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Biomedical subjects

S Deshpande

Publications and source records attributed to S Deshpande.

At least 73 records · Page 4Linked to original sources
PubMed1997

Molecular characterization of murine humoral immune response to botulinum neurotoxin type A binding domain as assessed by using phage antibody libraries.

To produce antibodies capable of neutralizing botulinum neurotoxin type A (BoNT/A), the murine humoral immune response to BoNT/A binding domain (H(C)) was characterized at the molecular level by using phage antibody libraries. Mice were immunized with BoNT/A H(C), the spleens were harvested, and single-chain Fv (scFv) phage antibody libraries were constructed from the immunoglobulin heavy and light chain variable region genes. Phage expressing BoNT/A binding scFv were isolated by selection on immobilized BoNT/A and BoNT/A H(C). Twenty-eight unique BoNT/A H(C) binding scFv were identified by enzyme-linked immunosorbent assay and DNA sequencing. Epitope mapping using surface plasmon resonance in a BIAcore revealed that the 28 scFv bound to only 4 nonoverlapping epitopes with equilibrium constants (Kd) ranging from 7.3 x 10(-8) to 1.1 x 10(-9) M. In a mouse hemidiaphragm assay, scFv binding epitopes 1 and 2 significantly prolonged the time to neuroparalysis, 1.5- and 2.7-fold, respectively, compared to toxin control. scFv binding to epitopes 3 and 4 showed no protection against neuroparalysis. A combination of scFv binding epitopes 1 and 2 had an additive effect on time to neuroparalysis, which increased to 3.9-fold compared to the control. The results suggest that there are two "productive" receptor binding sites on H(C) which lead to toxin internalization and toxicity. Blockade of these two epitopes with monoclonal antibodies may provide effective immunoprophylaxis or therapy against BoNT/A intoxication.

Amino Acid Sequence↗
PubMed1997

Computerized hand diagnostic/rehabilitation system using a force feedback glove.

This paper describes recent results of a unified computerized system for hand diagnosis and rehabilitation. Automatic diagnosis data collection and Virtual Reality rehabilitation exercises are the main characteristics of the system. The diagnosis subsystem includes a tactile sensing glove in addition to standard devices such as electronic dynamometer, pinchmeter and goniometer. Three standard rehabilitation exercises were simulated in a Virtual Reality environment, using the WorldToolKit graphics library. The first two exercises (ball squeezing and DigiKey) allow measurement of finger forces exerted during the rehabilitation routine. The third exercise (Peg board) involves the patient's visual-motor coordination. The rehabilitation subsystem uses a VPL DataGlove retrofitted with Rutgers Master (RM-I) and its interface. The exercises involve manipulation of objects with different stiffnesses and geometry. Grasping forces were modeled and fed back using the Rutgers Master worn on patient's hand. Data is gathered in real time from both diagnosis and rehabilitation subsystems. Finger specific forces recorded during rehabilitation exercises allow better diagnosis of the patient impairment. An ORACLE database is used to store and manipulate patients' records. Proof of concept trials were performed in a clinical environment. Some results of patient records analysis are presented in this paper. A new version of the system using an RM II haptic interface is presently under consideration.

Adult↗
PubMed1997

Neonatal insulin secretion: implications for the programming of metabolic homeostasis.

Patterns of metabolic adaptation are described in the neonate, which generate two fundamental concepts. First, that early nutritional experiences may have long-term effects on the control of metabolic homeostasis, and second, that insulin has a fundamental role in this process. The endocrine pancreas in the neonate is unable to regulate insulin secretion in relation to blood glucose concentration with the same level of tight control seen in the older child and adult. Moreover, the pattern of metabolic adaptation in the fullterm infant in the first postnatal week is different to that of the preterm baby and the infant born small-for-gestational-age (SGA), with both preterm and SGA infants being unable to generate counter-regulatory ketogenesis as blood glucose concentrations fall. The inability to initiate ketogenesis and switch off insulin secretion after birth persists for several weeks in preterm infants. Methods of feeding term and preterm infants have profound effects on the neonatal endocrine milieu and it is suggested that patterns of insulin secretion provoked in the newborn period may 'programme' the subsequent development of metabolic control. The recently described molecular mechanisms that underlie the pathogenesis of abnormal insulin secretion in the syndrome of persistent hyperinsulinaemic hypoglycemia of infancy (or pancreatic nesidioblastosis) may offer insights into how such programming may occur.

