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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 127 records · Page 7Linked to original sources
PubMed1995

Pediatric carbamazepine intoxication.

STUDY OBJECTIVE: To describe the clinical effects of carbamazepine ingestion in a pediatric population. DESIGN: Case series of prospectively evaluated patients and a historical retrospective group. PARTICIPANTS: All patients younger than 18 years who presented to an urban emergency department with history of carbamazepine ingestion and positive laboratory confirmation. INTERVENTIONS: Patient demographics, findings on physical examination, serum carbamazepine levels, analysis of 12-lead ECGs, and time and doses of activated charcoal were recorded. RESULTS: Seventy-seven patients were enrolled, of whom 17 were evaluated prospectively. Serum carbamazepine levels were greater than 12 micrograms/mL (50 mumol/L) in 61 patients. In those 61 patients, mean peak serum level was significantly higher in patients with dystonic reactions (P = .009), coma (P = .002), and apnea (P = .008) than in patients without these symptoms. There was no significant difference in mean peak serum levels between patients with and without seizures. Serum carbamazepine half-life was significantly shorter (P = .022) in patients who received multiple doses of activated charcoal (8.2 +/- 1.6 hours) than in those who received a single dose (12.1 +/- hours). CONCLUSION: Pediatric patients with suspected carbamazepine ingestion are at higher risk for dystonic reactions, coma, and apnea if the peak serum carbamazepine level exceeds 28 micrograms/mL (117 mumol/L). The development of seizures is not related to peak serum level. Multiple doses of activated charcoal can significantly shorten serum carbamazepine half-life.

Adolescent↗
PubMed1995

Treatment of urethral stones by retrograde manipulation and extracorporeal shock wave lithotripsy.

OBJECTIVE: To assess the effect of retrograde manipulation and extracorporeal shock wave lithotripsy (ESWL) as a monotherapy for urethral stones that are not associated with urethral strictures. PATIENTS AND METHODS: Between August 1993 and January 1995, 34 male patients (mean age 38.7 years, range 7-55) presented with urethral stones. No patient had a suggested or past history of urethral stricture. Lidocaine jelly (2%) was instilled and retained inside the urethra for 5 min. A 16 F urethral catheter was advanced gently to push the stone back to the urinary bladder. Twenty patients had ESWL of their stones in the bladder, using a Storz Modulith SL20, in the prone position. Tilting the patient about 15 degrees towards the side with the stone minimized movement of the stone during fragmentation. In-line co-axial echography (3.5 MHz) and intermittent pulsed fluoroscopy were used to monitor stone fragmentation. In situ fragmentation of posterior urethral stones was not possible because localization was difficult and the treatment was painful. Thirteen patients had cysto-urethroscopy and mechanical cystolitholapaxy under general anaesthesia. RESULTS: Stones impacted in the posterior urethra in 31 (91%) patients and in the anterior urethra in three (9%) patients. Stones ranged in size from 7 to 25 mm. One patient expelled an anterior urethral stone after the instillation of 2% lidocaine jelly. The urethral stones were pushed back to the bladder without complication in the remaining 33 patients. All 20 patients except one had their stones fragmented by ESWL in one session. The mean number of shock waves was 3600 +/- 1480 (range 1200-6000) and the generator voltage ranged between 5 kV (560 bar) to 8 kV (940 bar). No patient in the ESWL group required anaesthesia or analgesia. Thirteen patients had successful mechanical cystolitholapaxy with no complications. CONCLUSION: Both endoscopic lithotripsy and ESWL of urethral stones are safe and effective. However, transurethral lithotripsy requires general anaesthesia and carries a risk of bladder and urethral trauma. This study demonstrated that, in the absence of urethral stricture, urethral stones can be pushed back safely to the urinary bladder and fragmented effectively by ESWL. The success of the treatment depends on adequate anaesthesia of the urethra before inserting the urethral catheter. We propose that this new technique should be considered before resorting to endoscopic or surgical management of urethral stones, particularly in children.

Adolescent↗
PubMed1995

Dexamethasone treatment for acute bacterial meningitis: how strong is the evidence for routine use?

