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Biomedical subjects

S S Anand

Publications and source records attributed to S S Anand.

At least 19 recordsLinked to original sources
PubMed2005

Dose-dependent liver regeneration in chloroform, trichloroethylene and allyl alcohol ternary mixture hepatotoxicity in rats.

The present study was designed to examine the hypothesis that liver tissue repair induced after exposure to chloroform (CF) + trichloroethylene (TCE) + allyl alcohol (AA) ternary mixture (TM) is dose-dependent similar to that elicited by exposure to these compounds individually. Male Sprague Dawley (S-D) rats (250-300 g) were administered with fivefold dose range of CF (74-370 mg/kg, ip), and TCE (250-1250 mg/kg, ip) in corn oil and sevenfold dose range of AA (5-35 mg/kg, ip) in distilled water. Liver injury was assessed by plasma alanine amino transferase (ALT) activity and liver tissue repair was measured by (3) H-thymidine incorporation into hepatonuclear DNA. Blood and liver levels of parent compounds and two major metabolites of TCE [trichloroacetic acid (TCA) and trichloroethanol (TCOH)] were quantified by gas chromatography. Blood and liver CF and AA levels after TM were similar to CF alone or AA alone, respectively. However, the TCE levels in blood and liver were substantially decreased after TM in a dose-dependent fashion compared to TCE alone. Decreased plasma and liver TCE levels were consistent with decreased production of metabolites and elevated urinary excretion of TCE. The antagonistic interaction resulted in lower liver injury than the summation of injury caused by the individual components at all three-dose levels. On the other hand, tissue repair showed a dose-response leading to regression of injury. Although the liver injury was lower and progression was contained by timely tissue repair, 50% mortality occurred only with the high dose combination, which is several fold higher than environmental levels. The mortality could be due to the central nervous system toxicity. These findings suggest that exposure to TM results in lower initial liver injury owing to higher elimination of TCE, and the compensatory liver tissue repair stimulated in a dose-dependent manner mitigates progression of injury after exposure to TM.

Administration, Oral↗
PubMed2005

Thyroid dyshormonogenesis.

Dyshormonogenesis is an uncommon cause of congenital hypothyroidism. The most common abnormality is absent or insufficient thyroid peroxidase enzyme. Perchlorate discharge test can be used to diagnose thyroid peroxidase deficiency. We report three siblings with hypothyroidism due to thyroid dyshormonogenesis. Early institution of therapy in these patients can prevent mental retardation and other features of hypothyroidism.

Adolescent↗
PubMed2001

Risk factors, atherosclerosis, and cardiovascular disease among Aboriginal people in Canada: the Study of Health Assessment and Risk Evaluation in Aboriginal Peoples (SHARE-AP).

BACKGROUND: Little is known about the rates of cardiovascular disease (CVD), atherosclerosis, and their risk factors among Canada's Aboriginal people. To establish the relative prevalence of risk factors, atherosclerosis, and CVD, we undertook a population-based study among people of Aboriginal and European ancestry in Canada. METHODS: We randomly recruited 301 Aboriginal people from the Six Nations Reservation, and 326 people of European origin from Hamilton, Toronto, and Edmonton, Canada. Clinical CVD was defined by history or electrocardiographic findings, atherosclerosis was measured by B-mode carotid ultrasonography, and conventional and new CVD risk factors were measured using standardised methods. FINDINGS: Aboriginal people had significantly more carotid atherosclerosis (mean of the maximum intimal-medial thickness 0.82 (SD 0.20) mm vs 0.78 (0.20) mm, p=0.027), and had a higher frequency of CVD (18.5% vs 7.6%, p=0.00002) compared with Europeans. Aboriginal people had significantly higher rates of smoking, glucose intolerance, obesity, abdominal obesity, and substantially higher concentrations of fibrinogen, and plasminogen activator inhibitor-1. Aboriginal people had significantly higher rates of unemployment and a lower annual household income. For any given income level, Aboriginal people had higher rates of risk factors and CVD compared with the Europeans. INTERPRETATION: A significant proportion of Aboriginal people live in poverty which is associated with high rates of CVD and CVD risk factors. Improvement of the socioeconomic status of Aboriginal people might be a key to reduce CVD in this group.

