Outbreak of polyarthritis with pyrexia in Western Rajasthan.
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Arthritis↗
Biomedical subjects
S R Mehta
Publications and source records attributed to S R Mehta.
HIV-associated dementia and caudate atrophy.
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AIDS Dementia Complex↗
HIV-associated dementia and caudate atrophy.
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AIDS Dementia Complex↗
Distal spinal muscular atrophy.
Spinal muscular atrophies (SMA) are clinically heterogenous group of motor system disorders characterised by progressive pure lower motor neuron involvement. The distal form of SMA is an extremely rare disorder, which presents in the adults and has a relatively slow progression with almost no effect on the patients' life-span. Differential diagnosis of this syndrome include other forms of neuromuscular disorders with peroneal muscular atrophy like hereditary motor sensory neuropathy (HMSN) and distal myopathies, which need exclusion before confirming this rare entity. We present a young male with this disorder and briefly discuss the theoretical aspects.
Adult↗
Efficacy of hirudin in reducing cardiovascular events in patients with acute coronary syndrome undergoing early percutaneous coronary intervention.
AIMS: Although hirudin is superior to unfractionated heparin for prevention of death, myocardial infarction, or refractory ischaemia in patients with non-ST-elevation acute coronary syndrome, it is not clear whether hirudin is also of benefit in acute coronary syndrome patients undergoing early percutaneous coronary intervention. METHODS AND RESULTS: In the OASIS 2 trial, 10 141 patients with non-ST-elevation acute coronary syndrome were randomized to 72 h of intravenous hirudin or unfractionated heparin. Percutaneous coronary intervention was performed at the discretion of the investigator. One hundred and seventeen patients underwent percutaneous coronary intervention within the first 72 h ("early percutaneous coronary intervention"). In patients undergoing early percutaneous coronary intervention, hirudin compared with unfractionated heparin was associated with a significantly lower incidence of death or myocardial infarction at 96 h (6.4% vs 21.4%, OR 0.30; 95% CI: 0.10-0.88) and 35 days (6.4% vs 22.9%, OR 0.25; 95% CI: 0.07-0.86). In the unfractionated heparin group, death or myocardial infarction was significantly higher at 35 days in patients undergoing early percutaneous coronary intervention compared with those managed conservatively (22.9% vs 7.3%, OR 3.14, P<0.001) but this early percutaneous coronary intervention-related hazard was not observed in hirudin-treated patients (6.4% vs 6.8%, OR 0.94 P=1.0). A time-dependent covariate for percutaneous coronary intervention was not significant in a Cox regression model, suggesting a similar treatment benefit with hirudin before and after percutaneous coronary intervention. After adjustment for percutaneous coronary intervention propensity, the benefits of hirudin remained significant. There were three major bleeds in patients undergoing early percutaneous coronary intervention, all in patients randomized to hirudin. CONCLUSION: In patients with non-ST-elevation acute coronary syndrome undergoing early percutaneous coronary intervention, a direct thrombin inhibitor such as hirudin may be more effective than heparin in reducing the incidence of ischaemic complications.
Acute Disease↗
Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.
BACKGROUND: Despite the use of aspirin, there is still a risk of ischaemic events after percutaneous coronary intervention (PCI). We aimed to find out whether, in addition to aspirin, pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI. METHODS: 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been randomly assigned double-blind treatment with clopidogrel (n=1313) or placebo (n=1345). Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission, and for a median of 10 days overall. After PCI, most patients (>80%) in both groups received open-label thienopyridine for about 4 weeks, after which study drug was restarted for a mean of 8 months. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or urgent target-vessel revascularisation within 30 days of PCI. The main analysis was by intention to treat. FINDINGS: There were no drop-outs. 59 (4.5%) patients in the clopidogrel group had the primary endpoint, compared with 86 (6.4%) in the placebo group (relative risk 0.70 [95% CI 0.50-0.97], p=0.03). Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death, myocardial infarction, or any revascularisation (p=0.03), and of cardiovascular death or myocardial infarction (p=0.047). Overall (including events before and after PCI) there was a 31% reduction cardiovascular death or myocardial infarction (p=0.002). There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group (p=0.001). At follow-up, there was no significant difference in major bleeding between the groups (p=0.64). INTERPRETATION: In patients with acute coronary syndrome receiving aspirin, a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events, compared with placebo.
Aged↗
Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.
BACKGROUND: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. METHODS: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. RESULTS: The first primary outcome--a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke--occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome--the first primary outcome or refractory ischemia--occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86; 95 percent confidence interval, 0.79 to 0.94; P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.2 percent [corrected] vs. 1.8 percent; P=0.13) or hemorrhagic strokes (0.1 percent vs. 0.1 percent). CONCLUSIONS: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel.
