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Biomedical subjects

Ganesh Shanmugam

Publications and source records attributed to Ganesh Shanmugam.

35 records · Page 2Linked to original sources
PubMed2005

Adult congenital lung disease.

Congenital lung anomalies are increasingly diagnosed in adults, because they are missed in childhood, or as a consequence of incomplete resections at a younger age. They have unique manifestations, often mimic other thoracic pathology, and can present acutely and necessitate emergent evaluation and management. Misdiagnosis is common. This article deals with the patterns of presentation, clinical and radiological diagnosis, and the management of these disorders in adults. The lesions analysed include congenital cystic adenomatoid malformation, sequestration, congenital lobar emphysema and bronchogenic cysts. It is important to include these malformations in the differential diagnosis of adult thoracic pathology and to understand the modes of presentation, potential complications and management strategies. The radiological diagnosis is reliably made by computed tomography and/or magnetic resonance imaging. The potential for malignancy in these lesions is an important consideration. The management of asymptomatic lesions was considered controversial, but more lesions are now resected early, in recognition of the potential for subsequent complications. Complete resection is recommended. In contradistinction to childhood malformations, these lesions are more amenable to thoracoscopic resections, provided they are completely benign. Congenital lung malformations call for well-organized cooperation between paediatric and adult pulmonologists to ensure a smooth medical transition from childhood to adulthood.

Adult↗
PubMed2005

Tirofiban and emergency coronary surgery.

The final common pathway of platelet aggregation leading to coronary thrombosis involves cross-linking of platelet receptor glycoprotein IIb-IIIa by primarily fibrinogen. Glycoprotein IIb-IIIa antagonists are being increasingly used as adjunctive therapy during percutaneous coronary intevention, and have shown to reduce the risk of death and myocardial infarction. However, a proportion of these patients continue to remain ischemic and present for emergency coronary grafting. The profound platelet inhibition in these patients enhances the already heightened risk of post-operative bleeding. With the recent approval of tirofiban for patients with acute coronary syndromes, the number of patients receiving tirofiban who subsequently undergo coronary artery bypass grafting is expected to increase substantially. Little clinical data exist, on patients who require immediate coronary artery grafting after receiving tirofiban. This article reviews the evidence for bleeding following tirofiban, discusses the relevant mechanism of action and pharmacodynamics, and analyses the strategies available in patients who need emergency coronary artery grafting after tirofiban.

Acute Disease↗
PubMed2005

Structures of plant viruses from vibrational circular dichroism.

Vibrational circular dichroism (VCD) spectra in the amide I and II regions have been measured for viruses for the first time. VCD spectra were recorded for films prepared from aqueous buffer solutions and also for solutions using D(2)O buffers at pH 8. Investigations of four filamentous plant viruses, Tobacco mosaic virus (TMV), Papaya mosaic virus, Narcissus mosaic virus (NMV) and Potato virus X (PVX), as well as a deletion mutant of PVX, are described in this paper. The film VCD spectra of the viruses clearly revealed helical structures in the virus coat proteins; the nucleic acid bases present in the single-stranded RNA could also be characterized. In contrast, the solution VCD spectra showed the characteristic VCD bands for alpha-helical structures in the coat proteins but not for RNA. Both sets of results clearly indicated that the coat protein conformations are dominated by helical structures, in agreement with earlier reports. VCD results also indicated that the coat protein structures in PVX and NMV are similar to each other and somewhat different from that of TMV. The present study demonstrates the feasibility of measuring VCD spectra for viruses and extracting structural information from these spectra.

Capsid Proteins↗
PubMed2005

Surgical repair of double aortic arch: 16-year experience.

Double aortic arch (DAA) is a complete form of vascular ring causing tracheoesophageal compression. We analyzed long-term results of a series of DAAs, over a period of 16 years. Between 1987 and 2003, 29 children underwent surgery for airway and/or esophageal compression secondary to a DAA. Dominant symptoms were stridor, dysphagia, choking episodes, and life-threatening apneic spells (n = 7). Diagnosis was established by barium studies, bronchoscopy, echocardiogram, angiogram, computed tomography (CT), and magnetic resonance imaging (MRI). Seven patients had concurrent cardiac anomalies. Two children had an associated tracheoesophageal fistula. Surgery was accomplished by left thoracotomy (n = 25), right thoracotomy (n = 2) or median sternotomy (n = 2). The operative mortality was zero. There was one late death due to respiratory failure. Four (13.8%) patients had a surgical complication (chylothorax, 3 cases; acute renal failure, 1 case). Follow-up (mean 7.1 years; range 6 months to 16 years) was complete in all patients, and showed complete improvement in 22 patients and partial improvement in 6 patients. Early surgical repair of DAA is associated with low mortality, and results in marked symptomatic relief in most patients. Patients with tracheomalacia or associated asthma, constitute a high-risk group and may manifest persistent symptoms and require adjunctive procedures.