Adult↗
PubMed2001

Guidelines as rationing tools: a qualitative analysis of psychosocial patient selection criteria for cardiac procedures.

BACKGROUND: Cardiac procedure guidelines often include psychosocial criteria for selecting patients that potentially introduce social value judgements into clinical decisions and decisions about the rationing of care. The aim of this study was to investigate the terms and justifications for and the meanings of psychosocial patient characteristics used in cardiac procedure guidelines. METHODS: We selected English-language guidelines published since 1990 and chapters in textbooks published since 1989. These guidelines amalgamated multiple sources of evidence and expertise and made recommendations regarding patient selection for specific procedures. A multidisciplinary team of physicians and social scientists extracted passages regarding psychosocial criteria and developed categories and conceptual relationships to describe and interpret their content. RESULTS: Sixty-five papers met the criteria for inclusion in the study. Forty-five (69%) mentioned psychosocial criteria as procedure indications or contraindications. The latter fell into several categories, including behavioural and psychological issues, relationships with significant others, financial resources, social roles and environmental circumstances. INTERPRETATION: Psychosocial characteristics are portrayed as having 2 roles in patient selection: as risk factors intrinsic to the candidate or as indicators of need for special intervention. Guidelines typically simply list psychosocial contraindications without clarifying their specific nature or providing any justification for their use. Psychosocial considerations can help in the evaluation of patients for cardiac procedures, but they become ethically controversial when used to restrict access. The use of psychosocial indications and contraindications could be improved by more precise descriptions of the psychosocial problem at issue, explanations regarding why the criterion matters and justification of the characteristic using a biological rationale or research evidence.

Attitude of Health Personnel↗
PubMed2001

Prognostic significance of thrombocytopenia during hirudin and heparin therapy in acute coronary syndrome without ST elevation: Organization to Assess Strategies for Ischemic Syndromes (OASIS-2)study.

BACKGROUND: The development of thrombocytopenia in acute coronary syndromes (ACS) appears to be associated with adverse clinical outcomes. Unfractionated heparin is a recognized cause of thrombocytopenia, but the incidence, predictors, and prognostic significance of thrombocytopenia during hirudin therapy in ACS have not been reported. METHODS AND RESULTS: Patients with ACS without ST elevation were randomized in a double-blind manner to receive a 72-hour intravenous infusion of unfractionated heparin or hirudin. Platelet counts were measured at baseline and within 24 hours of completion of study drug. The overall incidence of thrombocytopenia (<100x10(9)/L) was 1% and was similar in unfractionated heparin- and hirudin-treated patients (P:=0.42). Thrombocytopenia during study drug infusion was an independent predictor of 7-day outcomes, including death (OR, 6.7; 95% CI, 1.9 to 25); the composite of death, myocardial infarction, and recurrent ischemia (OR, 2.0; 95% CI, 1.0 to 1.5); revascularization (OR, 4.0; 95% CI, 2.2 to 7.1); and major bleeding (OR, 8.3; 95% CI, 3.4 to 17.7). Among patients who developed thrombocytopenia, hirudin (OR, 5.4; 95% CI, 2.6 to 11.3) but not unfractionated heparin (OR, 2.0; 95% CI, 0.3 to 14.4) therapy was associated with a significantly increased risk of major bleeding. CONCLUSIONS: Early-onset thrombocytopenia in patients with ACS without ST elevation is strongly associated with adverse clinical outcomes, including death, ischemic events, and bleeding. The excess of major bleeding in hirudin-treated patients who develop thrombocytopenia suggests that thrombocytopenia may contribute to the increased risk of bleeding observed with hirudin.

Acute Disease↗
PubMed2001

Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Pinede L, Ninet J, Duhaut P et al for the Investigators of the 'Durée Optimale du Traitement Antivitamines K' (DOTAVK) study. Circulation 2001; 103: 2453-60.

