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Biomedical subjects

A Prakash

Publications and source records attributed to A Prakash.

At least 19 recordsLinked to original sources

Right and left atrial activation during external direct-current cardioversion shocks delivered for termination of atrial fibrillation in humans.

We examined the regional electrophysiologic effects of successful and unsuccessful direct-current cardioversion shocks on different right and left atrial regions in patients with sustained atrial fibrillation (AF). Patients with sustained AF undergoing external cardioversion underwent simultaneous mapping of the right and left atria. Electrogram changes after shock delivery, regional atrial activation, and effects of shock intensity were analyzed. Twenty-two patients with sustained AF received 52 shocks (mean 2.4/patient, 22 successful and 30 unsuccessful). The efficacy of 50, 100, 200, and 300 J was 18%, 39%, 100%, and 100%, respectively. In all 22 successful shocks, there was virtually simultaneous termination of electrical activity in all right and left atrial regions mapped. Unsuccessful shocks resulted in a significant increase in mean atrial cycle length at lateral right atrium, superior left atrium, and proximal, mid, and distal coronary sinus (p = 0.01), but not at the interatrial septum (p >0.2), which often disappeared before the next shock. This cycle length prolongation was accompanied by reduction in fragmented and chaotic electrograms (p <0.03) and emergence of discrete electrograms at all right and left atrial regions that persisted until the next shock. The changes in electrogram morphology failed to alter the surface electrocardiographic appearance of AF. There was no correlation between the shock intensity and the magnitude of these effects. We conclude that termination of AF with external cardioversion shocks is associated with the widespread extinction of regional atrial wave fronts. Unsuccessful shocks are associated with a temporary slowing of atrial activation at all regions except at the interatrial septum and emergence of organized and/or rapidly propagating wave fronts.

Adult↗

Effect of prophylactic ondansetron on postoperative nausea and vomiting after elective craniotomy.

This prospective, randomized, placebo-controlled, double-blind study was designed to evaluate the efficacy of ondansetron, a 5-HT3 antagonist, in preventing postoperative nausea and vomiting (PONV) after elective craniotomy in adult patients. The authors also tried to discover certain predictors for postcraniotomy nausea and vomiting. We studied 170 ASA physical status I and II patients, aged 15 to 70 years, undergoing elective craniotomy for resecting various intracranial tumors and vascular lesions. A standardized anesthesia technique and postoperative analgesia were used for all patients. Patients were divided into two groups and received either saline placebo (Group 1) or ondansetron 4 mg (Group 2) intravenously at the time of dural closure. Patients were extubated at the end of surgery and episodes of nausea and vomiting were noted for 24 hours postoperatively in the neurosurgical intensive care unit. Demographic data, duration of surgery, and anesthesia and analgesic requirements were comparable in both groups. Overall, a 24-hour incidence of postoperative emesis was significantly reduced in patients who received ondansetron compared with those who received a saline placebo (39% in Group 1 and 11% in Group 2, P = .001). There was a significant reduction in the frequency of emetic episodes and rescue antiemetic requirement in patients treated with ondansetron; however, ondansetron did not significantly reduce the incidence of nausea alone (14% in Group 2 vs 5% in Group 1, P = .065). Prophylactic ondansetron had a favorable influence on PONV outcome measures such as patient satisfaction and number needed to prevent emesis (3.5). Side effects were similar in both groups. We conclude that ondansetron 4 mg given at the time of dural closure is safe and effective in preventing emetic episodes after elective craniotomy in adult patients.

Adolescent↗

IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein.

Induction of interferon-alpha (IFNalpha) gene expression in virus-infected cells requires phosphorylation-induced activation of the transcription factors IRF3 and IRF7. However, the kinase(s) that targets these proteins has not been identified. Using a combined pharmacological and genetic approach, we found that none of the kinases tested was responsible for IRF phosphorylation in cells infected with Newcastle disease virus (NDV). Although the broad-spectrum kinase inhibitor staurosporine potently blocked IRF3 and -7 phosphorylation, inhibitors for protein kinase C, protein kinase A, MEK, SAPK, IKK, and protein kinase R (PKR) were without effect. Both IkappaB kinase and PKR have been implicated in IFN induction, but cells genetically deficient in IkappaB kinase, PKR, or the PKR-related genes PERK, IRE1, or GCN2 retained the ability to phosphorylate IRF7 and induce IFNalpha. Interestingly, PKR mutant cells were defective for response to double-stranded (ds) RNA but not to virus infection, suggesting that dsRNA is not the only activating viral component. Consistent with this notion, protein synthesis was required for IRF7 phosphorylation in virus-infected cells, and the kinetics of phosphorylation and viral protein production were similar. Despite evidence for a lack of involvement of dsRNA and PKR, vaccinia virus E3L protein, a dsRNA-binding protein capable of inhibiting PKR, was an effective IRF3 and -7 phosphorylation inhibitor. These results suggest that a novel cellular protein that is activated by viral products in addition to dsRNA and is sensitive to E3L inhibition is responsible for IRF activation and reveal a novel mechanism for the anti-IFN effect of E3L distinct from its inhibition of PKR.