Adaptation, Physiological↗
PubMed1996

Early detection of cervical cancer by visual inspection: a population-based study in rural India.

A total of 3784 women aged 35 and above living in 26 villages in rural Maharashtra state, India, were invited to undergo a pelvic examination, to evaluate the performance of unaided visual inspection by trained paramedical workers in detecting cervical cancer. Of this number, 2135 (56.4%) women complied with the invitation. Paramedical workers scored 1120 (57.3%) and 118 (6%) women as having abnormal cervices using the low- and high-threshold criteria respectively. There was good agreement between the visual findings of the paramedical workers and those of a gynaecologist. All subjects had a cervical smear. A total of 10 cervical cancers were detected by cytology/histology. The sensitivity of visual inspection by paramedical workers to detect cervical cancer was 90.0% using the low threshold and 60.0% with the high threshold to define a positive test. The values for specificity were 42.8% and 94.5% respectively. The results obtained by the gynaecologist were very similar. Cost savings implied by limiting cytology/other investigations to approximately half of the population pre-selected on the basis of visual inspection are likely to be offset by the necessity to repeat the test at frequent intervals, repeated follow-up visits and other investigations.

Adult↗
PubMed1996

Feasibility of atrial fibrillation detection and use of a preceding synchronization interval as a criterion for shock delivery in humans with atrial fibrillation.

OBJECTIVES: This study assessed the feasibility of detecting atrial fibrillation (AF) and delivery of appropriately timed R wave shocks using an implantable atrial defibrillator. BACKGROUND: For atrial defibrillation therapy to be feasible in an implantable form, AF must be detected in a specific fashion, and the risk of ventricular proarrhythmia should be minimized. METHODS: Eleven patients with AF underwent testing with an implantable atrial defibrillator (METRIX 3000 Automatic Atrial Defibrillator, InControl, Inc.). Wideband electrograms (EGMs) were recorded from the right ventricular (RV) bipolar catheter and from the multipolar catheters located in the right atrium (RA) and coronary sinus (CS). Atrial fibrillation detection was performed using two serial algorithms-quiet interval analysis and baseline crossing analysis-that detect atrial activity on the RA-CS channel. Ventricular sensing using a minimal preceding synchronization interval of 500 ms as a criterion for synchronous shock delivery was performed from filtered RV and RV-CS EGMs. RESULTS: The AF detection algorithms were applied to 53 AF data segments and 18 normal sinus rhythm data segments. Atrial fibrillation was detected appropriately in 49 instances, and the specificity for detecting AF and normal sinus rhythm was 100%. Synchronization criterion efficacy was assessed by delivering shock markers and shocks. Of the 2,025 R waves processed, 557 (27.5%) were marked as suitable for shock delivery. In addition, 69 therapeutic and 11 test shocks were delivered during AF. All shock markers and shocks were delivered synchronously with the R wave, and the synchronization criterion was never violated. CONCLUSIONS: Atrial fibrillation can be detected in a specific fashion using the RA-CS lead configuration and serial detection algorithms for atrial sensing. The delivery of properly timed shocks is feasible and should minimize the risk of ventricular proarrhythmia.

Adult↗
PubMed1996

Unmasking the trifascicular left intraventricular conduction system by ablation of the right bundle branch.

