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A Prasad

Publications and source records attributed to A Prasad.

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

N-acetylcysteine improves coronary and peripheral vascular function.

OBJECTIVES: We investigated whether N-acetylcysteine (NAC), a reduced thiol that modulates redox state and forms adducts of nitric oxide (NO), improves endothelium-dependent vasomotion. BACKGROUND: Coronary atherosclerosis is associated with endothelial dysfunction and reduced NO activity. METHODS: In 16 patients undergoing cardiac catheterization, seven with and nine without atherosclerosis, we assessed endothelium-dependent vasodilation with acetylcholine (ACH) and endothelium-independent vasodilation with nitroglycerin (NTG) and sodium nitroprusside (SNP) before and after intracoronary NAC. In 14 patients femoral vascular responses to ACH, NTG and SNP were measured before and after NAC. RESULTS: Intraarterial NAC did not change resting coronary or peripheral vascular tone. N-acetylcysteine potentiated ACH-mediated coronary vasodilation; coronary blood flow was 36 +/- 11% higher (p < 0.02), and epicardial diameter changed from -1.2 +/- 2% constriction to 4.7 +/- 2% dilation after NAC (p = 0.03). Acetylcholine-mediated femoral vasodilation was similarly potentiated by NAC (p = 0.001). Augmentation of the ACH response was similar in patients with or without atherosclerosis. N-acetylcysteine did not affect NTG-mediated vasodilation in either the femoral or coronary circulations and did not alter SNP responses in the femoral circulation. In contrast, coronary vasodilation with SNP was significantly greater after NAC (p < 0.05). CONCLUSIONS: Thiol supplementation with NAC improves human coronary and peripheral endothelium-dependent vasodilation. Nitroglycerin responses are not enhanced, but SNP-mediated responses are potentiated only in the coronary circulation. These NO-enhancing effects of thiols reflect the importance of the redox state in the control of vascular function and may be of therapeutic benefit in treating acute and chronic manifestations of atherosclerosis.

Acetylcysteine↗
PubMed2001

Anti-ischemic effects of angiotensin- converting enzyme inhibition in hypertension.

OBJECTIVES: We investigated whether augmentation of bradykinin (BK) bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated with reduced exercise-induced myocardial ischemia in hypertension. BACKGROUND: Bradykinin responses are depressed in hypertension, and endothelial dysfunction contributes to myocardial ischemia by promoting abnormal coronary vasomotion during stress. METHODS: Fourteen hypertensive (HT) and 17 normotensive (NT), mildly symptomatic patients with coronary artery disease (CAD) and ST-segment depression during exercise were studied before and after seven days of oral enalapril (EN), which was titrated from 2.5 to 20 mg daily. Patients underwent two treadmill exercise tests and determination of forearm vasodilator response to BK. RESULTS: Despite receiving a lower dose of EN (7.8 vs. 14.8 mg, p < 0.001), NT patients had a significant reduction in blood pressure compared to HT patients. Compared to pre-EN, the ischemic threshold, defined as the rate-pressure product at the onset of 1-mm ST depression (p = 0.045), the duration of exercise to 1-mm ST depression (180 +/- 54 s, p = 0.007) and the maximum exercise duration (94 +/- 18 s, p < 0.001) were greater after EN in HT patients, but not in NT subjects (all p > or = 0.3). Patients with a greater drop in blood pressure experienced no improvement in exercise-induced ischemia. Forearm blood flow responses to BK were improved with EN in all patients to a similar extent. Moreover, no correlation was observed between the basal response to BK or the magnitude of its improvement with EN and with either the dose of EN or the improvement in exercise ischemic threshold. CONCLUSIONS: Exercise-induced myocardial ischemia is ameliorated in HT patients with CAD by ACE inhibition.

Aged↗
PubMed2001

Angiotensin type 1 receptor antagonism reverses abnormal coronary vasomotion in atherosclerosis.

