenty five patients with post operative ischaemic deficits, following clipping of intracranial aneurysms, were studied. Hypertensive-hypervolaemic-haemodilution (triple H) therapy was given to all patients using colloids and crystalloids. CVP was used to monitor the fluid therapy. Dopamine was needed in 22 patients to elevate the systemic blood pressure. Vasospasm was confirmed in 20 patients with transcranial doppler studies (TCD). 20 (80%) patients survived, 10 (40%) with good outcome, 7 (28%) with fair, 2 (8%) with poor outcome and 1 (4%) with vegetative state. There were 5 (20%) deaths, 4 of which occurred due to infarct. All these patients had poor Hunt and Hess grade at admission, high Fisher grade haemorrhages in the initial CT scan and/or required prolonged temporary clipping at surgery. One death occurred due to central venous line induced septicaemia. The duration of 'triple H therapy' amongst the survivors varied from 2-7 days with an average of 4.6 days. The complications of 'triple H therapy' included hypokalaemia (3 patients), haemorrhagic infarct (1 patient) and septicaemia (1 patient). It is concluded that 'triple H therapy' is useful in treating vasospasm induced ischaemic deficits. It worsens brain oedema in presence of acute infarcts and hence is contraindicated in such patients. A further study involving a larger number of patients with strict haemodynamic and ICP monitoring is suggested to determine the usefulness of individual components of 'triple H therapy'.

Adolescent↗

Statistical estimation of height from arm span in north Indian subjects.

We measured height and arm span of 400 males and 231 female subjects between 16-83 years of age. Arm span exceeded height in 82.6% subjects. Mean height to arm span ratio was 0.9711 and 0.9816 in males and females respectively, and was not significantly correlated with age. Linear regression equations were generated for both sexes for prediction of height from arm span and age. The use of height to arm span ratio was found to be a less suitable method than the use of regression equations in estimating height from arm span.

Adolescent↗

Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal pheochromocytomas.

No reliable pathologic criteria have been identified that predict clinical behavior in adrenal and extra-adrenal pheochromocytomas (PHEOs). Reliable prognostic markers for the prediction of clinical outcome are needed to assign optimal treatment for potentially malignant tumors. In this report, we evaluated several molecular markers (topoisomerase II alpha, E-cadherin, HER-2/neu, and retinoblastoma (RB) gene protein) that have not been previously studied in PHEOs. Paraffin-embedded, formalin-fixed tissue blocks from 50 cases of PHEO (30 benign and 20 malignant, 31 adrenal and 19 extra-adrenal) were obtained from University of Utah Health Sciences Center, Salt Lake City, and the Medical College of Wisconsin, Milwaukee. Gross (tumor size, weight, local extension, cyst formation, hemorrhage, necrosis), microscopic (pleomorphism, hyaline globules, intranuclear inclusion, mitotic count, capsular and vascular invasion, ganglionic/neuronal differentiation), and immunohistochemical features (topoisomerase II alpha, p53, MIB-1, E-cadherin, RB, and HER-2/neu) were studied. With the exception of vascular invasion (P = 0.025), there were no unequivocal gross or microscopic characteristics that distinguished benign from malignant lesions (P approximately = 0.11-0.71). Topoisomerase III and MIB-1 indices in malignant lesions were significantly higher than those observed in benign lesions (P = 0.012 and 0.019). Differences in p53 expression were not statistically significant (P = 0.082). Loss in RB protein product expression was significantly more common in malignant lesions (P = 0.001), E-cadherin loss and HER-2/-neu overexpression were not observed in any of the benign or malignant lesions. We studied the immunohistochemical expression of topoisomerase II alpha, MIB-1, p53, RB gene protein product, E-cadherin, and HER-2/neu in a series of adrenal and extra-adrenal PHEOs. Overexpression of topoisomerase II alpha and MIB-1 and loss of RB protein product were more common in malignant lesions, whereas p53, E-cadherin, and HER-2/neu do not seem to have diagnostic utility in the prediction of biologic behavior in these neoplasms.

Adolescent↗

Incidence of tuberculosis among patients receiving treatment with oral corticosteroids.

