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Biomedical subjects

K Chandrasekaran

Publications and source records attributed to K Chandrasekaran.

At least 37 records · Page 2Linked to original sources

Advantage of autograft and homograft valve replacement for complex aortic valve endocarditis.

BACKGROUND: There are advantages to using homografts and autografts as aortic valve replacements, particularly in patients with infective endocarditis. To better define these advantages, we reviewed our 13-year experience with the surgical management of infective endocarditis involving the aortic valve and root. METHODS: From 1986 through 1998, 81 adults with aortic valve endocarditis underwent valve replacement (AVR). The mean age of the 65 men and 16 women was 44 +/- 14 years. Sixty-three (78%) patients had active endocarditis at the time of operation. Non-native valve endocarditis was present in 29 (36%) patients, in 9 of whom the infection was a recurrence. Aortic valve replacements were performed with 46 homografts (homo-AVR), 25 autografts (Ross-AVR), and 10 prosthetic valves (prosth-AVR). Among Ross-AVR and homo-AVR patients, 11 required mitral valve replacement or repair (homo-Ross DVR). Follow-up was 90% complete within 2 years of the end of the study with a mean of 3.7 +/- 3.4 years. RESULTS: Early mortality was 16% (13 of 81 patients). This was 12% (3 of 25 patients) for Ross-AVR, 17% (8 of 46 patients) for homo-AVR, and 20% (2 of 10 patients) for prosth-AVR. Overall late mortality was 10% (7 of 68 patients) with a valve-related late mortality of 7% (5 of 68 patients). Actuarial survival at 5 years was 88% +/- 9% in Ross-AVR, 69% +/- 11% in homo-AVR, and 29% +/- 22% in prosth-AVR (p = 0.03). Endocarditis recurred in 12.5% (1 of 8 patients) with prosth-AVR and 3% (2 of 60 patients) in homo-Ross AVR. CONCLUSIONS: Valve replacement in the presence of native and prosthetic endocarditis remains a formidable challenge. Autografts and homografts are the preferred replacement aortic valves for these patients even if concomitant mitral valve replacement is required, and risk of valve-related death or recurrent endocarditis is low at medium-term follow-up.

Adult↗

Low backache during pregnancy. Acute hemodynamic effects of a lumbar support.

OBJECTIVE: To determine whether a commercially available elastic/Velcro lumbar and abdominal support (Mother-To-Be, CMO, Inc., Barberton, Ohio) affects the hemodynamics of the fetus and pregnant woman. STUDY DESIGN: Healthy volunteers with low backache at 24-36 weeks' gestation were sought from our obstetric clinic population. The fetal heart rate (FHR), maternal blood pressure and maternal cardiac output were monitored for 20-minute intervals before, during and after placement of the support while standing and sitting. A sufficient number of subjects was used to detect a difference of 10% in cardiac output. RESULTS: Twenty-five women were enrolled between 24 and 36 weeks' gestation. No significant changes were encountered in the FHR baseline or beat-to-beat variability during placement of the support. The few FHR decelerations were isolated and not attributable to the support. The maternal systolic, diastolic and mean arterial blood pressures were unaffected by the support. The right-sided and left-sided cardiac outputs were unchanged during the monitoring periods. Each woman, when questioned two weeks later, reported improvement in back discomfort while sitting and standing. CONCLUSION: This elastic/Velcro lumbar and abdominal support, available to relieve low backache, did not acutely affect the hemodynamics of the fetus and mother.

Adult↗

Ross operation and aneurysm or dilation of the ascending aorta.

Aortic valve disease and aneurysmal dilation of the ascending aorta are managed by prosthetic valve conduit replacement or homograft replacement. Requirement of anticoagulation, risk of thromboembolism or bleeding, and increased risk for homograft degeneration in young patients suggest that a Ross root replacement with replacement or reduction of the ascending aorta could be a preferred alternative. To assess efficacy, the present review was undertaken. Between April 19, 1995, and February 1999, 64 patients (age, 8 months to 59 years; median age, 37 years) had a Ross operation, with resection of the ascending aorta in 30 and reduction aortoplasty in 34. Annular fixation was performed in 57 patients, with aortic annulus reduction in 39. Clinical evaluation with echocardiogram was completed within 1 year of closure in 62 patients. There was one operative death and one non-valve-related late death. Autograft valve insufficiency (AI) was 0 to trace in the perioperative period in all patients. One patient developed progressive annular dilation with moderate AI at 2 months. Reoperation with annular reduction and fixation restored autograft valve function. Postoperative mean aortic annulus diameter was 22.5+/-0.4 mm (Z-value, -0.2+/-0.2) and 23.2+/-0.8 mm (Z-value, -0.02+/-0.5) at 1 year. Aortic sinus diameter was 33+/-6 postoperative and 36+/-5 at 1 year. The autograft root sinus diameter was greater than 39 mm in 11 patients at the most recent echocardiogram. Mean echocardiography measurements of the aortic root have been constant during the postoperative follow-up period. Two patients have required reoperation for homograft obstruction 1.3 and 2.1 years after operation. Ross root replacement of the aortic valve with resection or reduction aortoplasty can be performed with a low operative risk and limited morbidity. Its early durability appears to be similar to other Ross operations.

