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V Kohli

Publications and source records attributed to V Kohli.

At least 19 recordsLinked to original sources

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

Computer Simulation↗

Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing.

We identified three splice variants of hSK1 whose C-terminal structures are determined by the independent deletion of two contiguous nucleotide sequences. The upstream sequence extends 25 bases in length, is initiated by a donor splice site within exon 8, and terminates at the end of the exon. The downstream sequence consists of nine bases that compose exon 9. When the upstream sequence (hSK1(-)(25b)) or both sequences (hSK1(-)(34b)) are deleted, truncated proteins are encoded in which the terminal 118 amino acids are absent. The binding of calmodulin to these variants is diminished, particularly in the absence of Ca2+ ions. The first 20 amino acids of the segment deleted from hSK1(-)(25b) and hSK1(-)(34b) contain a 1-8-14 Ca2+ calmodulin binding motif, and synthetic oligopeptides based on this region bind calmodulin better in the presence than absence of Ca2+ ions. When the downstream sequence (hSK1(-)(9b)) alone is deleted, only the three amino acids A452, Q453, and K454 are removed, and calmodulin binding is not reduced. On the basis of the relative abundance of mRNA encoding each of the four isoforms, the full-length variant appears to account for most hSK1 in the human hippocampus, while hSK1(-)(34b) predominates in reticulocytes, and hSK1(-)(9b) is especially abundant in human erythroleukemia cells in culture. We conclude that the binding of calmodulin by hSK1 can be modulated through alternative splicing.

Alternative Splicing↗

Discrete subvalvular aortic stenosis in adults.

Discrete subvalvular aortic stenosis is a relatively rare condition in adults. It is often diagnosed during first decade of life especially in association with other congenital malformations. Isolated form of discrete subvalvular aortic stenosis may however silently progress from innocent murmurs of childhood and adolescence to symptomatic left ventricular outflow tract obstruction in adults. Certain overt and subtle morphological abnormalities may underlie the initial expression as well as high recurrence rates after surgical resection of sub aortic membrane. Though surgical resection is the only treatment available, debate on the surgical technique and appropriate timing of surgery continues. Close followup with serial echocardiographic examinations in patients detected to have functional murmurs during childhood may be helpful in early detection of subvalvular aortic stertosis.

Adult↗

Comparison of ministernotomy with minithoracotomy regarding postoperative pain and internal mammary artery characteristics.

PURPOSE: This prospective clinical study focuses on postoperative pain and internal mammary artery (IMA) characteristics after ministernotomy versus left anterior minithoracotomy. METHOD: Patients were studied in two groups. Group A consisted of 267 consecutive single vessel (IMA to left anterior descending artery (LAD)) minimally invasive direct coronary artery bypass (MIDCAB) patients using ministernotomy from the tip of the xiphoid to the fourth intercostal space. Group B consisted of the same number of MIDCAB patients operated on through anterolateral minithoracotomy. Pain was graduated using the visual analog scale (VAS). Internal mammary artery (IMA) characteristics were compared in both the groups. RESULTS: Postoperative pain was not significant statistically on postop day (POD) 1 in either of the groups (p = 0.07). From POD 2 onwards Group A patients had less pain than Group B patients (p < 0.05), and the pain medication requirement from POD 2 onwards was less in Group A than in Group B. Length of harvested IMA was 15.6 +/- 2.1 cm in Group A as compared to 10.4 +/- 2.2 cm in Group B (p < 0.05). Free flow of IMA in group A was 56 +/- 16 ml/min., whereas in Group B the flow was 50 +/- 14 ml/min. (p = 0.04). CONCLUSION: Compared to patients undergoing MIDCAB using ministernotomy, anterolateral minithoracotomy patients suffer more pain from POD 2 onwards and their postoperative pain medication requirement is also higher. Length and free flow of IMA is better in patients operated on for MIDCAB using ministernotomy. Thus, ministernotomy is a better approach than minithoracotomy in terms of postoperative pain and IMA characteristics for single-vessel MIDCAB patients.

Adult↗

Discrete subvalvular aortic stenosis.

Discrete Subaortic Stenosis is one of the many lesions responsible for left ventricular outflow tract (LVOT) obstruction. It may present as in an isolated from as membranous or fibromuscular ring below the aortic valve or in association with other congenital anamolies such as VSD, PDA, coarctation of aorta, hypoplastic aortic annulus, double chamber right ventricle among others. The condition is rarely diagnosed antenataly or in infancy but often manifests in the first decade of life with features of progressive LVOT obstruction, LV hypertrophy and dysfunction aortic regurgitation due to damage to the aortic cusps because of the jet from the subaortic narrowing which may also render the aortic valve prone to infective endocarditis. Interaction of genetic predisposition and morphologically deformed long and narrow LVOT cause rheological abnormalities and increased shear stress in the region of subaortic stenosis and seem to be the main etiological factor alongwith poorly defined role of more extensive but subtle changes in the LV endocardium. Condition can be easily diagnosed by cross-sectional and Doppler echocardiography and confirmed by demonstrating a pressure gradient below aortic valve on cardiac catheterisation and LV angiography. Surgical membranectomy alongwith myotomy or myomectomy remain the mainstay of treatment but long term results are not satisfactory as there is a high rate of recurrences requiring reoperations. A close follow up with serial echocardiographic examinations is very helpful in early detection of subaortic obstruction in patients who have so called functional murmurs in the childhood.

