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Biomedical subjects

S Hegde

Publications and source records attributed to S Hegde.

At least 19 recordsLinked to original sources

Using combined x-ray and MR imaging for prostate I-125 post-implant dosimetry: phantom validation and preliminary patient work.

Post-implantation dosimetry is an important element of permanent prostate brachytherapy. This process relies on accurate localization of implanted seeds relative to the surrounding organs. Localization is commonly achieved using CT images, which provide suboptimal prostate delineation. On MR images, conversely, prostate visualization is excellent but seed localization is imprecise due to distortion and susceptibility artefacts. This paper presents a method based on fused MR and x-ray images acquired consecutively in a combined x-ray and MRI interventional suite. The method does not rely on any explicit registration step but on a combination of system calibration and tracking. A purpose-built phantom was imaged using MRI and x-rays, and the images were successfully registered. The same protocol was applied to three patients where combining soft tissue information from MRI with stereoscopic seed identification from x-ray imaging facilitated post-implant dosimetry. This technique has the potential to improve on dosimetry using either CT or MR alone.

Aged↗

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging.

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Algorithms↗

End stage renal disease due to bilateral renal malakoplakia.

Malakoplakia typically affects the bladders of immunocompromised adults who have defective intracellular killing of Escherichia coli. Renal malakoplakia is rare in children and generally has a good outcome. In the case presented, however, it caused end stage renal failure in a 5 year old girl. The management dilemmas surrounding renal transplantation are highlighted.

Anti-Bacterial Agents↗

What can structure tell us about in vivo function? The case of aminoglycoside-resistance genes.

Resistance to antibiotics used in the treatment of bacterial infections is an expanding clinical problem. Aminoglycosides, one of the oldest classes of natural product antibiotics, exert their bactericidal effect as the result of inhibiting bacterial protein synthesis by binding to the acceptor site of the 30 S ribosomal subunit. The most common mechanism of clinical resistance to aminoglycosides results from the expression of enzymes that covalently modify the aminoglycoside. We will discuss the enzymology and structure of two representative chromosomally encoded aminoglycoside N-acetyltransferases, Mycobacterium tuberculosis AAC(2')-Ic and Salmonella enterica AAC(6')-Iy, and speculate about their possible physiological function and substrates.

Acetyltransferases↗

Mapping of electrostatic potential in deep submicron CMOS devices by electron holography.

Quantitative two-dimensional maps of electrostatic potential in device structures are obtained using off-axis electron holography with a spatial resolution of 6 nm and a sensitivity of 0.17 V. Estimates of junction depth and variation in electrostatic potential obtained by electron holography, process simulation, and secondary ion mass spectroscopy show close agreement. Measurement artifacts due to sample charging and surface "dead layers" do not need to be considered provided that proper care is taken with sample preparation. The results demonstrate that electron holography could become an effective method for quantitative 2D analysis of dopant diffusion in deep-submicron devices.

Journal Article↗

Beta-endorphin infusion during exercise in rats does not alter hepatic or muscle glycogen.

The aim of this study was to determine whether beta-endorphin infusion influences liver or muscle glycogen concentration during exercise. Thirty-two rats (Harlan Co., IN, USA) with a body mass of 265-290 g were assigned at random to four groups, each of eight rats: (1) beta-endorphin infusion for 90 min at rest; (2) beta-endorphin infusion for 90 min while running on a rodent treadmill at 22 m x min(-1) and 0% grade; (3) saline infusion (0.9% NaCl) for 90 min at rest; and (4) saline infusion for 90 min while running on a rodent treadmill at 22 m x min(-1) and 0% grade. Beta-endorphin infusion elevated plasma beta-endorphin concentration by 2.5-fold at rest compared with saline infusion at rest, and by two-fold after exercise compared with saline infusion after exercise. Beta-endorphin infusion attenuated exercise-induced glucose concentration but did not alter the fasting hepatic glycogen concentration at rest or after exercise compared with saline infusion. Fasting hepatic glycogen decreased significantly as a result of 90 min of exercise independent of treatment. Deep intermedius muscle glycogen concentration at rest was similar after 90 min of both beta-endorphin and saline infusion and decreased significantly as a result of 90 min of exercise independent of treatment. Our results suggest that liver and muscle glycogenolysis is not responsible for the differences in plasma glucose with beta-endorphin infusion during exercise.

