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Biomedical subjects

D Mehta

Publications and source records attributed to D Mehta.

At least 19 recordsLinked to original sources

Prospective comparison of biphasic and monophasic shocks for implantable cardioverter-defibrillators using endocardial leads.

Bidirectional shocks using 2 current pathways have been used in endocardial lead systems for implantable cardioverter-defibrillators, but the optimal shock waveform for endocardial defibrillation is unknown. The clinical efficacy and electrical characteristics of bidirectional monophasic and biphasic shocks for endocardial cardioversion-defibrillation of fast monomorphic or polymorphic ventricular tachycardia (VT), or ventricular fibrillation (VF) were evaluated. Thirty-three patients (mean age 60 +/- 12 years, and mean left ventricular ejection fraction 34 +/- 13%) were studied. Defibrillation catheter electrodes were located in the right ventricular apex and superior vena cava/right atrial junction. A triple-electrode configuration including the 2 catheter electrodes and a left thoracic patch was used to deliver bidirectional shocks from the right ventricular cathode to an atrial anode (pathway 1) and the thoracic patch (pathway 2). The shock waveforms examined were sequential and simultaneous monophasic, and simultaneous biphasic. The efficacy of 580 V (20 J) shocks for fast monomorphic VT were comparable for the 3 waveforms (73% for sequential monophasic, 73% for simultaneous monophasic, and 100% for simultaneous biphasic). However, for polymorphic VT and VF, 580 V sequential monophasic shocks had a significantly lower efficacy (25%) than did simultaneous monophasic (75%; p = 0.01) or biphasic (89%; p less than 0.001) shocks. Single-shock defibrillation thresholds with simultaneous biphasic shocks were significantly lower (9 +/- 5 J) than were those with simultaneous monophasic shocks (15 +/- 4 J; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Electric Countershock

Survival of implantable cardioverter-defibrillator recipients: role of left ventricular function and its relationship to device use.

The quantitative benefit of ICD therapy in patients with malignant ventricular tachyarrhythmia with different degrees of left ventricular dysfunction is unclear. We evaluated patterns of ICD use and survival in 112 patients with moderate to severe left ventricular dysfunction. Group 1 included 57 patients with moderate left ventricular dysfunction (defined as left ventricular ejection fraction greater than 30%) and group 2 comprised 55 patients with severe left ventricular dysfunction (defined as ejection fraction equal to or less than 30%). The follow-up period ranged from 1 to 78 months. Age, incidence of coronary artery disease, and presenting arrhythmia in the two groups were similar. The mean left ventricular ejection fraction in group 1 was 44.6 +/- 8.2% and in group 2 was 21.6 +/- 6% (p < 0.0001). At 3 years of follow-up 65% of the patients in group 1 and 71% in group 2 (p = NS) had ICD activation for presumed ventricular tachycardia. Survival was calculated by means of actuarial analysis. Arrhythmia or sudden death mortality at 4 years of follow-up was 5% in group 1 and 9% in group 2 (NS). Cardiac mortality was higher in patients with severe left ventricular dysfunction reaching levels of statistical significance at 2 years of follow-up. At 2 years of follow-up it was 12% in group 1 and 40% in group 2 (p = 0.05), and at 4 years of follow-up it was 15% in group 1 and 43% in group 2 (p < 0.01). In both groups there was no difference in cardiac mortality in patients who did and did not have appropriate ICD shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Comparison of clinical benefits and outcome in patients with programmable and nonprogrammable implantable cardioverter defibrillators.