A methodological appraisal of the published randomised controlled trials on the use of dexamethasone as an adjunct treatment in acute bacterial meningitis was carried out to examine whether the available evidence is strong enough to support the routine use of the drug. Studies were eligible for inclusion if they were published in indexed journals after 1966, written in English, and were randomised controlled trials with dexamethasone as adjunct to antimicrobials in patients with acute bacterial meningitis. All studies were extracted and their adherence to eight methodological principles was graded as adequate, inadequate, or unclear. A sensitivity analysis was done to examine the robustness of the conclusions. Seven studies met the eligibility criteria. No report adhered to all the principles. Major threats to validity of the conclusions included potential bias in analysis in all the studies, and lack of adjustment for baseline imbalances in four. Inadequate reporting of adverse effects hindered risk-benefit analysis. Sensitivity analysis showed that the numbers of patients withdrawn from analysis were enough to invalidate the conclusions. It is concluded that the available evidence is not strong enough to support a routine use of dexamethasone in acute bacterial meningitis. Further research is needed to determine the effect of a policy to use dexamethasone early in the management of suspected acute bacterial meningitis. Future studies should adopt a pragmatic approach, be methodologically rigorous, and meticulously measure the risk as well as the benefit of this policy.

Acute Disease↗
PubMed1995

Beneficial effects of antioxidants in hemorrhagic shock.

The present study was undertaken to investigate the role of endogenous hydrogen peroxide (H2O2) in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. To achieve this objective, the changes in the cardiac function and contractility, plasma creatine kinase (CK) and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), and cardiac malondialdehyde (MDA) concentration in anesthetized dogs were determined before and during shock and reinfusion in the presence of absence of catalase (a metabolizer of H2O2). The dogs were divided into three groups randomly. Group I: sham, four hour duration; group II: two hours of shock followed by two hours of reinfusion; group III: same as group II but pretreated with catalase. Hemorrhage shock was produced in the dogs by lowering the mean arterial pressure to 50 +/- 5 mm Hg by bleeding into standard blood bank bags containing 63 mL of citrate, phosphate, dextrose, and adenine (CPDA) anticoagulant for 450 mL of blood. The shock was maintained for two hours by bleeding or reinfusing the shed blood as needed. Cardiac function and contractility were depressed while plasma CK, CK-MB, and lactate increased during shock. Reinfusion after two hours of shock tended to return hemodynamic parameters and plasma lactate levels toward control values. Plasma CK and CK-MB and PMNL-CL increased further. Cardiac MDA content also increased after shock and reinfusion, suggesting oxidative damage. Pretreatment with catalase attenuated the deleterious effects of shock and reinfusion on the cardiovascular function and contractility, and the rise in plasma CK, CK-MB, and lactate, PMNL-CL, and cardiac MDA. However, the protection with catalase was not complete. These results suggest that hydrogen peroxide (H2O2) may partly be involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.

Analysis of Variance↗
PubMed1994

ATPase activity associated with the uncoating of clathrin baskets by Hsp70.

In the presence of ATP, bovine brain hsp70 has been shown to remove clathrin from bovine brain clathrin-coated vesicles in a rapid stoichiometric initial burst followed by slow steady-state uncoating. In addition, it has been found recently that a 100-kDa cofactor is required for hsp70 to uncoat clathrin baskets prepared with the assembly protein AP-2. In this study the ATPase activity associated with uncoating was investigated, with baskets formed from clathrin and assembly proteins. Mixed assembly proteins or assembly protein AP-2 could not be used in ATPase studies because they activated the hsp70 ATPase activity even in the absence of clathrin. However, this was not the case with assembly protein AP180. A stoichiometric initial burst of ATP hydrolysis was found to accompany the initial burst of uncoating of AP180-clathrin baskets by hsp70, with 1 mol of hydrolyzed ATP/mol of released clathrin heavy chain. Furthermore, the presence of a 100-kDa cofactor was needed for both processes. These results suggest that an initial burst of uncoating occurs with all clathrin baskets, that an initial burst of ATP hydrolysis accompanies this initial burst of uncoating, and that a 100-kDa cofactor is required for both.

Adenosine Triphosphatases↗
PubMed1994

Purpurogallin, a scavenger of polymorphonuclear leukocyte-derived oxyradicals.

Purpurogallin (PPG) is a phenolic compound extracted from nutgalls formed on oak trees. It has been used as an additive to edible or nonedible oils or fats, and to hydrocarbon fuels or lubricants to retard their oxidation. We investigated by luminol-dependent chemiluminescence (PMNL-CL), the ability of PPG to scavenge oxygen free radicals (OFRs) generated by zymosan-activated polympophonuclear leukocytes (PMNLs). Its OFR-scavenging ability was also investigated by the use of nitro blue tetrazolium (NBT). We also investigated by the dye-exclusion method, if PPG affects the viability of PMNLs. PPG in the concentrations of 0.005-0.4 mM was used in this study. PPG scavenged OFRs produced by zymosan-activated PMNLs in a concentration-dependent manner. Almost complete scavenging was observed at a concentration of 0.2 mM. The NBT test indicated that PPG (0.2 mM) did not completely prevent the activation of PMNLs by zymosan. Viability of PMNLs in the absence or presence of PPG (0.4 mM) were 95.77 +/- 0.56% and 96.78 +/- 0.60% respectively. The results suggest that PPG scavenges OFRs produced from activated PMNLs in a concentration-dependent manner and that the cell viability is not affected by PPG. PPG is a potent scavenger of OFRs and should be of value in the prevention and treatment of diseases in the pathophysiology of which OFRs are invovled.