OBJECTIVES: This study was performed to determine whether angiotensin type 1 (AT1) receptor inhibition improves abnormal coronary vasomotion and endothelial dysfunction in patients with atherosclerosis or its risk factors. BACKGROUND: Endothelial dysfunction, an early feature of atherosclerosis, contributes to abnormal vasomotion during stress. Angiotensin II may contribute to endothelial dysfunction in atherosclerosis. METHODS: In 25 patients, mean age 59 +/- 2 years, with atherosclerosis or its risk factors, we measured coronary vasomotion during flow-mediated dilation (FMD) in response to adenosine, cold pressor test (CPT) and exercise before and after AT1 receptor blockade with intracoronary losartan (5 mg). RESULTS: Losartan did not alter resting coronary vascular tone, but epicardial FMD improved from 5.6 +/- 1.5% to 8.9 +/- 1.8% (p = 0.02). Abnormal epicardial vasomotion during CPT and exercise also improved with losartan from -1.7 +/- 0.8% to 1.5 +/- 0.1% (p = 0.02) and -0.6 +/- 0.9% to 3.4 +/- 1.2% (p = 0.009), respectively. Improvement in epicardial vasomotion was most prominent in segments with baseline endothelial dysfunction evidenced as constriction during stress. Microvascular dilation during adenosine, an endothelium-independent response, was unchanged with losartan. CONCLUSIONS: Inhibition of the coronary vascular AT1 receptors in patients with atherosclerosis improves epicardial vasomotion during stress, probably by improving endothelial dysfunction. Whether AT1 receptor blockade will provide long-term therapeutic benefits in atherosclerosis needs further investigation.

Angiotensin Receptor Antagonists↗
PubMed2001

Ca2+ signaling in the transformation of promastigotes to axenic amastigotes of Leishmania donovani.

The present study is an attempt to look into the role of Ca2+ in signaling the transformation of promastigotes to axenic amastigotes. An estimation of intracellular free calcium concentration at 6 h intervals during the conversion of promastigotes to axenic amastigotes (72 h) revealed a 10 fold increase in [Ca2+]i at the initial 6-12 h during the conversion. This was followed by declining levels till 60 h and the concentration thereafter remained constant. Axenic amastigotes (72 h) had a 5 fold higher [Ca+]i as compared to the promastigotes. A 30-40% decrease in [Ca2+]i after pretreatment of cells with dentrolene and a gradual rise of intracellular Ca2+ in [Ca2+] free medium indicates the role of intracellular calcium pools in the elevation of [Ca2+]i. A sudden increase in [Ca2+]i on addition of NH4Cl (20 mM) in the cells grown in Ca2+ free medium indicates the presence of acidocalcisomes, as intracellular Ca2+ storing pool, in L. donovani. To study the role of Ca2+ influx from the external medium in the morphogenetic transformation and in the elevation of [Ca2+]i a 45Ca2+ uptake study was performed. Maximum uptake of 45Ca2+ was observed in the initial 24 h of transformation and maximum Ca2+ ATPase activity was also observed between 24-42 h. So the presence of low Ca2+ in the cytosol, existence of intracellular Ca2+ pools and presence of mechanisms to maintain the Ca2+ homeostasis in the cells suggests that Ca2+ can be an appropriate candidate for a second messenger during the morphogenetic transformation of L. donovani.

Ammonium Chloride↗
PubMed2001

Tuberculous biliary strictures: uncommon cause of obstructive jaundice.

Tuberculous biliary stricture is a very rare cause of obstructive jaundice. A case of a man who had had pulmonary tuberculosis 20 years ago is reported. He now presented with obstructive jaundice due to multiple strictures just below the confluence of the hepatic ducts and in the right hepatic duct. At surgery these turned out to be tuberculous in origin. There was also tuberculous involvement of the gall bladder and cystic duct. The commonest differential diagnosis in such cases is cholangiocarcinoma (as in the present case). Imaging helps in defining the extent of bile duct obstruction. Suspicion of the disease and establishing a tissue diagnosis is very important in treating this potentially curable condition, especially with the worldwide resurgence of tuberculosis.