Technological advances in implantable cardioverter defibrillators (ICDs) have provided a variety of programmable parameters and antitachycardia therapies whose utility and impact on clinical outcome is presently unknown. ICDs have capabilities for cardioversion defibrillation alone (first generation ICDs), or in conjunction with demand ventricular pacing (second generation ICDs), or with demand pacing and antitachycardia pacing (third generation ICDs). We examined the pattern of antitachycardia therapy use and long-term survival in 110 patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Group I included 62 patients with nonprogrammable first generation ICDs that delivered committed shock therapy after ventricular tachyarrhythmia detection based on electrogram rate and/or morphology was satisfied. Group II included 48 patients with multiprogrammable ICDs (including second and third generation ICDs) that had programmable tachyarrhythmia detection based on rate and tachycardia confirmation prior to delivery of electrical treatment with either programmable shocks and/or, as in the third generation ICDs, antitachycardia pacing. Incidence and patterns of antitachycardia therapy use and long-term survival were compared in the two groups. The incidence of appropriate shocks in patients who completed 1 year of follow-up was significantly greater in group I (30 of 43 patients = 70% vs 11 of 26 patients = 42%; P less than 0.05). In the total follow-up period, a significantly larger proportion of group I patients as compared to group II patients used the shock therapies (46 of 62 patients = 74% vs 25 of 48 patients = 52%; P less than 0.01), with the majority doing so within the first year of implantation (96% and 92%, respectively). Although the frequency of antitachycardia therapy activation was similar, the number of shocks delivered per patient was lower in group II, particularly in the initial 3 months of follow-up (P = 0.06). No clinical variable aided in identifying users from nonusers of antitachycardia therapy. Arrhythmic mortality was virtually eliminated in both groups. Two-year actuarial cardiac survival in the two groups was similar (group I = 78% vs group II = 84%; P greater than 0.2). Survival from cardiac mortality in users and nonusers of antitachycardia therapies was also similar in both groups (P greater than 0.2) and in the total patient group (P greater than 0.2). We conclude that programmable ICDs continue to confer advantages in prevention of sudden death that were observed with nonprogrammable ICDs and can be expected to improve patient tolerance and physician acceptance of device therapy for VT/VF.

Adult

Streptococcus associated toxic shock.

In the past few years, there appears to have been a change in the spectrum of disease caused by group A beta-haemolytic streptococcus (GABHS), and a toxic shock-like syndrome caused by this organism has recently been described in adults. We report four children with an acute illness characterised by rapid progression of shock, erythematous rash, multisystem organ involvement, electrolyte derangements, and desquamation who fulfil the previously established diagnostic criteria for toxic shock syndrome. Three of the children had extensive cutaneous and soft tissue infection and the fourth had peritonitis. All four developed bacteraemia. Treatment included aggressive cardiovascular resuscitation and antibiotic therapy. Although no patient died, they suffered multiple and severe complications requiring prolonged treatment and hospitalisation. Streptococcal toxic shock syndrome is a separate and clearly defined entity occurring in previously healthy children.

Cardiopulmonary Resuscitation

Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality.

OBJECTIVE: A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart. DESIGN: Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing. PATIENTS: 23 patients with right VT associated with a clinically normal heart were studied. OUTCOME MEASURES: The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests. SETTING: Patients were studied in a tertiary referral centre. RESULTS: All three drugs suppressed ventricular salvos (> 3, < 5 consecutive ventricular premature contractions) (p < 0.01) and VT (p < 0.05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0.01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and non-sustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0.01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology. CONCLUSIONS: Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in > 89% of patients) and is a suitable choice for first line treatment.

Adult

Experience with a third-generation implantable cardioverter-defibrillator.

A Medtronic 7216A pacemaker cardioverter-defibrillator was implanted in 16 patients (mean age 56 years) with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and organic heart disease with a mean left ventricular ejection fraction of 33%. Endocardial and epicardial defibrillation shock efficacy was evaluated before or at implant using 1 to 3 shock patterns, i.e., monophasic single, sequential or simultaneous shocks with dual and triple electrode configurations. Endocardial leads used a common right ventricular cathode and dual anodes, whereas epicardial leads used 2 or 3 helical coil patches. VT termination was evaluated using pacing or shock therapy, or both, whereas only shocks were used in VF. Programmable bradycardia pacing, individual zones for VT and VF detection and individualized pacing and shock therapy for VT and VF were used. Monophasic shocks had epicardial defibrillation thresholds ranging from 3 to 18 (mean 10) J and were comparable for sequential and simultaneous shocks (p greater than 0.2). VT detection rates ranged from 340 to 470 ms and VF detection rates from 270 to 330 ms. VT or VF induction, or both, was performed noninvasively in 13 patients after implant and was reproducibly terminated by rapid pacing alone (5 patients), low-energy shocks (2 patients), high-energy shocks (3 patients) and combined therapy (3 patients). Intermediate or high-energy shocks terminated all induced VF episodes. During follow-up (2 to 12 months), there have been 2 noncardiac deaths. Electrical therapy was delivered in 7 patients, for VT (3 patients), VT and VF (3 patients) and indeterminate tachyarrhythmia (1 patient). All VT/VF episodes were successfully terminated, with 78 of 96 (81%) spontaneous VT episodes terminated by pacing. Follow-up reprogramming was required in 5 patients. It is concluded that successful application of individualized electrical therapy prescriptions in patients with VT/VF is feasible. Pacing therapies, which are effective for induced VT, can be reliably used for effective long-term spontaneous VT termination in conjunction with shock therapy and can permit reduced patient exposure to shock therapy. Thus, a programmable hybrid pacemaker cardioverter-defibrillator system provides nonthoracotomy implantation, effective VT/VF termination, demand ventricular pacing and noninvasive modes for arrhythmia induction, event monitoring and clinical trouble-shooting.