Angiography↗

Calpain inhibition prevents sinusoidal endothelial cell apoptosis in the cold ischemic rat liver.

BACKGROUND: Cold preservation of the liver followed by reperfusion results in sinusoidal endothelial cell (SEC) apoptosis. Calpain-like activity is dramatically increased during reperfusion and inhibition of calpains results in lower graft injury and longer survival. Recently, calpains have been implicated in inducing apoptosis. Our aim was to determine the effect of calpain inhibition on SEC apoptosis. METHODS: Livers were stored in the University of Wisconsin solution for 24 hr (survival conditions) and 40 hr (nonsurvival conditions) and ex vivo reperfused for 1 hr at 37 degrees C. Calpain-like activity was inhibited in some experiments using an i.p. injection of a selective inhibitor 2 hr before explantation. Apoptosis was quantified using the terminal deoxynucleotidyl trans. ferase-mediated dUTP nick end-labeling assay. Cross-inhibition by the inhibitor was determined for caspases 1 and 3. RESULTS: Apoptosis of exclusively the SEC was a key feature of reperfusion injury after both storage periods in University of Wisconsin solution after 1 hr normothermic reperfusion. Inhibition of calpain activity with Cbz-Val-Phe methyl ester resulted in a 50% reduction of apoptotic SEC in the 40-hr preserved liver, and an almost complete abrogation of SEC apoptosis after 24 hr preservation. Only minimal cross-inhibition of caspases was determined at high concentrations in vitro by the calpain inhibitor. CONCLUSION: Apoptosis of exclusively SEC is a key feature of reperfusion injury partially mediated through calpain-dependent processes. Calpain inhibition reduces the number of apoptotic SEC. Based on these data and our previous work, calpain inhibition may prove to be useful in clinical transplantation.

Animals↗

Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.

BACKGROUND: Ischemic injury of the liver is generally considered to result in necrosis, but it has recently been recognized that mediators of apoptosis are activated during ischemia/reperfusion. This study was designed to characterize the extent and the type of cells within the liver that undergo apoptosis at different periods of ischemia and reperfusion. METHODS: Male Wistar rats were subjected to 30 or 60 min of normothermic ischemia. Liver sections were evaluated at the end of ischemia and at 1, 6, 24, and 72 hr after reperfusion. Apoptosis was determined by DNA fragmentation as evaluated by laddering on gel electrophoresis, in situ staining for apoptotic cells using TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL), and morphology on electron microscopy. RESULTS: In situ staining of liver biopsy specimens using TUNEL showed significant apoptosis after reperfusion. Sinusoidal endothelial cells (SEC) showed evidence of apoptosis earlier than hepatocytes. For example, at 1 hr of reperfusion after 60 min of ischemia, 22+/-4% of the SEC stained TUNEL positive compared with 2+/-1% of the hepatocytes (P<0.001). With a longer duration of ischemia, a greater number of SEC and hepatocytes became TUNEL positive. An increase in TUNEL-positive cells was also noted with an increasing duration of reperfusion. The presence of apoptotic SEC and hepatocytes was supported by DNA laddering on gel electrophoresis and cell morphology on electron microscopy. Several Kupffer cells were seen containing apoptotic bodies but did not show evidence of apoptosis. Only rare hepatocytes showed features of necrosis after 60 min of ischemia and 6 hr of reperfusion. CONCLUSION: These results suggest that apoptosis of endothelial cells followed by hepatocytes is an important mechanism of cell death after ischemia/reperfusion injury in the liver.

Animals↗

Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.

