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Biomedical subjects

S Nath

Publications and source records attributed to S Nath.

At least 19 recordsLinked to original sources
PubMed2001

Role of calcium in acute hyperthermic myocardial injury.

INTRODUCTION: We hypothesized that intracellular calcium overload may play an important role in heat-induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free-calcium concentration and the fluorescence changes of Fluo-3 AM dye was measured as a direct indicator of cytosolic free-calcium concentration. METHODS AND RESULTS: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high-flow tissue bath and superfused with Tyrode's solution at 37 degrees +/- 0.5 degrees C. The temperature was rapidly changed to between 38.0 degrees and 56.0 degrees C for 60 seconds and then returned to 37.0 degrees C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45 degrees and 50 degrees C and irreversible contracture at > or =50 degrees C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 microM Fluo-3 AM dye demonstrated that the hyperthermia-induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 microM thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45 degrees and 50 degrees C and significant increases in Fluo-3 fluorescence at 48 degrees C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 microM verapamil did not attenuate the heat-induced increase in resting tension and Fluo-3 fluorescence. CONCLUSION: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel-independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.

Acute Disease↗
PubMed2000

Kinetic model of ATP synthase: pH dependence of the rate of ATP synthesis.

Recently, a novel molecular mechanism of torque generation in the F(0) portion of ATP synthase was proposed [Rohatgi, Saha and Nath (1998) Curr. Sci. 75, 716-718]. In this mechanism, rotation of the c-subunit was conceived to take place in 12 discrete steps of 30 degrees each due to the binding and unbinding of protons to/from the leading and trailing Asp-61 residues of the c-subunit, respectively. Based on this molecular mechanism, a kinetic scheme has been developed in this work. The scheme considers proton transport driven by a concentration gradient of protons across the proton half-channels, and the rotation of the c-subunit by changes in the electrical potential only. This kinetic scheme has been analyzed mathematically and an expression has been obtained to explain the pH dependence of the rate of ATP synthesis by ATP synthase under steady state operating conditions. For a single set of three enzymological kinetic parameters, this expression predicts the rates of ATP synthesis which agree well with the experimental data over a wide range of pH(in) and pH(out). A logical consequence of our analysis is that DeltapH and Deltapsi are kinetically inequivalent driving forces for ATP synthesis.

Adenosine Triphosphate↗
PubMed2000

Kinetic modeling of ATP synthesis by ATP synthase and its mechanistic implications.

Based on the torsional mechanism of ATP synthesis by ATP synthase, a kinetic scheme has been developed in this work. The scheme considers adenine nucleotide transport, binding of substrates ADP and P(i), unbinding of product ATP, and ATP synthesis. This kinetic scheme has been analyzed mathematically, and a kinetic model has been obtained to explain the experimentally observed hyperbolic Michaellian dependence of the rate of ATP synthesis on the ADP concentration by ATP synthase under physiological steady-state operating conditions. The principal results of the kinetic model have been compared with the experimental data and an estimate of the enzymological kinetic parameters V(max), K(M), and K(I) has been determined. Mechanistic implications arising from further analysis of the kinetic model have been discussed. These biological implications provide deep insight into the sequence of events leading to ATP synthesis.

Adenosine Diphosphate↗
PubMed2000

Debilitating chronic pain syndromes after presumed intraneural injections.

This report presents seven patients with severe disability established at the time of a peripheral nerve block. In most of the cases, the injection was administered as a routine procedure by an experienced anesthesiologist. The patient histories suggest that the condition, which can be resistant to all treatment, in most cases could have been avoided if careful attention had been given to the occurrence of pain during the nerve block. It is likely that the risk of devastating iatrogenic disability can be minimized if a few basic principles are respected during the administration of peripheral nerve blocks.

Adult↗
PubMed2000

Dosimetric effects of needle divergence in prostate seed implant using 125I and 103Pd radioactive seeds.