Animals↗

Entamoeba histolytica: rapid detection of indian isolates by cysteine proteinase gene-specific polymerase chain reaction.

Amoebiasis, caused by Entamoeba histolytica, is still one of the major problems for developing countries like India. Early detection of the parasite is a must for its prevention and control. In this study, PCR analysis of the cysteine proteinase gene from clinical isolates of symptomatic intestinal and amoebic liver abscess (ALA) cases has been compared with the stool microscopy, serology, and ultrasonography methods. The clinical isolates negative for E. histolytica by stool microscopy demonstrated the presence of the cysteine proteinase gene by PCR amplification. Also the gene copy number was increased in ALA samples compared with intestinal cases. Hence an accurate, early, and easier detection was possible by cysteine proteinase gene amplification directly from the clinical samples.

Adult↗

Catheter mapping of spontaneous and induced atrial fibrillation in man.

The clinical electrophysiologic study of atrial fibrillation [AF] has recently progressed from static characterization of the substrate to the dynamic investigation of both induced and spontaneous AF in man. Prior studies have demonstrated inhomogeneity and greater dispersion of atrial refractoriness in patients with AF, but recently atrial electrical remodeling with consequent abbreviation of atrial refractory periods has also been reported. Yet further experimental observations have suggested the existence of additional arrhythmogenic mechanisms for certain AF subsets. These include studies that have demonstrated a stable atrial flutter circuit in one atrium with fibrillatory conduction or a focal atrial tachyarrhythmia arising commonly in the left atrium. Efforts at catheter mapping of AF are now in progress. New mapping techniques and novel devices are currently being employed. We have performed catheter mapping simultaneously in right and left atrial sites at onset and during sustained pacing-induced and spontaneous AF in patients with ischemic and/or hypertensive heart disease. Atrial premature complexes that initiated spontaneous AF typically had coupling intervals ranging from 260 to 400 ms and most frequently arose in the crista terminalis, right atrioventricular junction or superior left atrium. AF at onset showed discrete electrograms at virtually all right and left atrial regions mapped and the region of earliest atrial activation during AF was in close proximity to the premature complexes in over 90% of patients. The regional atrial activation sequence for the first 10 AF beats demonstrated stable or unstable patterns in individual patients. In contrast to spontaneous AF, the initial arrhythmia of induced AF was seen to have a significantly different site of earliest atrial activation but similar discrete electrograms in different atrial regions. However, as with spontaneous AF, the site of extrastimulus delivery was in close proximity to the first induced beat. We conclude that regional catheter mapping of AF is feasible and safe in man and organized electrical activity is frequently observed at AF onset in patients with heart disease. Both right and left atrial regions can be the source of atrial premature complexes and at the onset of spontaneous AF. Induced AF may have differing activation patterns than spontaneous AF but both demonstrate earliest activation in proximity to the initiating atrial premature complex. These findings may help explain therapeutic benefits of right and left atrial interventions and pacing therapies in AF.

Atrial Fibrillation↗

Antioxidant content of whole grain breakfast cereals, fruits and vegetables.

BACKGROUND: Considerable scientific evidence suggests that whole grains, as commonly consumed in the United States and Europe, reduce risk for chronic disease including cancer and heart disease. Whole grains provide a wide range of nutrients and phytochemicals that may work synergistically to optimize human health. Fruits and vegetables provide protection against age related diseases. It is believed their high content of antioxidant compounds is key to such protection. OBJECTIVE: This research compares the antioxidant activity of whole grain, ready-to-eat (RTE) breakfast cereals to that of fruits and vegetables. METHOD: Antioxidant activity was determined by dispersing finely ground samples in a 50% aqueous methanol solution of the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). DPPH, which forms a deep purple solution, reacts with antioxidants and color loss at 515 nm correlates to antioxidant content, which is expressed as Trolox equivalents/100 grams (TE). RESULTS: Whole grain breakfast cereals analyzed in this study contained from 2,200-3,500 TE. By comparison, fruits generally ranged from 600-1,700 TE, with a high of 2,200 TE for red plums. Berries averaged 3,700 TE and. vegetables averaged 450 TE with a high of 1,400 TE for red cabbage. A 41 gram average serving of RTE breakfast cereal provides 1,120 TE, while an average 85 gram serving of vegetables or fruits provides 380 and 1,020 TE, respectively. CONCLUSION: Whole grain breakfast cereals, fruits and vegetables are all important dietary sources of antioxidants.