Twenty-five patients underwent transcatheter right bundle ablation either for bundle branch reentrant tachycardias or inadvertent or deliberate right bundle ablation during atrioventricular junctional ablation for rate control. Electrophysiologic data and 12-lead electrocardiograms before and after right bundle ablation were available in all patients. Eleven of the patients had no significant intraventricular conduction abnormalities by surface electrocardiograms (group I), whereas 14 patients had underlying intraventricular conduction delays (group II). All group I patients had typical electrocardiographic changes of right bundle branch block after right bundle ablation, with minimal changes in initial or mean QRS axis. In group II, 5 patients had an initial 40 ms QRS axis shift of > 45 degrees, in 7 patients the mean QRS axis changed significantly (leftward in 4 and rightward in 3), and a qR pattern in V1 was seen in 12 of 14 patients including 2 with structurally normal hearts. These changes, namely new Q waves, and rightward and leftward axis shifts are most likely the result of septal fascicular, left posterior fascicular, and left anterior fascicular delay/block, which were exposed by exclusive conduction via a diseased left bundle and its fascicles. The trifascicular nature of left intraventricular conduction is more apparent when diseased and unmasked by concomitant block in the right bundle branch.

Aged↗
PubMed1996

Distribution of atrial electrogram types during atrial fibrillation: effect of rapid atrial pacing and intercaval junction ablation.

OBJECTIVES: This study examined the anatomic distribution types and possible determinant of atrial electrogram types during atrial fibrillation. BACKGROUND: Different types of atrial electrograms during atrial fibrillation have been observed and classified, but their anatomic distribution patterns, determinants and potential usefulness in guiding future catheter ablation are unknown. METHODS: Two animal models of atrial fibrillation were used: the sterile pericarditis model (n = 10) and the rapid atrial pacing model (400 beats/min for 6 weeks, n = 6). The atrial electrogram of atrial fibrillation and the atrial effective refractory period were obtained from multiple sites of the right and left atrium. In addition, decremental rapid atrial stimulation was applied to the site of shortest and longest atrial effective refractory periods until atrial fibrillation induction in a subgroup of nine dogs. Ablation of the intercaval junction was performed using the radiofrequency catheter technique in dogs with atrial fibrillation duration > 1 min. RESULTS: In both models, organized atrial electrograms (type I) were predominantly observed at the left atrial sites and the right atrial appendage, whereas disorganized atrial electrograms (type III) were mainly observed at the right posterolateral atrium. The distribution of the atrial electrogram types closely followed that of the atrial effective refractory period, with the shortest atrial effective refractory period corresponding to organized atrial electrograms (type I) and the longest atrial effective refractory period corresponding to disorganized atrial electrograms (type III). The correlation of atrial electrogram type with the atrial effective refractory period was further demonstrated by the effect of rapid atrial stimulation. When rapid atrial stimulation was applied to the site with the shortest atrial effective refractory period, disorganized atrial electrograms were observed at sites with the longest atrial effective refractory period, whereas 1:1 atrial capture was still present at the stimulation site. Ablation of the intercaval junction made atrial fibrillation noninducible or tended to shorten the atrial fibrillation duration (from 26.4 +/- 24.2 to 8.8 +/- 22.6 min in the pericarditis group, p = 0.02, and from 33.7 +/- 29.2 to 12.1 +/- 23.8 min in the rapid pacing group, p = 0.09) but did not change the atrial electrogram types during atrial fibrillation. CONCLUSIONS: Various types of atrial electrograms are present at different locations during atrial fibrillation. The atrial electrogram characteristics of atrial fibrillation at a specific location are related to the atrial effective refractory period, with short effective refractory periods associated with organized atrial electrograms and long effective refractory periods associated with disorganized electrograms.

Animals↗
PubMed1996

Sudden death in patients with implantable cardioverter-defibrillators.

