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Biomedical subjects

D Mukherjee

Publications and source records attributed to D Mukherjee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes.

BACKGROUND: Diabetes mellitus is a major risk factor for adverse outcomes after acute coronary syndromes (ACS). Because this disease may be associated with increased platelet aggregation, we investigated whether diabetic patients with ACS derive particular benefit from platelet glycoprotein (GP) IIb/IIIa receptor inhibition. METHODS AND RESULTS: We performed a meta-analysis of the diabetic populations enrolled in the 6 large-scale platelet GP IIb/IIIa inhibitor ACS trials: PRISM, PRISM-PLUS, PARAGON A, PARAGON B, PURSUIT, and GUSTO IV. Among 6458 diabetic patients, platelet GP IIb/IIIa inhibition was associated with a significant mortality reduction at 30 days, from 6.2% to 4.6% (OR 0.74; 95% CI 0.59 to 0.92; P=0.007). Conversely, 23 072 nondiabetic patients had no survival benefit (3.0% versus 3.0%). The interaction between platelet GP IIb/IIIa inhibition and diabetic status was statistically significant (P=0.036). Among 1279 diabetic patients undergoing percutaneous coronary intervention (PCI) during index hospitalization, the use of these agents was associated with a mortality reduction at 30 days from 4.0% to 1.2% (OR 0.30; 95% CI 0.14 to 0.69; P=0.002). CONCLUSIONS: This meta-analysis, including the entire large-scale trial experience of intravenous platelet GP IIb/IIIa inhibitors for the medical management of non-ST-segment-elevation ACS, shows that these agents may significantly reduce mortality at 30 days in diabetic patients. Although not based on a randomized assessment, the survival benefit appears to be of greater magnitude in patients undergoing PCI. Therefore, the use of platelet GP IIb/IIIa inhibitors should be strongly considered in diabetic patients with ACS.

Diabetes Complications↗
PubMed2001

Clinical application of procedural platelet monitoring during percutaneous coronary intervention among patients at increased bleeding risk.

The goal of platelet function testing in the catheterization laboratory is to provide information about the platelet contributions to the risk of thrombotic or hemorrhagic events and optimization of anti-platelet therapy for percutaneous interventions. We present several illustrative cases in which platelet monitoring with the Rapid Platelet Function Assay (RPFA, Accumetrics) was used to guide dosing of a glycoprotein (GP) IIb/IIIa inhibitor for coronary and peripheral intervention among patients at increased bleeding risk.

Abciximab↗
PubMed2001

Fas-induced apoptosis in mouse hepatocytes is dependent on C/EBPbeta.

Apoptotic cell death in the liver in response to activation of the Fas pathway has been implicated in human disease states as well as liver remodeling and tissue repair. C/EBPbeta, a member of the CCAAT enhancer binding protein family of bZIP transcription factors has been linked to both growth response and apoptotic targets in the liver, and, therefore, is a likely candidate for the regulation of apoptotic liver injury. We investigated differences in apoptotic cell death in the livers of C/EBPbeta-null mice using the Jo-2 agonistic anti-Fas antibody. Apoptotic injury was dramatically reduced in C/EBPbeta -/- livers as shown by a nearly 20-fold reduction in apoptotic hepatocytes 6 hours post-Jo-2 treatment in C/EBPbeta -/- hepatocytes compared with controls (P < .04) and reduced activation of caspase 3. Bid cleavage occurred in Jo-2 treated C/EBPbeta -/- livers indicating a block of Fas-induced injury distal to the death-inducing signaling complex. The level of the antiapoptotic protein bcl-x(L) was increased greater than tenfold in the mutant animals (P < .04), which can, at least in part, account for the protection from Fas-mediated apoptosis. In contrast, bcl-x(L) mRNA levels were unchanged. These observations link C/EBPbeta to Fas-induced hepatocyte apoptosis through a mechanism that likely involves translational or posttranslational regulation of bcl-x(L).

Animals↗
PubMed2001

Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization.

BACKGROUND: Newer methods of coronary revascularization are being investigated in patients who are not candidates for coronary artery bypass grafting or percutaneous intervention. Our objective was to determine the proportion of patients eligible for newer methods of revascularization and determine their 1-year clinical outcome. METHODS: Five hundred consecutive charts and angiograms from patients undergoing diagnostic angiography for coronary artery disease from January to May of 1998 were reviewed to assess the suitability for revascularization. Patients ineligible for conventional revascularization were followed up for 1 year. RESULTS: Fifty-nine patients of the 500 studied were identified who had refractory ischemia but were not candidates for traditional revascularization. The 59 patients ineligible for traditional methods of revascularization had a rehospitalization rate of 128% (76 total hospitalizations), a 25.5% rate of myocardial infarction (15 of 59), and a mortality rate of 16.9% (10 of 59). CONCLUSIONS: The prognosis of many patients eligible for newer methods of revascularization on maximal medical therapy is poor.