Acute Disease↗
Stroke in relation to cardiac procedures in patients with non-ST-elevation acute coronary syndrome: a study involving >18 000 patients.
BACKGROUND: There are few published data on risk factors for stroke in patients with non-ST-elevation acute coronary syndrome (ACS). We investigated prognostic factors for stroke in 2 large cohorts of patients from the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry (8010) and the OASIS-2 trial (10 141). METHODS AND RESULTS: A total of 18 151 patients with non-ST-elevation ACS were enrolled in the OASIS program. Data from these 2 studies were pooled (a test for heterogeneity was nonsignificant, P=0.34). Overall, 238 patients (1.3%) had a stroke over a 6-month follow-up. Those who experienced stroke had a 4-fold increase in 6-month mortality (27.0% versus 6.3%, P<0.001). A Cox multivariate regression analysis identified CABG surgery as the most important predictor of stroke (hazard ratio [HR], 4.6), followed by history of stroke (HR, 2.3), diabetes mellitus (HR, 1.7), older age (HR, 1.6 per 10-year increase), higher heart rate (HR, 1.1 per 10-bpm increase), and on-site catheterization facility (HR, 1.4). There was no significant excess in stroke in patients undergoing percutaneous coronary intervention (P=0.21). Patients who underwent early CABG surgery were at a substantially increased risk compared with those who had later CABG (3.3% versus 1.6%; HR, 2.1; P=0.003) or who had no surgery (3.3% versus 1.1%; HR, 3.95; P=0.0001). CONCLUSIONS: In this large cohort of patients with ACS, stroke was an uncommon but serious event associated with high mortality. The performance of early CABG surgery was a powerful independent predictor of stroke.
Acute Disease↗
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↗
Impact of right ventricular involvement on mortality and morbidity in patients with inferior myocardial infarction.
OBJECTIVES: We sought to evaluate the prognostic impact of right ventricular (RV) myocardial involvement in patients with inferior myocardial infarction (MI). BACKGROUND: There is uncertainty regarding the risk of major complications in patients with inferior MI complicated by RV myocardial involvement. Whether these complications are related to RV myocardial involvement itself or simply to the extent of infarction involving the left ventricle (LV) is also unknown. METHODS: We examined the incidence of death and mechanical and electrical complications in patients with (n = 491) and without (n = 638) RV myocardial involvement and in patients with anterior MI (n = 971) in an analysis from the Collaborative Organization for RheothRx Evaluation (CORE) trial. Left ventricular infarct size was assessed by technetium-99m-sestamibi single-photon emission computed tomography and peak creatine kinase, and LV function was assessed by radionuclide angiography. We also performed a meta-analysis in which we pooled the results of our study with previous smaller studies addressing the same question. RESULTS: Six-month mortality was 7.8% in inferior MI compared with 13.2% in anterior MI. Among patients with inferior MI, serious arrhythmias were significantly more common in patients with RV myocardial involvement who also had a trend toward higher mortality, pump failure and mechanical complications. However, this was not associated with a difference in LV infarct size or function. A meta-analysis of six studies (n = 1,198) confirmed that RV myocardial involvement was associated with an increased risk of death (odds ratio [OR] 3.2, 95% confidence interval [CI] 2.4 to 4.1), shock (OR 3.2, 95% CI 2.4 to 3.5), ventricular tachycardia or fibrillation (OR 2.7, 95% CI 2.1 to 3.5) and atrioventricular block (OR 3.4, 95% CI 2.7 to 4.2). CONCLUSIONS: Patients with inferior MI who also have RV myocardial involvement are at increased risk of death, shock and arrhythmias. This increased risk is related to the presence of RV myocardial involvement itself rather than the extent of LV myocardial damage.
Arrhythmias, Cardiac↗
Carbon monoxide poisoning.