Adult

Effect of automobile exhaust on the distribution of trace elements and its modulation following Fe, Cu, and Zn supplementation.

The effect of automobile exhaust on the distribution of trace elements with special reference to Pb and its modulation following Cu, Zn, and Fe supplementation, in mouse organs, has been studied using Energy Dispersive X-ray Fluorescence technique. Seven elements, namely K, Fe, Cu, Zn, Br, Rb, and Pb, were detected in all the organs. The maximum concentration of Pb was found in lungs followed by that in liver and kidney. The effect of automobile exhaust was found to be significant on the concentrations of Fe and Pb; their concentrations were found to increase in all the organs. However, the concentrations of Cu and Zn were found to be decreased significantly in the liver. In the animals given Fe, Cu, or Zn supplementation along with motor exhaust, the percentage change in the concentration of Pb in lungs was decreased, and that of Fe was increased significantly. In kidney, no significant change was observed for the animals given Cu and Zn, whereas for animals given Fe, the level of Pb decreased significantly. In liver, the reduction in the level of Zn in the exhaust-exposed animals was made up and the level of Pb was reduced following Zn supplementation. These results clearly indicate that Fe and Zn play an important role in Pb metabolism and tend to lower the absorption of Pb. The effect of Fe is more pronounced than that of Zn, whereas the effect of Cu seems to be insignificant.

Administration, Inhalation

Signal averaging of the electrocardiogram in the remote differential diagnosis of broad complex tachycardias.

The diagnosis of the origin of a broad complex tachycardia may be difficult, especially in the absence of a 12-lead electrocardiogram of the tachycardia. This study investigates the value of signal averaging in the differential diagnosis of broad complex tachycardia. Signal averaging during sinus rhythm was performed in 102 consecutive patients who presented with broad complex tachycardia (QRS width greater than 110 ms), in whom a definitive electrophysiological diagnosis was made. The presence of late potentials was determined on the basis of two definitions, the second including total QRS duration. The patients studied included 75 with ventricular tachycardia; 33 of these patients had suffered previous myocardial infarction, five had dilated cardiomyopathy, and 37 had a 'normal' heart. Of the 27 patients with supraventricular tachycardia, 22 had an atrioventricular accessory pathway (seven with a delta wave in sinus rhythm), three had atrioventricular nodal tachycardia and two had atrial tachycardia. The sensitivity of late potentials for the diagnosis of ventricular tachycardia was low utilizing both definitions (28% and 45%) although specificity was high (96% and 95%). The sensitivity for the diagnosis of ventricular tachycardia was higher for patients with ischaemic heart disease (43% and 70%) but very low for patients with ventricular tachycardia and a normal heart (16% and 22%). In conclusion, signal averaging in the remote diagnosis of broad complex tachycardia is specific but not sensitive for ventricular tachycardia, which limits its usefulness in selecting patients for electrophysiological study.

Coronary Disease

Density-dependent regulation of epidermal growth factor receptor expression.

