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K Chandrasekaran

Publications and source records attributed to K Chandrasekaran.

At least 19 recordsLinked to original sources
PubMed2006

Disease mapping using mixture distribution.

BACKGROUND & OBJECTIVES: Data on infectious diseases like tuberculosis (TB) have been analyzed in the past without giving adequate attention to spatial variations. Earlier studies also attempted to display disease status of sub regions, usually census tracts, by categorizing them into quartiles, that helps the authorities to identify high- or low-risk areas. This approach is based mainly on binomial and Poisson models for disease data, and the recent attempts focus on using mixture models of Poisson distribution. We carried out this study to find wards of Madurai Corporation having high risks for TB disease, to develop a model of mixture of Poisson distributions for the number of cases and to classify each ward to one of many risk groups for TB disease, and to represent spatial distribution of TB incidence in Madurai city. METHODS: produced the observed counts of TB patients in 72 wards of Madurai Corporation. The number of risk groups and the Poisson parameters of each group were found by maximum likelihood approach using the computer package C.A.MAN (Computer Assisted Mixture ANalysis). Bayesian methods were used to associate each ward to a particular risk group. The results were geographically presented in maps by using ArcView mapping software. RESULTS: Using binomial model, 26 wards were categorized as high risk wards, and with mixture model approach 15 wards showed standardized morbility ratio (SMR) >1. The wards along river Vaigai and densely populated wards had high risk. INTERPRETATION & CONCLUSION: Our findings demonstrate the usefulness of the mixture models for disease data with geographical variations.

Bayes Theorem↗
PubMed2005

Clinical presentation, investigation, and management of pulmonary vein stenosis complicating ablation for atrial fibrillation.

BACKGROUND: Although segmental or circumferential ablation is effective in eliminating pulmonary vein (PV)-mediated atrial fibrillation (AF), this procedure may be complicated by the occurrence of PV stenosis. METHODS AND RESULTS: To establish the clinical presentation, diagnostic manifestations, and interventional management of PV stenosis, 23 patients with stenosis of 34 veins complicating ablation of AF were evaluated. Each patient became symptomatic 103+/-100 days after undergoing ablation. In 8 veins, the ablation producing the PV stenosis was a repeated procedure for continued AF. Nineteen patients presented with dyspnea on exertion, 7 with dyspnea at rest, 9 with cough, and 6 with chest pain. On multirow spiral computed tomography examination, the narrowest lumen of the affected PVs measured 3+/-2 mm compared with 13+/-3 mm at baseline (P< or =0.001). The relative perfusion of affected lung segments on isotope scans was reduced to 4+/-3% of total perfusion compared with 22+/-10% in unaffected segments. At percutaneous intervention, these veins showed 80+/-13% stenosis, with a mean gradient of 12+/-5 mm Hg. This was significantly reduced to a residual stenosis of 9+/-8% (P< or =0.001) and a residual gradient of 3+/-4 mm Hg (P< or =0.001). Twenty veins were treated with balloon dilatation alone, whereas 14 veins were stented with standard 10-mm-diameter bare-metal stents. Although the symptomatic response was nearly immediate and impressive, 14 patients developed in-stent or in-segment restenosis, requiring repeated interventions in 13. CONCLUSIONS: Percutaneous intervention produces rapid and dramatic symptom relief in patients with highly symptomatic PV stenosis after radiofrequency ablation for AF. Nevertheless, alternative treatment methods will be required to decrease recurrent in-stent or in-segment restenosis.

Adult↗
PubMed2004

In situ matrix evaporation by isothermal distillation of high-purity reagents for the determination of trace impurities by ion chromatography.

In situ matrix evaporation of high-purity acids based on isothermal distillation was achieved in a high-density polyethylene (HDPE) container on a water bath, to avoid contamination from the laboratory environment. The solubility of water and acid vapours in glycerol due to co-association was utilized to achieve complete evaporation. All major sources which contribute to the process blank were taken care of in a simple and effective way. A 50-fold preconcentration with >99.9% matrix removal was achieved for the analysis of low-boiling acids, HCl, HF, HNO3 and H2O2. The non-volatile ions NH4+, Li+, Na+, K+, Mg2+, Ca2+, SO4(2-) and PO4(3-) were determined by ion chromatograph with conductivity detection. The detection limits were 6-130 ng/l with recoveries of 85-110% for all ions studied.

