Biomedical subjects
S Malhotra
Publications and source records attributed to S Malhotra.
Mortality and long-term course in schizophrenia with a poor 2-year course: a study in a developing country.
BACKGROUND: The short-term course of schizophrenia is reported to be better in some developing country settings. The long-term course in such settings, however, has rarely been studied. AIMS: To examine the long-term course and mortality of schizophrenia in patients with a poor 2-year course. METHOD: The report is based on two incidence cohorts of first-contact patients in urban and rural Chandigarh, India, originally recruited for the World Health Organization Determinants of Outcome of Severe Mental Disorders study. Patients were assessed using standardised instruments at 2- and 15-year follow-ups. RESULTS: Ninety-two per cent of the patients with a poor 2-year course had a poor long-term course and 47% died - a nine times higher mortality rate than among patients with other 2-year course types. CONCLUSIONS: In this developing country setting, a poor 2-year course was strongly predictive of poor prognosis and high mortality, raising questions about the adequacy of care for such patients.
Recovery from psychotic illness: a 15- and 25-year international follow-up study.
BACKGROUND: Poorly defined cohorts and weak study designs have hampered cross-cultural comparisons of course and outcome in schizophrenia. AIMS: To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts. To compare mortality, 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables. METHODS: Historic prospective study. Standardised assessments of course and outcome. RESULTS: About 75% traced. About 50% of surviving cases had favourable outcomes, but there was marked heterogeneity across geographic centres. In regression models, early (2-year) course patterns were the strongest predictor of 15-year outcome, but recovery varied by location; 16% of early unremitting cases achieved late-phase recovery. CONCLUSIONS: A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome. Sociocultural conditions appear to modify long-term course. Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains.
Drug-related visits to the medical emergency department: a prospective study from India.
OBJECTIVE: To analyze the contribution of adverse drug events (ADEs) to the overall number of visits to the medical emergency and to determine the proportion of events leading to hospital admissions. PATIENTS AND METHODS: All visits to the medical emergency were recorded in a prospective, non-interventional design study over a period of 8 months. The ADEs were divided into 5 categories: adverse drug reactions (ADRs), drug interactions, patient non-compliance, physician non-compliance, and drug overdose. The cases were then followed-up to assess the prorportion of ADEs lead to hospitaliztion. RESULTS: A total of 4764 patients were included in the study. 5.9% of all visits were considered to be drug-related. The highest percentage of ADEs was observed in the age group less than 20 and more than 80 years. ADRs accounted for 45% of all ADEs, followed by patient non-compliance (28%). Patient and physician non-compliance were the main causes of drug-related hospital admissions. 52% of all ADE-related visits and 55% of ADE-related admissions were considered to be preventable. Non-steroidal antiinflammatory agents, oral hypoglycemics and antitubercular drugs were responsible for 37% of all ADRs. Non-compliance was mainly seen in hypertensives, asthmatics and epileptics. CONCLUSION: ADEs account for a sizable proportion of all visits to a medical emergency unit and some are serious enough to require hospitaliztion. A large number of ADE-related visits and admissions are preventable which highlights the importance of public education on the proper use of drugs, and also the need for regulation of the practice of unregistered medical practitioners in developing countries.
Effect of calcium antagonists on stress-induced rise in blood pressure and heart rate: a double-blind, placebo-controlled study.
OBJECTIVE: The current study was designed to evaluate the effect of treatment with calcium antagonists on stress-induced increases in blood pressure and heart rate. SUBIECTS, MATERIAL AND METHODS: Two models of stress were chosen, cold stress and isometric handgrip exercise. Six healthy volunteers were randomized to receive amlodipine (5 mg), lacidipine (4 mg) for a two-day period in a double-blind, crossover design. Thirty hypertensive patients received the same treatment for a period of one week in a double-blind, parallel design. The effects of stress on blood pressure and heart rate were taken at baseline and after drug treatment. RESULTS: Cold stress and handgrip exercise significantly increased the systolic and diastolic blood pressure as well as the heart rate. In normotensive volunteers, the resting heart rate and blood pressure were not altered by the drugs. The increase in systolic and diastolic blood pressure produced by cold stress and isometric exercise were unchanged by amlodipine and lacidipine. In hypertensive patients, both drugs reduced the resting blood pressure (p < 0.05). As in normotensive individuals, the pressor response to stress was not altered by the drugs. CONCLUSION: Cold stress and handgrip exercise produced a significant rise in blood pressure and heart rate in normotensive volunteers and patients with hypertension. Cardiovascular reactivity to cold stress and handgrip exercise is not altered by the administration ofamlodipine and lacidipine.
A randomized trial to compare the efficacy, safety, cost and platelet aggregation effects of enoxaparin and unfractionated heparin (the ESCAPEU trial).