Aged↗
PubMed2001

Endoscopic retrograde cholangiopancreatography in the management of pancreaticobiliary disorders in children.

BACKGROUND AND AIM: The role of endoscopic retrograde cholangiopancreatography (ERCP) is not yet fully established in children. The purpose of this study was to assess the use of ERCP in the diagnosis and management of various pancreaticobiliary disorders in children. METHODS: Eighty-four ERCPs were performed over 5.5 years in 72 children with suspected pancreaticobiliary tract disorders with an adult-type duodenoscope. In all cases, indications, procedure time, ERCP findings, complications, patients course and therapeutic intervention (if any) were recorded. RESULTS: The mean (+/- SD) age of these children was 8.8 +/- 3.3 years. Successful cannulation was possible in 70 (97%) cases. Of the 44 cases with suspected biliary tract disease, 14 had a choledochal cyst, 13 had portal biliopathy, two each had CBD stones, primary sclerosing cholangitis and a bile leak, one had biliary ascariasis, eight had a normal cholangiogram, and CBD cannulation failed in two. Eight of the 28 children with suspected pancreatic disorders had chronic pancreatitis, five had pancreatic duct disruption, three had pancreas divisum and the rest had a normal pancreatogram (including all eight children with unexplained abdominal pain). Therapeutic ERCP was performed in 22 children, endoscopic nasobiliary or a nasocystic drain was placed in 16, biliary stenting was conducted in two, pancreatic duct stenting was conducted in three, and minor papilla dilation was conducted in one child. Six children had mild procedure-related complications. CONCLUSION: Endoscopic retrograde cholangiopancreatography is very useful in the treatment of cholangitis, bile leak, pseudocyst and pancreatic fistulae in children. However, its role in unexplained abdominal pain is doubtful.

Abdominal Pain↗
PubMed2001

Propofol and midazolam in the treatment of refractory status epilepticus.

PURPOSE: To explore outcome differences between propofol and midazolam (MDL) therapy for refractory status epilepticus (RSE). METHODS: Retrospective chart review of consecutive patients treated for RSE between 1995 and 1999. RESULTS: We found 14 patients treated primarily with propofol and six with MDL. Propofol and MDL therapy achieved 64 and 67% complete clinical seizure suppression, and 78 and 67% electrographic seizure suppression, respectively. Overall mortality, although not statistically significant, was higher with propofol (57%) than with MDL (17%) (p = 0.16). Subgroup mortality data in propofol and MDL patients based on APACHE II (Acute Physiology and Chronic Health Evaluation) score did not show statistically significant differences except for propofol-treated patients with APACHE II score > or = 20, who had a higher mortality (p = 0.05). Reclassifying the one patient treated with both agents to the MDL group eliminated this statistically significant difference (p = 0.22). CONCLUSIONS: In our small sample of RSE patients, propofol and MDL did not differ in clinical and electrographic seizure control. Seizure control and overall survival rates, with the goal of electrographic seizure elimination or burst suppression rather than latter alone, were similar to previous reports. In RSE patients with APACHE II score > or = 20, survival with MDL may be better than with propofol. A large multicenter, prospective, randomized comparison is needed to clarify these data. If comparable efficacy of these agents in seizure control is borne out, tolerance with regard to hemodynamic compromise, complications, and mortality may dictate the choice of RSE agents.

APACHE↗
PubMed2001

Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis.

