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S K Sharma

Publications and source records attributed to S K Sharma.

At least 199 records · Page 11Linked to original sources

Incidence and mechanism of creatine kinase-MB enzyme elevation after coronary intervention with different devices.

The present study was conducted to evaluate the incidence of CK-MB elevation and to identify the possible mechanisms of CK-MB release after various coronary interventional devices. We prospectively studied 1,675 consecutive patients following various coronary interventions for CK-MB elevation, from January 1997 to February 1998 and followed them for in-hospital events. CK-MB elevation was detected in 313 patients (18.7%); with 1-3 x normal in 12.8%, 3-5 x normal in 3.5%, and >5 x normal in 2.4%. CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after balloon angioplasty; P < 0.01). Among the newer nonballoon devices, rotational atherectomy alone had a lower CK-MB elevation compared to stent-alone group (16.0% vs. 20.5%; P = 0.07). On univariate analysis, due to selective use of abciximab in high-risk coronary interventions, there was higher incidence of CK-MB elevation with abciximab (24.5% vs. 15.0% without abciximab; P < 0.01). Some kind of procedural complication was observed in 49% of the CK-MB elevation group, with side-branch closure being the most frequent (22.7%). In conclusion, CK-MB elevation is common after successful coronary interventions and is higher after nonballoon devices. Cathet. Cardiovasc. Intervent. 48:123-129, 1999.

Abciximab↗

Biochemical and immunological changes on oral glutamate feeding in male albino rats.

High altitude stress leads to lipid peroxidation and free radical formation which results in cell membrane damage in organs and tissues, and associated mountain diseases. This paper discusses the changes in biochemical parameters and antibody response on feeding glutamate to male albino Sprague Dawley rats under hypoxic stress. Exposure of rats to simulated hypoxia at 7576 m, for 6 h daily for 5 consecutive days, in an animal decompression chamber at 32 +/- 2 degrees C resulted in an increase in plasma malondialdehyde level with a concomitant decrease in blood glutathione (reduced) level. Supplementation of glutamate orally at an optimal dose (27 mg/kg body weight) in male albino rats under hypoxia enhanced glutathione level and decreased malondialdehyde concentration significantly. Glutamate feeding improved total plasma protein and glucose levels under hypoxia. The activities of serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) and the urea level remained elevated on glutamate supplementation under hypoxia. Glutamate supplementation increased the humoral response against sheep red blood cells (antibody titre). These results indicate a possible utility of glutamate in the amelioration of hypoxia-induced oxidative stress.

Administration, Oral↗

Effects of platelet glycoprotein IIb/IIIa inhibition with abciximab on thrombin generation and activity during percutaneous coronary intervention.

BACKGROUND: Antagonists of the platelet glycoprotein IIb/IIIa decrease acute ischemic complications after percutaneous coronary interventions (PCI). Abciximab (c7E3 Fab, ReoPro) has been reported to decrease thrombin generation in vitro. We investigated in vivo the effect of abciximab therapy on thrombin generation, thrombin activity, and the activated clotting time (ACT) during PCI. METHODS: We studied 32 consecutive patients who underwent PCI for unstable coronary syndromes. Group I (n = 11) was treated with heparin plus aspirin, and group II (n = 21) was treated with heparin plus aspirin plus standard-dose abciximab, administered 5 minutes after the initial heparin bolus. Patients received a standardized heparin bolus at time 0, and arterial blood specimens for prothrombin fragment F1.2, fibrinopeptide A (FPA), and ACT were obtained from the guiding catheter at 5 minutes, 10 minutes (ACT only), 20 minutes, and at the end of the PCI. Standard-dose abciximab was administered in group II only. Each patient served as his or her own control, and the changes against the baseline were compared between the 2 groups. RESULTS: There were no significant differences between the 2 groups regarding baseline characteristics, hematocrit, and platelet count. Group I patients had higher ACT and lower F1.2 and FPA compared with group II at baseline. Subsequent measurements demonstrated a gradual decrease in FPA and F1.2 in group II; the end of procedure versus baseline changes that occurred in F1.2 were significantly different compared with group I (decrease of 0.59 +/- 0.22 nmol/L in group II vs increase of 0.22 +/- 0.3 nmol/L in group I, P =.04), and a trend in the same direction was evident for FPA changes (decrease of 1.46 +/- 1.16 ng/mL in group II vs increase of 2.25 +/- 1.58 ng/mL in group I, P =.07). The ACT response to abciximab was variable, but a 6.3% increase (+20 sec) in ACT was documented 5 minutes after abciximab bolus in group II compared with the 3.4% decrease (-10 sec) observed in group I at the same time point (P =.1). CONCLUSION: Addition of abciximab to heparin plus aspirin during PCI was associated with a significant decrease in thrombin generation and a borderline decrease in thrombin activity.