QUESTION: Is anticoagulant treatment for calf vein thrombosis for 6 weeks duration associated with acceptable recurrence and safety outcomes? Is anticoagulant therapy for 3 months duration for proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) associated with acceptable recurrence and safety outcomes? POPULATION: Men and women with a first episode of symptomatic calf vein thrombosis or proximal DVT confirmed by ultrasound or venography, or PE confirmed by lung scan or angiography. Patients with pregnancy, thrombophilia, severe PE, and cancer were excluded. DESIGN AND METHODS: After treatment with heparin and oral anticoagulants targeting an INR of 2-3, patients with calf DVT were randomized to 6 weeks (n = 105) versus 3 months (n = 92) of treatment, and patients with proximal DVT and/or PE were randomized to 3 months (n = 270) versus 6 months (n = 269) of treatment. The outcome events were recurrences and major, minor, or fatal bleeding complications. The mean follow-up time was 12 months. RESULTS: A total of 736 patients were enrolled. For calf vein thrombosis the recurrence of DVT or PE after 6 weeks of therapy was 2/105 (2.0%) versus 3/92 (3.4%) with 3 months of therapy, relative risk of 0.58 (95% CI: 0.10-3.36). The rates of major bleeding were 1/105 (1.0%) and 3/92 (3.4%) respectively, relative risk of 0.29 (95% CI: 0.03-2.72). For proximal DVT or PE, the recurrence rate after 3 months of therapy was 21/270 (8.1%) versus 23/269 (8.7%) after 6 months of treatment, relative risk of 0.93 (95% CI: 0.53-1.65). The rates of major bleeding were 5/270 (1.9%) versus 7/269 (2.6%) respectively, relative risk of 0.73 (95% CI: 0.24-2.27). CONCLUSION: After isolated calf vein DVT, 6 weeks of oral anticoagulation is sufficient. For proximal DVT or PE, 3 and 6 months of anticoagulant therapy is equivalent. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient.

Administration, Oral↗
PubMed2001

On prognostic models, artificial intelligence and censored observations.

The development of prognostic models for assisting medical practitioners with decision making is not a trivial task. Models need to possess a number of desirable characteristics and few, if any, current modelling approaches based on statistical or artificial intelligence can produce models that display all these characteristics. The inability of modelling techniques to provide truly useful models has led to interest in these models being purely academic in nature. This in turn has resulted in only a very small percentage of models that have been developed being deployed in practice. On the other hand, new modelling paradigms are being proposed continuously within the machine learning and statistical community and claims, often based on inadequate evaluation, being made on their superiority over traditional modelling methods. We believe that for new modelling approaches to deliver true net benefits over traditional techniques, an evaluation centric approach to their development is essential. In this paper we present such an evaluation centric approach to developing extensions to the basic k-nearest neighbour (k-NN) paradigm. We use standard statistical techniques to enhance the distance metric used and a framework based on evidence theory to obtain a prediction for the target example from the outcome of the retrieved exemplars. We refer to this new k-NN algorithm as Censored k-NN (Ck-NN). This reflects the enhancements made to k-NN that are aimed at providing a means for handling censored observations within k-NN.

Algorithms↗
PubMed2000

Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE)

BACKGROUND: Cardiovascular disease rates vary greatly between ethnic groups in Canada. To establish whether this variation can be explained by differences in disease risk factors and subclinical atherosclerosis, we undertook a population-based study of three ethnic groups in Canada: South Asians, Chinese, and Europeans. METHODS: 985 participants were recruited from three cities (Hamilton, Toronto, and Edmonton) by stratified random sampling. Clinical cardiovascular disease was defined by history or electrocardiographic findings. Carotid atherosclerosis was measured with B-mode ultrasonography. Conventional (smoking, hypertension, diabetes, raised cholesterol) and novel risk factors (markers of a prothrombotic state) were measured. FINDINGS: Within each ethnic group and overall, the degree of carotid atherosclerosis was associated with a higher prevalence of cardiovascular disease. South Asians had the highest prevalence of this condition compared with Europeans and Chinese (11%, 5%, and 2%, respectively, p=0.0004). Despite this finding, Europeans had more atherosclerosis (mean of the maximum intimal medial thickness 0.75 [0.16] mm) than South Asians (0.72 [0.15] mm), and Chinese (0.69 [0.16] mm). South Asians had an increased prevalence of glucose intolerance, higher total and LDL cholesterol, higher triglycerides, and lower HDL cholesterol, and much greater abnormalities in novel risk factors including higher concentrations of fibrinogen, homocysteine, lipoprotein (a), and plasminogen activator inhibitor-1. INTERPRETATION: Although there are differences in conventional and novel risk factors between ethnic groups, this variation and the degree of atherosclerosis only partly explains the higher rates of cardiovascular disease among South Asians compared with Europeans and Chinese. The increased risk of cardiovascular events could be due to factors affecting plaque rupture, the interaction between prothrombotic factors and atherosclerosis, or as yet undiscovered risk factors.