Animals↗

Clotting and fibrinolytic activity change during the 1 h after a submaximal run.

PURPOSE: To determine the changes in clotting and fibrinolytic activity during the 1-h period after an acute submaximal exercise at a specific relative exercise intensity to ascertain whether during this time there is a greater risk for developing a clot formation or thrombus. METHODS: Ten healthy men reported between 0700 and 1000 h and ran at 70-75% VO2max or walked at 1.2 mph for 30 min in a random counter-balanced order. Venous blood was obtained at rest, immediately after, and every 20 min during the 1-h recovery. RESULTS: There were no differences in the resting parameters for each treatment. Walking did not alter the activity of any of the measures analyzed compared with rest. Clotting indicators activated partial thromboplastin time (APTT) was significantly decreased by approximately 2 s and remained at this level during the 1-h recovery, and factor VIII activity was elevated 66% immediately after the run and remained elevated at this level during the 1-h recovery period. Fibrinolytic indicators, t-PA, and D-dimers were significantly increased immediately after the run. However, t-PA demonstrated a quadratic negative slope during the 1-h recovery time. D-dimers remained elevated during the 1-h recovery time. CONCLUSIONS: These results suggest that running at 70-75% VO2max resulted in elevated clotting and fibrinolytic activity. However, the clotting activity was sustained during a time when fibrinolytic activity declined, which suggests a more favorable situation for clot formation during this time after exercise.

Adult↗

Management of an impacted, dilacerated mandibular left permanent first molar: a case report.

A case of an unerupted mandibular left permanent first molar, a partially erupted permanent second molar, and a congenitally absent third molar in a 12-year-old girl is described. The permanent first molar, being dilacerated and impacted, required surgical exposure of the crowns of the first and second molars and distalization of the second molar, with the help of a space regainer, to bring the molars into occlusion.

Anodontia↗

Effects of dopamine beta-hydroxylase inhibition with nepicastat on the progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure.

BACKGROUND: Inhibition of dopamine beta-hydroxylase (DBH) results in a decrease in norepinephrine synthesis. The present study was a randomized, blinded, placebo-controlled investigation of the long-term effects of therapy with the DBH inhibitor nepicastat (NCT) on the progression of left ventricular (LV) dysfunction and remodeling in dogs with chronic heart failure (HF). METHODS AND RESULTS: Moderate HF (LV ejection fraction [LVEF] 30% to 40%) was produced in 30 dogs by intracoronary microembolization. Dogs were randomized to low-dose NCT (0.5 mg/kg twice daily, n=7) (L-NCT), high-dose NCT (2 mg/kg twice daily, n=7) (H-NCT), L-NCT plus enalapril (10 mg twice daily, n=8) (L-NCT+ENA), or placebo (PL, n=8). Transmyocardial (coronary sinus-arterial) plasma norepinephrine (tNEPI), LVEF, end-systolic volume, and end-diastolic volume were measured before and 3 months after initiating therapy. tNEPI levels were higher in PL compared with NL (86+/-20 versus 13+/-14 pg/mL, P:<0.01). L-NCT alone and L-NCT+ENA reduced tNEPI toward normal (28+/-4 and 39+/-17 pg/mL respectively), whereas HD-NCT reduced tNEPI to below normal levels (3+/-10 pg/mL). In PL dogs, LVEF decreased but was unchanged with L-NCT and increased with L-NCT+ENA. L-NCT and L-NCT+ENA prevented progressive LV remodeling, as evidenced by lack of ongoing increase in end-diastolic volume and end-systolic volume, whereas H-NCT did not CONCLUSIONS: In dogs with HF, therapy with L-NCT prevented progressive LV dysfunction and remodeling. The addition of ENA to L-NCT afforded a greater increase in LV systolic function. NCT at doses that normalize tNEPI may be useful in the treatment of chronic HF.

