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Biomedical subjects

R Krishna Kumar

Publications and source records attributed to R Krishna Kumar.

At least 19 recordsLinked to original sources

Testing bridge-mediated differences in dinuclear valence tautomeric behavior.

Two structurally characterized dinuclear valence tautomers are described. Cobalt ions are bridged by p- and m-phenylene units connected to 2,2'-bipyridines. X-ray crystal structures show that the molecules are in the [(Co(III))(Co(III))] forms at ca. 125 K, while spectroscopic studies show that both molecules can achieve the [(Co(II))(Co(II))] form above 400 K and confirm the [(Co(III))(Co(III))] form below 10 K. Magnetic susceptibility studies are also included. Our results highlight the necessity of studying both crystalline and amorphous samples to distinguish the effects of intrinsic electronic structure and intermolecular forces on valence tautomeric behavior.

Journal Article↗

Somatic growth after ventricular septal defect in malnourished infants.

OBJECTIVE: To assess somatic growth after ventricular septal defect (VSD) repair in severely malnourished infants. STUDY DESIGN: Ninety consecutive infants (age at surgery: 7.2 +/- 3.2 months) were followed after VSD closure at a referral center in southern India to evaluate somatic growth. RESULTS: At surgery, 44% and 30% of patients had weight and height Z score <-3, respectively. On follow-up (age 5.4 +/- 0.8 years), despite a significant improvement from baseline (Z score -1.8 +/- 1.2 vs -2.8 +/- 1.3, P <.001), weight was significantly lower compared with healthy Indian children, particularly for boys. Height Z score improved significantly only in girls (-0.8 +/- 1.3 vs -1.8+/-2.1, P = .01). Weight, height, and combined weight and height Z scores (failure to thrive) of <-2 were observed in 42%, 27%, and 18 % of patients, respectively. On multivariate analysis, weight Z score <-2 on follow-up was predicted by weight Z score at surgery and male sex, height Z score <-2 by maternal height and male sex, and failure to thrive by maternal height and caloric intake. CONCLUSIONS: There is suboptimal recovery of somatic growth after repair of VSD in severely malnourished infants. Preoperative malnutrition affected only weight on follow-up, whereas height recovery and failure to thrive were influenced by constitutional factors.

Anthropometry↗

4,4'-Dimethoxytrityl group derived from secondary alcohols: are they removed slowly under acidic conditions?

Removal of 4,4'-dimethoxytrityl (DMT) groups from primary and secondary hydroxyl functionality was investigated. It was observed that deblocking of DMT group from secondary hydroxyl group of molecules attached to solid support under acidic conditions occurred relatively slowly compared to primary hydroxyl group. Marginal difference in rate of detritylation was observed between DMT group attached to 5'-hydroxyl group of deoxyribonucleoside and 2'-O-methoxyethylribonucleoside when attached to one kind of support. Removal of DMT from nucleoside attached to OligoPrep solid support was found to be slow.

Acids↗

Influence of lumen shape and vessel geometry on plaque stresses: possible role in the increased vulnerability of a remodelled vessel and the "shoulder" of a plaque.

OBJECTIVE: To use finite element modelling to look at the impact of lumen shape and vessel geometry on stress distribution in a vessel. METHODS: A finite element model of an atherosclerotic plaque in a coronary artery was created and a non-linear analysis with Ogden strain energy function was done. The three most common shapes seen in an artery with an eccentric plaque--namely an elliptical lumen inside a circular vessel (A), a circular lumen inside an elliptical vessel, typical of a vessel with positive remodelling (B), and a circular lumen inside a circular vessel (C)--were modelled with and without lipid. Stress was analysed in the region of the fibrous cap separating the lumen from the plaque and the region of maximum stress along the circumference of the lumen was noted. RESULTS: In a normal circular shaped coronary artery, the haemodynamic stresses were uniformly distributed all around the circle. However, if the circle was changed to an ellipse, the stresses were redistributed along the major axis and dropped substantially along the minor axis. The stresses in a positively remodelled vessel (B) were significantly greater than in A and C, by almost 100%. Moreover, the haemodynamic stresses increased significantly towards the major axis or the shoulder in A and B, due to lumen shape and vessel geometry alone, even in the absence of lipid in the model. The stresses also had a direct relation with the thickness of the lipid pool and an inverse relation with cap thickness and lumen stenosis. CONCLUSIONS: The increased vulnerability of the shoulder region of a plaque and a remodelled coronary artery are due, apart from other factors, to increased biomechanical stresses as a result of lumen shape and vessel geometry.