Chromatography, Ion Exchange↗
PubMed2004

Ion chromatographic determination of trace level phosphorus in purified quartz.

Trace levels of phosphorus in purified quartz are determined by ion chromatography. In situ reagent purification, matrix digestion and oxidation of phosphorus to orthophosphate ion are carried out simultaneously in a vapour phase digestion (VPD) assembly using a mixture of HF, HNO3 and H2O2. A drastic reduction (475 times) in phosphate blank from reagents (HF/H2O2) was achieved in the VPD through in situ purification of the reagent. The residues remaining after volatilisation (solvent/matrix), mostly consisting of insoluble phosphate/fluoride salts of divalent and trivalent cations, were solubilised by ion-exchange dissolution. Phosphate was analysed on the IonPac AS17 column with suppressed conductivity detection. The results of the ion chromatography (IC) method were compared with a spectrophotometric method. Accuracy was evaluated by analysing a certified reference material (silicon, NIST 57a). The method detection limit was 0.05 microg g(-1).

Chromatography, Liquid↗
PubMed2004

Determination of trace metallic impurities in high-purity quartz by ion chromatography.

A method has been developed for the determination of relevant trace impurities (alkali, alkaline and transition metals) in high purity quartz by ion-chromatography. In situ reagent (HF) purification and simultaneous sample dissolution was achieved in a multichannel vapour phase digestion assembly. Twenty-one samples can be digested at a time in this vapour phase system. Significant decrease in the process blank levels for all the analytes was observed. Drastic reduction (250 times) of NH4+ blank was achieved in the described vapour phase digestion, which enables the determination of trace concentration of sodium in high purity quartz. After volatilisation of the matrix and unreacted HF, the clear water leached solutions were injected into an ion-chromatograph equipped with conductivity detector for the determination of alkali and alkaline earth metals. In the case of transition metals, the trace residues were leached with 10 mM HCl and after separation on a mixed bed analytical column (IonPac CS5) were detected by spectrophotometry after post column derivatisation using 4-(2-pyridylazo)resorcinol (PAR). The accuracy of the result was checked by their comparison with those obtained by independent methods like inductively coupled plasma (ICP) MS and ICP atomic emission spectrometry. The achievable detection limits are between 0.4 ng/g (Li) and 22 ng/g (Mn). The application of the method to the determination of the above trace metals in two high-purity-grade quartz samples is demonstrated.

Chromatography, Liquid↗
PubMed2004

Predictors of left ventricular dysfunction in patients with Takayasu's or giant cell aortitis.

OBJECTIVES: The aim of this study was to determine the clinical and angiographic predictors of left ventricular systolic dysfunction (LVSD) from a relatively large and angiographically characterized Takayasu's or Giant Cell aortitis (TA/GCA) population. BACKGROUND: LVSD in patients with TA/GCA has been described in case reports and attributed variously to hemodynamic and immunologic factors. The predictors of LVSD in patients with angiographically confirmed TA/GCA are not known. METHODS: We identified 78 patients with angiographically confirmed TA/ GCA that underwent transthoracic echocardiography (TTE) at Mayo Clinic. Echocardiograms were then reviewed independently by reviewers blinded to clinical and angiographic data. LVSD was defined as an ejection fraction (LVEF) less than 50%. RESULTS: The study population was 84% Caucasian (54/78), 91% female (58/78), and had a mean age of disease onset of 30 years (+/- 15 years). LVSD was present in 14 of 78 patients (18%) with TA/GCA. The mean LVEF in the LVSD group (n = 14) was 37% +/- 7%, compared to an LVEF of 62% +/- 6% (p < 0.0001) in those without LVSD (n = 64). LVSD was not associated with hypertension or aortic regurgitation (p > 0.5). However, LVSD was found in 43% (9/21) of patients with aortic arch involvement, versus only 9% (5/57) of patients without aortic arch involvement (p = 0.0013). Patients with LVSD had a median of 2 (range 1-4) involved aortic segments compared to a median of 1 (range 1-4) among those without LVSD (p = 0.013). CONCLUSIONS: In TA/GCA aortitis, LVSD is associated with involvement of the aortic arch and with the greater extent of aortic involvement. The hemodynamic variables, aortic regurgitation and systemic hypertension, were not associated with LVSD, consistent with reports that cardiac inflammation is responsible for LVSD in a majority of cases. Ours is the first study to estimate an incidence of LVSD in patients with TA/GCA aortitis, which was 18%.