Airway Obstruction↗
PubMed2005

Film techniques for vibrational circular dichroism measurements.

Vibrational circular dichroism (VCD) spectra in the 1800-900 cm(-1) region have been measured recently for protein films and for carbohydrate films prepared from aqueous solutions. In addition to the advantages of avoiding the interference from strong infrared absorption of water at 1650 cm(-1) and requiring a two-orders-of-magnitude-smaller amount of sample for film measurements (than those required for the same in water solutions), the VCD bands in film measurements are found to be the same as those in solution measurements and to be independent of film orientation. This latter observation indicated the possibility for routine VCD measurements in the film state. In this manuscript we report different film techniques for VCD measurements. These techniques include preparation of supported films, free-standing films, film-on-film, and facilitation of film formation for substances that otherwise do not form amorphous films. The experimental data for films prepared by each of these techniques are presented and the relative merits of these different methods are discussed.

Absorption↗
PubMed2005

Pediatric mitral valve replacement: incremental risk factors impacting survival and reintervention.

BACKGROUND AND AIM OF THE STUDY: Predictors of survival and reintervention in children undergoing mitral valve replacement (MVR) were assessed. METHODS: A total of 37 children underwent MVR, with a mean prosthesis size of 22.5 mm. RESULTS: Six patients died during the study. Actuarial and event-free survivals (including operative mortality) at 10 and 20 years were 85 and 85%, and 55 and 37%, respectively. The linearized rate of bleeding was 0.67% per patient-year (pt-yr). There were no instances of thromboembolism, endocarditis or structural valve dysfunction. Six patients required reintervention for somatic outgrowth at a mean postoperative interval of 104 months. Freedom from reintervention at five, 10 and 20 years was 92, 73 and 48%, respectively. There were no deaths or complications following reintervention. The mean follow up was 96 months (range: 3 to 276 months); total cumulative follow up was 296 pt-yr. Multivariate predictors of mortality were age < 6 months, NYHA class IV, congestive cardiac failure, internal orifice diameter (IOD) < 14 mm and effective orifice area (EOA) < 1.5 cm2. Predictors for reintervention were age < 6 months (p = 0.0021), predicted annulus size < 16 mm (p < 0.0001), IOD < 18 mm (p = 0.05), IOD index (IODI) > 50 mm/m2 (p = 0.007), EOA < 2.5 cm2 (p = 0.05), EOA index (EOAI) > 7 cm2/m2 (p < 0.0001) and prosthesis size-body surface area (BSA) index (SI) > 69 mm/m2 (p = 0.007). CONCLUSION: Early mortality occurs in neonates and infants with associated lesions, particularly atrioventricular septal defect. Risk factors for mortality include age, NYHA class, and small IOD and EOA. Risk factors for reintervention include age < 6 months, small predicted annulus size, IOD and EOA, IODI > 50 mm/m2, EOAI > 7 cm2/m2 and SI > 69 mm/m2.

Child, Preschool↗
PubMed2005

Mechanical aortic valve replacement: long-term outcomes in children.