Coronary Artery Disease↗

Management of infants with large, unrepaired ventricular septal defects and respiratory infection requiring mechanical ventilation.

OBJECTIVES: We sought to describe the hospital management and early outcome of critically ill infants presenting with large ventricular septal defects and pneumonia requiring mechanical ventilation at a referral center in a developing country. Infants with large ventricular septal defects who have pneumonia might present with respiratory failure requiring mechanical ventilation. In the developing world this presentation is relatively common, but few data exist describing patient management strategies. METHODS: Hospital data of consecutive infants admitted with large ventricular septal defects and pneumonia requiring mechanical ventilation were reviewed and analyzed. RESULTS: We identified 18 infants (mean age, 3.6 +/- 3.0 months). On admission, all the infants were significantly malnourished, and echocardiography showed bidirectional shunting (predominantly right-to-left shunting) in 6 infants. Thirteen (72%) patients improved with intensive medical management that included mechanical ventilation for 1 to 16 days (median, 6.5 days); unequivocal left-to-right shunting was subsequently documented by means of echocardiography in all 13 patients. Twelve patients underwent surgical repair, and 11 (91.6%) were discharged after median mechanical ventilation of 100 hours (range, 42-240 hours) and intensive care unit stay of 8 days (range, 4-15 days). Five of 6 unoperated patients died, 4 of them within a few hours of admission. One child with multiple ventricular septal defects was discharged and subsequently underwent pulmonary artery banding. CONCLUSION: Corrective cardiac surgery for selected critically ill infants with large ventricular septal defects, severe malnutrition, and pneumonia requiring mechanical ventilation is feasible and should be considered a viable management strategy.

Anti-Bacterial Agents↗

Retinal nerve fiber layer measurements in indian eyes using the scanning laser polarimeter, GDx.

PURPOSE: To obtain retinal nerve fiber layer (RNFL) measurements in normal Indian subjects of different age groups; and to determine the differences between the right and the left eye of a subject and variations between male and female gender using the scanning laser polarimeter GDx. MATERIALS AND METHODS: Prospective cross-sectional study of 180 eyes of 94 subjects. The RNFL values were obtained with the nerve fiber analyser GDx using default quadrant positions supplied by the manufacturer. Fourteen parameters were studied. Of these 6 were average-based parameters (average thickness, superior maximum, inferior maximum, ellipse average, superior average, inferior average), 4 ratio-based parameters (symmetry, superior ratio, inferior ratio, superior/nasal), 4 "other" parameters (maximum modulation, number, ellipse modulation, superior integral). The main outcome measures were effect of age on RNFL values, comparison of males and females and the right and the left eye of a subject. RESULTS: There was a negative linear correlation with age. Three ratio-based parameters showed a statistically significant negative correlation with age. "Number" increased with age. Superior maximum, superior average, superior integral, symmetry and superior ratio were higher for the left eye. 'Number' was higher for the right eye. Superior ratio and maximum modulation were more in females than males, no difference was noted with other parameters. CONCLUSION: There was a gradual decrease of RNFL values with increasing age - the superior quadrant values were higher for the left eye than the right eye, suggesting asymmetry. No significant differences were detected between males and females.

Adolescent↗

Trends in exchange coupling for trimethylenemethane-type Bis(semiquinone) biradicals and correlation of magnetic exchange with mixed valency for cross-conjugated systems.

A magnetostructural correlation (conformational electron spin exchange modulation) within an isostructural series of biradical complexes is presented. X-ray crystal structures, variable-temperature electron paramagnetic resonance spectroscopy, zero-field splitting parameters, and variable-temperature magnetic susceptibility measurements were used to evaluate molecular conformation and electron spin exchange coupling in this series of molecules. Our combined results indicate that the ferromagnetic portion of the exchange couplings occurs via the cross-conjugated pi-systems, while the antiferromagnetic portion occurs through space and is equivalent to incipient bond formation. Thus, molecular conformation controls the relative amounts of ferro- and antiferromagnetic contributions to exchange coupling. In fact, the exchange parameter correlates with average semiquinone ring torsion angles via a Karplus-Conroy-type relation. Because of the natural connection between electron spin exchange coupling and electronic coupling related to electron transfer, we also correlate the exchange parameters in the biradical complexes to mixed valency in the corresponding quinone-semiquinone radical anions. Our results suggest that delocalization in the cross-conjugated, mixed-valent radical anions is proportional to the ferromagnetic contribution to the exchange coupling in the biradical oxidation states.