Animals↗
PubMed1994

Protective effects of lazaroids against oxygen-free radicals induced lysosomal damage.

Lipid peroxidation of membranes by oxygen free radicals has been implicated in various disease states. Different antioxidants and iron chelators have been used to reduce lipid peroxidation. Lazaroids have been used for the acute treatment of central nervous system disorders such as trauma and ischemia wherein lipid peroxidative processes take place. In this study we evaluated the effect of lazaroids (U-78518F and U-74389F) on the release of acid phosphatase activity and formation of malondialdehyde (MDA) in rat liver lyosomes subjected to exogenously generated oxygen free radicals. There was a significant increase in the acid phosphatase release and MDA formation in the presence of oxygen free radicals. This was prevented by both the lazaroids. In a separate study the effect of lazaroid U-74389F was seen on the zymosan-stimulated polymorphonuclear (PMN) leukocyte-derived chemiluminescence. The PMN leukocyte chemiluminescent activity was attenuated by the lazaroid in a dose-dependent manner. These studies suggest that lazaroids may inhibit lipid peroxidation and stabilize the membrane.

Acid Phosphatase↗
PubMed1994

Hydroxyl radical-scavenging property of indomethacin.

The ability of indomethacin to scavenge hydroxyl radical (.OH) using high pressure liquid chromatography (HPLC) was investigated. .OH radical was generated by photolysis of H2O2 (1.5-10 mmoles/L) with UV light and was trapped with salicyclic acid (500 nmoles). H2O2 produced .OH in a concentration-dependent manner as estimated by .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). Indomethacin in increasing concentrations (5-600 mumoles/L) produced increasing inhibition of generation of 2,3-DHBA (7-67%) and of 2,5-DHBA (7-77%). The results indicate that indomethacin scavenges .OH in a concentration-dependent manner.

Chromatography, High Pressure Liquid↗
PubMed1994

Evaluation of hydroxyl radical-scavenging property of purpurogallin using high pressure liquid chromatography.

Purpurogallin (PPG) has been used as an additive to edible and non-edible oils or fats to retard oxidation. Its antioxidant mechanism is not known. We investigated the ability of PPG to scavenge exogenously generated hydroxyl radicals (.OH) using a sensitive high pressure liquid chromatographic (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10 mumoles) with UV light and was trapped with salicylic acid (500 nmoles). Salicylic acid is hydroxylated to produce .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). H2O2 produced concentration-dependent .OH as estimated by generation of 2,3- and 2,5-DHBA. PPG (100, 200, 300, 400, 500, and 600 nmoles) produced concentration-dependent decreases in .OH adduct products (approximately 70% inhibition with 600 nmoles of PPG). It did not affect the peak of standard 2,3- and 2,5-DHBA indicating that the decrease in the adduct product generated by H2O2 is due to scavenging of .OH. These results indicate that photolysis of H2O2 by UV light produces .OH and that PPG scavenges .OH.

Antioxidants↗
PubMed1994

Complex formation between clathrin and uncoating ATPase.

The bovine brain uncoating ATPase, a constitutive 70-kDa heat shock protein, uncoats clathrin-coated vesicles in an ATP-dependent reaction. The uncoating ATPase-clathrin complex formed from the uncoating reaction was compared to the complex formed by directly binding free clathrin to uncoating ATPase. The amount of the latter complex shows a simple hyperbolic dependence on either free clathrin or free uncoating ATPase concentration, whichever is in excess, with a binding stoichiometry of one uncoating ATPase per clathrin heavy chain. ATP markedly increases the rates of formation and dissociation of this complex while ADP profoundly inhibits these rates. At low uncoating ATPase concentrations, much more complex is formed by uncoating than by directly binding clathrin to enzyme. However, during column chromatography or dilution for electron microscopy, both types of complex dissociate in ATP but not ADP, and electron microscopy of both types of complex diluted into ADP shows binding only to the vertex of the clathrin triskelion. We conclude that the uncoating ATPase forms only one type of complex with clathrin and has only one site for nucleotide; ADP at this site prevents either formation or dissociation of complex, whereas ATP at this site allows both processes to occur rapidly.