Adult↗
PubMed2003

Characterization of the N-acetylaspartate biosynthetic enzyme from rat brain.

Aspartate N-acetyltransferase (Asp-NAT; EC 2.3.1.17) activity was found in highly purified intact mitochondria prepared by Percoll gradient centrifugation as well as in the three subfractions obtained after the sucrose density gradient centrifugation of Percoll purified mitochondria; citrate synthase was used as a marker enzyme for mitochondria. The proportion of recoverable activities of Asp-NAT and citrate synthase were comparable in mitochondrial and synaptosomal fractions but not in the fraction containing myelin. Asp-NAT was solubilized from the pellet of the rat brain homogenate (26 000 g for 1 h) for the recovery of maximum activity and partially purified using three protein separation methods: DEAE anion exchange chromatography, continuous elution native gel electrophoresis and size-exclusion high performance liquid chromatography. Asp-NAT activity and the optical density pattern of the eluted protein from size-exclusion column indicated a single large protein (approximately 670 kDa), which on sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed at least 10 bands indicative of an enzyme complex. This seemingly multi-subunit complex Asp-NAT was stable towards ionic perturbations but vulnerable to hydrophobic perturbation; almost 95% of activity was lost after 10 mm 3-[(3-cholamidopropyl)dimethylammonia]-1-propanesulfonate (CHAPS) treatment followed by size-exclusion chromatography. Asp-NAT showed an order of magnitude difference in Km between l-aspartate (l-Asp, approximately 0.5 mm) and acetyl CoA (approximately 0.05 mm). Asp-NAT showed high specificity towards l-Asp with 3% or less activity towards l-Glu, l-Asn, l-Gln and Asp-Glu. A model on the integral involvement of NAA synthesis in the energetics of neuronal mitochondria is proposed.

Acetyl Coenzyme A↗
PubMed2003

Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death.

In this study, we compared the protective effect of bilobalide, a purified terpene lactone component of ginkgo biloba extract EGb 761, (definition see editorial) and EGb 761 against ischemic injury and against glutamate-induced excitotoxic neuronal death. In ischemic injury, we measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In rat cerebellar neuronal cultures, addition of bilobalide or EGb 761 protected in a dose-dependent manner against glutamate-induced excitotoxic neuronal death (effective concentration [EC (50)] = 5 microg/ml (12 microM) for bilobalide and 100 microg/ml for EGb 761. These results suggest that both EGb 761 and bilobalide are protective against ischemia-induced neuronal death in vivo and glutamate-induced neuronal death in vitro by synergistic mechanisms involving anti-excitotoxicity, inhibition of free radical generation, scavenging of reactive oxygen species, and regulation of mitochondrial gene expression.

Animals↗
PubMed2001

Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia.

The neuroprotective effect of Ginkgo biloba extract (EGb 761) against ischemic injury has been demonstrated in animal models. In this study, we compared the protective effect of bilobalide, a purified terpene lactone from EGb 761, and EGb 761 against ischemic injury. We measured neuronal loss and the levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunit III mRNA in vulnerable hippocampal regions of gerbils. At 7 days of reperfusion after 5 min of transient global forebrain ischemia, a significant increase in neuronal death and a significant decrease in COX III mRNA were observed in the hippocampal CA1 neurons. Oral administration of EGb 761 at 25, 50 and 100 mg/kg/day and bilobalide at 3 and 6 mg/kg/day for 7 days before ischemia progressively protected CA1 neurons from death and from ischemia-induced reductions in COX III mRNA. In addition, both bilobalide and EGb 761 protected against ischemia-induced reductions in COX III mRNA in CA1 neurons prior to their death, at 1 day of reperfusion. These results suggest that oral administration of bilobalide and EGb 761 protect against ischemia-induced neuron death and reductions in mitochondrial gene expression.