OBJECTIVES: To study the incidence and pattern of tuberculosis in patients taking systemic corticosteroids (CS). METHODS: Seventy seven patients taking oral CS for various respiratory diseases and eighty patients suffering from similar diseases but not receiving steroids were followed up for one year to study the incidence of tuberculosis. RESULTS: Five patients (6.5%) receiving CS developed tuberculosis as against none amongst the controls (p < 0.05). Of these, three patients had sputum positive pulmonary tuberculosis and one each had sputum negative pulmonary tuberculosis and tubercular meningitis. All patients were treated with standard anti-tubercular therapy; four patients improved whereas one died due to complications of disease. CONCLUSION: Systemic CS therapy causes a significant increase in incidence of tuberculosis.

Administration, Oral↗

Familial aggregation of cancer in patients with bronchogenic carcinoma.

History of cancer among first degree relatives was obtained in 124 patients with bronchogenic carcinoma [probands] and 248 controls, and differences in familial aggregation evaluated by calculation of odds ratio [OR] and their 95 percent confidence intervals [95% CI]. Probands were more likely than controls to have relatives with cancers [OR 1.27, 95% CI 0.49-3.10], both among smokers and nonsmokers [OR 1.31, 95% CI 0.27-6.79 and OR 1.21, 95% CI 0.12-6.16 respectively]. Sisters of probands were particularly at a higher risk [OR 8.72, 95% CI 0.85-430.08]. A genetic component, possibly independent of smoking habits, may be important in the causation of lung cancer.

Adenocarcinoma↗

Hypothalamo-pituitary-adrenal axis function in asthmatics taking low dose inhaled beclomethasone dipropionate.

OBJECTIVES: Anti-inflammatory drugs, particularly inhaled corticosteroids remain the mainstay of treatment of bronchial asthma. However, these drugs have potential side effects. This study was undertaken to evaluate the effects of inhaled beclomethasone dipropionate (400 and 800 micrograms) over a period of six months on the hypothalamo-pituitary-adrenal axis (HPA) suppression. METHODS: Assessment of the hypothalamo-pituitary-adrenal axis function was carried out by tetracosactrin test at time zero, (before start of treatment), three months, and six months. The baseline values served as the controls for each patient. Serum cortisol was estimated by radioimmuno assay. The response to short tetracosactrin test was classified as normal if serum cortisol levels rose at least 200 nmol/L to a minimum of 500 nmol/L. RESULTS: There were seven patients who were inhaling beclomethasone dipropionate in a dose of 400 micrograms/day and another seven patients were taking the same drug in a dose of 800 micrograms/day. There was no side effect of the drug in any patient except in one patient who had dysphonia. The mean basal cortisol levels were normal in all the subjects at 0, 3 and 6 months of therapy. Tetracosactrin stimulation test was also normal in all patients at all the times who were receiving the dose of 400 micrograms/day. However, one patient (14%) receiving 800 micrograms/day had HPA axis suppression at six months. Two patients in this group also had low basal cortisol levels. There was no clinical evidence of such suppression/deficiency. CONCLUSION: Beclomethasone dipropionate in a dose of 800 micrograms/day may suppress the hypothalamo-pituitary-adrenal axis if used for long periods (six months). However, this may not have any clinical significance.

Administration, Inhalation↗

Structure of the carbonic anhydrase VI (CA6) gene: evidence for two distinct groups within the alpha-CA gene family.

The secreted carbonic anhydrase (CA VI) is believed to be one of the oldest mammalian CAs in evolutionary terms. To elucidate its gene structure and compare it with other members of the alpha-CA family, we cloned genomic fragments encoding the bovine CA6 gene and determined its exon/intron organization. The gene spans approx. 25 kb and consists of eight exons and seven introns. Exon 1 encodes the 5' untranslated region, the signal peptide and the N-terminus of the mature enzyme. Exon 8 encodes the 3' untranslated region and the C-terminal extension that is unique to CA VI. Exons 2-7 encode the CA domain, which shows significant sequence similarity to other CAs. Two distinct groups exist in the alpha-CA family on the basis of a comparison of the known gene structures. One group consists of the cytoplasmic (CA I, II, III and VII) and mitochondrial (CA V) members. The other group consists of the membrane-bound (CA IV and IX) and secreted (CA VI) members. In particular, the seven exon/intron boundaries in the CA domain of the CA6 gene are conserved in the CA9 gene, which encodes the multidomain protein CA IX that is overexpressed in tumours and has transforming potential.