Aged↗
PubMed2001

Extra-anatomic arterial reconstruction with ligation of common iliac arteries and embolization of the aneurysm for the treatment of abdominal aortic aneurysms in high-risk patients.

PURPOSE: The mortality of an unrepaired abdominal aortic aneurysm (AAA) generally exceeds the mortality associated with surgical repair. However, as our longevity increases, more frequently we see patients whose risk of surgical repair approximates the risk of rupture. We present an extra-anatomic bypass graft with complete aneurysm exclusion by iliac ligation and coil embolization of the aneurysm as an alternative for these high-risk patients. METHODS: An extra-anatomic bypass graft, followed by bilateral iliac artery ligation (retroperitoneal approach) and complete coil embolization of the AAA, was performed in eight patients (mean age, 77 years) found to be at prohibitive operative risk because of multiple comorbidities (American Society of Anesthesiologists class IV). Most patients (5 of 8) were symptomatic on presentation with a mean AAA diameter of 7 cm (range, 6.7-9.5 cm). We repair approximately 30 infrarenal aneurysms per year electively at our institution. RESULTS: All patients tolerated the surgical procedures. The average hospital stay was 8 days. All but two aneurysms demonstrated complete thrombosis by 48 hours. After 48 months there was no incidence of graft thrombosis, peripheral ischemia, visceral ischemia or thrombus infection. There was one perioperative death from aspiration pneumonia. Seventy-five percent (6 of 8) of patients have survived at least 1 year without surgical complications. No patient has had a ruptured aneurysm. CONCLUSION: Combining an extra-anatomic bypass graft and complete exclusion of the AAA by ligation of the common iliac arteries and a coil embolization is an effective, less invasive treatment option for patients with AAA and prohibitive operative risk. We emphasize the need for complete embolization documented by decreased aneurysm size.

Aged↗
PubMed2001

Hearing aids versus ventilation tubes in persistent otitis media with effusion: a survey of clinical practice.

A postal survey was carried out to determine the current clinical practice amongst consultant otolaryngologists in the UK, regarding re-insertion of ventilation tubes or recommendation of hearing aids in cases of recurrence of otitis media with effusion (OME) after ventilation tube extrusion. Amongst the 319 respondents, 15 (4.70 per cent) routinely, 146 (45.77 per cent) sometimes, and 158 (49.53 per cent) either never, or very rarely, recommend hearing aids. Hearing aids and ventilation tubes were both suggested to be equally good options by some consultants but they preferred surgery for a number of reasons. There were inconsistencies in practice and some of the reasons for re-inserting ventilation tubes are not evidence-based. A hearing aid is a non-invasive option and this survey shows a need for a randomized control trial of hearing aids and ventilation tubes in the management of persistent and recurrent OME.

Child↗
PubMed2001

Update on peripheral vascular diseases: from smoking cessation to stenting.

Newer pharmacologic agents including gene therapy hold promise for the treatment of atherosclerotic peripheral vascular disease (PVD), as do advances in endovascular revascularization techniques. Nonetheless, the two most important treatments remain the same: stopping smoking and starting a walking program.

Arteriosclerosis↗
PubMed2001

Percutaneous intervention for symptomatic vertebral artery stenosis using coronary stents.

BACKGROUND: There is very limited experience with percutaneous treatment of symptomatic vertebral artery disease. Angioplasty and stenting for vertebral artery stenosis are still evolving and have generally been performed for asymptomatic disease. We performed vertebral artery stenting in 12 patients with vertebrobasilar transient ischemic attacks and present our short- and intermediate-term results. METHODS: A total of 12 lesions affecting the vertebral artery were treated by coronary stent placement. The mean age was 72 +/- 8 years and 83% were males (10 males, 2 females). Baseline characteristics included hypertension (11/12); hypercholesterolemia (8/12); coronary artery disease (8/12); and diabetes (5/12). Mean lesion length was 8.6 +/- 2.7 mm, mean calipered stenosis was 78 +/- 8%, and mean arterial diameter was 4.1 +/- 0.3 mm. All patients were symptomatic, fulfilling our criteria for vertebral artery angioplasty. All patients were followed for at least 6 months after treatment. RESULTS: All 12 lesions were successfully stented, with a mean residual stenosis of 11 +/- 6%. Clinical follow-up showed resolution or improvement of symptoms in all patients. One patient had symptomatic restenosis seven months after the initial procedure requiring repeat angioplasty. CONCLUSIONS: Stent placement for symptomatic stenosis involving the vertebral artery is safe and effective for alleviating symptoms of vertebrobasilar ischemia. Coronary stents appear to be well suited to treat atherosclerotic lesions of the vertebral artery.

Aged↗
PubMed2001

Self-expanding stents for carotid interventions: comparison of nitinol versus stainless-steel stents.