Animals↗
PubMed2001

A combined treatment approach using Fenton's reagent and zero valent iron for the removal of arsenic from drinking water.

Studies on the development of an arsenic remediation approach using Fenton's reagent (H2O2 and Fe(II)) followed by passage through zero valent iron is reported. The efficiency of the process was investigated under various operating conditions. Potable municipal water and ground water samples spiked with arsenic(III) and (V) were used in the investigations. The arsenic content was determined by ICP-QMS. A HPLC-ICPMS procedure was used for the speciation and determination of both As(III) and (V) in the processed samples, to study the effectiveness of the oxidation step and the subsequent removal of the arsenic. The optimisation studies indicate that addition of 100 microl of H2O2 and 100 mg of Fe(II) (as ferrous ammonium sulphate) per litre of water for initial treatment followed by passing through zero valent iron, after a reaction time of 10 min, is capable of removing arsenic to lower than the US Environmental Protection Agency (EPA) guideline value of 10 microg/l, from a starting concentration of 2 mg/l of As(III). Using these suggested amounts, several experiments were carried out at different concentrations of As(III). Residual hydrogen peroxide in the processed samples can be eliminated by subsequent chlorination, making the water, thus, processed, suitable for drinking purposes. This approach is simple and cost effective for use at community levels.

Arsenic↗
PubMed2001

Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminum exposure in PC12S cells.

Aluminum (Al) has been implicated in several neurological diseases including dialysis dementia and Alzheimer's disease (AD). One possible mechanism of Al neurotoxicity could involve alteration of mitochondrial gene expression. We exposed PC12 cells to 0.1-100 microM AlCl3 for 6h at pH 7.4. Internalized Al, measured by atomic absorption spectrometry, was linearly proportional to the extracellular Al concentration. Northern blot analyses showed that cytochrome c oxidase subunit III (COX III) mRNA was significantly reduced by 70% after addition of 1 microM AlCl3. Higher concentrations of AlCl3 did not show a significant further effect. These results suggest that Al neurotoxicity involves a specific impairment of cytochrome c oxidase.

Aluminum Chloride↗
PubMed2001

Characterization of reentrant circuit in macroreentrant right atrial tachycardia after surgical repair of congenital heart disease: isolated channels between scars allow "focal" ablation.

BACKGROUND: The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD). METHODS AND RESULTS: Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (</=0.5 mV) involved most of the free wall in all patients and contained 2 to 7 dense scars or lines of double potentials, forming 29 narrow channels (width </=2.7 cm) between scars in all but 1 patient, who had a single scar and only focal AT. All 15 MacroATs were propagated through narrow channels. Ablation within the channel eliminated all 15 MacroATs with 1 to 3 (median 1) radiofrequency applications. Ablation was performed in 9 other channels identified during MacroAT (5 patients) and in 5 channels identified during atrial pacing (2 patients). Conduction block was obtained across 28 of 29 channels. After ablation, reproducible sustained right AT was not induced in any patient. During follow-up (median 13.5 months), new MacroATs, atrial fibrillation, or palpitations occurred in 3 of 16 patients. CONCLUSIONS: MacroAT after SR-CHD requires a large area of low voltage containing >/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.

Adult↗
PubMed2001

Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: urologic and cardiovascular implications.

Erectile dysfunction (ED) occurs in varying degrees in an estimated 20 to 30 million American men and is associated with adverse effects on quality of life; particularly personal well-being, family and social interrelationships. Research into ED has focused primarily on the physiologic mechanisms of corpus cavernosum smooth muscle relaxation, and penile erection as the end result of smooth muscle relaxation. These processes are mediated by cholinergic, nonadrenergic, noncholinergic (NANC, e.g., nitric oxide), vasoactive intestinal peptide (VIP), and potentially calcitonin gene-related peptide (CGRP) containing nerves. Release of nitric oxide following sexual stimulation from non-adrenergic, non cholinergic nerves and vascular endothelium activates guanylyl cyclase and induces intracellular cGMP synthesis. In turn, cGMP results in lowering intracellular concentrations, inhibits contractility of the penile smooth muscle, and induces an erectile response. Phosphodiesterase type 5 (PDE 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, and subsequent penile flaccidity. Sildenafil citrate is a potent PDE type 5 reversible and selective inhibitor which blocks cGMP hydrolysis effectively. FDA approval of sildenafil citrate as the first oral agent for ED in males has resulted in significant interest. We discuss the clinical and pharmacologic properties of sildenafil citrate as well as the urologic and cardiac implications.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression.

