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Biomedical subjects

A Kapoor

Publications and source records attributed to A Kapoor.

At least 19 recordsLinked to original sources

Percutaneous coronary intervention through a Cabrol composite graft.

There are several different surgical techniques used to repair acute type-A aortic dissections. One such technique is called the Cabrol procedure which uses a Dacron tube graft to re-attach the native coronary arteries. Stenosis of this graft-native coronary anastomosis is a recognized complication of the procedure and one amenable to percutaneous intervention. However, knowledge of the complex anatomy involved with the Cabrol repair is required in order to potentially carry out successful intervention. We report one such case involving a critical stenosis at the anastomosis of the Cabrol graft with the native left main stem.

Aortic Dissection↗

ERK activity facilitates activation of the S-phase DNA damage checkpoint by modulating ATR function.

Although Erk kinase has been recently reported to function in the DNA damage response, the mechanism governing this process is unknown. We report here that hydroxyurea (HU) activates Erk via MEK1, a process that is sensitized by a constitutively active MEK1 (MEK1Q56P) and attenuated by a dominant-negative MEK1 (MEK1K97M). While ectopic MEK1Q56P sensitized HU-induced S-phase arrest, inhibition of Erk activation via U0126, PD98059, and MEK1K97M attenuated the arrest, and thereby enhanced cells to HU-induced toxicity. Taken together, we demonstrate an important contribution of Erk to the activation of the S-phase DNA damage checkpoint. This can be attributed to Erk's regulatory role in modulating ATR function. Inhibition of Erk activation with U0126/PD98059 and MEK1K97M substantially reduced HU-induced ATR nuclear foci, leading to a dramatic reduction of gammaH2AX and its nuclear foci. Reduction of MEK1 function by a small interference RNA (siRNA) MEK1 and ectopic MEK1K97M significantly decreased HU-induced gammaH2AX. Conversely, ectopic MEK1Q56P enhanced gammaH2AX foci. Furthermore, immunofluorescent and cell fractioning experiments revealed cytosolic and nuclear localization of ATR. HU treatment caused the redistribution of ATR from the cytosol to the nucleus, a process that is inhibited by U0126. Collectively, we show that Erk kinase modulates HU-initiated DNA damage response by regulating ATR function.

3T3 Cells↗

Chronic prenatal ethanol exposure increases glucocorticoid-induced glutamate release in the hippocampus of the near-term foetal guinea pig.

Exposure to high cortisol concentration can injure the developing brain, possibly via an excitotoxic mechanism involving glutamate (Glu). The present study tested the hypothesis that chronic prenatal ethanol exposure (CPEE) activates the foetal hypothalamic-pituitary-adrenal axis to produce high cortisol exposure in the foetal compartment and alters sensitivity to glucocorticoid-induced Glu release in the foetal hippocampus. Pregnant guinea pigs received daily oral administration of ethanol (4 g/kg maternal body weight/day) or isocaloric-sucrose/pair-feeding from gestational day (GD) 2 until GD 63 (term, approximately GD 68) at which time they were euthanised, 1 h after their final treatment. Adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined in foetal plasma. Basal and electrically stimulated Glu and gamma-aminobutyric acid (GABA) efflux in the presence or absence of dexamethasone (DEX), a selective glucocorticoid-receptor agonist, were determined ex vivo in foetal hippocampal slices. Glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA expression were determined in situ in the hippocampus and dentate gyrus. In the near-term foetus, CPEE increased foetal plasma ACTH and cortisol concentrations. Electrically stimulated glutamate, but not GABA, release was increased in CPEE foetal hippocampal slices. Low DEX concentration (0.3 microM) decreased stimulated glutamate, but not GABA, release in both CPEE and control foetal hippocampal slices. High DEX concentration (3.0 microM) increased basal release of Glu, but not GABA, in CPEE foetal hippocampal slices. GR, but not MR, mRNA expression was elevated in the hippocampus and dentate gyrus, whereas NR1 mRNA expression was increased in the CA1 and CA3 fields of the foetal hippocampus. These data demonstrate that CPEE increases high glucocorticoid concentration-induced Glu release in the foetal hippocampus, presumably as a consequence of increased GR expression. These effects of CPEE, coupled with increased glutamate release and increased NMDA receptor expression, may predispose the near-term foetal hippocampus to GR and Glu-NMDA receptor-mediated neurodevelopmental toxicity.