Arteriosclerosis↗
PubMed2000

Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis.

BACKGROUND: In acute coronary syndrome without ST elevation, the role of unfractionated and low-molecular-weight heparin in aspirin-treated patients remains unclear, and there is conflicting evidence regarding the efficacy and safety of low-molecular-weight heparin (LMWH) relative to unfractionated heparin. We did a systematic overview of the randomised trials to assess the effect of unfractionated heparin and LMWH on death, myocardial infarction, and major bleeding. METHODS: Randomised trials comparing unfractionated heparin or LMWH with placebo or untreated control, or comparing unfractionated heparin with LMWH, for the short-term and long-term management of patients with acute coronary syndrome without ST elevation, were identified by electronic and manual searches and through contact with experts and industry representatives. Odds ratios for death, myocardial infarction, and major bleeding were calculated for each trial, and results for the individual trials were combined by a modification of the Mantel-Haenszel method. FINDINGS: 12 trials, involving a total of 17157 patients, were included. The summary odds ratio (OR) for myocardial infarction or death during short-term (up to 7 days) unfractionated heparin or LMWH compared with placebo or untreated control was 0.53 (95% CI 0.38-0.73; p=0.0001) or 29 events prevented per 1000 patients treated; during short-term LMWH compared with unfractionated heparin was 0.88 (0.69-1.12; p=0.34); and during long-term LMWH (up to 3 months) compared with placebo or untreated control was 0.98 (0.81-1.17; p=0.80). Long-term LMWH was associated with a significantly increased risk of major bleeding (OR 2.26, [95% CI 1.63-3.14], p<0.0001), which is equivalent to 12 major bleeds per 1000 patients treated. INTERPRETATION: In aspirin-treated patients with acute coronary syndrome without ST elevation, short-term unfractionated heparin or LMWH halves the risk of myocardial infarction or death. There is no convincing difference in efficacy or safety between LMWH and unfractionated heparin. Long-term LMWH has not been proven to confer benefit additional to aspirin and there is no evidence to support its use after the first 7 days.

Acute Disease↗
PubMed2000

Using practice guidelines to allocate medical technologies. An ethics framework.

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.

Biomedical Technology↗
PubMed2000

Association between high homocyst(e)ine and ischemic stroke due to large- and small-artery disease but not other etiologic subtypes of ischemic stroke.

BACKGROUND AND PURPOSE: Elevated plasma homocyst(e)ine may be a causal and modifiable risk factor for ischemic stroke, but the results of previous studies have been conflicting. One possible explanation is that homocyst(e)ine may only be associated with certain pathophysiological subtypes of ischemic stroke. METHODS: We conducted a case-control study of 219 hospital cases with a first-ever ischemic stroke and 205 randomly selected community control subjects stratified by age, sex, and postal code. With the use of established criteria, cases of stroke were classified by etiologic subtype in a blinded fashion. The prevalence of conventional vascular risk factors, fasting plasma homocyst(e)ine levels, vitamin levels, and nucleotide 677 methylene tetrahydrofolate reductase (MTHFR) genotypes were determined in cases and controls. RESULTS: Increasing homocyst(e)ine was a strong and independent risk factor for ischemic stroke (adjusted OR 2.7, 95% CI 1.4 to 5.1 for a 5-micromol/L increase in fasting plasma homocyst(e)ine from 10 to 15 micromol/L). Compared with the lowest quartile, the highest quartile of homocyst(e)ine was associated with an adjusted OR of ischemic stroke of 2.2 (95% CI 1.1 to 4.2). Mean plasma homocyst(e)ine was significantly higher in cases of ischemic stroke due to large-artery disease (14.1 micromol/L, 95% CI 12.5 to 15.9, P<0.001) and small-artery disease (12.7 micromol/L, 95% CI 11. 4 to 14.1, P=0.004) compared with control subjects (10.5 micromol/L; 95% CI 10.0 to 11.0) but not in cardioembolic or other etiologic subtypes of ischemic stroke. Compared with the lowest quartile of homocyst(e)ine, the upper 3 quartiles were associated with an adjusted OR of ischemic stroke due to large-artery disease of 3.0 (95% CI 0.8 to 10.8) for the second quartile, 5.6 (95% CI 1.6 to 20) for the third quartile, and 8.7 (95% CI 2.4 to 32) for the fourth quartile (P for trend=0.0005). However, despite a clear association between the TT MTHFR genotype and elevated fasting plasma homocyst(e)ine, there was no association between MTHFR genotype and ischemic stroke or subtype of ischemic stroke. CONCLUSIONS: There is a strong, graded association between increasing plasma homocyst(e)ine and ischemic stroke caused by large-artery atherosclerosis and, to a much lesser extent, small-artery disease, but not cardioembolic or other etiologic subtypes of ischemic stroke. Our results are consistent with the hypothesis that the deleterious effect of high homocyst(e)ine is mediated primarily via a proatherogenic effect.