BACKGROUND & AIMS: Calpain proteases have been implicated in cell death by necrosis and more recently by apoptosis. Experiments were designed to determine the role of calpain proteases in ischemic rat liver injury by measurement of cytosolic calpain activity after different periods of ischemia-reperfusion and by evaluation of the effects of calpain inhibition on tissue injury and animal survival. METHODS: Calpain activity was measured in the cytosol using Suc-Leu-Leu-Val-Try-7 amino-4 methyl coumarin, a specific fluorogenic substrate, and Cbz-Leu-Leu-Tyr-CHN2, a specific inhibitor. RESULTS: Calpain activity increased significantly with the duration of ischemia-reperfusion and was inhibited more than 80% by the inhibitor. Calpain inhibition resulted in a significant decrease in transaminase release and tissue necrosis and converted nonsurvival ischemic conditions to survival conditions. When the in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay for apoptosis was used, 35% +/- 6% of nonparenchymal cells and 16% +/- 3% of hepatocytes stained positively after 60 minutes of ischemia and 6 hours of reperfusion. In contrast, animals pretreated with the calpain inhibitor showed minimal evidence of apoptosis. This was further substantiated by gel electrophoresis assay for DNA fragmentation and by electron-microscopic evaluation. CONCLUSIONS: These data suggest that calpain proteases play a pivotal role in warm ischemia-reperfusion injury of the rat liver through modulation of apoptosis and necrosis.

Alanine Transaminase↗

Controlled ventilation enhances catheter stability during radiofrequency ablation.

Variations in the amplitude of the atrial and ventricular depolarization waves of the intracardiac electrogram occur during different phases of respiration. Therefore, we tested whether controlled ventilation would reduce ablation attempts and increase the rate of success in patients undergoing radiofrequency ablation with general anesthesia. Thirty-eight children were divided into two groups: (1) controlled and (2) noncontrolled or cyclic ventilation. In the controlled ventilation group, the mapping electrogram was recorded during sustained inspiration, sustained expiration, and cyclic ventilation. Ablation was done in the phase of ventilation that had the least variability in atrial and ventricular amplitudes. Seventeen patients in the controlled ventilation group had tracings adequate for review. In eight patients, ablation was done during sustained inspiration with the percentage change of atrial and ventricular amplitudes (15% +/- 16% and 13% +/- 16%, respectively) being < that during sustained expiration (38% +/- 27%, P = 0.04 and 20% +/- 21%) or during cyclic ventilation (57% +/- 27%, P < 0.01 and 54% +/- 26%, P = 0.003). In nine patients, ablation was done during sustained expiration with the percentage change of atrial and ventricular amplitudes (5% +/- 5% and 5% +/- 2%) being less than that during sustained inspiration (21% +/- 14%, P = 0.01 and 11% +/- 6%, P = 0.01) or during cyclic ventilation (68% +/- 23%, P < 0.001 and 48 +/- 26%, P = 0.001). We achieved success with each patient in both groups, but the number of ablation attempts were less in the controlled ventilation group 1 (3 +/- 2), as compared to the cyclic ventilation group 2 (8 +/- 8; P < 0.02). We concluded that controlled ventilation reduced the number of ablation attempts and facilitated the ablation procedure.

Adolescent↗

Paired ventricular pacing: an alternative therapy for postoperative junctional ectopic tachycardia in congenital heart disease.

Junctional ectopic tachycardia (JET) is one of the most life-threatening postoperative arrhythmias in children with congenital heart disease, and medical management is difficult. Paired ventricular pacing (PVP) may provide a safe alternative mode of management. We evaluated the safety and efficacy of PVP for the management of postoperative JET in patients with congenital heart disease. A retrospective collection of data was done from 1981-1995. PVP was successfully tried in five postoperative patients (age range: 37 days to 22 years, median: 10 months). Onset of JET was 3-60 hours (mean +/- SD, 19 +/- 23 hours) postoperatively. The maximal JET rate was 261 +/- 39 beats/min. PVP was used as the first line of management in three patients and was successful in all patients. It resulted in an instantaneous increase in blood pressure from 66 +/- 9 to 94 +/- 15 mmHg (42% increase) and was required for 12 +/- 14 hours (range 2-36 hours). No complications were noted. Therefore, in our experience, this is a safe alternative modality for the control of postoperative JET.

Adult↗

The effect of native-language retention and insecurity on Asian Indian fertility in the United States.

The relationship of social/psychological insecurity and native-language retention to fertility was explored among a nationally representative sample of 3,408 endogamously wed Asian Indian women living in the United States. Native-language retention had a negative impact on Asian Indian women's fertility that cannot be explained by the normative dimension of the minority group status hypothesis (Goldscheider & Uhlenberg, 1969); therefore, alternative explanations for minority fertility differentials are required.

Acculturation↗

Comparison of frequency-distance relationship and Gaussian-diffusion-based methods of compensation for distance-dependent spatial resolution in SPECT imaging.