Adrenocorticotropic Hormone↗

Development of a simple restriction fragment length polymorphism assay for subtyping of coxsackie B viruses.

Coxsackie B viruses (genus, Enterovirus; family, Picornaviridae) can cause aseptic meningitis, encephalitis, pleurodynia, myocarditis and are implicated in the pathogenesis of dilated cardiomyopathy. The differentiation of the group B coxsackieviruses into their subtypes has potential clinical and epidemiological implications. In the present study, a simple restriction fragment length polymorphism (RFLP) assay was developed for typing of group B coxsackieviruses into subtypes 1-6. It is a two step process, first, virus isolation and identification by virus neutralization assay, using pools of polyclonal antisera, second, the reverse transcription polymerase chain reaction (RT-PCR) using a single primer pair selected from the conserved 5'-untranslated region (5'-UTR) of enterovirus genome followed by RFLP. A 440 bp product was amplified from the reference strains of each subtype of group B coxsackievirus and 29 clinical isolates (positive for group B coxsackieviruses by neutralization assay). The amplified products were subjected to restriction endonuclease digestion by enzyme BsaJI. The assay was able to distinguish all six serotypes of coxsackie B viruses. The results were comparable to serotyping and showed that due to the relatively conserved nature of 5'-UTR in enterovirus genome, this region can be used for subgeneric molecular identification of enteroviruses.

5' Untranslated Regions↗

Percutaneous intramedullary supracondylar nailing for fractures of distal femur.

A prospective study of 25 patients with supracondylar and intercondylar fracture of the femur was carried out from January 1999 to June 2003 at SSG Hospital, Baroda, India. Twenty-eight percent fractures were open and 72% were closed. Twelve pecent of the fractures had intraarticular extension. AO classification was used to classify the fractures. Eighty-four percent of the fractures were due to high velocity trauma. All the cases were operated by percutaneous supracondylar nailing. No postoperative complication related to fracture treatment was seen. Average follow up was 20.1 months (range 6-40 months). Average age of the patients was 31.5 years. Average time of union was 3.1 months (range 2-4 months). Average knee range of motion was 117 degrees. Even in open injuries, 85.7% had more than 110 infinity range of motion. All patients could return to their pre-injury lifestyle. Rating scale developed by Hospital for Special Surgery was used to quantify the results. Eighty-four percent showed excellent, 8% showed good and 8% showed fair results. Percutaneous supracondylar nailing is thus, an excellent method of treating fractures of distal femur.

Adult↗

Genetic association analysis of KCNQ3 and juvenile myoclonic epilepsy in a South Indian population.

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsy that shows a complex pattern of inheritance. We have tested the association between JME phenotype and an intragenic marker in KCNQ3 by using the transmission disequilibrium test in 119 probands and their parents. Mutations in KCNQ3 are known to cause benign familial neonatal convulsions and are involved in the physiologically important M current in neurons. Our results provide suggestive evidence of allelic association between JME and KCNQ3 ( P-value=0.008) and raise an interesting possibility of a genetic contribution to JME, viz., of a gene that causes a monogenic form of human epilepsy.

Brain↗

Hypothyroidism alters the expression of Bcl-2 family genes to induce enhanced apoptosis in the developing cerebellum.