BACKGROUND: Inflammation is a central feature of coronary artery disease (CAD) that is characterized by increased expression of cellular adhesion molecules with the exception of L-selectin. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD. The renin-angiotensin system (RAS) is implicated in atherogenesis and up-regulates these molecules. OBJECTIVES: The aim of this study was to investigate the effect of angiotensin type 1 (AT1) receptor antagonism on serum and leukocyte adhesion molecule expression in patients with CAD. Blood samples were collected from 31 patients before and after 8 weeks of treatment with losartan (44 +/- 2 mg/d, mean +/- SE), an AT1 receptor antagonist. We measured serum intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule, and C-reactive protein (CRP). By flow cytometry, we also measured the expression of leukocyte CD11a, CD11b, CD11c, CD18, CD31, CD49d, and CD62L (L-selectin) in 13 patients. RESULTS: Treatment with losartan decreased systolic blood pressure (141 +/- 3 vs 135 +/- 4 mm Hg, P =.04) and increased plasma renin activity (1.2 +/- 0.4 vs 2.7 +/- 0.5 ng/mL/h, P =.001). There was a significant increase in L-selectin expression on monocytes (86 +/- 6 vs 118 +/- 10 MESF units, P =.007), lymphocytes (52 +/- 10 vs 79 +/- 8, P =.01), and granulocytes (124 +/- 7 vs 156 +/- 18, P =.056). However, there were no changes in the other leukocyte and serum adhesion molecules or CRP. CONCLUSIONS: These findings suggest that AT1 receptor antagonism selectively modulates L-selectin expression on leukocytes and that endogenous stimulation of AT1 receptors by the RAS contributes to the activation of leukocytes and decreased expression of L-selectin in CAD.

Angiotensin Receptor Antagonists↗
PubMed2001

Cholecystogastric fistula: laparoscopic repair.

We describe a patient with a cholecystogastric fistula treated by the laparoscopic approach. The use of intracorporeal suturing allows laparoscopic management of cholecystogastric fistulae without the need for an endoscopic transecting stapler.

Adult↗
PubMed2001

Bronchoconstriction following nebulised colistin in cystic fibrosis.

Nebulised colistin is regularly used as antipseudomonal therapy in children with cystic fibrosis. We assessed bronchoconstriction in response to nebulised colistin in 58 children. Nebulised colistin significantly reduced FEV(1), MEF(25%), and SaO(2) for 15 minutes. In 20 children the reduction was greater than 10% from baseline FEV(1), and was still at that level in five at 30 minutes. Subjective assessment, baseline FEV(1), and serum IgE were unable to identify susceptible children. It is recommended that children receiving colistin should be carefully assessed for bronchoconstriction.

Administration, Inhalation↗
PubMed2001

Neurocysticercal serodiagnosis--updated.

For diagnosis of neurocysticercosis the gold standard would be a stereotactic biopsy and histological confirmation which are not universally available or acceptable to patients, hence the necessity of immunodiagnosis. The authors have narrated beautifully the serodiagnostic aspects of neurocysticercosis in its updated form and have discussed the subject with proper references.

Antigens, Helminth↗
PubMed2000

Host response to cytomegalovirus infection as a determinant of susceptibility to coronary artery disease: sex-based differences in inflammation and type of immune response.

BACKGROUND: Positive and negative associations between cytomegalovirus (CMV) infection and coronary artery disease (CAD) have been reported. We postulated that the susceptibility to CMV-induced CAD might relate to patterns of inflammatory and immune responses to CMV infection and that sex might have an effect on these responses. METHODS AND RESULTS: In 151 men and 87 women being evaluated for CAD, blood samples were tested for humoral (Ab+) and cellular (Tc+) responses to CMV and for C-reactive protein (CRP). In men, an elevated CRP level was a significant determinant of CAD even after adjustment for CAD risk factors (OR, 3.1; 95% CI, 1.21 to 7. 97). CMV seropositivity was associated with elevated CRP levels on multivariate analysis (P:=0.006). In contrast, in women, CMV seropositivity was independently predictive of CAD (OR, 41.8; 95% CI, 4.12 to 423.74). CRP level in women with CAD was >25% higher than those without CAD, but the difference did not reach statistical significance. Importantly, compared with CMV Ab-/Tc- women, CAD prevalence was higher in Ab+/Tc- and Ab+/Tc+ (13% versus 68% and 64%, both P:<0.005) but not in Ab-/Tc+ women (25%). There were no differences in age, smoking, diabetes, hypertension, and hypercholesterolemia among women with different types of immune responses to CMV infection. CONCLUSIONS: The mechanisms by which CMV predisposes to CAD in men and women may be different. In men, CMV appears to contribute to CAD risk, insofar as it predisposes to inflammation. In women, other mechanisms, possibly related to the type of immune response generated by the host, appear to be responsible for the proatherogenic effects of CMV.