Adolescent↗

No association between Alzheimer plaques and decreased levels of cytochrome oxidase subunit mRNA, a marker of neuronal energy metabolism.

It has been proposed that neuritic plaques or toxic substances diffusing from them contribute to neurodegeneration in Alzheimer disease. We examined this hypothesis by looking for evidence of decreased neuronal energy metabolism in the proximity of neuritic plaques. Levels of mitochondrial DNA-encoded mRNA for subunit III of cytochrome oxidase, a marker of neuronal energy metabolism, were determined in post mortem brain samples. Consistent with earlier results, overall cytochrome oxidase subunit III mRNA levels were decreased in Alzheimer midtemporal cortex compared with controls. However, this reduction did not correlate with plaque density. In Alzheimer brains, cytochrome oxidase subunit III mRNA levels in neurons bearing neurofibrillary tangles were lower than in tangle-free neurons. However, neuronal cell bodies in close proximity of neuritic plaques showed no decrease in cytochrome oxidase subunit III mRNA or total polyadenylated mRNA compared with more distant neurons. Cytochrome oxidase enzyme activity in neuronal processes also showed no local reduction around neuritic plaques. These results suggest that neuritic plaques do not contribute to reduced neuronal energy metabolism in Alzheimer disease.

Aged↗

Downregulation of oxidative phosphorylation in Alzheimer disease: loss of cytochrome oxidase subunit mRNA in the hippocampus and entorhinal cortex.

Messenger RNA (mRNA) for cytochrome oxidase subunit II (COX II) was localized by in situ hybridization in the entorhinal cortex and hippocampal formation of postmortem brain tissue from normal human subjects and from patients with Alzheimer disease (AD). In the control entorhinal cortex, COX II mRNA was detected mainly in neuronal cell bodies of layers II and IV. In control hippocampal formation, highest levels were localized in neuronal cell bodies of the dentate gyrus and the CA3 and CA1 regions, neurons that are involved in the major input and output pathways of the hippocampal formation. In AD brain, COX II mRNA was markedly reduced in the entorhinal cortex and the hippocampal formation compared with control brain. In the AD hippocampal formation, reductions were in regions severely affected by AD pathology as well as in regions that were relatively spared. These results are consistent with the hypothesis that reduced mitochondrial energy metabolism reflects loss of neuronal connections in AD.

Aged↗

Large pulmonary vein varix diagnosed by transesophageal echocardiography: an unusual site for thrombus in atrial fibrillation.

An elderly man with pulmonary vein varix and atrial fibrillation is described. The diagnosis of pulmonary varix, a localized dilatation of pulmonary vein, was made by transesophageal echocardiography. The patient had chronic atrial fibrillation, and transesophageal echocardiography demonstrated thrombus in the pulmonary varix. In patients with atrial fibrillation, pulmonary varix may be an unusual site for thrombus formation.

Aged↗

Emboli observed with use of transesophageal echocardiography immediately after tourniquet release during total knee arthroplasty with cement.

The right atrium and the right ventricle of fifty-five patients were imaged with transesophageal echocardiography during fifty-nine total knee arthroplasties performed with cement and the use of general anesthesia. The patients ranged in age from thirty-two to eighty-three years (mean, 65.5 years). Cardiopulmonary parameters were measured with use of hemodynamic monitoring systems, such as pulse oximeters, pulmonary artery catheters, and radial artery catheters. In addition, a femoral vein catheter was inserted on the side of the operation in ten of the fifty-five patients. Showers of echogenic material traversing the right atrium, the right ventricle, and the pulmonary artery after the tourniquet was deflated were observed to various degrees in all patients and lasted three to fifteen minutes. The mean peak intensity occurred within thirty seconds (range, twenty-four to forty-five seconds) after the tourniquet was released. The mean mixed venous oxygen saturation (and standard error of the mean) decreased (from 83+/-0.9 to 72+/-1.5 per cent) and the mean pulmonary arterial pressure increased (from 20+/-1.0 to 27+/-1.0 millimeters of mercury [2.67+/-0.13 to 3.60+/-0.13 kilopascals]), compared with the values before the tourniquet was released, in all patients. The pulmonary vascular resistance index increased after release of the tourniquet (to a maximum of 328+/-29 dyne.s.cm(-5).m2; p = 0.00002) only in the patients who had echogenic material that was at least 0.5 centimeter in diameter. Clinical pulmonary embolism developed postoperatively in three patients; all three had had echogenic particles that were more than 0.5 centimeter in maximum diameter on imaging. Blood aspirated from one of the pulmonary artery catheters and from five of the ten femoral vein catheters demonstrated fresh venous thrombus. Histological evaluation of the aspirates failed to demonstrate fat, marrow, or particles of polymethylmethacrylate. Surgeons should consider acute pulmonary embolism as a diagnosis when evaluating a patient who has hemodynamic collapse during total knee arthroplasty performed with cement.