Amino Acid Sequence↗

Group testing in presence of classification errors.

We modify Dorfman's and Sterrett's group testing protocols to make them suitable for testing blood samples for the presence of HIV antibodies, as well as for many industrial applications, when false negatives cannot be tolerated. We first propose that test kit sensitivity be increased to nearly 100 per cent by altering the reactive versus non-reactive threshold. Subsequently, group and repeat testing are used with a careful selection of group size and the number of times a test is repeated, in order to maximize efficiency while keeping the false positive predictive value (FPPV) within a specified limit. Numerical calculations show that our testing protocol is efficient, has low procedural complexity and keeps both types of classification errors below specified tolerance limits.

Blood Banks↗

Bacterial peptidoglycan induces CD14-dependent activation of transcription factors CREB/ATF and AP-1.

Peptidoglycan (PGN), the major cell wall component of Gram-positive bacteria, induces secretion of cytokines in macrophages through CD14, the pattern recognition receptor that binds lipopolysaccharide and other microbial products. To begin to elucidate the mechanisms that regulate the transcription of cytokine genes, we wanted to determine which transcription factors are activated by PGN in mouse RAW264.7 and human THP-1 macrophage cells. Our results demonstrated that: (i) PGN induced phosphorylation of the transcription factors ATF-1 and CREB; (ii) ATF-1 and CREB bound DNA as a dimer and induced transcriptional activation of a CRE reporter plasmid, which was inhibited by dominant negative CREB and ATF-1; (iii) PGN induced phosphorylation of c-Jun, protein synthesis of JunB and c-Fos, and transcriptional activation of the AP-1 reporter plasmid, which was inhibited by dominant negative c-Fos; and (iv) PGN-induced activation of CREB/ATF and AP-1 was mediated through CD14. This is the first study to demonstrate activation of CREB/ATF and AP-1 transcription factors by PGN or by any other component of Gram-positive bacteria.

Activating Transcription Factor 1↗

Change in the lipid profile, lipogenic and related enzymes in the livers of experimental diabetic rats: effect of insulin and vanadate.

Administration of sodium orthovanadate to diabetic animals exhibits insulin-like effects and has been effective in the reversal of biochemical complications. This study evaluates the effect of sodium orthovanadate (0.6 mg/ml) treatment for 21 days on the hepatic glucose homeostasis and lipid metabolism in alloxan diabetic rats. The activities of two lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme; and related enzymes, hexokinase and glucose-6-phosphatase were measured in the liver cytosolic fractions of diabetic rats and diabetic rats treated separately with insulin and sodium orthovanadate. The total lipids, triglycerides and cholesterol levels were estimated in the livers of the diabetic and the treated rats. The activities of both the lipogenic enzymes and hexokinase isozymes were significantly decreased, whereas the activity of glucose-6-phosphatase was significantly increased in the diabetic liver. During diabetes, the levels of total lipids and triglycerides increased significantly with a decrease in the cholesterol levels in the liver. Insulin and vanadate were able to restore the altered enzyme activities to almost control levels. Both insulin and vanadate were found to partially restore the altered levels of total lipids, triglycerides and cholesterol in the livers of diabetic rats. The results indicate that vanadate administration to diabetic animals normalizes blood glucose and causes marked improvement of altered lipid metabolism during diabetes. The present study and earlier reports suggest the possible use of vanadate as insulin replacement in the therapy of diabetes when administered at pharmacological doses.

Animals↗

Passive smoking and lung cancer in Chandigarh, India.