OBJECTIVES: We studied the clinical profile and autopsy findings of carbon monoxide (CO) poisoning encountered at a hospital located at the altitude of 5,000 ft above mean sea level. METHODS: Clinical and postmortem findings in 25 and 15 cases of accidental CO poisoning respectively were evaluated. The diagnosis was made on circumstantial evidences, definite history of "Bukhari" burning and positive Kunkel's test for carboxyhaemoglobin (COHb). Detailed routine investigations including pulse oxymetry, X-ray chest and electrocardiographical monitoring was carried out in all the 25 patients. Oxygen (100%) via an endotracheal tube in all the comatosed patients and by conventional non-rebreathing plastic face masks was the mainstay of treatment. All patients were monitored and followed up for any delayed neurological sequelae. RESULTS: Most of the patients were young adults and the duration of exposure varied between three to eight hours. The initial diagnosis was stroke in three, seizure in one, encephalitis in two and ischaemic heart disease (IHD) in four. Neurological and respiratory signs and symptoms were noted in 19 and 18 of 25 patients respectively. SPO2 measured by pulse oxymetry was normal in all cases. ECG was suggestive of IHD in four patients. No delayed neurological sequelae was noted in any patients. Autopsy revealed deep red discoloration of skin and serous membranes in 80%, pulmonary oedema in 100% and cerebral oedema with widespread multiple pin point haemorrhages mainly in thalamus and globus pallidus in 40%. CONCLUSION: A high level of suspicion and routine history about the kind of indoor heating, specially in cold climate areas during winter will help in early diagnosis and decrease the incidence of misdiagnosis of CO poisoning. Oxygen (100%) or hyperbaric oxygen, if available should be administered without waiting for COHb levels to decrease morbidity and mortality.
Adolescent↗
A fatal case of systemic brucellosis.
A 65 years man presented with fever, drenching sweats, progressive dyspnoea, backache and weight loss. On examination, he had wide pulse pressure, clubbing, retinal hemorrhages, aortic and mitral regurgitation, hepatosplenomegaly, lower spinal tenderness and bilateral basal crepitations. Transthoracic 2D-echocardiography showed a large vegetation on the aortic valve. Antibody titers for brucella were positive. X-ray spine was suggestive of brucella spondylitis. Early surgical intervention was planned and the patient was given combination antibiotic therapy. The course was complicated by renal failure and the patient succumbed while being taken up for surgery.
Aged↗
Venous thromboembolism and cancer.
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Anticoagulants↗
Risk of intracranial haemorrhage with bolus versus infusion thrombolytic therapy: a meta-analysis.
BACKGROUND: Although thrombolytic therapy given by bolus injection seems to be as effective as infusion over 60-90 min, no single trial has been adequately powered to detect clinically important safety differences between the two strategies. We did a meta-analysis to find out whether bolus administration of thrombolytics is associated with an increased frequency of intracranial haemorrhage. METHODS: We identified randomised trials comparing bolus with infusion thrombolytic therapy by a search of electronic databases, reference lists, and conference proceedings. Odds ratios for primary intracranial haemorrhage, non-haemorrhagic stroke, mortality, and reinfarction were calculated for each trial and were combined in a fixed-effects model. FINDINGS: Seven trials, involving a total of 103,972 patients, met our inclusion criteria. Bolus treatment was associated with an increased risk of intracranial haemorrhage compared with infusion (0.8 vs 0.6%; odds ratio 1.25 [95% CI 1.08-1.45]; p=0.003). The increased risk was most striking in trials comparing bolus with infusion administration of the same agent (1.75 [1.32-2.33], p=0.0001), but was also evident in trials comparing a newer-generation bolus agent with standard infusion therapy (1.25 [1.03-1.50]; p=0.02). The rates of non-haemorrhagic stroke (0.94 [0.81-1.09]), 30-day mortality (1.01 [0.97-1.06]), or reinfarction (1.04 [0.97-1.11]) did not differ between the two strategies. INTERPRETATION: The increased risk of bolus thrombolytic treatment seems to be primarily associated with the method of administration rather than properties of the agents. Although the increased risk of intracranial haemorrhage is small, physicians should balance this risk against the putative benefits of easier administration with no difference in mortality or reinfarction.
Fibrinolytic Agents↗
The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease.