Adult↗

Lack of arrhythmogenicity with ST-segment elevation during high-dose of dobutamine atropine stress in patients with documented or suspected coronary artery disease.

The angiographic, echocardiographic, and electrocardiographic correlates of ST-segment elevation during high-dose dobutamine-atropine stress were prospectively looked at in a group of high-risk patients. Unlike exercise-induced ST elevation, ST-segment elevation with dobutamine-atropine stress, while indicating transmural ischemia, did not increase rate of arrhythmias and hence by itself may not be an indication to terminate the test.

Aged↗

Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease.

We recently reported 50% decreases in mRNA levels of mitochondrial DNA (mtDNA)-encoded cytochrome oxidase (COX) subunits I and III in Alzheimer disease (AD) brains. The decreases were observed in an association neocortical region (midtemporal cortex) affected in AD, but not in the primary motor cortex unaffected in AD. To investigate whether the decreases are specific to mtDNA-encoded mRNA, we extended this analysis to nuclear DNA (nDNA)-encoded subunits of mitochondrial enzymes of oxidative phosphorylation (OXPHOS). Brains from five AD patients showed 50-60% decreases in mRNA levels of nDNA-encoded subunit IV of COX and the beta-subunit of the F0F1-ATP synthase in midtemporal cortex compared with mRNA levels from midtemporal cortex of control brains. In contrast, these mRNAs were not reduced in primary motor cortices of the AD brains. The amount of nDNA-encoded beta-actin mRNA and the amount of 28S rRNA were not altered in either region of the AD brain. The results suggest that coordinated decreases in expression of mitochondrial and nuclear genes occur in association cortex of AD brains and are a consequence of reduced neuronal activity and downregulation of OXPHOS machinery.

Aged↗

Study of the feasibility of involving male student volunteers in case holding in an urban tuberculosis programme.

This paper reports the feasibility of involving unpaid National Service Scheme (NSS) male student volunteers in a city-based tuberculosis (TB) programme in supplying drugs and retrieving non-complaint TB patients. Twenty-five students were selected after assessing their attitude and were trained on TB drug delivery, home visits and motivation of non-compliant patients. Twenty-three sputum positive patients identified in a medical camp were started on an 8-month short-course chemotherapy regimen. Students supplied the drugs on a weekly basis and defaulters were visited. The treatment completion rate was 83% and defaulter retrieval was 57%. All patients had sputum smear conversion by 2 months and one relapsed during the 24-month follow-up.

Adolescent↗

Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer's disease patients.

Gene expression of mitochondrial DNA-encoded ND4 in brains of Alzheimer's disease (AD) patients and age-matched controls was measured using Northern blot. The level of ND4 message in temporal cortex of control subjects was higher than in motor cortex, whereas the level of ND4 gene expression in temporal cortex of AD brains was decreased compared with that in temporal cortex of controls. A control probe showed no difference in expression between the two areas of AD and control brains. These and previous data suggest that neurons vulnerable to AD express higher levels of enzymes of oxidative phosphorylation than do spared neurons, and that this difference may promote selective neuronal vulnerability of AD.

Alzheimer Disease↗

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease.

We studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early-stage neurofibrillary tangles as compared to tangle-free neurons (p < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle-free neurons of 4 AD brains to tangle-free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle-free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.

Aged↗

Evidence for physiological down-regulation of brain oxidative phosphorylation in Alzheimer's disease.

In vivo imaging of patients with Alzheimer's disease using positron emission tomography (PET) demonstrates progressive reductions in brain glucose metabolism and blood flow in relation to dementia severity, more so in association than primary cortical regions. These reductions likely follow regional synaptic loss or dysfunction and reflect physiological down-regulation of gene expression for glucose delivery, oxidative phosphorylation (OXPHOS), and energy consumption in brain. Indeed, the pattern of down-regulation of expression for both mitochondrial and nuclear genes coding for subunits of OXPHOS enzymes in the Alzheimer brain resembles the pattern of down-regulation in normal brain caused by chronic sensory deprivation. In both cases, down-regulation likely is mediated by changes in transcriptional and posttranscriptional regulatory factors. Physiological down-regulation of OXPHOS gene expression in Alzheimer's is consistent with PET evidence that cognitive or psychophysical activation of mildly to moderately demented Alzheimer's patients can augment brain-blood flow and glucose metabolism to the same extent as in control subjects. If the primary neuronal defect that leads to reduced brain energy demand in Alzheimer's disease could be prevented or treated, brain glucose transport and OXPHOS enzyme activities might recover to normal levels.

Alzheimer Disease↗