Abciximab↗

A simple and rapid serum bactericidal assay and its evaluation in clinical isolates of Klebsiella pneumoniae.

A simple and rapid assay for the determination of serum bactericidal activity was developed and evaluated in 125 clinical isolates of Klebsiella pneumoniae. The serum reactivity against these isolates was concomitantly determined by the conventional viable count technique in order to compare the efficacy of the two techniques. The rapid assay could be completed within 5-8 h and the results were recorded in terms of visible change of colour of the culture medium. Of the 125 strains tested, more than 50% were found to be resistant to 20% normal human serum. There was an excellent agreement between the two methods. The degree of discordance observed in the results obtained by the two methods was statistically not significant (P>0.05). The conventional technique is labor intensive, cumbersome and time-consuming. The assay described here, on the other hand, is simple, easy and rapid enough to allow testing of a large number of bacterial isolates or recombinant clones in a single day. Thus, the assay can serve as an excellent alternative to the conventional technique for determining the bacterial serum susceptibility.

Bacteriological Techniques↗

Creatine kinase-MB elevation after coronary intervention correlates with diffuse atherosclerosis, and low-to-medium level elevation has a benign clinical course: implications for early discharge after coronary intervention.

OBJECTIVES: The study evaluated the incidence and predictors of creatine kinase-MB isoenzyme (CK-MB) elevation after successful coronary intervention using current devices, and assessed the influence on in-hospital course and midterm survival. BACKGROUND: The CK-MB elevation after coronary intervention predominantly using balloon angioplasty correlates with late cardiac events of myocardial infarction (MI) and death. Whether CK-MB elevation after nonballoon devices is associated with an adverse short and midterm prognosis is unknown. METHODS: The incidence and predictors of CK-MB elevation after coronary intervention were prospectively studied in 1,675 consecutive patients and were followed for in-hospital events and survival. RESULTS: CK-MB elevation was detected in 313 patients (18.7%), with 1-3x in 12.8%, 3-5x in 3.5% and >5x normal in 2.4% of patients. Procedural complications or electrocardiogram changes occurred in only 49% of the CK-MB-elevation cases; CK-MB elevation was more common after nonballoon devices (19.5% vs. 11.5% after percutaneous transluminal coronary angioplasty; p < 0.01). Predictors of CK-MB elevation on multivariate analysis were diffuse coronary disease (p = 0.02), systemic atherosclerosis (p = 0.002), stent use (p = 0.04) and absence of beta-blocker therapy (p = 0.001). Adverse in-hospital cardiac events were more frequent in patients with >5x CK-MB elevation, with no significant difference between 1-5x CK-MB elevation versus normal CK-MB group. During a mean follow-up of 13 +/- 3 months, the incidence of death in the CK-MB-elevation group was 1.6% versus 1.3% in the normal CK-MB group (p = NS). CONCLUSIONS: The CK-MB elevation after coronary intervention was observed even in the absence of discernible procedural complications and was more common in patients with diffuse atherosclerosis. In-hospital clinical events requiring prolonged monitoring were higher in >5x CK-MB-elevation patients only. Midterm survival of CK-MB-elevation patients was similar to those with normal CK-MB. Our prospective analysis shows a lack of adverse in-hospital cardiac events and suggests that early discharge of stable 1-5x normal CK-MB-elevation patients after successful coronary intervention is safe.

Aged↗

Developments with targeted enzymes in cancer therapy.

Cancer therapy based on the delivery of enzymes to tumour sites has advanced in several directions since antibody-directed enzyme/prodrug therapy was first described. It has been shown that methoxypolyethylene glycol (MPEG) can be used to deliver enzyme to a variety of solid tumours. MPEG-enzyme conjugates show reduced immunogenicity and may allow repeated treatment with enzymes of bacterial origin. Enzyme delivery to tumours by polymers can be used to convert a low toxicity prodrug to a potent cytotoxic agent. An example of such a prodrug is CB1954, which can be activated by a human enzyme in the presence of a cosubstrate. Tumour-located enzymes can also be used in conjunction with a combination of antimetabolites and rescue agents. The rescue agent protects normal tissue but is degraded at cancer sites by the enzyme, thus deprotecting the tumour and allowing prolonged antimetabolite action.