Animals↗

Bilateral single-session percutaneous nephrolithotomy: a feasible and safe treatment.

BACKGROUND AND PURPOSE: The treatment of bilateral urinary calculus disease is often staged, irrespective of the modality of the treatment. Bilateral simultaneous percutaneous nephrolithotomy (PCNL) is still considered by many to be adventurous and risky. We carried out this prospective study of bilateral PCNL under a single anesthesia to study the feasibility, success rate, and complications if any. PATIENTS AND METHOD: From September 1996 to May 1999, 25 consecutive medically fit patients with bilateral renal calculi needing PCNL were subjected to bilateral PCNL under a single anesthesia. RESULTS: The PCNL could be accomplished bilaterally in 24 patients (96%). In one patient, the second-side PCNL was abandoned because of excessive bleeding on the first side. A total of 58 tracts and 27 sessions were required for complete treatment of the 48 renal units in the 24 successfully treated patients. The average operating time required for the procedure was 122 minutes. Nineteen patients were rendered stone free in one session, and two more patients were made stone free in a second session. Four renal units in three patients with residual calculi were cleared with double-J stenting and SWL. CONCLUSION: Bilateral PCNL in a single session is feasible and safe and can be carried out without increased morbidity. We advocate that an endourologist be prepared for bilateral PCNL in the patients in whom it is indicated. The opposite-side PCNL can be done if the first-side treatment is accomplished smoothly and in a reasonable time.

Adult↗

High-risk corneal allografts are capable of stimulating complement dependent cytolytic antibodies.

PURPOSE: To prospectively characterize serum antibody responses in high-risk corneal allografts. METHODS: Orthotopic and heterotopic C3H (H-2k) corneas were transplanted to CB6F1 (H-2b/d) recipient mice. Individual serum samples were collected at days 7, 14, 21, and 28 from orthotopically and heterotopically grafted mice. Samples were tested for anti-C3H antibodies using an enzyme-linked immunosorbent assay (ELISA). Serum samples were also tested for the ability to lyse target cells in the presence of complement. RESULTS: In high-risk donor-host combinations, 100% corneal allograft rejection occurs in the absence of IgG1 production. Both orthotopic and heterotopic corneal allografts induced cytolytic complement fixing antibody isotypes. CONCLUSIONS: Allospecific corneal antibody may be involved in corneal graft rejection in high-risk donor-host combinations.

Animals↗

Beta-endorphin infusion during exercise in rats: blood metabolic effects.

UNLABELLED: Beta-endorphin (betaE) bolus (0.05 mg x kg(-1)) infusion (0.05 mg x kg(-1) x h(-1)) was previously shown in rats to attenuate the decline in plasma glucose during exercise. PURPOSE: The present investigation compared betaE and saline infusion in rats without a bolus of betaE to determine whether 1) the attenuation in the glucose decline was attributable to the type of administration (bolus betaE + continuous betaE infusion vs continuous betaE infusion), and 2) whether circulating catecholamines or FFAs were in part involved in the glucose decline. METHODS: Forty untrained Sprague-Dawley rats were randomly assigned to one of four treatments: 1) betaE infusion at rest (betaR), 2) betaE infusion during exercise (betaX), 3) saline infusion at rest (SR), and 4) saline infusion during exercise (SX). Infusions (betaE or saline) with running (22 m x min(-1), 0% grade) lasted 90 min. RESULTS: A 2 x 2 ANOVA indicated betaE infusion significantly attenuated the decline in plasma glucose due to exercise at 90 min (SX = 4.16 +/- 0.1 vs betaX = 4.61 +/- 0.1 mM). BetaE infusion elevated plasma betaE about 2.5-fold at rest compared with SR and two-fold after exercise (betaX) compared with SX. BetaE infusion had no effect at rest on any of the other variables measured. Exercise significantly increased catecholamines, FFAs and glucagon compared with resting levels. BetaE infusion enhanced the glucagon response to exercise (SX = 577 +/- 67.5 vs betaX = 913 +/- 153 ng x L(-1), P < 0.02). Epinephrine and norepinephrine and FFAs were similar with betaE infusion either at rest or during exercise compared with saline infusion. CONCLUSION: These results suggest that betaE infusion independent of the betaE bolus can attenuate the decline in glucose during exercise by enhancing glucagon levels and the betaE infusion did not influence circulating catecholamines or FFA's response to exercise.