Journal Article↗

Clinical course and management strategies for hemolysis after transcatheter closure of patent arterial ducts.

Residual flows following transcatheter coil or device closure of the patent ductus arteriosus (PDA) can result in hemolysis. Of 611 patients who underwent transcatheter PDA closure at our institution, 5 patients (age, 6-63 years) developed overt hemolysis (after coil occlusion in 4 and Amplazter device closure in 1). All had ducts > 3 mm and residual flows after the procedure. In one patient, hemolysis occurred 3 months after coil occlusion following a period of uncontrolled hypertension. The occurrence of hemolysis correlated significantly with both age as well as duct size (P < 0.00001). Hemolysis was associated with a fall in hemoglobin of 3-6 g/100 ml (n = 3), jaundice (n = 2), and renal failure (n = 1). Hemolysis subsided spontaneously in one patient and four patients required flow elimination. Deploying additional coils in three patients eliminated residual flows. In one patient (after Amplatzer device closure for 12.5 mm duct with aneurysm), flow persisted after 25 additional coils, transient balloon occlusion, and gel foam instillation. Flow elimination was eventually achieved through thrombin instillation after balloon occlusion of the ampulla. All patients recovered completely and were well on follow-up. Although hemolysis after duct occlusion is rare (0.8% in this series), residual flow at the end of the procedure merits careful monitoring. Aggressive elimination of residual flows is often necessary to control hemolysis.

Adult↗

2-Methyl-5-tert-butylthiophenol--an odorless deprotecting reagent useful in synthesis of oligonucleotides and their analogs.

A solution of 2-methyl-5-tert-butylthiophenol and triethylamine in acetonitrile efficiently removed the methyl protecting groups from phosphate and phosphorothioate triesters and yielded oligonucleotides of high quality. This inexpensive odorless liquid is not toxic and is a suitable replacement for hazardous thiophenol and other reagents often used for this purpose.

Acetonitriles↗

Solid phase synthesis of phosphorothioate oligonucleotides utilizing diethyldithiocarbonate disulfide (DDD) as an efficient sulfur transfer reagent.

Diethyldithiodicarbonate (DDD), a cheap and easily prepared compound, is found to be a rapid and efficient sulfurizing reagent in solid phase synthesis of phosphorothioate oligodeoxyribonucleotides via the phosphoramidite approach. Product yield and quality based on IP-LC-MS compares well with high quality oligonucleotides synthesized using phenylacetyl disulfide (PADS) which is being used for manufacture of our antisense drugs.

Carbonates↗

A practical approach for the diagnosis and management of dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) refers to a group of conditions of diverse etiology in which both ventricles are enlarged with reduced contractility. Certain correctable conditions associated with ventricular dysfunction can masquerade as DCM. Most of them can be identified with relatively inexpensive and readily available tests. A typical diagnostic work-up for a child with DCM also includes a number of investigations to identify the underlying cause, some of which are expensive and sophisticated. The average center in the developing world often does not have the facilities to carry out these investigations. The results of many of these investigations typically do not translate into a specific management strategy that makes a difference to prognosis. A significant number of children with DCM will eventually develop end-stage heart failure that requires cardiac transplantation with or without bridging procedures. This is an unrealistic option for the developing world. The management strategy of childhood DCM in the developing world needs to be tailored to the resources available with in a manner such that the overall prognosis is not substantially affected.

Adolescent↗

Coil occlusion of the small patent arterial duct without arterial access.