BACKGROUND: Other than aspirin, there are few oral antithrombotic treatments with proven efficacy in patients with acute coronary syndrome. In this report, we present the rationale, design and baseline characteristics of the Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events (CURE) trial, which includes a meta-analysis of the effects of thienopyridines in patients with vascular disease. METHODS AND RESULTS: Combined data from randomized trials of thienopyrindines in patients with atherosclerotic disease demonstrated a 29% reduction in vascular events when compared with placebo/control (n=2392) (OR 0.71, 95% CI 0.58-0.86, P=0.0006) and a 10% reduction in vascular events when compared with aspirin (n=22 254) (OR 0.91, 95% Cl 0.84-0.99, P=0.039). Similarly, randomized trials of aspirin plus thienopyridines in patients undergoing intracoronary stenting, demonstrated a marked benefit of aspirin plus ticlopidine in reducing death or myocardial infarction compared with aspirin alone (OR 0.23, 95% CI 0.11-0.49, P=0.0001) or aspirin plus warfarin (OR 0.51, 95% CI 0.33-0.78, P=0.002). Whether these benefits extend to the much larger population of patients with acute coronary syndrome is unknown. CURE is an international, randomized, double-blind trial, in which patients with acute coronary syndrome will be randomized to receive either a bolus dose of clopidogrel (300 mg) followed by 75 mg per day for 3-12 months, or matching placebo. Both groups will receive aspirin. The co-primary efficacy end-points of CURE are: (1) the composite of cardiovascular death, myocardial infarction or stroke; and (2) the composite of cardiovascular death, myocardial infarction, stroke or refractory ischaemia. CURE will recruit approximately 12 500 patients with acute coronary syndrome (from 28 countries) and its power to detect moderate treatment benefits will be in the region of 80-90%, while maintaining an overall type I error (alpha) of 0.05. The baseline characteristics of the study population are consistent with at least a moderate risk group of patients with acute coronary syndrome. CONCLUSIONS: Randomized trials of thienopyridines in patients with vascular disease demonstrate that thienopyridines are effective in reducing vascular events when compared with placebo/control or aspirin, as well as when used in combination with aspirin in patients undergoing intracoronary stent implantation. The CURE trial is a large international study to determine if acute and long-term treatment with the combination of clopidogrel and aspirin is superior to aspirin alone in patients with acute coronary syndrome.
Angina, Unstable↗
Near drowning in cold water.
Drowning and near drowning is a common cause of accidental death all over the world; specially in road traffic accidents over bridges, swimming pool and boat tragedies. Cold water drowning resulting in hypothermia can lead to instant death before actual drowning. Five cases of near drowning (ND) in cold water, who presented with varied clinical picture like coma with decerebrate rigidity and fixed dilated pupils, hypertension with coma and delayed pulmonary oedema (Secondary drowning) are reported. Energetic management with continuous positive airway pressure was very rewarding in all patients with ND except in one who had transient organic psychosis persisting for two weeks followed by minimal cognitive defect in the form of slow mentation, lack of drive and mild irritability (Bender Gestald Test Score of 53). We have tried to analyse some of the clinical features of ND and the sequel associated with it. The management as well as recent developments in the field are also discussed.
Cold Temperature↗
Near drowning in cold water.
Drowning and near drowning is a common cause of accidental death all over the world; specially in road traffic accidents over bridges, swimming pool and boat tragedies. Cold water drowning resulting in hypothermia can lead to instant death before actual drowning. Five cases of near drowning (ND) in cold water, who presented with varied clinical picture like coma with decerebrate rigidity and fixed dilated pupils, hypertension with coma and delayed pulmonary oedema (Secondary drowning) are reported. Energetic management with continuous positive airway pressure was very rewarding in all patients with ND except in one who had transient organic psychosis persisting for two weeks followed by minimal cognitive defect in the form of slow mentation, lack of drive and mild irritability (Bender Gestald Test Score of 53). We have tried to analyse some of the clinical features of ND and the sequel associated with it. The management as well as recent developments in the field are also discussed.
Adult↗
Transient stimulation of the c-Jun-NH2-terminal kinase/activator protein 1 pathway and inhibition of extracellular signal-regulated kinase are early effects in paclitaxel-mediated apoptosis in human B lymphoblasts.
We demonstrate here that paclitaxel exposure to RPMI-1788 B lymphoblasts caused a dose- and time-dependent increase in nuclear factor activator protein 1 (AP-1) DNA binding activity. The basal DNA binding activities of nuclear factors NF-kappaB and Ets were not affected by paclitaxel. Consistent with these biochemical events, paclitaxel stimulated AP-1-dependent chloramphenicol acetyltransferase (CAT) reporter gene transcription in vivo, as directed from a tetradecanoyl phorbol acetate-inducible promoter. AP-1 binding activity of nuclear extracts isolated from paclitaxel treated cells was reduced following immunodepletion with antibodies directed against individual Jun family proteins, whereas anti-cFos, anti-Fra1, and anti-FosB antibodies were not inhibitory. Paclitaxel caused a rapid and transient increase in c-Jun NH2-terminal kinase (JNK) activity, a proposed mediator of stress activation pathways. By contrast, exposure to paclitaxel produced a transient reduction in the extracellular signal-regulated mitogen-activated protein kinase 2 (ERK2) activity, a proposed mediator of growth factor-stimulated proliferation pathways. Transient activation of the c-Jun-NH2-terminal kinase/AP-1 pathway, together with down-regulation of ERK2 activity, may be a key event in the early response of RPMI-1788 B lymphoblasts to paclitaxel exposure.
Antineoplastic Agents, Phytogenic↗