UNLABELLED: Of the 733 patients with implantable cardioverter-defibrillators (ICDs) from 1982 to 1995 in our center, 20 died suddenly while the ICD was activated. This number included 16 men and four women with a mean age of 60 +/- 8 years and ejection fractions of 24.2% +/- 8.6%. ICDs were implanted for drug refractory ventricular tachycardia (VT) in 13 patients and for resucitated cardiac arrest in seven patients. The clinical VT was associated with syncope in 7 of 13 patients. VT was induced in 18 patients and was hemodynamically unstable in 12 patients. Shock therapies associated with syncope were delivered in 7 of 15 patients during the follow-up. This subgroup of patients survived a median of only 18 months after ICD implant. Ventricular fibrillation-defibrillation was found to surround death in nine patients. CONCLUSIONS: (1) Sudden death victims of the ICD population are characterized by poor left ventricular function and hemodynamically unstable ventricular tachyarrhythmias. (2) Ventricular tachyarrhythmias are the major cause of sudden death in ICD patients.

Aged↗
PubMed1996

Relative efficacy of different tilts with biphasic defibrillation in humans.

OBJECTIVE: The goal of this study was to assess if tilt bears any impact on defibrillation efficacy of biphasic shocks. BACKGROUND: Although it has been shown that biphasic waveform may increase the defibrillation efficacy, this pulsing method has not been as extensively studied in patients, and information regarding the effect of different tilts is lacking. METHODS: This study consisted of two similar but distinct protocols including 33 patients undergoing transvenous defibrillator implant. In 17 patients (Part I) defibrillation threshold was obtained delivering biphasic waveforms with 50%, 65%, and 80% tilt in random fashion. Similarly, in 16 patients (Part II) testing of biphasic waveform with 40%, 50%, and 65% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 33 patients. RESULTS: In Part I, tilt of 50% demonstrated a defibrillation threshold significantly lower than 65% tilt (7.5 +/- 4.3 J vs 9.7 +/- 5.0 J; P = 0.04) and 80% tilt (7.5 +/- 4.3 J vs 11.7 +/- 5.9 J; P < 0.01). Similarly, 65% tilt provided a lower defibrillation threshold than 80% tilt (9.7 +/- 5.0 J vs 11.7 +/- 5.9 J; P = 0.02). In Part II, no significant difference was observed in terms of defibrillation threshold between 40% tilt and the two tilts of 50% and 65%. However, as in Part I, 50% tilt provided a significant reduction of the energy to defibrillate as compared to 65% tilt (6.3 +/- 3.6 J vs 9.0 +/- 4.8 J; P < 0.01). The 50% tilt resulted in better defibrillation efficacy than 65% tilt independent of the lead system used for testing (Medtronic Transvene and CPI Endotak-C). CONCLUSIONS: Biphasic shocks with 50% tilt required less energy for defibrillation than 40%, 65%, and 80% tilts. However, in the clinical setting a programmable tilt may be preferable to account for some patient-to-patient variability.

Adult↗
PubMed1996

Primary synovial chondromatosis--a case report.

Synovial chondromatosis are rare tumours encountered in hip, knee and shoulder joints. Synovial chondromatosis at metatarso-phalangeal joints are still rarer. Herein is reported a case of primary synovial chondromatosis of metatarsophalangeal joint in 54-year-old male. A brief review of previous published articles has been dealt herewith.

Chondromatosis, Synovial↗
PubMed1995

Provocation of hypotension during head-up tilt testing in subjects with no history of syncope or presyncope.