Previous studies have demonstrated that binding of peptide growth factors such as epidermal growth factor (EGF) decreases as cell density increases. We now report that binding of EGF to MDA 468 breast carcinoma cells is reduced as cells increase in density with time in culture. Cells at low density bound more EGF per cell than cells at higher density. The reduction of EGF binding was due to a reduction in receptor number. Metabolic labeling of MDA 468 cells with [35S]-methionine followed by immunoprecipitation of the EGF receptor (EGFR) indicated that the amount of total receptor protein was decreased. Using RNA blot hybridization, we found that high-density cells contained decreased amounts of EGFR transcripts. Northern analysis revealed that both the 10- and 5.6-kilobase mRNA transcripts encoding the EGFR were decreased. These data suggest that increasing cell density with time in culture results in modulation of EGFR content, with changes at the level of both protein and mRNA expression.

Blotting, Northern

Acute electrophysiologic effects of an HT2-serotonin antagonist, ketanserin, in humans.

The acute electrophysiologic effects of an intravenous bolus of ketanserin, a 5HT2 serotonin blocker, were studied in ten patients (four females, six males) during invasive electrophysiology. Following baseline electrophysiologic measurements during sinus rhythm and fixed-rate atrial pacing at 600 ms, a bolus of 0.2 mg/kg ketanserin was given over a 3-minute period. After 30 minutes all measurements were repeated. Systemic blood pressure was measured at regular intervals throughout. During sinus rhythm, there was no significant change in the basic cycle length or in the PA, AH, HV, QRS, QT, and QTc intervals. During atrial pacing there was a nonsignificant increase in the QT interval, from 342 +/- 13 ms to 366 +/- 16 ms, and a significant increase in the QTc interval, from 422 +/- 27 ms to 449 +/- 29 ms (p less than 0.05). There was no reduction in blood pressure. Thus ketanserin produced a significant prolongation of the QTc interval, in the absence of hypokalemia, in humans.

Adult

Prospective evaluation of a protocol for induction of sustained ventricular tachycardia in patients referred to a tertiary centre.

All eight stages of a stimulation protocol that used one then two extrastimuli from the right ventricular apex in sinus rhythm and three ventricular drive rates (100, 120, and 140 beats/min) were performed in 24 patients with recurrent spontaneous sustained ventricular tachycardia despite drug treatment. Twenty two of the patients had sustained a previous myocardial infarct and 18 were on long term treatment with amiodarone. Sustained (greater than 30 s) ventricular tachycardia was induced in all patients. Two extrastimuli were significantly more likely to induce sustained ventricular tachycardia than one extrastimulus, both overall and individually for the three ventricular drive rates. A ventricular drive rate of 140 beats/min was significantly more likely to induce ventricular tachycardia than ventricular drive rates of 100 and 120 beats/min which were significantly more effective than sinus rhythm. A ventricular drive rate of 140 beats/min with one or two extrastimuli induced ventricular tachycardia in 23/24 (95%) of the patients in this study. The full eight stage protocol was progressive separately for both extrastimuli and ventricular drive rate but the last two stages (ventricular drive rate of 140 beats/min with one or two extrastimuli) were as effective as the entire protocol in inducing ventricular tachycardia.

Aged

Increased leukocyte phospholipase A2 activity and plasma lysophosphatidylcholine levels in asthma and rhinitis and their relationship to airway sensitivity to histamine.

This study was carried out to determine leukocyte phospholipase A2 (PLA2) activity and plasma lysophosphatidylcholine (LPC) levels in normal subjects and in patients with asthma and rhinitis and to examine their relationship to airway sensitivity to histamine. Leukocyte PLA2 activity and plasma LPC levels were highly correlated (rs = 0.90), and were found significantly raised in both the disease groups, more so in the asthmatics. Both PLA2 activity and LPC levels showed overall negative correlations with the log dose of histamine producing a 35% fall in specific airway conductance (PD35 histamine) when the patients and the normal subjects were examined together (rs = -0.77 and rs = -0.83, respectively). The patients with leukocyte PLA2 activity more than 1.8 U (nmol 14C-AA released/mg protein/10 min at 30 degrees C) or plasma LPC levels more than 8.7% of total phospholipids (mostly asthmatics) showed high airway sensitivity to histamine (PD35 histamine less than or equal to 1 mg/ml). On the other hand, the PD35 histamine values of patients with leukocyte PLA2 activity equal to or less than 1.96 U or plasma LPC levels equal to or less than 8.7% overlapped with those of normal subjects in the range of 1.2 to 10 mg/ml. Lowering of plasma LPC levels, which probably reflect tracheobronchial LPC content as shown in guinea pigs, seems to be an essential step in the return of airway reactivity toward normal.