Thyroid hormone (TH) deficiency results in delayed proliferation and migration of cerebellar granule cells. Although extensive cell loss during the development of the cerebellum under hypothyroid conditions is known, its nature and its mechanism are poorly understood. Bcl-2 family gene expression is known to determine the fate of cells to undergo apoptosis. We evaluated the effect of hypothyroidism on Bcl-2 family gene expression in the developing rat cerebellum. Electrophoresis and Western blotting were used to analyze DNA fragmentation and expression of DNA fragmentation factor (DFF-45), Bcl-2, Bcl-xL and Bax genes respectively. In the hypothyroid condition, extensive DNA fragmentation and enhanced cleavage of DFF-45 were seen throughout development (postnatal day 0 to day 24) and adulthood whereas they were absent in the euthyroid state. The anti-apoptotic genes Bcl-2 and Bcl-xL were down-regulated and the pro-apoptotic gene Bax was expressed at higher levels compared with the euthyroid state. These results suggest that normal levels of TH prevent cerebellar apoptosis to a large extent, whereas hypothyroidism not only increases the extent but also the duration of apoptosis by down-regulating the anti-apoptotic genes and maintaining a high level of the pro-apoptotic gene Bax.

Animals↗

Etiology, clinical profile, gender identity and long-term follow up of patients with ambiguous genitalia in India.

There is little information on the profile of children with ambiguous genitalia in India. Presented here is an analysis of patients with ambiguous genitalia registered in a general endocrine clinic during the last 2 decades. Seventy-four patients (age 4 months to 36 years) were registered during this period. Fifty-two were more than 5 years old at the time of registration. Thirty-five were reared as females, 29 as males; nine children (4 months to 1 year old) were brought for sex assignment, and one (with epispadias) was brought for correction of urinary incontinence. Investigations revealed 28 patients with congenital adrenal hyperplasia, 14 dysgenetic male pseudohermaphroditism, ten true hermaphroditism, six partial androgen insensitivity, four castration and one epispadias. There were eight patients with perineal hypospadias with normal Leydig cell reserve (normal LH, FSH and testosterone response to LHRH). Sex of rearing and gender identity were concordant in all except the patients with perineal hypospadias with normal Leydig cell response. These observations support the theory that prenatal androgen exposure masculinizes the brain.

Adolescent↗

Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and progression of acute allograft rejection.

The identification of early inflammatory events after transplant in solid tissue organ grafts that may direct T cell recruitment and promote acute allograft rejection remain largely unknown. To better understand temporal aspects of early inflammatory events in vascularized organ grafts, we tested the intragraft expression of four different chemokines in heterotopically transplanted A/J (H-2(a)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipient mice from 1.5 to 48 h after transplant. Similar temporal expression patterns and equivalent levels of chemokine expression were observed in both syngeneic and allogeneic cardiac allografts during this time period. Expression of the neutrophil chemoattractant growth-related oncogene alpha (KC) was observed first and reached peak levels by 6 h after transplant and was followed by the monocyte/macrophage chemoattractant protein-1 (JE) and then macrophage inflammatory proteins 1beta and 1alpha. Administration of rabbit KC antiserum to allograft recipients within 30 min of cardiac transplantation attenuated downstream events including intra-allograft expression of the T cell chemoattractants IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma, cellular infiltration into the allograft, and graft rejection. Similarly, depletion of recipient neutrophils at the time of transplantation significantly extended allograft survival from day 8 to 10 in control-treated recipients up to day 21 after transplant. These results indicate the induction of highly organized cascades of neutrophil and macrophage chemoattractants in cardiac grafts and support the proposal that early inflammatory events are required for optimal recruitment of T cells into allografts during the progression of acute rejection of cardiac allografts.

Acute Disease↗

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

BACKGROUND: Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. METHODS AND RESULTS: Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure </=130/85 mm Hg) and receiving no antihypertensive medications. In contrast, there was no significant decrease in systolic blood pressure or antihypertensive medication use in the patients receiving an isolated kidney transplant. CONCLUSIONS: Successful kidney/pancreas transplantation results in a marked improvement in hypertension treatment that is not observed in patients undergoing isolated kidney transplantation. These data underscore the importance of diabetes in the pathogenesis of hypertension in patients with diabetes and kidney failure.