Antioxidants↗

Phosphorylation-induced dimerization of interferon regulatory factor 7 unmasks DNA binding and a bipartite transactivation domain.

Interferon regulatory factor 7 (IRF7) is an interferon (IFN)-inducible transcription factor required for activation of a subset of IFN-alpha genes that are expressed with delayed kinetics following viral infection. IRF7 is synthesized as a latent protein and is posttranslationally modified by protein phosphorylation in infected cells. Phosphorylation required a carboxyl-terminal regulatory domain that controlled the retention of the active protein exclusively in the nucleus, as well as its binding to specific DNA target sequences, multimerization, and ability to induce target gene expression. Transcriptional activation by IRF7 mapped to two distinct regions, both of which were required for full activity, while all functions were masked in latent IRF7 by an autoinhibitory domain mapping to an internal region. A conditionally active form of IRF7 was constructed by fusing IRF7 with the ligand-binding and dimerization domain of estrogen receptor (ER). Hormone-dependent dimerization of chimeric IRF7-ER stimulated DNA binding and transcriptional transactivation of endogenous target genes. These studies demonstrate the regulation of IRF7 activity by phosphorylation-dependent allosteric changes that result in dimerization and that facilitate nuclear retention, derepress transactivation, and allow specific DNA binding.

Animals↗

Metoprolol: a review of its use in chronic heart failure.

UNLABELLED: Metoprolol, a relatively selective beta1-blocker, is devoid of intrinsic sympathomimetic activity and possesses weak membrane stabilising activity. The drug has an established role in the management of essential hypertension and angina pectoris, and more recently, in patients with chronic heart failure. The effects of metoprolol controlled-release/extended-release (CR/XL) in patients with stable, predominantly mild to moderate (NYHA functional class II to III) chronic heart failure have been evaluated in the large Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) trial and the much smaller Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. Treatment with metoprolol CR/XL was initiated at a low dosage of 12.5 to 25 mg once daily and gradually increased at 2-weekly intervals until the target dosage (200 mg once daily) or maximal tolerated dosage had been attained in patients receiving standard therapy for heart failure. At 12 months, metoprolol CR/XL was associated with a 34% reduction in relative risk of all-cause mortality in patients with chronic heart failure due to ischaemic or dilated cardiomyopathy in the MERIT-HF trial. The incidence of sudden death and death due to progressive heart failure were both significantly decreased with metoprolol CR/XL. Similarly, a trend towards decreased mortality in the metoprolol CR/XL group compared with placebo was observed in the RESOLVD trial. Data from small numbers of patients with severe (NYHA functional class IV) heart failure indicate that metoprolol CR/XL is effective in this subset of patients. However, no firm conclusions can yet be drawn. Improvement from baseline values in NYHA functional class, exercise capacity and some measures of quality of life with metoprolol CR/XL or immediate-release metoprolol were significantly greater than those with placebo. The drug is well tolerated when treatment is initiated in low dosages and gradually increased at intervals of 1 to 2 weeks. CONCLUSIONS: Metoprolol CR/XL effectively decreases mortality and improves clinical status in patients with stable mild to moderate (NYHA functional class II or III) chronic heart failure due to left ventricular systolic dysfunction, and the drug is effective in patients with ischaemic or dilated cardiomyopathy. Although limited data indicate that metoprolol CR/XL is effective in patients with severe (NYHA functional class IV) chronic heart failure, more data are needed to confirm these findings. Treatment with metoprolol CR/XL significantly reduced the incidence of sudden death and death due to progressive heart failure.

Adrenergic beta-Antagonists↗

Insecticide susceptibility status of Culex tritaeniorhynchus giles, vector of Japanese encephalitis in Delhi.