Antineoplastic Agents↗

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 5: Pulse radiolysis studies on the antioxidant action of 7,8-diacetoxy-4-methylcoumarin.

7,8-Dihydroxy-4-methylcoumarin (1, DHMC) and 7,8-diacetoxy-4-methylcoumarin (2, DAMC) were shown to possess radical scavenging property and strongly inhibit membrane lipid peroxidation. Although free polyphenolic compounds are known to be antioxidants, the antioxidant action of the acetoxy compound DAMC was intriguing. Hence, pulse radiolysis studies were undertaken to explain the antioxidant action of DAMC. Accordingly, DAMC and DHMC were separately reacted with the system generating azide radicals and the resulting transient spectra were recorded. The spectra so obtained in both the cases demonstrated peak at 410 nm, characteristic of phenoxyl radical. The rate constants for the formation of phenoxyl radical from DHMC and DAMC were 34 x 10(8) M(-1) s(-1) and 6.2 x 10(8) M(-1) s(-1), respectively. We propose that the free radical mediated oxidation of DAMC initially produces a radical cation that loses an acetyl carbocation to yield the phenoxyl radical. It is possible to conclude that the mechanism of the antioxidant action of DAMC follows the pathway similar to that of DHMC involving the formation of a stable phenoxyl radical.

Antioxidants↗

Molecular properties of a hemagglutinin purified from type A Clostridium botulinum.

Clostridium botulinum causes the food poisoning disease botulism by producing botulinum neurotoxin, the most potent toxin known. The neurotoxin is produced along with a group of neurotoxin-associated proteins, or NAPs, which protect it from the low pH and proteases of the gastrointestinal tract. Recently, we isolated one of the major components of NAPs, a 33-kDa hemagglutinin (Hn-33) [Fu et al. (1998), J. Protein Chem. 17, 53-60]. In this study, we present molecular properties of Hn-33 derived from several biochemical and biophysical techniques. Hn-33 in pure form requires a 66-fold lower concentration of sugar inhibition of its hemagglutination activity than in its complexed form with the neurotoxin and other NAPs. However, its protease resistance is not affected by sugar binding. Based on FT-IR and circular dichroism (CD) analysis, Hn-33 is a predominantly beta-sheet protein (74-77%). Hn-33 analysis by laser desorption mass spectrometry and size exclusion column chromatography reveals that it exists predominantly in a dimeric form in the aqueous solution. Even a very low concentration of SDS (0.05%) irreversibly destroyed the biological activity of Hn-33 by changing its secondary structure as revealed by far-UV CD analysis.

Bacterial Proteins↗

Solid-phase total synthesis of polymyxin B1.

The total solid-phase synthesis of polymyxin B1 (PMB1) has been achieved in 20% yield using the orthogonal protecting group N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl-(Dde). This report demonstrates that a complex peptide macrocycle can be synthesized in high yields using solid-phase synthesis. According to MS and HPLC, the synthetic peptide was identical to the naturally occurring antibiotic.

Chromatography, High Pressure Liquid↗

Binding and catalytic properties of the Cdc2 and Crp proteins of Dictyostelium.

Dictyostelium expresses at least two proteins of the cyclin-dependent kinase (Cdk) family, Cdc2 and Crp. Cdc2 levels remain relatively constant during differentiation, whereas the levels of Crp increase dramatically as differentiation progresses. Crp is highly related to the mammalian Cdk5, and p25 (a truncated form of p35, the activating subunit of Cdk5 from mammalian brain) stimulates the histone H1 kinase activity of GST-Crp by several fold. In contrast, p25 does not stimulate the histone H1 kinase activity of GST-Cdc2 or the Cdc2 activity present in cell extracts from vegetative Dictyostelium cells. GST-Cdc2, in vitro translated Cdc2 and Cdc2 from all stages of differentiation bind to p13suc1. In contrast, GST-Crp, in vitro translated Crp and the Crp protein present in cell extracts do not bind to p13suc1. We have confirmed a previous report by Arakane and Maeda [J. Plant Res. (1997) 110, 81-85] that there is a peak of p13suc1 bound histone H1 kinase activity during late development, but we found that there was no corresponding peak of p13suc1 bound Cdc2 protein that corresponds to this activity. Taken together, these data suggest that neither Cdc2 nor Crp is responsible for the late developmental peak of histone H1 kinase activity that binds to p13suc1.

Animals↗

Haemoptysis in patients with a normal chest radiograph: bronchoscopy-CT correlation.