BACKGROUND: Angioplasty and stenting are becoming increasingly accepted techniques for the treatment of carotid stenosis. However, the optimal stent for carotid intervention is not known. METHODS: We compared the short- and intermediate-term results of carotid stenting using either nitinol or stainless-steel self-expanding stents in 178 high surgical risk patients undergoing carotid stenting at our institution. Of these 178 patients, eighty-nine received stainless-steel stents and 89 received nitinol stents. The groups were similar with respect to age, gender, diabetes, hypertension, left ventricular function, and symptom status. There were more patients with contralateral carotid occlusion in the nitinol stent group. Independent neurological evaluation was performed in all patients pre- and post-carotid stenting. RESULTS: At 6 months, there was a similar incidence of stroke (3.3% versus 2.2%) in the stainless-steel group and nitinol stent group, respectively. There was higher 6-month mortality noted in the stainless-steel stent group, but there were no neurological deaths in either group. CONCLUSIONS: In a single-center patient cohort with similar baseline characteristics, patients receiving nitinol stents and stainless-steel stents had similar neurological outcomes.

Aged↗
PubMed2001

Dual antiplatelet therapy with clopidogrel and aspirin after carotid artery stenting.

BACKGROUND: Carotid artery stenting is being used as an alternative to carotid endarterectomy, both within the context of clinical trials and in non-surgical candidates. Though stenting is known to activate platelets, the role of antithrombotic therapy in carotid stenting has not been fully characterized. METHODS AND RESULTS: Consecutive patients (n = 162) were followed in a single-center carotid stent registry. The cumulative rate of 30-day death, stroke, transient ischemic attack and myocardial infarction in those patients receiving a thienopyridine was determined, as were rates of stent thrombosis and intracranial hemorrhage. The mean age of the patients was 70.3 years and there was an extremely high prevalence of cardiovascular comorbidities, including 40% with unstable angina. The carotid lesion was symptomatic in 59% of patients. The average pre-treatment stenosis was 83%. The cumulative 30-day rate of death, stroke, transient ischemic attack and myocardial infarction was 5.6%. Specifically, in the patients who received ticlopidine (n = 23), the rate was 13%, versus 4.3% in the patients who received clopidogrel (n = 139) (p = 0.01). In this series, there were no cases of stent thrombosis and 1 intracranial hemorrhage. CONCLUSION: Dual antiplatelet therapy with clopidogrel plus aspirin in patients receiving carotid artery stents is associated with a low rate of ischemic events. Furthermore, clopidogrel appears superior to ticlopidine. Thus, our findings lend support to the dual antiplatelet strategy of clopidogrel plus aspirin for patients undergoing carotid artery stenting.

Aged↗
PubMed2000

Identification of maturation-inducing steroid in a freshwater perch Anabas testudineus and differential responses of intact follicles and denuded oocytes to cyclic AMP in oocyte maturation.

Postvitellogenic follicles of freshwater perch Anabas testudineus incubated with [(3)H]pregnenolone as exogenous precursor produced several metabolites, including 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (DHP) and 5 beta-pregnane-3 alpha, 17 alpha,20 beta-triol (5 beta-3 alpha,17 alpha,20 beta-P). These were identified by chromatography, microchemical reactions, and crystallization to constant specific activity. Following stimulation with fish (perch) pituitary extract (FPE) there was significant high production of DHP and 5 beta-3 alpha,17 alpha,20 beta-P, concomitant with a high percentage of germinal vesicle breakdown (GVBD). Inhibitor of steroidogenesis (trilostane) and inhibitors of protein synthesis (cycloheximide and actinomycin-D) completely blocked FPE-induced pregnenolone metabolism and oocyte maturation. The effectiveness of various C(21) steroids in inducing GVBD was examined. Results indicate that DHP was the most potent inducer of GVBD than other structurally related C(21) steroids. In intact follicles, FPE-stimulated production of DHP was shown to be mediated through the adenylate cyclase-cAMP pathway. Addition of IBMX or forskolin, which increases the endogenous cAMP level, as well as directly supplementing dbcAMP to the incubation medium, had no inhibitory effect on DHP-induced GVBD in the intact follicles. But all these agents were shown to inhibit GVBD in fully denuded oocytes. This study provides evidence that DHP, produced by postvitellogenic follicles through the adenylate cyclase-cAMP pathway, is the maturation-inducing steroid in freshwater perch and that the role played by cAMP in the induction of GVBD in intact follicles is different from that in the denuded oocytes. J. Exp. Zool. 287:294-303, 2000.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Achieving tissue-level perfusion in the setting of acute myocardial infarction.

Treatment for ST-elevation myocardial infarction (MI) has advanced rapidly in the last few years with improvements in early fibrinolytic therapy, primary percutaneous revascularization, and use of potent platelet glycoprotein IIb/IIIa inhibitors. It is now obvious that establishing epicardial patency after myocardial infarction is not synonymous with tissue-level perfusion. Techniques and therapies are now available that measure true tissue-level perfusion and that may improve tissue-level perfusion after myocardial infarction.

Abciximab↗
PubMed2000

Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration.

OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.

Animals↗