Regulation of expression of mitochondrial DNA- (mtDNA-) encoded genes of oxidative phosphorylation can occur rapidly in neural cells subjected to a variety of physiological and pathological conditions. However, the intracellular signal(s) involved in regulating these processes remain unknown. Using mtDNA-encoded cytochrome oxidase subunit III (COX III), we show that its mRNA expression in a differentiated rat pheochromocytoma cell line PC12S is decreased by chronic exposure to agents that increase intracellular sodium. Treatment of differentiated PC12S cells either with ouabain, an inhibitor of Na/K-ATPase, or with monensin, a sodium ionophore, decreased the steady-state levels of COX III mRNA by 50%, 3-4 h after addition of the drugs. No significant reduction in mtDNA-encoded 12S rRNA or nuclear DNA-encoded beta-actin mRNA were observed. Removal of the drugs restored the normal levels of COX III mRNA. Determination of half-lives of COX III mRNA, 12S rRNA, and beta-actin mRNA revealed a selective decrease in the half-life of COX III mRNA from 3.3 h in control cells to 1.6 h in ouabain-treated cells, and to 1 h in monensin-treated cells. These results suggest the existence of a mechanism of posttranscriptional regulation of mitochondrial gene expression that is independent of the energetic status of the cell and may operate under pathological conditions.

Journal Article↗
PubMed2001

ATP synthesis is coupled to rat liver mitochondrial RNA synthesis.

Rat liver mitochondria respond to changes in energy demand by modulating the amount of RNA synthesized. Coupled rat liver mitochondria were used to determine the relationship between mitochondrial respiration, ATP levels, and mitochondrial transcription. This system included oxidizable substrates (malate and glutamate) and constituents that could support both mitochondrial respiration and transcription. The respiratory inhibitor rotenone, phosphorylation inhibitor oligomycin, and the uncoupler of oxidative phosphorylation carbonyl-cyanide p-triflouromethoxyphehylhydrazone inhibited RNA synthesis. Addition of ADP stimulated mitochondrial transcription and peak RNA synthesis was observed at 1-2 mM ADP. At ADP concentrations above 2 mM, RNA synthesis decreased. These results demonstrate that mitochondrial transcription is tightly coupled to ATP levels.

Adenosine Diphosphate↗
PubMed2001

Patent foramen ovale transcatheter closure device thrombosis.

The role of patent foramen ovale (PFO) in patients with cryptogenic stroke (stroke of unknown cause) remains controversial, although an association seems likely in younger patients with atrial septal aneurysms and PFO. The mechanism of cryptogenic stroke in these patients is presumed to be paradoxical embolism via right-to-left shunt across the PFO. The available options for treatment include medical therapy with antiplatelet or anticoagulant therapy or closure of the PFO surgically or with use of transcatheter PFO closure devices. We describe 2 cases of bilateral device thrombosis associated with use of a transcatheter PFO closure device (CardioSEAL). To our knowledge, only 1 other case of thrombosis associated with use of this device has been reported.

Catheterization↗
PubMed1999

85 kDa cytosolic phospholipase A2 is a target for chronic lithium in rat brain.

The mechanism by which chronic lithium exerts its therapeutic effect in brains of bipolar patients is not known. One possibility, suggested by our demonstration in the rat brain, is that chronic lithium inhibits turnover of arachidonic acid (AA) by reducing the activity of an AA-specific phospholipase A2 (PLA2). To test this further, mRNA levels of two AA-specific PLA2s, cytosolic PLA2 (cPLA2) type IV and intracellular PLA2 (iPLA2) type VIII, and protein level of cPLA2 were quantified in the brain of rats given lithium for 6 weeks. Chronic lithium markedly reduced brain mRNA and protein level of cPLA2, but had no effect on mRNA level of iPLA2. These results suggest that the final common path effect of chronic lithium administration is to reduce turnover of AA in brain by down-regulating cPLA2.

Animals↗