The exact role of fibre-optic bronchoscopy (FOB) and CT of the chest in the diagnosis of patients presenting with haemoptysis and a normal or non-localizing chest radiograph has not been clearly defined. A study was designed to evaluate 50 patients presenting with haemoptysis and a normal or non-localizing chest radiograph using FOB and high-resolution computed tomography (HRCT). A definitive diagnosis was established in 17 (34%) patients. The aetiologies included bronchiectasis (24%), bronchial adenoma (6%), tuberculosis (2%) and bronchitis (2%). The diagnosis was made by HRCT in 15 (30%) patients, while FOB was diagnostic in five (10%) patients. The diagnosis was made by HRCT and FOB in all patients with focal airway abnormalities. Therefore, HRCT effectively delineated abnormalities of both the central and peripheral airways. It is concluded that CT should be obtained prior to FOB in all patients presenting with haemoptysis and a normal or non-localizing chest radiograph.

Adenoma↗

Shape-selective recognition of a model Okazaki fragment by geometrically-constrained bis-distamycins.

Okazaki fragments represent interesting targets for the design of anticancer drugs because of their selective occurrence during DNA replication, a process often elevated in aggressive malignancies. Structural studies have indicated a bend occurs in the helical axis at the junction region (JR) that joins the DNA duplex region (DDR) and the RNA-DNA hybrid duplex region (HDR) of model Okazaki fragments. To identify a structural motif that provides a shape complementary to the Okazaki fragment minor groove, we have investigated the binding of geometrically-constrained bis-distamycins to a model Okazaki fragment, [OKA], with a sequence derived from the genome of simian virus 40 (SV40). Both the JR and the DDR of [OKA] contain consecutive A/T base pairs that could accommodate distamycin binding. Of the six bis-distamycins selected for analysis, the two with a para configuration of the distamycins on the benzene or pyridine scaffold bound [OKA] tightly (Kd approximately 10(-6) M from gel-shift assays; Kd approximately 10(-8) M from deltaT(M)) while the four with a meta orientation did not bind. The two mono-distamycins studied also did not bind [OKA]. Molecular modeling of the complex between the para bis-distamycin MT-9 and [OKA] revealed MT-9 adopted an S- shape complementary to the minor groove of the model Okazaki fragment.

Antineoplastic Agents↗

Iodine status of food and drinking water of a sub-Himalayan zone of India.

Iodine content of rice (42) and drinking water (108) from a goitre-endemic belt of Assam, a sub-Himalayan zone of India, was evaluated. Iodine content of staple food (rice) and drinking water was found to be poor. Mean iodine content of rice was found to be 11.8 +/- 7.3 micrograms/100g. Lower level of iodine was also observed in drinking water samples (mean of 1.52 +/- 0.48 micrograms/l).

Diet↗

Assessing platelet and fibrinogen contribution to clot strength using modified thromboelastography in pregnant women.

UNLABELLED: The monoclonal antibody fragment c7E3 Fab (ReoPro), by binding to platelet surface fibrinogen receptors (glycoprotein, GPIIb/IIIa), inhibits platelet aggregation and its interaction with fibrinogen. In this study, we used thromboelastography with ReoPro to evaluate the independent contribution of fibrinogen and platelets to clot strength. Thromboelastography was performed in 21 healthy, term parturients scheduled for elective cesarean delivery with 360 microL of celite-activated whole blood and with 5 microL of (2 mg/mL) ReoPro added to 355 microL of celite-activated whole blood. The contribution of platelets to clot strength (MAplt) was derived by subtracting MAfib (maximal amplitude with ReoPro) from MAwb (maximal amplitude with whole blood). Thus, MAwb - MAfib = MAplt. The value for MAwb (mean +/- SD) was 73+/-4 mm, for MAfib it was 33+/-5 mm, and for MAplt it was 40+/-3 mm. The contribution of fibrinogen and platelets to the MAplt was 45% and 55%, respectively. Modified thromboelastography using ReoPro in healthy parturients can be used to determine the contribution of fibrinogen and platelets to blood clot strength. IMPLICATIONS: Determining the independent contribution of platelets and fibrinogen to the maximal amplitude of thromboelastography using c7E3 Fab may further improve the use of thromboelastography in detecting and treating coagulation defects.

Abciximab↗

Assessment of changes in coagulation in parturients with preeclampsia using thromboelastography.