Animals↗

The role of cytotoxic T lymphocytes in corneal allograft rejection.

PURPOSE: Immunologic rejection constitutes a major barrier to the success of allogeneic corneal transplants, but the specific mediators and mechanisms of graft rejection are poorly understood. Several studies have implicated cytotoxic T-lymphocyte (CTL) responses, typically associated with CD8(+) T cells, in promoting corneal graft rejection. This study sought to test the hypothesis that CTLs are essential in promoting corneal graft rejection. METHODS: BALB/c donor corneas were grafted orthotopically onto C57BL/6, perforin knockout, or CD8(+) T-cell knockout mice. The tempo and incidence of graft rejection were observed for each group. In separate experiments, donor-specific CTL and delayed-type hypersensitivity (DTH) responses were tested at the time of graft rejection by a standard chromium release assay and an ear swelling assay, respectively. RESULTS: Perforin knockout and CD8(+) T-cell knockout mice were as effective as wild-type C57BL/6 control mice in rejecting BALB/c donor corneas. Furthermore, animals in all three groups were found to develop robust donor-specific DTH, not CTL, responses at the time of graft rejection. Histopathologically, the rejected corneas from all three groups contained a predominantly mononuclear cellular infiltrate. CONCLUSIONS: This study rejects the hypothesis that CD8(+) CTLs are essential in promoting corneal graft rejection and instead further implicates donor-specific DTH reactions as the relevant immune response during graft failure.

Animals↗

Inhibition of cholesteryl ester transfer protein by substituted dithiobisnicotinic acid dimethyl ester: involvement Of a critical cysteine.

SC-71952, a substituted analog of dithiobisnicotinic acid dimethyl ester, was identified as a potent inhibitor of cholesteryl ester transfer protein (CETP). When tested in an in vitro assay, the concentration of SC-71952 required for half-maximal inhibition was 1 microm. The potency of SC-71952 was enhanced 200-fold by preincubation of the inhibitor with CETP, and was decreased 50-fold by treatment with dithiothreitol. Analogs of SC-71952 that did not contain a disulfide linkage were less potent, did not display time dependency, and were not affected by dithiothreitol treatment. Kinetic and biochemical characterization of the inhibitory process of CETP by SC-71952 suggested that the inhibitor initially binds rapidly and reversibly to a hydrophobic site on CETP. With time, the bound inhibitor irreversibly inactivates CETP, presumably by reacting with one of the free cysteines of CETP. Liquid chromatography/mass spectroscopy (LC/MS) analyses of tryptic digests of untreated or SC-71952-inactivated CETP was used to identify which cysteine(s) were potentially involved in the time-dependent, irreversible component of inactivation by the inhibitor. One disulfide bond, Cys143-Cys184, was unaffected by treatment with the inhibitor. Inactivation of CETP by SC-71952 correlated with a progressive decrease in the abundance of free Cys-13 and Cys-333. Conversion of Cys-13 to alanine had no effect on the rapid reversible component of inactivation by SC-71952. However, it abolished the time-dependent enhancement in potency seen with the inhibitor when using wild-type CETP. These data indicate that Cys-13 is critical for the irreversible inactivation of CETP by SC-71952 and provides support for the structural model that places Cys-13 near the neutral lipid-binding site of CETP.

Amino Acid Substitution↗

Muscarinic receptor ligands and their therapeutic potential.

Over the past year, the introduction of novel ligands has accelerated the classification of muscarinic receptor subtypes and has led to a better understanding of their physiological role. Important in this respect is the recent recognition of the exquisite selectivity of a series of snake toxins, enabling better definition of the muscarinic subtype 4 receptor. Moreover, several compounds, both agonists and antagonists, are progressing in advanced clinical trials for the treatment of several conditions, including Alzheimer's disease, pain, urinary incontinence and chronic obstructive pulmonary disease.

Humans↗