Adult↗

Facile, regioselective [4 + 2] cycloaddition involving 1-aryl-4-phenyl-1-azadienes and allenic esters: an efficient route to novel substituted 1-aryl-4-phenyl-1,4-dihydropyridines.

[reaction: see text]1-Aryl-4-phenyl-1-azadienes undergo facile, regioselective [4 + 2] cycloaddition to the C2,C3 pi-bond of allenic esters in refluxing benzene, and the formed adducts undergo a 1,3-H shift to afford novel 2-alkyl-1-aryl-3-ethoxycarbonyl-4-phenyl-1,4-dihydropyridines (78-97%). However, when the reaction is carried at room temperature, besides the [4 + 2] addition, the [2 + 2] mode of addition involving C=N of azadiene and C3,C4 pi-bond of allenic esters also intervenes. The resulting N-aryl-2-ethoxy-carbonyl-methylidene-4-styrylazetidines (17-28%) undergo reorganization on silica gel to afford 2-cyclohexen-1-ones.

Journal Article↗

Non-polio enteroviruses in acute flaccid paralysis.

OBJECTIVE: Human enteroviruses are the major cause of aseptic meningitis and also cause a wide range of other acute illnesses, including neonatal sepsis like disease, meningitis, acute flaccid paralysis and acute hemorrhagic conjunctivitis. Infection in neonates is particularly life threatening. METHODS: Stool samples of 523 children (age < 4 years) showing symptoms of acute flaccid paralysis (AFP) were studied. National Polio Surveillance Project workers from different parts of Uttar Pradesh and Bihar collected the samples during June to October 1998. Non-polio enteroviruses (NPEV) were isolated in 191 cases only, by cell culture based neutralization assay. These NPEV isolates were further studied to find the frequent enterovirus serotype detected in stool of children having AFP. RESULTS: Data generated will help future studies on NPEV serotypes circulating in this area. CONCLUSION: In addition it may reduce unnecessary hospitalization, allow immune globulin batches of high titres to frequently circulating serotypes, to be reserved for intravenous therapy of neonates and guide the formulation of antigens for rapid and less expensive diagnosis.

Child, Preschool↗

Prevalence of missed opportunities for measles immunization in rural areas of Gujarat.

To assess the prevalence of missed opportunities for measles immunization, reason for their occurrence and potential aspect of avoiding them on measles immunization coverage a cross sectional study in 40 clusters of 4 villages, Ardi, Valasan, Chikhodra and Bamroli having a population of twenty four thousand was carried out. A total of 300 children between the age group 9-24 months were included in the study. Immunization status of each child was recorded either from immunization card or maternal recall. Coverage for measles vaccine was 78.66%. Prevalence of missed opportunity was 15.33%. It was found that significant increase in measles coverage can be achieved upto 94% if all missed opportunities for measles vaccine are avoided.

Cluster Analysis↗

Improving operative performance using a laparoscopic hernia simulator.

BACKGROUND: Traditionally, the acquisition of surgical skill has occurred entirely in the operating room. To meet the expanding challenges of cost containment and patient safety, novel methods of surgical training utilizing ex-vivo workstations are being developed. The purpose of our study was to evaluate the impact of a laparoscopic training curriculum on surgical residents' operative performance. METHODS: Twenty-one surgery residents completed baseline laparoscopic total extraperitoneal (TEP) hernia repairs. Operative performance was evaluated using a validated global assessment tool. Each resident was then randomized to a control group or a trained group. A CD ROM, video, and simulator were used for training. At the end of the study, each resident's operative performance was again evaluated. RESULTS: Improvement was significantly greater in the trained group in five of the eight individual global assessment areas as well as the composite score (P <0.05). Questionnaire data suggested that training resulted in improved understanding of the TEP hernia repair (P = 0.01) and an increased willingness to offer the operation to patients with nonrecurrent unilateral hernias (P = 0.02). CONCLUSIONS: A multimodality laparoscopic TEP hernia curriculum improves residents' knowledge of the TEP hernia repair and comfort in performing the procedure, and may also improve actual operative performance.