Laboratory studies were carried out to ascertain the current susceptibility status of adult and larval stages of the Culex tritaeniorhynchus mosquito, vector of Japanese encephalitis, to various insecticides used under public health programs in India. The present study revealed that exposure of adult mosquitoes to diagnostic concentrations of DDT - 4.0%, malathion - 5.0%, fenitrothion - 1.0%, and propoxur - 0.1% could induce only 50.0, 10. 0, 15.0, and 5.0% mortality, respectively, indicating that the species was resistant to all of these insecticides. The LT50 and LT95 values calculated using diagnostic concentrations of DDT, malathion, fenitrothion, and propoxur were found to be 56.4 and 136, 138 and 272, 185 and 258, and 187 and 249 min, respectively. However, when adult mosquitoes were exposed to the diagnostic concentration of synthetic pyrethroids, viz., deltamethrin - 0.025%, permethrin - 0.25%, and lambdacyhalothrin - 0.1%, 100.0% mortality was observed, indicating that the species was highly susceptible to these adulticides. Larval susceptibility tests carried out using diagnostic dosages of DDT- 0.008, temephos- 0.02, fenthion- 0.008, fenitrothion- 0.125, and malathion- 0.005 mg/l failed to induce any mortality, indicating that larvae were resistant to these larvicides. The LC50 and LC90 values calculated for commonly used larvicides, viz., temephos and fenthion, were 0.1511 and 1.9098, and 0.6151 and 2.395 mg/l, respectively. Increase in tolerance level were estimated at 95.5- and 299.4-fold when these LC90 values were compared with diagnostic dosages of temephos and fenthion, respectively.

Animals↗

Epidemiology of malaria outbreak (April/May, 1999) in Titabor Primary Health Centre, district Jorhat (Assam).

An investigation was undertaken of a malaria outbreak in the Primary Health Centre Titabor, district Jorhat, Assam during May/June 1999. The fever rate in the community since March 1999, was 44.4 per cent with an average case load of 2.5 per family. The fever cases peaked in the third week of May. Slide positive and slide falciparum rates in mass blood survey, in the study village were 16.1 and 14.5 per cent respectively with 90 per cent infection of Plasmodium falciparum. Males (SPR 17.5%) suffered relatively more than females (SPR 14.7%). Malaria prevalence was significantly less in individuals above 15 yr of age (SPR 11.0%) as compared to those below 15 yr (SPR 22.9%). Prevalence of malaria as well as mosquito densities in different clusters of the village were inversely related to the distance from the forested Naga hills. Anopheles minimus and A. dirus were collected in good numbers with comparatively higher densities of the former. Several factors like unusual climatic conditions, inadequate surveillance, unsatisfactory laboratory services and inadequate indoor residual insecticide spray were instrumental for the outbreak.

Adolescent↗

Epidemic dropsy--a clinical study of the Delhi outbreak.

BACKGROUND: A major outbreak of epidemic dropsy occurred in Delhi, India, in August-September 1998, due to the consumption of contaminated mustard oil. METHODS: The clinical data of 212 adult patients of epidemic dropsy who presented to our hospital is analysed. RESULTS: Pitting pedal oedema (100%), skin erythema (75%), limb tenderness (63%), diarrhea (51%) and hepatomegaly (34%) were the prominent clinical manifestations observed in the patients. Superficial retinal haemorrhages and retinal venous dilatation was observed on fundus examination and 9% of patients developed an open angle glaucoma over a three month follow up period. Cardiac failure was present in 14% of patients. Most patients had mild disease which responded to cessation of mustard oil consumption, bed rest, diuretics and antioxidants. There were six deaths, all of whom had intractable cardiac failure. A unique feature of this outbreak was the documentation of acute renal failure in three patients, a phenomenon never described previously. CONCLUSIONS: Strict law enforcement to prevent the contamination of edible oils is essential to avoid the occurrence of future similar outbreaks.

Adolescent↗

Regional endocardial mapping of spontaneous and induced atrial fibrillation in patients with heart disease and refractory atrial fibrillation.

We performed simultaneous catheter mapping of right and left atrial regions at onset and during sustenance of spontaneous atrial fibrillation (AF) in patients with ischemic and/or hypertensive heart disease. Seventeen patients with structural heart disease had spontaneous and electrically induced AF episodes mapped from their onset simultaneously in multiple right and left atrial regions. Atrial premature complexes (APCs) that initiated spontaneous AF had coupling intervals ranging from 260 to 400 ms (mean 332 +/- 61), most commonly arising from the lateral right atrium (31%), right atrioventricular junction (13%), atrial septum (6%), superior left atrium (25%), or inferior left atrium (25%). APC morphology on surface electrocardiograms did not correlate with origin in specific atrial regions. The earliest regions of atrial activation for the first AF cycle were the lateral right atrium (n = 5), superior left atrium (n = 4), distal or mid coronary sinus (n = 4), atrial septum (n = 2), and right atrioventricular junction at the His bundle location (n = 2). Spontaneous AF at onset usually showed discrete but irregular electrograms at virtually all right and left atrial sites mapped, with a reproducible region of AF initiation in all 8 patients with multiple events. The region of earliest atrial activation at spontaneous AF onset was in close proximity to the APC origin in 15 of 16 patients (94%), and 39 of 40 episodes (97%) mapped. Stable patterns of right and left atrial activation were observed at AF onset in 14 patients. Induced AF elicited with right atrial stimulation demonstrated different sites of earliest regional atrial activation at onset compared with spontaneous AF events in 4 of 8 patients. However, discrete intracardiac electrograms were also present in induced AF in all of the mapped atrial regions. Furthermore, the site of extrastimulus delivery in induced AF was also found to be in close proximity to the earliest region of atrial activation for the first AF beat. We conclude that spontaneous AF is initiated by APCs arising in different right or left atrial regions in patients with structural heart disease and the initial region of atrial activation in AF is in proximity to the region of APC origin. Organized and repetitive electrical activation is frequently observed in both right and left atria at AF onset. Although electrically induced AF may have different activation patterns than spontaneous AF at onset in many patients, both types of AF demonstrate organization and earliest atrial activation in proximity to the initiating APC.