In prostate seed implants, radioactive seeds are implanted into the prostate through a guiding needle with the help of a template and real-time imaging. The ideal locations of the guiding needles and the relative positions of the seeds in each needle are determined before the implantation under the assumption that the needles inserted at different locations will remain parallel. In actual implantation, the direction of the needle is subject variation. In this work, we studied how the dosimetry quality of an implant may be affected when the guiding needles deviate from its planned orientations. Needle divergence of varying degree was simulated on spherical models and actual patient implants. It was found that needle divergence degraded the dosimetric quality of an implant: The minimum target dose, the target dose coverage and therefore the tumor biological effective dose were quantitatively decreased as compared to the reference implant. The magnitude of degradation increased almost linearly with respect to the magnitude of needle divergence. For iodine-125 implants, the average reduction in minimum target dose was about 10% and 20% for needle divergence of standard deviation of 5(0) and 10(0), respectively. The dose coverage in the target was reduced by about 1% and 3% for needle divergence of standard deviation of 5(0) and 10(0), respectively. Implants designed with palladium-103 showed additional 5% reduction in minimum target dose while the effect on dose coverage was about the same as compared to the iodine-125 implants. The degree of dosimetry degradation was shown to be dependent on the size of target volume, the seed spacing used, the use of seeding margin, and on the actual configuration of needle orientations in a given implant. One needs to minimize the physical causes of needle divergence in order to minimize its impact on planned dosimetry. The study suggests that the displacement between a needle image and its planned grid point at the base of prostate should be kept less than 5 mm in order to minimize the reduction in D(min)(<5%) and the increase in cell-survival (< a factor of 10) from the planned dosimetry.

Biophysical Phenomena↗
PubMed1999

Surface Tension of Nonideal Binary Liquid Mixtures as a Function of Composition.

The composition dependence of the surface tension of highly nonideal organic-organic and aqueous-organic nonelectrolyte solutions is described, based on the assumption that the surface layer can be treated as a separate phase located between vapor and bulk liquid phases. The Wilson, NRTL, and UNIFAC methods are used for activity coefficients of surface and bulk phases and three techniques for calculation of molar surface areas, based on Paquette areas, Rasmussen areas, and a Langmuir-type approach are tested. Comparisons of the calculated surface tensions with experimental data yield mean absolute errors, in the best case, of less than 2.5% for the systems studied, all of which exhibit highly nonideal behavior. The surface tension predictions are found to be extremely sensitive to the values of the molar surface areas used in the computation. A Langmuir-type adsorption model is formulated to determine the surface mole fractions from a knowledge of the mixture surface tension as a function of bulk composition. A novel procedure is developed to obtain the partial molar surface area of the larger organic component as a function of composition in binary aqueous-organic systems, assuming that the two components are very dissimilar in size, and that deviations in the partial molar surface area of the smaller component (water) from its pure component molar surface area contribute negligibly to the total molar surface area of the mixture. This removes the approximation of equality of partial and pure component molar surface area for the larger organic component. Use of the Langmuir-type approach with partial molar surface areas improves surface tension predictions of highly nonideal aqueous-organic mixtures by 20% over use of pure component molar surface areas. It is an important first step in the development of a thermodynamically consistent theory of surfaces for liquid mixtures based on an accurate determination of the composition dependence of partial molar surface areas for all components. Copyright 1999 Academic Press.

Journal Article↗
PubMed1998

Total loss of upper and lower lips: challenges in reconstruction.

A 2-year-old girl lost both lips after an aggressive attack of noma (gangrenous stomatitis). After an unsuccessful attempt to reconstruct her upper lip, a bipedicled chin flap was used to reconstruct both lips. The cosmetic result was good and the functional result was acceptable.

Child, Preschool↗
PubMed1998

Cancrum oris: management, incidence, and implications of human immunodeficiency virus in Zambia.

The University Teaching Hospital is situated in the Zambian capital, Lusaka. In a 15-year period (1979 to 1993), 81 child patients with cancrum oris were admitted to the pediatric plastic surgery unit. There were 29 boys and 52 girls, of whom 58 were below 3 years of age. The majority of them were from certain provinces where the population is comparatively much lower than in other provinces of Zambia. The dietary habits in cancrum orisprone provinces are quite different than those of other provinces of Zambia. Of 81 patients, 3 refused surgery, 11 died during early medical treatment, and 12 died following early minor surgery. A total of 55 patients had reconstructive surgery by one of the authors (Nath). Problems encountered during management, such as anesthesia, trismus, and choice of appropriate flaps, are discussed in this paper. The implication of human immunodeficiency virus is also addressed.