BACKGROUND: Preeclampsia is associated with a risk of abnormal hemostasis that occurs most commonly secondary to thrombocytopenia. Thromboelastography measures whole blood coagulation and has been used to manage coagulation defects in obstetric patients. The authors conducted this investigation in a large number of preeclamptic women to assess changes in coagulation using thromboelastography. METHODS: Thromboelastography and platelet counts were performed in 52 healthy pregnant women, 140 mild preeclamptic women, and 114 severe preeclamptic women in active labor using disposable plastic cups and pins and native whole blood. In preeclamptic patients with a platelet count <100,000/mm3, conventional coagulation tests were also performed. Epidural analgesia was provided in some women when they requested pain relief. RESULTS: Fifteen percent of all preeclamptic women (38 of 254) and 2% (1 of 52) of healthy pregnant women had a platelet count <100,000/mm3. The incidence of thrombocytopenia <100,000/mm3 was 3% (4 of 140) and 30% (34 of 114) in mild preeclamptic patients and severe preeclamptic patients, respectively. Severe preeclamptic patients with a platelet count <100,000/mm3 were significantly hypocoagulable when compared to the other study groups. Ten severe preeclamptic women with a platelet count <100,000/mm3 had a maximum amplitude <54 mm (the lower limit of maximum amplitude in healthy pregnant women enrolled in this investigation). None of the mild preeclamptic women had a maximum amplitude <54 mm. Five severe preeclamptic women with a platelet count <100,000/mm3 had an abnormal coagulation profile, whereas all four mild preeclamptic women with a platelet count <100,000/mm3 had a normal coagulation profile. CONCLUSION: This study shows that severe preeclamptic women with a platelet count <100,000/mm3 are hypocoagulable when compared to healthy pregnant women and other preeclamptic women.

Adult↗

Epidural analgesia during labor and maternal fever.

BACKGROUND: In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor. METHODS: Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature > or = 38.0 degrees C) versus those without was performed using Student t test and Fisher exact test to determine statistical significance (P < 0.05). RESULTS: Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression. CONCLUSIONS: Epidural analgesia is associated with maternal fever. However, nulliparity and dysfunctional labor are also significant cofactors in the fever attributed to epidural analgesia.

Analgesia, Epidural↗

The effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling.

BACKGROUND: Patients with angina after a Q-wave myocardial infarction benefit from elective revascularization, but it is not known whether asymptomatic patients, including those with a totally occluded infarct-related artery, improve after revascularization. OBJECTIVE: To determine the effect of early postinfarction revascularization of asymptomatic patients on left ventricular remodeling. METHODS: We prospectively studied 31 consecutive asymptomatic patients (aged 57 +/- 2 years, 24 with anterior infarcts) after Q-wave myocardial infarction with > or = 70% stenosis of the infarct-related artery (IRA) who underwent early elective revascularization (days 4-10 after myocardial infarction). Group I consisted in patients with a totally occluded IRA (n = 10), and group II consisted in patients with a patent, though stenosed, IRA (n = 21). Resting echocardiography and low-dose dobutamine echocardiography were performed at baseline (day 3 +/- 1), and rest echocardiography was repeated after an 8-week follow-up. Significant myocardial viability was defined as > or = 2 wall segments improved (in a 16-segment model of left ventricle) versus baseline, and significant functional recovery as > or = 2 segments improved versus baseline on follow-up examination. Left ventricular end-systolic volume indices (ESVI) and end-diastolic volume indices and ejection fractions were measured by using a modified version of Simpson's rule (using apical two-chamber and four-chamber views). RESULTS: The left ventricular ESVI of patients in group I had decreased by 4.2 +/- 1.9 ml/m2, whereas for patients in group II the left ventricular ESVI had increased by 4.2 +/- 1.7 ml/m2 (P = 0.006). Similarly, the left ventricular end-diastolic volume index had decreased by 0.7 +/- 2.4 ml/m2 versus baseline at follow-up for patients in group I and increased by 7.8 +/- 2.1 ml/m2 for patients in group II (P = 0.02). The left ventricular ejection fraction increased by 7.3 +/- 3% for patients in group I and decreased by 0.4 +/- 2% for patients in group II (P = 0.04). CONCLUSION: There is less global left ventricular remodeling, a potentially deleterious process, after elective revascularization early after Q-wave myocardial infarction in asymptomatic patients who had had a totally occluded IRA before revascularization than there is in patients who had already had a patent, though stenosed, IRA before revascularization. These results suggest that restoration of patency of IRA after a Q-wave myocardial infarction is beneficial even for asymptomatic patients.

Coronary Disease↗