Aged↗
PubMed1999

Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis.

CONTEXT: Despite years of use in coronary artery disease (CAD) and several studies of its effectiveness, the role of oral anticoagulants (OAs) remains controversial. OBJECTIVE: To determine the effects of long-term OA therapy, stratified by the intensities of anticoagulation and aspirin therapy, on outcomes in patients with CAD. DATA SOURCES: Studies were identified by MEDLINE, EMBASE, and CURRENT CONTENTS searches (1960-July 1999) and by reviewing reference lists and inquiring with experts and pharmaceutical companies. STUDY SELECTION: Studies were included if they were published between 1960 and July 1999, were randomized, had recruited patients with CAD, who had used OA therapy for at least 3 months. Of 43 articles identified, 30 articles (31 trials) were analyzed. DATA EXTRACTION: Information on type, duration, and method of monitoring OA therapy, as well as rates of death, myocardial infarction (MI), thromboembolic complications, stroke, and bleeding were abstracted by 2 independent observers. DATA SYNTHESIS: With high-intensity (international normalized ratio [INR], 2.8-4.8) OAs vs control (16 trials, 10056 patients), clear reductions in mortality (odds reduction [ORed], 22%; 95% confidence interval [CI], 13%-31%), MIs (ORed, 42%; 95% CI, 34%-48%), and thromboembolic complications including stroke (ORed, 63%; 95% CI, 53-71%) were observed, but were associated with a 6.0-fold (95% CI, 4.4- to 8.2-fold) increase in major bleeding. For moderate OAs (INR, 2-3) vs control (4 trials, 1365 patients) the ORed for death was 18% (95% CI, -6% to 37%); for MI, 52% (95% CI, 37%-64%); and for stroke, 53% (95% CI, 19%-73%), but it increased bleeding by 7.7-fold (95% CI, 3.3- to 18-fold). For moderate- to high-intensity OAs (INR, > or =2) vs aspirin (7 trials, 3457 patients), no reduction in death, MI, or stroke was observed, and it was associated with a 2.4-fold (95% CI, 1.6- to 3.6-fold) increase in major bleeding. For moderate- to high-intensity OAs and aspirin vs aspirin alone (3 trials, 480 patients), the ORed for death, MI, or stroke was 56% (95% CI, 17%-77%) and major bleeding increased by 1.9-fold (0.6- to 6.0-fold). For low-intensity OAs (INR, <2.0) and aspirin vs aspirin alone (3 trials, 8435 patients), no significant reduction in death, MI, or stroke was observed, and major bleeding increased by 1.3-fold (95% CI, 1.0- to 1.8-fold). CONCLUSIONS: Among patients with CAD, high-intensity and moderate-intensity OA are effective in reducing MI and stroke but increase the risk of bleeding. In the presence of aspirin, low-intensity OA does not appear to be superior to aspirin alone, while moderate- to high-intensity OA and aspirin vs aspirin alone appears promising and the bleeding risk is modest, but this requires confirmation from ongoing trials.

Administration, Oral↗