Adenosine Diphosphate↗
PubMed1994

Oxygen free radicals and cardiac depression.

The present investigation deals with the in vivo effects of oxygen free radicals (OFRs) in the absence and presence of scavengers of OFRs (superoxide dismutase, SOD, and catalase) on the cardiac function and contractility and with the in vitro effects of exogenous OFRs and various pH and pO2 on the release of acid hydrolases from dog myocardial lysosomes. The hemodynamic measurements were made before and at various intervals after administration of OFRs for up to 2 h. Xanthine plus xanthine oxidase (X-XO) and opsonized zymosan were used to generate OFRs. Oxygen free radicals produced a decrease in the cardiac function and indices of myocardial contractility. SOD alone or in combination with catalase tended to protect the cardiac function against the deleterious effects of OFRs. There was about a threefold increase in the release of cathepsin D activity in vitro from the lysosomes in the preparations treated with X-XO as compared to those without such treatment. The presence of SOD prevented the release of cathepsin D from the lysosomes. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. However, the presence of OFRs at each pH resulted in a similar increase (about threefold) in the release of cathepsin D. Similarly the changes in pO2 alone did not cause the release of cathepsin D, but there were marked increases in the release of cathepsin D at each pO2 in the presence of OFRs. These data indicate that it is the oxygen free radicals and not the alterations in pH or pO2 that are primarily responsible for the release of lysosomal hydrolases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Lazaroid pretreatment preserves gas exchange in endotoxin-treated dogs.

PURPOSE: The lazaroids are a new class of potent free-radical scavengers. We tested whether U-74389G, a lazaroid, could attenuate some of the adverse cardiopulmonary effects of sepsis. METHODS: Dogs were randomized to receive either 10 mg/kg U-74389G (n = 10), or a saline control (n = 11). After baseline measurements of hemodynamics and gas exchange, they were then randomized to receive either 0.2 mg/kg endotoxin or a saline infusion. Measurements of hemodynamics and gas exchange were repeated. The study was concluded 70 minutes after endotoxin infusion and the lungs were then removed for histologic evaluation. RESULTS: In endotoxin-treated control animals, PO2 decreased (278 +/- 123 mm Hg to 67 +/- 13 mm Hg, P < .05) and intrapulmonary shunt increased (12.9% +/- 1.1% to 28.2% +/- 11.4%, P < .05) after endotoxin. Pretreatment with U-74389G attenuated the decrease in PO2 (476 +/- 61 mm Hg to 226 +/- 143) and the increase in intrapulmonary shunt (12.6% +/- 6.1% to 14.3% +/- 6.8%) observed after endotoxin. The extent of lung injury and systemic hemodynamics were similar between control or U-74389G-treated dogs. CONCLUSIONS: A free-radical-scavenger can attenuate the gas exchange defect commonly associated with endotoxin but it does not improve the derangement of systemic hemodynamics.

Analysis of Variance↗
PubMed1994

Randomized controlled trial of dexamethasone in tuberculous meningitis.

SETTING: The patients admitted to the Neurology ward of the All India Institute of Medical Sciences Hospital. OBJECTIVE: To assess the role of dexamethasone as an adjunct to antimicrobial therapy in the treatment of tuberculous meningitis. DESIGN: A randomised controlled trial of 47 patients was conducted over a 13-month period. 41 patients completed the trial. Patients were stratified into mild, moderate and severe groups and randomly allocated to steroid and non-steroid groups. All patients received a standardized antituberculosis drug regime. The end point was 3 months, or death if earlier. The evaluation at the end point included survival, resolution of symptoms, sequelae and activities of daily living. Results were analysed using the Wilcoxon rank sum test. RESULTS: The patients in the dexamethasone group fared better. 75% of this group had mild sequelae as opposed to 62% of the control group. Amongst the survivors, those who received dexamethasone sensorium improved earlier, and there was greater improvement in mental function and daily activities. The difference, however, did not reach statistical significance. CONCLUSIONS: Dexamethasone appears useful as an adjunct in the treatment of tuberculous meningitis especially in patients who have severe disease. The results need confirmation by a larger trial.

Adolescent↗
PubMed1994

Diagnostic criteria for tuberculous meningitis and their validation.