Adult

Echocardiographic and histologic evaluation of the right ventricle in ventricular tachycardias of left bundle branch block morphology without overt cardiac abnormality.

The right ventricle was investigated by multiple biopsies and detailed echocardiographic evaluation, including measurement of cavity dimensions at the level of the inflow, body and outflow tract, in 27 patients with right ventricular tachycardia who had no clinical evidence of an underlying morphologic abnormality. Nine (33%) patients had abnormal biopsy results, with a quantifiable increase in interstitial fibrosis. Abnormal echocardiograms, defined as an increase in greater than or equal to 2 dimensions of the right ventricular cavity or wall motion abnormalities or both, were seen in 9 patients. There was a strong association between abnormal myocardial histologies and abnormal right ventricular echocardiograms (p less than 0.001). An abnormal echocardiogram was 94% specific and 80% sensitive for an abnormal biopsy. The findings of echocardiography and biopsy were correlated with the electrocardiographic features of the tachycardia. Evidence of right ventricular disease was seen in all 6 patients with superior frontal plane axis of clinical tachycardia as compared with 4 of 21 with inferior axis (p less than 0.001). Thus, 2-dimensional echocardiography is a sensitive means of diagnosing right ventricular disease in patients with nonischemic tachycardias of left bundle branch block morphology. A superior frontal plane axis of ventricular tachycardia in this group strongly suggests right ventricular disease, whereas an inferior frontal plane axis is frequently not associated with any morphologic or histologic abnormality of the right ventricle.

Adult

Signal-averaged electrocardiography and the significance of late potentials in patients with "idiopathic" ventricular tachycardia: a review.

High-frequency, low-amplitude electrical activity during and in continuation with the ventricular electrogram in sinus rhythm is now accepted as an indirect marker for reentrant pathways in ventricular muscle. Because the amplitude of these signals is low, much effort has recently been directed toward finding methods of recording these noninvasively. This essentially involves averaging the electrocardiogram, amplifying it, and filtering out the low frequency and nonrepetitive signals. This review discusses the methods presently available for signal-averaged electrocardiography and their background. The clinical application of signal-averaged electrocardiograms in patients with or suspected to have ventricular tachycardia is summarized. Data regarding the incidence of abnormal signal-averaged electrocardiography in patients with "idiopathic" ventricular tachycardia compared with normal subjects and patients with ventricular tachycardia related to ischemic heart disease are presented.

Action Potentials

Megaprostheses in the treatment of primary malignant and metastatic tumors in the hip region.

Twenty patients with malignant bone tumors of the hip region were treated surgically by resection and reconstruction with an endoprosthesis. Histologic types included five primary bone tumors and 15 metastatic lesions. At review four primary bone tumor patients are still alive without evidence of disease. The length of the observation period varied from 26 to 104 months. Eleven patients with metastatic bone disease died. The average postsurgical survival time was 23 months. All patients were able to walk with or without a cane. Failure of an endoprosthesis occurred in one case. According to the Enneking Evaluation System 11 patients had a good and 9 a fair result.

Adolescent

Correlation artifacts in speed of sound estimation in scattering media.

A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the second order statistical properties of the stairstep artifact are derived.

Computer Simulation

Correction of refraction and other angle errors in beam tracking speed of sound estimations using multiple tracking transducers.

The beam tracking approach to the estimation of the speed of sound has shown potential for making unbiased estimates in tissues. The speed of sound in a medium can be found from the arrival times of echoes as a function of the position of a tracking transducer. There is a problem in this approach if the angle between the direction of tracked beam and the direction of tracking translation is not zero due to refraction or other effects. An angle error as small as 1 degree would result in an error that is too large for diagnostic applications. A modified technique using three or more tracking transducers is described. This yields a corrected speed of sound estimate, and calculates the angle error. A simulation program has shown that this modified technique could indeed correct for the angle errors.

Computer Simulation