The aim of this study is to assess the relationship between exposure to environmental tobacco smoke (ETS) and lung cancer in non-smokers, a case-control study among lifetime non-smokers was conducted in Chandigarh, India. Cases consisted of 58 non-smoking histologically confirmed lung cancer patients; two controls for each case were selected, one among other patients admitted to the wards and one among the visitors to hospital patients. Subjects were asked about ETS exposure from different tobacco products in childhood and in adulthood at home, at the work place and in vehicles. Multivariate logistic regression analysis was used to assess the effects of the ETS exposure variables on lung cancer. Exposure to ETS during childhood was strongly associated with lung cancer (odds ratio (OR) = 3.9; 95% confidence interval (CI) = 1.9-8.2), the effect mostly arising from exposure to cigarettes smoke. The excess risk was observed with either a smoking father or mother. An increasing risk was found with increasing number of smokers and duration of exposure. Restricting the analysis to women produced higher estimates of the risk. No increased risk was found with exposure to a smoking spouse, except for those exposed only to cigarette smoke (OR = 5.1; 95% CI = 1.5-17). A weak association was seen between lung cancer and ETS exposure at the workplace, which increased with the number of years of exposure. Exposure in vehicles also was detected as a risk factor for lung cancer in non-smokers. This study suggests that ETS exposure may be a strong risk factor for lung cancer also in India, a country with low prevalence of smoking and, therefore, low rates of lung cancer. Other studies need to be conducted in similar settings to confirm the role played by ETS exposure early in life in the causation of lung cancer.

Adenocarcinoma↗

Molecular basis of the polydispersity of mucins: implications for the generation of saccharide diversity.

Secreted epithelial mucins are large macromolecules which exhibit extreme polydispersity, the molecular basis of which is not fully understood. We have obtained partial sequences of two genes (BSM1 and BSM2) coding for two distinct molecules. This is the first time that such closely-related genes have been identified for any mucin from an animal. We propose that a combination of multiple homologous genes, alternative splicing, differential glycosylation, and additional post-translational processing all contribute to the extreme polydispersity of mucins. The multiple domain structure and non-identical tandem repeats are also very important for the generation of the saccharide diversities of mucins.

Amino Acids↗

CD34+-selected peripheral blood progenitor cell transplantation in patients with multiple myeloma: tumour cell contamination and outcome.

Thirty-six patients with multiple myeloma (23 PR1, nine PR2, four stable disease) were entered into a pilot study evaluating the use of CD34+-selected peripheral blood progenitor cell transplantation (PBPCT) following high-dose melphalan alone or high-dose melphalan and total body irradiation. Peripheral blood progenitor cells (PBPCs) were mobilized with cyclophosphamide and granulocyte colony stimulating factor (G-CSF). CD34+ selection using the Cellpro Ceprate-SC system was performed in 22 cases with an adequate yield in 20. 10 patients failed to mobilize sufficient cells to permit selection and in four cases selection was not performed for other reasons. 16 patients therefore received unselected PBPC. Tumour cell contamination was evaluated by IgH gene fingerprinting (fpPCR). Harvested PBPC were fpPCR positive in 13/20 CD34+-selected cases and remained positive after selection in seven. Harvested PBPC were studied in 9/16 patients receiving unselected cells; fpPCR was positive in five and negative in four. There was no difference in event-free survival (EFS) between the CD34+-selected group and the unselected group (median 21 and 26 months, respectively, P=ns). The CD34+-selection process therefore reduced contamination but did not eliminate it completely, and in this small non-randomized study there was no apparent clinical benefit of CD34+ selection.

Adult↗

Phenotypic and molecular analysis of six human cell lines derived from patients with plasma cell dyscrasia.