SETTING: Tuberculous meningitis (TBM) has high morbidity and mortality. Demonstration of tubercle bacilli in cerebrospinal fluid (CSF), the only reliable method of diagnosis, is time consuming and has a low yield. Early diagnosis and treatment are of utmost importance for favourable outcome. OBJECTIVE: The study was conceived to define easy to use criteria. METHODS: A set of criteria using clinical features, CSF examination and computed tomography (CT) findings were defined. 76 patients suspected of having TBM were divided into definite, highly probable, probable and possible TBM based on the criteria. The validity of criteria was tested using information from bacterial isolation, polymerase chain reaction (PCR) test for tuberculosis, response to treatment and autopsy. RESULTS: PCR was positive in over 75% of patients in the highly probable and probable groups. 91% of patients with highly probable and 66% with probable TBM improved on antituberculosis therapy. CONCLUSION: The criteria are reliable in making early diagnosis of TBM.

Adult↗
PubMed1994

Management of pregnancy when maternal blood has a very high level of fetal haemoglobin.

Fetal blood normally has a higher oxygen affinity than maternal blood because of the predominance of haemoglobin (Hb) F in the former and of Hb A in the latter; this predominance facilitates the transfer of oxygen from maternal to fetal blood. We report two patients who had exclusively or predominantly Hb F in their blood and were managed differently. When patient 1 became pregnant she had regular exchange blood transfusions in order to reduce her Hb F from 80% to below 50%; patient 2, who had 100% Hb F, was not transfused before, during or after her pregnancy. Each patient delivered a normal healthy baby. We conclude that the differential oxygen affinity produced by the combination of Hb A in the maternal blood and Hb F in the fetal blood is not indispensable to ensure an oxygen supply adequate for normal fetal development and growth.

Adult↗
PubMed1994

Platelet-activating-factor-induced changes in cardiovascular function and oxyradical status of myocardium in presence of the PAF antagonist CV-6209.

The effects of platelet-activating factor (PAF) on cardiac function and contractility and its mechanism of action are not fully understood. The authors investigated the effects of PAF in the absence or presence of a potent PAF antagonist CV-6209 on the cardiac function and contractility; lipid peroxidation product malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV-6209 (1 mg/kg, IV) did not produce significant changes in the various parameters studied. PAF (1 microgram/kg, IV) produced decreases in the cardiac function (cardiac index, left ventricular work index) and indices of cardiac contractility [(+) and (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, Vmax] and increases in the systemic and pulmonary vascular resistance. It also produced increases in cardiac MDA, serum CK, blood lactate, and H+ and decreases in blood pH and HCO3-. CV-6209 completely prevented the PAF-induced changes in the hemodynamic and biochemical parameters. These results suggest that PAF-induced cardiac depression may be due to PAF-induced release of oxyradicals from neutrophils and that PAF antagonist may be useful in counteracting the deleterious effects of PAF on the cardiovascular system.

Animals↗
PubMed1994

Role of oxyradicals in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion: effect of SOD and catalase.

We investigated the effects of hemorrhagic shock and reinfusion on the cardiac function and contractility, plasma CK and CK-MB activity and lactate concentration, oxyradical-producing activity of polymorphonuclear leukocytes (PMNL-CL), cardiac chemiluminescence (LV-CL), antioxidant enzymatic activity [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)], and malondialdehyde (MDA) concentration in anesthetized dogs, to determine the role of oxyradicals in cardiac depression and cellular injury in hemorrhagic shock and reinfusion. The dogs were assigned to four groups: group I (sham), 4 hrs duration; group II, 4 hr of shock; group III, 2 hr of shock, followed by reinfusion for 2 hr; and group IV, as in group III, but pretreated with SOD and catalase. Hemorrhagic shock was produced by withdrawing blood to maintain the mean arterial pressure at 50 +/- 5 mm Hg. Cardiac function and contractility were depressed during hemorrhagic shock. Plasma CK; CK-MB and lactate; and cardiac MDA, Mn-SOD, and CuZn-SOD increased, while catalase activity decreased during shock. Following reinfusion after 2 hr of shock, hemodynamic parameters and plasma lactate tended to return toward control values. Plasma CK and CK-MB, PMNL-CL and cardiac MDA, total SOD, Mn- and CuZn-SOD increased further, while LV-CL and GSH-Px decreased. In spite of the increased antioxidant reserve, oxidative damage was noted. Pretreatment with SOD and catalase attenuated the deleterious effects of shock and reinfusion on the cardiovascular function, plasma CK, CK-MB, and lactate, PMNL-CL, cardiac MDA and SOD, and LV-CL. Protection was incomplete for cardiovascular function and plasma CK and CK-MB. These results suggest that oxyradicals (O2-, H2O2) may be partly involved in the deterioration of cardiovascular function and cellular injury during hemorrhagic shock and reinfusion.

Animals↗