AIDS-Related Opportunistic Infections↗
PubMed1997

Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or midseptal regions in most cases.

Adult↗
PubMed1997

Influence of patient characteristics in the selection of patients for defibrillator implantation (the AVID Registry). Antiarrhythmics Versus Implantable Defibrillators.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial is a prospective, randomized study of treatment for life-threatening ventricular arrhythmias. Patients who are eligible for the main trial but who are not enrolled for any reason are followed in a registry. The objective of the present study was to determine whether there are identifiable patient characteristics among these registry patients that may influence whether a patient is treated with an implantable defibrillator. The 914 patients in the registry were divided into 2 groups according to whether the primary treatment was an implantable defibrillator. The mean age of defibrillator patients was 60 years, compared with 65 years in the nondefibrillator group (p <0.001). Only 11.2% of defibrillator recipients were minorities, whereas the percentage of minorities in the nondefibrillator group was 18.7% (p <0.003). A history of recurrent ventricular fibrillation was more likely in the group treated with defibrillators (8.9% vs 4.4%, p <0.01), whereas a history of atrial fibrillation or diabetes mellitus were both significantly more likely in the nondefibrillator group. Among defibrillator patients, a higher proportion had ventricular fibrillation as the index arrhythmia; patients with ventricular tachycardia were significantly more likely to be treated without devices. In this prospective but nonrandomized cohort of patients treated for life-threatening ventricular arrhythmias, older age, minority status, and comorbidity reduced the chances that a patient would be treated with a defibrillator.

Aged↗
PubMed1997

The inhibition of growth and down-regulation of gonadotropin releasing hormone (GnRH) receptor in alphaT3-1 cells by GnRH agonist.

Gonadotropin releasing hormone (GnRH) and its analogs inhibit the growth of hormone-dependent tumors in vivo and in vitro. The inhibition of growth and proliferation of tumor cells in vitro by GnRH and its analogs indicates that the tumor suppressing effect of the hormone is only partially due to suppression of pituitary gonadotropin release which reduces circulating steroid levels that are required for proliferation. Demonstration of GnRH-binding sites on some tumors suggests a direct inhibitory effect of GnRH and its analogs. However, the mechanism by which GnRH and its analogs inhibit tumor cell growth is not known. Our hypothesis is that the inhibition of growth and proliferation of tumor cells by GnRH and its analogs are mediated through down-regulation of its receptor expression. To test this hypothesis, mouse pituitary gonadotrope cell line (alphaT3-1) was selected as a model since this is the only cell line which expresses a sufficiently high level of GnRH receptors for precise measurements of the mRNA for the receptor. Addition of GnRH agonist (D-Lys6)GnRH to the cell cultures caused a time-dependent decrease in both cell growth, as measured by cell number, and cell proliferation, as measured by [3H]thymidine incorporation into DNA. After 1 h of treatment of alphaT3-1 cells with 1 microM of (D-Lys6)GnRH, the cell number was reduced to 83.0 +/- 13.4 compared to control, decreased to 75.1 +/- 3.2 at 2 h, 63.2 +/- 0.66 at 4 h and 52.2 +/- 0.87 at 24 h. This decrease in cell number was accompanied by a parallel decrease in [3H]thymidine incorporation into DNA. The inhibition of cell growth and [3H]thymidine incorporation by treatment with 1 microM of (D-Lys6)GnRH was sustained for at least 72 h. Inhibition of alphaT3-1 cell growth and [3H]thymidine incorporation was dose-dependent; thus 10(-9) M (D-Lys6)GnRH resulted in about 30% inhibition within 4h which was comparable to 10(-6) M (D-Lys6)GnRH, whereas 10(-12) M (D-Lys6)GnRH was ineffective. Measurement of mRNA for the GnRH receptor by Northern blot analysis showed a decrease in levels of mRNA by 5% within 2 h of treatment of alphaT3-1 cells with 1 microM (D-Lys6)GnRH, by 30% at 4 h and by 50% at 24 h. In conclusion these data demonstrate that treatment of alphaT3-1 cells with (D-Lys6)GnRH causes an inhibition of cell growth and proliferation, and down-regulates the GnRH receptor mRNA levels.