BACKGROUND: Head-up tilt test is increasingly being used to evaluate patients with syncope. This study was designed to evaluate the specificity of head-up tilt testing using different tilt angles and isoproterenol infusion doses in normal volunteers with no prior history of syncope or presyncope. METHODS AND RESULTS: One hundred fifty volunteers were randomized to two groups of 75 each. In group 1, subjects were further randomized to have head-up tilt testing at a 60, 70, or 80 degree angle at baseline followed by repeat tilt testing during a low-dose isoproterenol infusion that increased the heart rate by an average of 20%. In group 2, after having a baseline head-up tilt test at a 70 degree angle for a maximum of 20 minutes, subjects were randomized to have a repeat tilt table testing at a 70 degree angle during a low-dose, 3 micrograms/min, or 5 micrograms/min isoproterenol infusion. In group 1, syncope or presyncope along with hypotension developed in 2 subjects during the baseline test at 60 and 70 degrees of tilt and in 5 subjects during tilting at 80 degrees. The addition of low-dose isoproterenol reduced the specificity minimally from 92% to 88% at both 60 and 70 degrees of tilt but substantially to 60% at an 80 degrees angle. However, 6 of the 10 subjects with a positive test at an 80 degree angle had an abnormal response after 10 minutes of tilt testing. In group 2, using various isoproterenol doses with tilt table testing at a 70 degree angle, low-dose (mean infusion dose, 1.5 +/- 0.45 microgram/min), 3 micrograms/min, and 5 micrograms/min isoproterenol infusions elicited an abnormal response in 1 (4%), 5 (20%), and 14 (56%) of the subjects, respectively. Using multiple logistic regression analysis, head-up tilt testing at an 80 degree angle (P = .01) or during 3 micrograms/min (P = .02) and 5 micrograms/min isoproterenol infusion rates (P < .001) was the most significant predictor of an abnormal response. CONCLUSIONS: Head-up tilt testing at a 60 or 70 degree angle with or without low-dose isoproterenol infusion provides an adequate specificity. Caution is needed, however, in interpreting the results if the head-up tilt test at 80 degrees is extended beyond 10 minutes or if high doses of isoproterenol are used.

Adult↗
PubMed1995

Comparison of flash-induced light-scattering transients and proton efflux from auxinic-herbicide resistant and susceptible wild mustard protoplasts: a possible role for calcium in mediating auxinic herbicide resistance.

Comparison of flash-induced light-scattering signals from protoplasts of auxinic herbicide-resistant ('R') and -susceptible ('S') wild mustard biotypes suggest that ATP-dependent activity manifested as a conformational change differs between the biotypes. The signal obtained from R protoplasts is unaffected by 50 microM picloram, an auxin analogue. In comparison, the signal amplitude from the S protoplasts decreases 40% in 20 microM picloram and is abolished in 50 microM picloram. Signal amplitude from the R protoplasts can be decreased by simultaneous incubation with 50 microM picloram and 50 microM verapamil, a calcium channel blocker. Incubation of the S protoplasts with the calcium ionophore A23187 in the presence of 0.5 mM calcium reduced the inhibitory effect of picloram. Absorbance spectrophotometry using acridine orange as a pH indicator suggests that picloram affects the proton flux in the S biotype only. Based on these results, we hypothesize that picloram affects the calcium and hydrogen dynamics in the S biotype. Because the scattering characteristics of S protoplasts incubated with picloram can be nearly reproduced in the R protoplasts by simultaneous incubation with picloram and verapamil, calcium may have a significant role in modulating auxinic herbicide resistance. To our knowledge, this is the first report to implicate such a role for calcium.

Acridine Orange↗
PubMed1995

Termination of atrioventricular nodal reentrant tachycardia by premature stimulation from ablating catheter. A reliable guide to identify site for slow-pathway ablation.

BACKGROUND: Slow-pathway ablation is currently used more frequently to control atrioventricular nodal reentrant tachycardia (AVNRT). However, in patients with the common type of AVNRT, successful ablation of the slow pathway can be difficult and time-consuming. We tested a simple method to predict a site for slow-pathway ablation in patients with AVNRT of the common variety. METHODS AND RESULTS: Twenty patients with symptomatic common AVNRT (13 women and 7 men; mean age, 41 +/- 21 years) were included in the study. Once the AVNRT had a stable cycle length (+/- 10 ms) for at least 20 cycles, single extrastimuli were delivered from the ablating catheter tip beginning with 20 ms less than the tachycardia cycle length and decrementing by 10 ms until tachycardia terminated or loss of capture occurred at the pacing site. The pacing protcol was performed systematically in a stepwise fashion at four adjacent sites starting from the posterior/inferior interatrial septum near the tricuspid annulus and moving progressively more anteriorly. The pacing protocol was then repeated in the same sequence, followed by delivery of radiofrequency current at each site to determine its effect at sites where AVNRT could not be terminated with a pacing protocol. AVNRT could be terminated in the anterograde direction from at least one site in 19 patients. Tachycardia could be terminated at two or more adjacent sites in 5 patients. The longest atrial coupling interval at the site of tachycardia termination was 67 +/- 27 ms (range, 30 to 130 ms) less than the AVNRT cycle length. Resetting of subsequent His bundle depolarization (H2), producing an H-H2 interval prolongation of 26 +/- 24 ms (range, 10 to 80 ms), occurred in 17 patients before termination of the tachycardia. In 18 of the 19 patients, the slow pathway was successfully ablated at the site at which AVNRT was terminated at the longest atrial coupling interval. CONCLUSIONS: Termination of tachycardia in the anterograde direction at the longest atrial coupling interval by extrastimuli delivered from the ablating catheter can be helpful for identification of an optimal site for slow-pathway ablation in patients with the common variety of AVNRT.