Cell lines RPMI 8226, JJN3, U266 B1, NCI-H929 (all EBV-) and ARH77 and HS-Sultan (both EBV+) have been extensively characterized in this study. EBV- lines expressed the phenotype (CD138-, CD19+, CD20+) whereas EBV+ were (CD138+, CD19-, CD20-). CD56 expression was restricted to EBV- cell lines, with the exception of U266 B1, whereas PCA-1 was strongly expressed on five of the six cell lines. Only EBV+ cell lines bound peanut-agglutinin (PNA). However, all cell lines bound the lectin Jacalin that binds the same receptor as PNA, irrespective of the receptors sialylation status. By RT-PCR and direct sequencing of their IgH V/D/J domains, ARH77 was demonstrated to use the germline sequence VH4-34/dm1/JH6b, whereas no arrangement was demonstrated for RPMI 8226, suggesting IgH gene deletion or mutation. HLA class I and II antigens were detected using HLA typing on all cell lines warranting their use as suitable targets for HLA-restricted cytotoxic T cells. By sensitive RT-PCR, mRNA for IL-6, IL-6R and TNFbeta was found expressed in all cell lines. IL-1 mRNA expression was predominantly associated with the EBV+ phenotype. Although mRNA for IL-3 and GM-CSF was never detected, transcripts for c-kit ligand and, more commonly, its receptor were. Likewise GM-CSF, M-CSF and erythropoietin mRNA transcripts were detected in the majority of cell lines.

Base Sequence↗

Fine needle aspiration biopsy of the spleen in pyrexia of unknown origin.

To evaluate the diagnostic utility, value and potential risk of fine needle aspiration biopsy of spleen (sFNAB) in patients with splenomegaly in pyrexia of unknown origin (PUO), a retrospective analysis of medical records and cytological material of 31 patients on whom FNAB was performed between April 1994 and October 1997 was done. The patients were HIV- and presented with PUO. All other relevant investigations were negative. The spleen was either palpable or detected to have space-occupying lesions on ultrasonography (USG). The splenic aspirates showed tuberculosis in 11 patients (35.4%) and inconclusive or reactive changes in nine patients (25.8%). One case out of this group proved to be Kaposi's sarcoma on autopsy. The other diseases encountered were leishmaniasis (n = 3), non-Hodgkin's lymphoma (n = 4), fungal infections (n = 2), Hodgkin's lymphoma (n = 1). The patients who were diagnosed as having tuberculosis had epithelioid cells, giant cells, necrosis and inflammatory cells in various combinations. AFB positivity was 63.6%. The other cases which showed granulomas but no AFB were diagnosed on empirical grounds and all responded to the anti-tuberculosis therapy. No complications were encountered with the procedure. Therefore the authors conclude that sFNAB is rewarding in patients where all other non-invasive modalities of diagnosis have failed.

Adult↗

Successful management of pulmonary tuberculosis in renal allograft recipients in a single center.

BACKGROUND: Pulmonary infections, especially tuberculosis, are responsible for significant mortality and morbidity among renal transplant recipients in developing countries. Conventional diagnostic modalities are associated with a low yield, delaying specific therapy. METHODS: All patients transplanted within a 1.5-year period were prospectively followed-up for one year. Patients were on a cyclosporine-based triple immunosuppressive regimen. None received isoniazid prophylaxis, and those transplanted in the last seven months of the study period received daily cotrimoxazole. Patients exhibiting unequivocal evidence of pulmonary infections underwent further evaluation. Search for offending organisms was made by sputum examination and bronchoalveolar lavage (BAL). RESULTS: . Thirty-nine infection episodes were recorded in 34 patients. M. tuberculosis was isolated during 10 episodes, pyogenic bacteria and Pneumocystis carinii in 6 each, candida in 4, aspergillus in 3, cytomegalovirus (CMV) in 3, and nocardia and mucor in one episode each. More than one organism was isolated during five episodes. Bacterial pneumonia and tuberculosis were diagnosed in another seven and two patients, respectively, on the basis of a therapeutic response to specific chemotherapy. Over two thirds of the organisms were identified by examination of BAL fluid. BAL was useful in the diagnosis of tuberculosis and P. carinii pneumonia but was relatively insensitive for CMV and bacterial infections. An increased frequency of acute rejection and higher serum creatinine were factors that predisposed to infections. All patients with pulmonary tuberculosis made a full recovery. CONCLUSIONS: Tuberculosis and P. carinii are the most common nonpyogenic infections in the first year after transplantation in developing countries. An aggressive search for tubercle bacilli should be made using bronchoscopy and examination of BAL fluid in patients not responding to a short trial of antibiotics. A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuberculosis in patients on cyclosporine. We recommend routine prophylactic use of one single-strength tablet of cotrimoxazole daily for at least six months after transplantation.

Adolescent↗