BACKGROUND: Arterial access is traditionally considered mandatory during coil occlusion of the patent arterial duct. Arterial access necessitates heparinization and carries the risk of femoral artery occlusion in small children. METHODS AND RESULTS: Between July 1999 and May 2001, we attempted coil occlusion of patent arterial ducts in 104 patients without arterial access. The patients were aged from 3 months to 14 years. The median age was 2 years. They weighed 3-35 kg. The median weight was 9.8 kg. The duct diameter at pulmonary artery insertion was 1.8-3.5 mm. The patients were selected on basis of echocardiographic evaluation of duct diameter at pulmonary artery insertion and morphology of the ampulla. Doppler color flow imaging was used in the catheterization laboratory to confirm duct closure. Arterial access was required in 21 patients. The reasons included accidental puncture in 5 patients, failure to obtain venous access in 1 patient, aortic embolization in 3 patients, poor echo images in 2 patients, requirement for additional coils in 8 patients and, failure to cross the duct from pulmonary artery in 2 patients. The fluoroscopic time ranged from 2.2 to 20 min with a mean of 5.3+/-3.8 min. Immediate closure was achieved in 98 patients and this included 79 of the 83 patients in whom arterial access was avoided. Color Doppler 3-24 h later showed residual flow in 2 patients. Four patients had new-onset left pulmonary artery turbulence with peak gradients below 5 mm of mercury. Coil embolization occurred in 6 patients and all coils were retrieved. Three-month follow up information was available for 78 patients. Small residual ductal leaks were seen in 4 patients, 2 of whom had leaks at 24 h. Two patients had recanalized their ducts. CONCLUSION: It is feasible to occlude small patent arterial ducts with coils using venous access alone in carefully selected patients with excellent immediate and short-term results.

Adolescent↗

Outcome of ventricular septal defect repair in a developing country.

OBJECTIVES: To examine the impact of nutrition and lung infection on outcome early after ventricular septal defect (VSD) repair in infants in a developing country. STUDY DESIGN: One hundred consecutive infants (age, 7.4 +/- 3.3 months) with large VSD(s) who underwent surgical repair at one institution in South India from July 1998 to June 2000 were analyzed. Primary outcome variables were postoperative death, duration of mechanical ventilation, intensive care unit (ICU) stay, and hospital stay. Preoperative variables analyzed included age, weight and length Z scores, and lung infection. RESULTS: Preoperative nutrition was poor (weight Z score, -2.8 +/- 1.3), and 25 patients had pneumonia. Six patients died after repair. No preoperative variable was associated with death. Mechanical ventilation, ICU stay, and hospital stay were longer for younger patients (r (s) for ventilation, -0.23, P =.02; for ICU stay, -0.33, P <.001; for hospital stay, -0.27, P =.007) and for those with preoperative pneumonia (median ventilation duration, 46 vs 24 hours, P <.001; median ICU stay 7 vs 4 days, P <.001; median hospital stay 10 vs 7 days, P =.001). Preoperative weight and length Z scores were not associated with any outcome variable. CONCLUSIONS: Poor nutritional status, preoperative pneumonia, and age do not increase mortality rates after VSD repair. Repair of large VSDs should not be delayed because of these preoperative characteristics.

Female↗

Catheter interventions for congenital heart disease in third world countries.

The term "Third World" loosely encompasses a group of middle- and low-income countries. Considerable differences exist in health care delivery and health indices among these countries. The vast majority of children in the Third World do not have health insurance for congential heart disease (CHD). Catheter interventions for CHD are expensive because of installation costs of expensive biplane equipment, the requirement of dedicated personnel, and the need to stock a large inventory of expensive hardware. As a result, many catheter intervention procedures are beyond the reach of the average patient in the developing world. The following cost-effective strategies have evolved in selected institutions that have attempted to perform catheter interventions for CHD at an affordable cost: sharing of space, equipment, and support personnel with a busy adult cardiology program; use of single plane equipment; the development of sedation protocols to reduce the need for anesthesiologists; strategies to reduce procedure time; reuse of hardware through ethylene oxide sterilization; improvisations to use adult hardware items for CHD interventions; judicious case selection; and improvised alternatives to occlusive devices. These strategies may help reduce costs and allow a larger proportion of patients in developing countries with CHD to undergo interventions. However, the safety of these strategies and the cost savings need to be carefully evaluated prospectively.

Anesthesia↗

Synthesis of high quality phosphorothioate oligonucleotides as antisense drugs. Use of I-linker in the elimination of 3'-terminal phosphorothioate monoesters.

Detritylation of a 5'-O-DMT-2'-deoxyadenosine moiety attached to solid support under acidic condition leads to depurination during oligonucleotide synthesis. Deprotection followed by reversed phase HPLC purification leads to desired oligonucleotide contaminated with significant levels of 3'-terminal phosphorothiaote (3'-TPT) monoester (n-1)-mer. However, it is demonstrated that attachment of dA nucleoside through its exocyclic amino group to solid support leads to substantial reduction of 3'-TPT formation thereby improving the quality of oligonucleotide synthesized.

Base Sequence↗