Animals↗
PubMed1996

Atrial rhythm after atrioventricular junctional ablation.

Atrioventricular (AV) junctional ablation followed by pacemaker implantation is an established treatment for patients with refractory paroxysmal atrial arrhythmias. The stability of the underlying atrial rhythm after AV junctional ablation is unknown. This study evaluates the atrial rhythm after AV junctional ablation in 49 patients with medically refractory atrial arrhythmias. The group included 25 men and 24 women, of whom 36 had known structural heart disease. Paroxysmal atrial fibrillation was the primary rhythm disturbance in 41 patients, whereas 8 manifested either atrial tachycardias or atrial flutter. All patients had failed therapy with > or = 1 antiarrhythmic drug. Chronic pacing modes were DDIR or DDDR, with mode switching in 15 patients and VVIR in 34 patients. After AV junctional ablation, chronic antiarrhythmic drug therapy was prescribed in only 4 patients (8%). Routine electrocardiograms (ECGs; 6.5 +/- 6.1/patient) during long-term follow-up (18.6 +/- 15.6 months) showed that 7 patients (14%) had an atrial arrhythmia detected on all ECGs, 30 patients (61%) had sinus or atrial-paced rhythms on all recordings, and 12 patients (25%) had both atrial arrhythmias and sinus rhythm documented. Sinus or an atrial-paced rhythm was present on the last available ECG in 33 of 49 patients (67%). Pacing mode was not a predictor of continued sinus rhythm. In conclusion, most patients with a history of paroxysmal atrial tachyarrhythmias will not convert to chronic atrial arrhythmias after AV junctional ablation, even in the absence of antiarrhythmic drug therapy. Use of dual-chamber pacing modes will allow maintenance of at least intermittent atrial function in these patients.

Aged↗
PubMed1996

Sensing lead-related complications in patients with transvenous implantable cardioverter-defibrillators.

The widespread use of the redesigned Endotak lead (CPI, St. Paul, Minnesota), which combines transvenous pacing, sensing, and defibrillation on a single transvenous lead in patients receiving transvenous implantable cardioverter-defibrillators (ICDs), has reduced morbidity and shortened length of hospital stay after ICD implantation. We describe the incidence and management of Endotak sensing lead-related failures in a series of 348 consecutive patients from 4 institutions who underwent implantation between 1990 and 1995. We retrospectively reviewed the databases for patients receiving an ICD with an Endotak lead for the incidence of lead-related sensing abnormalities. Ten patients (2.8%) with lead-related sensing abnormalities were detected at a mean of 15 +/- 11 months after ICD implantation. Sensing abnormalities were detected in 6 patients after they received inappropriate shocks. Noise or oversensing was noted in 7 patients from interrogation of the devices' data logs. Eight patients had a new transvenous sensing lead placed, 1 patient had a new Endotak lead placed, and 1 had a chronic pacemaker sensing lead converted to function as a sensing lead. No further sensing problems were noted in 8 of 10 patients during a mean follow-up of 14 +/- 8 months. The site of the sensing lead failure was localized to the subrectus pocket in 5 patients and to the clavicle-first rib area in 3 patients; it was undetermined and presumed to be in the clavicle-first rib area in the other 2 patients. One patient had late failure of the defibrillation lead. We conclude that Endotak sensing lead failure does not require insertion of a new Endotak lead, but can be managed with close follow-up and insertion of a new transvenous sensing lead. Endotak lead fractures are frequently localized to the ICD pocket.

Aged↗
PubMed1996

Effects of dispersive electrode position and surface area on electrical parameters and temperature during radiofrequency catheter ablation.

Positioning of the dispersive electrode has no significant effect during radiofrequency ablation. Doubling the surface are of the dispersive electrode results in a lower impedance, higher current delivery, and increased tip temperatures, particularly if the baseline impedance is >100 ohms. These findings may have important implications for optimizing radiofrequency energy delivery using currently available radiofrequency generators.

Cardiac Catheterization↗