Clinical Competence↗

Inoue balloon mitral valvotomy in patients with atrial septal aneurysm.

Atrial septal aneurysms (ASA) are not uncommonly detected in patients with rheumatic mitral stenosis and pose problems during transeptal puncture in patients undergoing balloon mitral valvotomy. From a period of August 1995 to May 1998, we performed a total of 680 Inoue Balloon Mitral Valvotomy (IBMV) procedures with ASA noted in 30 patients, 13 of diffuse and 17 localized type. Transesophageal echocardiography (TOE) was used in all patients with suspected aneurysm on transthoracic echo (TTE) for exact three-dimensional delineation of the location and extent of the aneurysm. The localized type of aneurysms were further subcategorized into five types viz. antero-superior and leftwards (6), postero-superior and rightwards (2), antero-inferior and leftwards (2), postero-inferior and rightwards (5), and central (2), depending on their location in the atrial septum. The site for transeptal puncture was decided after this localization and the remainder of the IBMV procedure was as usual. In the set of thirteen patients with diffuse type of atrial septal aneurysms all but one case had a successful transeptal puncture using standard technique except for a somewhat inferior puncture site so as to be perpendicular to the plane of atrial septum and a successful mitral valve dilatation was possible at first attempt. In the set of 17 patients with localized type of aneurysms, all had a successful transeptal puncture except one. In patients with aneurysms localized antero-superiorly and leftwards the septal puncture was done in a slightly inferior location with transeptal needle pointing some what more posterior, i.e. 5 or 6 o'clock position and in patients with aneurysms localized postero-inferiorly the puncture was done more cephalic with needle directed somewhat anterior, i.e. 3-2 o'clock position. In the two patients with Atrial septal aneurysms located postero-superiorly and to the right the puncture was done slightly inferior but with transeptal needle pointing to about 3 or 2 o'clock position and in the single patient with antero-inferior location the puncture was done in slightly higher but with a more posterior directed needle, i.e. 5-6 o'clock position. The two patients with centrally located localized type of aneurysms had successful transeptal puncture with standard needle direction (4 o'clock) but at a slightly inferior location. We conclude that a good localization of atrial septal aneurysms using transesophageal echocardiography and our technique of transeptal puncture leads to a successful outcome in majority of cases undergoing Inoue balloon mitral valvotomy with associated atrial septal aneurysms.

Adult↗

Slow coronary flow: a distinct angiographic subgroup in syndrome X.

Patients evaluated for chest pain with angiographically normal coronary arteries are usually labelled syndrome X. A portion of these patients may not have a cardiac cause for their symptoms. The authors aimed to study a subset within this group who showed the phenomenon of slow coronary flow (SCF) as evidenced by a slow antegrade progression of the dye on the coronary arteriogram to see if this could be used as a marker of myocardial ischemia. This observational study included 207 patients being evaluated for suspected coronary artery disease and found to have normal coronary angiograms. SCF was seen in 49 of these patients (23.7%) while the remaining 158 (76.3%) had normal coronary flow (NCF), as detected by the corrected thrombosis in myocardial infarction (TIMI) frame count method (TIMI frame count more than 2 SD of normal). Forty of the 49 patients (82%) in the SCF group had classical angina as compared with only 51 of the 158 patients (32%) in the NCF group (p<0.01). Also, a definitively positive exercise test was observed more commonly in the SCF group than in the NCF group (71% vs 42%, p < 0.01). The authors conclude that SCF patients constitute a definite subset within the wide spectrum of syndrome X and that the phenomenon of SCF could be used as a marker for myocardial ischemia.

Adult↗