OBJECTIVE: To compare the efficacy, safety, cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients. PATIENTS AND METHODS: Ninety-three patients with unstable angina were randomized to receive either unfractionated heparin (UFH) or enoxaparin in an open design clinical trial with blinded end point evaluation. The effects of the heparins on platelet aggregation were also compared. RESULTS: The composite end point of myocardial infarction, cardiac death, recurrent angina and need for intervention was observed in 62% of patients treated with UFH and in 37% of patients treated with enoxaparin (RR 1.7, 95% CI 0.75 to 3.71, p = 0.04). There was no difference in the frequency or severity of adverse events. A cost-effectiveness analysis showed both the heparins to be similar. Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin. CONCLUSIONS: Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety. No difference in costs was detected in this study. The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH.
Gallbladder cancer: recent advances and current guidelines for surgical therapy.
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Combination vascular delivery of herpes simplex oncolytic viruses and amplicon mediated cytokine gene transfer is effective therapy for experimental liver cancer.
BACKGROUND: Herpes simplex type I (HSV)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. The current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone. MATERIALS AND METHODS: A replication competent oncolytic HSV (G207) and a replication incompetent HSV amplicon carrying the gene for the immunomodulatory cytokine IL-2 (HSV-IL2) were tested in murine syngeneic colorectal carcinoma and in rat hepatocellular carcinoma models. Liver tumors were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2) G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV- IL2), and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV-IL2). RESULTS: Tumor burden was significantly reduced in all treatment groups in both rats and mice treated with high-dose G207, HSV-IL2, or both (p < 0.02). When a low dose of virus was used in mice, anti-tumor efficacy was improved by use of G207 and HSV-IL2 in combination or with HSV-IL2 packaged by G207 (p < 0.001). This improvement was abolished when CD4(+) and CD8(+) lymphocytes were depleted, implying that the enhanced anti-tumor response to low-dose combined therapy is immune mediated. CONCLUSIONS: Vascular regional delivery of oncolytic and amplicon HSV vectors can be used to induce improved anti-tumor efficacy by combining oncolytic and immunostimulatory strategies.
Immune complexes and IFN-gamma decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages.
The enzyme cholesterol 27-hydroxylase, expressed by arterial endothelium and monocytes/macrophages, is one of the first lines of defense against the development of atherosclerosis. By catalyzing the hydroxylation of cholesterol to 27-hydroxycholesterol, which is more soluble in aqueous medium, the enzyme promotes the removal of cholesterol from the arterial wall. Prior studies have suggested that immune reactants play a role in the pathogenesis of atherosclerosis; we report here that immune reactants, IFN-gamma and immune complexes bound to C1q, but not interleukin-1 and tumor necrosis factor, diminish the expression of cholesterol 27-hydroxylase in human aortic endothelial cells, peripheral blood mononuclear cells, monocyte-derived macrophages, and the human monocytoid cell line THP-1. In addition, our studies demonstrate that immune complexes down-regulate cholesterol 27-hydroxylase only after complement fixation via interaction with the 126-kD C1qRp protein on endothelial cells and THP-1 cells. These results are consistent with the prior demonstration that IFN-gamma contributes to the pathogenesis of atherosclerosis and suggest a role for C1q receptors in the atherogenic process. Moreover, these observations suggest that one mechanism by which immune reactants contribute to the development of atherosclerosis is by down-regulating the expression of the enzymes required to maintain cholesterol homeostasis in the arterial wall.
Calcium supplementation in pre-eclampsia.
OBJECTIVE: The objective of this prospective, open, randomised trial was to determine the role of calcium supplementation in preventing pre-eclampsia. METHODS: One hundred uncomplicated normotensive primigravidae were enrolled in the study before 20 weeks of pregnancy. Fifty each were randomised to receive either two gram elemental calcium daily from 20 weeks of gestation to delivery (study group) or no calcium supplementation (control group). Prior to 20 weeks of gestation each underwent a complete clinical and laboratory evaluation. Serum and urine calcium was measured first at 20 weeks of gestation and then at 24-28 weeks and at 32-36 weeks of pregnancy. RESULTS: Patient characteristics at the start of therapy were similar in the two groups. Blood pressure profile was similar throughout pregnancy in the groups. The incidence of pre-eclampsia was similar (18% in the study group and 16% in the control group), but severe pre-eclampsia was significantly less in the study group. There was no significant difference between the two groups with regards to intra- and postpartum characteristics, perinatal outcome and maternal or fetal side effects. Serum and urinary calcium levels did not differ between the two groups. CONCLUSION: While calcium supplementation did not lower the incidence of pre-eclampsia it did reduce its severity.