Adult↗
PubMed1995

Relevance of asystole during head-up tilt testing.

The prognosis of patients manifesting prolonged asystole during head-up tilt testing is unclear. In 209 consecutive patients with a history of syncope and positive head-up tilt tests, 19 had asystole lasting > 5 seconds (mean duration 15 +/- 10) (group 1a). When compared with patients without asystole (group 1b), group 1a patients were younger (32 +/- 12 vs 47 +/- 21 years, p < 0.005), but clinical manifestations were not any more dramatic (the number of episodes of syncope [7 +/- 5 vs 8 +/- 6 episodes, p = NS] and injury during syncope [2 vs 13 patients, p = NS] were similar). During follow-up (mean 2 +/- 1 year), with the patient taking pharmacologic therapy such as beta blockers, ephedrine, theophylline, or disopyramide, the recurrence rate was 11% and 8% in groups 1a and 1b (p = NS). No patient in the asystole group underwent pacemaker implantation. Additionally, of 75 normal volunteers (group 2) with no history of syncope undergoing tilt tests to define its specificity, 3 had asystole (mean duration 10 seconds). During > 1 year of follow-up, despite no treatment, all 3 are symptom free. Thus, asystole during head-up tilt testing does not predict either a more malignant outcome or a poor response to pharmacologic therapy. Moreover, an asystolic response does not enhance the specificity of the head-up tilt test because it may be present in asymptomatic "normal" volunteers.

Adolescent↗
PubMed1995

Comparison of biphasic and monophasic pulses: does the advantage of biphasic shocks depend on the waveshape?

With present implantable defibrillators, the ability to vary the defibrillation technique has been shown to increase the number of patients suitable for transvenous system. As newer waveforms become available, the need for a flexible device may change. In addition, although it has been shown that the option of biphasic waveform may increase the defibrillation efficacy, this may depend upon the shape of the biphasic waveform used. Thirty patients undergoing transvenous defibrillator implant were included in the study. In 20 patients (group I), defibrillation efficacy of simultaneous monophasic, sequential monophasic, and biphasic waveform with 50% tilt was determined randomly. Similarly, in ten patients (group II) testing of simultaneous monophasic shocks and biphasic waveforms with 65% and 80% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 30 patients. In group I, 50% tilt biphasic waveform consistently provided similar or better defibrillation efficacy compared to monophasic waveforms (biphasic 7.5 +/- 5.1 joules vs simultaneous 17 +/- 7.8 joules, P < 0.01; and vs sequential 17 +/- 8.4 joules, P < 0.01). In group II, 65% tilt biphasic pulse required less energy for defibrillation as compared with simultaneous monophasic shocks (9.6 +/- 4.5 joules vs 15.6 +/- 5.1 joules, P = 0.04). No significant difference was observed in terms of defibrillation threshold between 80% tilt biphasic shocks and simultaneous monophasic pulses (11.8 +/- 6 joules vs 15.6 +/- 5.1 joules, P = NS). Biphasic shocks with smaller tilt delivered using a triple lead system more uniformly improved defibrillation threshold over standard monophasic waveforms.

Defibrillators, Implantable↗