The goal of this investigation was to compare resolution recovery versus noise level of two methods for compensation of distance-dependent resolution (DDR) in SPECT imaging. The two methods of compensation were restoration filtering based on the frequency-distance relationship (FDR) prior to iterative reconstruction, and modelling DDR in the projector/backprojector pair employed in iterative reconstruction. FDR restoration filtering was computationally faster than modelling the detector response in iterative reconstruction. Using Gaussian diffusion to model the detector response in iterative reconstruction sped up the process by a factor of 2.5 over frequency domain filtering in the projector/backprojector pair. Gaussian diffusion modelling resulted in a better resolution versus noise tradeoff than either FDR restoration filtering or solely modelling attenuation in the projector/backprojector pair of iterative reconstruction. For the pixel size investigated herein (0.317 cm), accounting for DDR in the projector/backprojector pair by Gaussian diffusion, or by applying a blurring function based on the distance from the face of the collimator at each distance, resulted in very similar resolution recovery and slice noise level.

Computer Simulation↗

Calpain is a mediator of preservation-reperfusion injury in rat liver transplantation.

Proteases as well as alterations in intracellular calcium have important roles in hepatic preservation-reperfusion injury, and increased calpain activity recently has been demonstrated in liver allografts. Experiments were designed to evaluate (i) hepatic cytosolic calpain activity during different periods of cold ischemia (CI), rewarming, or reperfusion, and (ii) effects of inhibition of calpain on liver graft function using the isolated perfused rat liver and arterialized orthotopic liver transplantation models. Calpain activity was assayed using the fluorogenic substrate Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl coumarin (AMC) and expressed as mean +/- SD pmol AMC released/min per mg of cytosolic protein. Calpain activity rose significantly after 24 hr of CI in University of Wisconsin solution and further increased with longer preservation. Activity also increased within 30 min of rewarming, peaking at 120 min. Increased durations of CI preceding rewarming resulted in significantly higher activity (P < 0.01). Calpain activity increased rapidly upon reperfusion and was significantly enhanced by previous CI (P < 0.01). Calpain inhibition with Cbz-Val-Phe methyl ester significantly decreased aspartate aminotransferase released in the isolated perfused rat liver perfusate (P < 0.05). Duration of survival after orthotopic liver transplantation using livers cold-preserved for 40 hr was also significantly increased (P < 0.05) with calpain inhibitor. In conclusion, calpain proteases are activated during each phase of transplantation and are likely to play an important role in the mechanisms of preservation-reperfusion injury.

Adenosine↗

Similar time-dependent recovery property of fast and slow atrioventricular nodal pathways.

The purpose of this study was to determine whether fast and slow atrioventricular (AV) nodal pathways have the same recovery property. AV nodal recovery property is studied by delivering atrial extrastimuli coupled to atrial beats and plotting nodal coupling intervals against nodal conduction time. In patients with dual pathways the resultant curves will include a fast to fast (F-F) and a fast to slow (F-S) pathway coupled curves. Although fast pathway recovery property can be represented by the former, slow pathway recovery property requires further assessment by studying slow to slow (S-S) pathways coupled curve. In 9 patients with dual pathways F-F, F-S, S-F, and S-S curves were obtained by pacing protocols. In 8 patients (control) without dual pathways, F-F curve and atrial extrastimuli coupled to a preceding slowly conducted fast pathway beat (also designated as S-F curve) were obtained. (1) The S-S curve had a similar time constant as the F-F curve. (2) Although the S-S curve was markedly shifted upward and leftward from the F-F curve, the degree of leftward and upward shifts of the S-S curve from the F-F curve were both close to the difference of the basic fast and slow pathway conduction time (a constant). (3) Although the effective refractory period of the fast pathway in dual pathway patients was longer than that of the control patients, the slow pathway effective refractory period when corrected was close to that of fast pathway in control patients. These results suggest that the fast and slow AV nodal pathways have a similar time-dependent recovery property.

Adolescent↗

Influence of OSEM, elliptical orbits and background activity on SPECT 3D resolution recovery.

In maximum-likelihood expectation-maximization (MLEM) reconstruction of SPECT images, if both attenuation correction (AC) and detector response correction (DRC) are included, the reconstruction can be too time consuming to be clinically useful. With use of the ordered-subset expectation-maximization (OSEM) reconstruction, it has been reported that the reconstruction time can be substantially reduced. We investigated the reconstruction of point sources in a non-uniform attenuation medium in terms of the normalized FWHM of these sources. We compared MLEM versus OSEM reconstructions; circular versus elliptical orbits; and the presence versus the absence of background activity in the object. We found: (i) that OSEM does speed up the reconstruction by a factor of 10 over MLEM; (ii) that the resolution recovery does not depend on the type of orbit if both AC and DRC are included in the reconstruction; however, when there is background activity, a significant number of iterations are required to alleviate the effect of orbit; (iii) that background activity significantly slows down the resolution recovery of the point sources; and (iv) that if reconstruction only includes AC, and not DRC, changing orbit can change isotropy of recovered resolution, whereas introducing background activity may degrade the recovered resolution and also changes the isotropy.

Computer Simulation↗