Ocular fireworks injuries. Clinical features and visual outcome.
In a prospective analysis of ocular fireworks injuries over three consecutive years (1997 to 1999) during the Indian festival of Diwali, 42 patients presented with various types of fireworks-related ocular injuries. Twenty two (52%) patients had to be admitted for the management of their ocular injuries.
The Mid-Infrared Spectra of Normal Galaxies.
The mid-infrared spectra (2.5-5 and 5.7-11.6 µm) obtained by ISOPHOT reveal the interstellar medium emission from galaxies powered by star formation to be strongly dominated by the aromatic features at 6.2, 7.7, 8.6, and 11.3 µm. Additional emission appears in between the features, and an underlying continuum is clearly evident at 3-5 µm. This continuum would contribute about a third of the luminosity in the 3-13 µm range. The features together carry 5%-30% of the 40-120 µm far-infrared (FIR) luminosity. The relative fluxes in individual features depend very weakly on galaxy parameters such as the far-infrared colors, direct evidence that the emitting particles are not in thermal equilibrium. The dip at 10 µm is unlikely to result from silicate absorption since its shape is invariant among galaxies. The continuum component has a fnu~nu+0.65 shape between 3 and 5 µm and carries 1%-4% of the FIR luminosity; its extrapolation to longer wavelengths falls well below the spectrum in the 6-12 µm range. This continuum component is almost certainly of nonstellar origin and is probably due to fluctuating grains without aromatic features. The spectra reported here typify the integrated emission from the interstellar medium of the majority of star-forming galaxies and could thus be used to obtain redshifts of highly extincted galaxies up to z=3 with SIRTF.
Analgesics for pediatric use.
The use of nimesulide is increasing and recently, concerns have been raised regarding its hepatotoxicity, especially in children. At least two deaths due to fulminant hepatic failure have been attributed to nimesulide. In India, nimesulide has been approved and about twelve pediatric preparations are available. Lack of effective postmarketing surveillance means that adverse drug reactions may not be picked or reported. Therefore, quick approval of those drugs for which substitutes are available may not be desirable in India and in other developing countries.
A study of drug utilisation and cost of treatment in patients hospitalised with unstable angina.
OBJECTIVE: The current study was designed to investigate drug utilisation in the management of unstable angina in India and to calculate the costs incurred by patients in the treatment of a single episode of unstable angina. METHODS: We conducted a prescription survey to examine the use of antianginal drugs in patients with unstable angina in a tertiary care Indian hospital. The use of concurrent medications such as antidiabetic, antihypertensive and lipid-lowering agents was also examined. Data on the cost of treatment, investigations, income, and family size were collected from the case histories or direct interviews with the patients/relatives. RESULTS: A total of 336 consecutive prescriptions were evaluated. Aspirin was the most frequently prescribed drug (98%) followed by nitroglycerin infusion (90%) and enoxaparin (52%). One of the heparins was used by 89% of all patients and beta-blockers by up to 62% of the patients. Besides antianginals, antihypertensive (49%) and antidiabetic (16%) drugs were commonly coadministered. The mean (+/- SD) cost of treatment of a single episode of unstable angina in the hospital was US $494 (+/- 271) against an annual per capita income of US $245. The mean (+/- SD) cost incurred by the patients due to drugs alone during the hospital stay was US $70 (+/- 18) and enoxaparin accounted for 60% of the expenditure due to drugs. CONCLUSIONS: The results of our study show that low-molecular-weight heparin, enoxaparin, is replacing unfractionated heparin in the treatment of unstable angina. In view of the use of costly new drugs, there is an urgent need for carrying out pharmacoeconomic analysis in developing countries as the treatment of a single episode of unstable angina imparts a considerable economic burden on the patient.
The relationship between depression and cardiovascular disorders.
Expanding scientific evidence supports a long-recognized link between cardiovascular disease and depression. As an independent risk factor, depression increases patient vulnerability to both cardiac events and mortality. Several important pathophysiologic mechanisms have been proposed, including hypothalamic-pituitary axis hyperactivity, autonomic nervous system dysfunction, and increased platelet reactivity, among others. The recently completed Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) inaugurates a series of studies intended to address the impact of antidepressant therapy on cardiovascular risk.
Intravesical migration of copper-T.
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Filaria associated hemolysis in pregnancy.
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Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase.
Silymarin, a mixture of flavonolignans, comprised mainly of three isomers, silybin, silydianin and silychristin isolated from the fruits of Silybum marianum, is currently in therapeutic use as a hepatoprotective agent. Silymarin on evaluation exhibited significant antiinflammatory and antiarthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats. Results of the study indicate its action through inhibition of 5-lipoxygenase for antiinflammatory and antiarthritic activities.