Aged↗

Electrophysiology and endocardial mapping of induced atrial fibrillation in patients with spontaneous atrial fibrillation.

We analyzed the patterns of atrial activation and characterized the electrophysiologic properties of regional atrial sites in the, right atrium and left atrium at the onset of atrial fibrillation (AF) induced with programmed right atrial (RA) stimulation. Intraatrial conduction, atrial electrogram return cycle lengths for the first AF cycle, RA and left atrial (LA) activation maps during AF, and the stability and reproducibility of atrial activation sequences at AF onset and maintenance were analyzed in 23 patients with AF. Correlation of intracardiac electrograms with surface electrocardiographic morphology was attempted. Maximum intraatrial conduction delay for high RA premature beats was observed at the coronary sinus ostium (n = 15), His bundle region (n = 13) or interatrial septum (n = 15). The return cycle lengths for the first AF cycle showed increasing conduction delay with increasing prematurity of the last extrastimulus in most patients. Suprisingly, discrete atrial electrograms with regular or irregular cycle lengths were present at the onset of electrocardiographic documented coarse AF in 13 of 15 patients (87%). Fragmented or chaotic atrial activity were present in 2 of 15 patients (13%) in coarse AF but observed at > or = 1 atrial sites in 7 of 8 patients (88%) with fine AF (p = 0.001). The atrial activation sequence at the onset of the induced AF elicited by high RA extrastimuli usually showed the earliest activation site at the crista terminalis (9 patients) or interatrial septum (9 patients). In contrast, induced AF elicited from other RA sites usually showed earliest atrial activation at the septum (3 patients) or coronary sinus ostium (3 patients). Atrial activation sequences for the first induced AF cycle were usually reproducible in most patients. Atrial activation patterns during the first 10 cycles for AF were stable in RA and LA regions in 6 of 23 patients (260%) but demonstrated significant change(s) at > or = 1 region in 17 of 23 patients (74%) (p <0.05). We conclude that pacing induced AF elicited by RA premature beats commences as a regular or irregular rapid atrial tachycardia consistent with a transitional, but often organized, arrhythmia. The activation sequence and electrophysiologic behavior of the first induced AF cycle is consistent with intraatrial reentry and reproducible in most patients. More than 1 atrial activation sequence can sometimes be observed, emphasizing the dynamic nature of the initial RA reentrant circuits.

Aged↗

Interactions of antiarrhythmic drugs with implantable defibrillator therapy for atrial and ventricular tachyarrhythmias.

Implantable cardioverter defibrillators (ICDs) have proven highly successful in the treatment of recurrent ventricular and atrial arrhythmias. Despite their high efficacy in terminating arrhythmias, concomitant therapy with antiarrhythmic drugs in ICD recipients remains common. Antiarrhythmic drugs are employed in an attempt to to limit patient exposure to high-energy shocks, primarily by reducing the number of arrhythmia reccurrences, suppressing coexisting arrhythmias, affecting rate and organization of tachycardias, and increasing efficacy of painless pacing therapies. Data regarding interaction of antiarrhythmic drugs with ICDs are incomplete and mostly based on animal models; however, it is clear that antiarrhythmic drugs affect all aspects of function of devices such as defibrillation threshold, pacing threshold, and sensing of both atrial and and ventricular arrhythmias. Because significant change in any of these functions may result in a nonfunctional device, and magnitude of drug effect in an individual patient is unpredictable, careful assessment of ICD function after an institution of therapy with antiarrhythmic drugs is mandatory.

Anti-Arrhythmia Agents↗