Adult↗
PubMed2000

Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans.

OBJECTIVES: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone. METHODS: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 microg/min) and BK (62.5 ng/min and 4 microg/min), and endothelium-independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin-converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS: There was progressive impairment in ACH-mediated microvascular dilation with increasing numbers of risk factors (p = 0.025, analysis of variance). By contrast, BK- and sodium nitroprusside-mediated microvascular dilation was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or dilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constricted with pacing. Finally, epicardial BK responses were depressed in patients with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS: Endothelial dysfunction in atherosclerosis appears to be receptor-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteries during physiologic stress is better represented by BK and not by ACH responses. Bradykinin activity and, hence, physiologic coronary vasomotion appears to be influenced by serum ACE levels and the ACE insertion/deletion genotype.

Acetylcholine↗
PubMed2000

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity.

OBJECTIVES: We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function. BACKGROUND: The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene. METHODS: In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-NG monomethyl arginine. RESULTS: Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 +/- 26% vs. 121 +/- 11%, p = 0.003, and diameter increase 21.9 +/- 2% vs. 17 +/- 1%, p = 0.03, ACE II vs. DD, respectively). L-NG monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow -10 +/- 4% vs. 11 +/- 5%, p = 0.003, ACE DD vs. II and diameter constriction -6.3 +/- 1.2% vs. -1.9 +/- 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH. CONCLUSIONS: Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.

Acetylcholine↗
PubMed2000

Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition.

BACKGROUND: The aim of this study was to examine whether angiotensin-converting enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to the ACE insertion-deletion (I/D) polymorphism. METHODS AND RESULTS: In 56 patients with atherosclerosis or its risk factors, we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and those with ACE DD or ID genotypes (P=0.002) but not those homozygous for the I allele had the greatest improvement by multivariate analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted (endothelial dysfunction): from -10.1+/-1% to -1.4+/-2% (P<0.001) after enalaprilat. No augmentation was observed in segments that dilated (normal endothelial dysfunction) with acetylcholine. Patients with the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater improvement. CONCLUSIONS: Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of the D allele.

Acetylcholine↗
PubMed2000

Embryonic striatal neurons from niemann-pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness.

Niemann-Pick type C (NP-C) disease is a progressive and fatal neuropathological disorder previously characterized by abnormal cholesterol metabolism in peripheral tissues. Although a defective gene has been identified in both humans and the npc(nih) mouse model of NP-C disease, how this leads to abnormal neuronal function is unclear. Here we show that whereas embryonic striatal neurons from npc(nih) mice can take up low density lipoprotein-derived cholesterol, its subsequent hydrolysis and esterification are significantly reduced. Given the importance of cholesterol to a variety of signal transduction mechanisms, we assessed the effect of this abnormality on the ability of these neurons to respond to brain-derived neurotrophic factor (BDNF). In contrast to its effects on wild type neurons, BDNF failed to induce autophosphorylation of the TrkB receptor and to increase neurite outgrowth in npc(nih) neurons, despite expression of TrkB on the cell surface. The results suggest that abnormal cholesterol metabolism occurs in neurons in the brain during NP-C disease, even at embryonic stages of development prior to the onset of phenotypic symptoms. Moreover, this defect is associated with a lack of TrkB function and BDNF responsiveness, which may contribute to the loss of neuronal function observed in NP-C disease.

Animals↗