BACKGROUND AND AIM OF THE STUDY: Early and late outcomes following mechanical aortic valve replacement (AVR) in children were analyzed. METHODS: Between January 1980 and December 2003, 55 patients underwent mechanical AVR at the authors' institution. Of these patients, 12 had aortic regurgitation (AR), 31 had aortic stenosis (AS), and 12 had mixed disease. Preoperatively, 25 patients (45.5%) were in NYHA classes III and IV. Among patients, 22 had a previous valvotomy and 19 had associated cardiac defects. Isolated AVR was performed in 37 cases. Twelve patients required root enlargement procedures, two had aortic root replacement, three had a double valve replacement, and one patient had a concurrent mitral annuloplasty. The mean prosthesis size was 22.6 mm (range: 16-31 mm). Mean follow up was 12.28 +/- 6 years (range: 1-23 years); total follow up was 665 patient-years (pt-yr). RESULTS: There was one late death. Actuarial survival at 20 years was 98 +/- 2%. Event-free survival at one, five and 20 years was 96 +/- 3%, 92 +/- 4% and 88 +/- 5%, respectively. Four patients required reoperation (two for valve outgrowth, one each for paravalvular leak and prosthetic valve endocarditis (PVE)). Freedom from reintervention at one, five and 20 years was 98 +/- 2%, 96 +/- 3% and 92 +/- 4%, respectively. There was one event of anticoagulation-related hemorrhage. Freedom from anticoagulant-related hemorrhage at 20 years was 98 +/- 2%, and freedom from PVE at five and 20 years was 98 +/- 2% and 96 +/- 3%, respectively. There were no instances of thromboembolism or structural valve dysfunction. Linearized rates of bleeding and endocarditis were 0.15 and 0.3% per pt-yr, respectively. At follow up, 54 children were in NYHA classes I or II. CONCLUSION: Mechanical AVR, with aortic root enlargement if necessary, is associated with low mortality and morbidity, and is an excellent treatment option in children. Late embolic and hemorrhagic complications are infrequent in the current era.

Adolescent↗
PubMed2004

Vibrational circular dichroism spectra of protein films: thermal denaturation of bovine serum albumin.

Vibrational circular dichroism (VCD) spectroscopy has been used for the first time to investigate the thermal denaturation of proteins in H(2)O solutions. Films prepared from heated aqueous solutions were used for these investigations. A well-known alpha-helical protein, bovine serum albumin (BSA), is used for this first study. Both VCD and infrared absorption results obtained for BSA films indicate that the heat treatment of BSA induces significant amounts of beta-sheet structure and that the denaturation process is irreversible. To verify the irreversible nature of thermal denaturation, optical rotation was also measured as a function of temperature in both heating and cooling cycles. These results also indicate that thermal denaturation of BSA in solution is irreversible. This study establishes the usefulness of films for VCD investigations and offers new avenues for VCD studies on biologically important systems.

Animals↗
PubMed2004

Vibrational circular dichroism of protein films.

Vibrational circular dichroism (VCD) spectra in the 1800-1400 cm(-)(1) region have been measured for the first time for protein films prepared from aqueous buffer solutions. These measurements demonstrate several advantages of significant importance. First, the interference from infrared absorption of water in the amide I region, which is a serious limitation for measurements in water solutions, is eliminated. Second, the amounts of protein samples required for VCD measurements on films are approximately 2 orders of magnitude smaller than those required for the same in water solutions. In addition, the amide I absorption and VCD bands of protein films are found to be independent of film orientation. Furthermore, characteristic VCD patterns have been observed for protein films whose secondary structure is dominated by alpha-helix, beta-sheet, and alpha + beta combinations. These results demonstrate that VCD can be used to study the structure of proteins in the film state.

Animals↗
PubMed2004

Structural analysis of amyloid beta peptide fragment (25-35) in different microenvironments.

Amyloid beta (Abeta) peptides are one of the classes of amphiphilic molecules that on dissolution in aqueous solvents undergo interesting conformational transitions. These conformational changes are known to be associated with their neuronal toxicity. The mechanism of structural transition involved in the monomeric Abeta to toxic assemblage is yet to be understood at the molecular level. Early results indicate that oriented molecular crowding has a profound effect on their assemblage formation. In this work, we have studied how different microenvironments affect the conformational transitions of one of the active amyloid beta-peptide fragments (Abeta(25-35)). Spectroscopic techniques such as CD and Fourier transform infrared spectroscopy were used. It was observed that a stored peptide concentrates on dissolution in methanol adopts a minor alpha-helical conformation along with unordered structures. On changing the methanol concentration in the solvated film form, the conformation switches to the antiparallel beta-sheet structure on the hydrophilic surface, whereas the peptide shows transition from a mixture of helix and unordered structure into predominantly a beta-sheet with minor contribution of helix structure on the hydrophobic surface. Our present investigations indicate that the conformations induced by the different surfaces dictate the gross conformational preference of the peptide concentrate.

Amyloid beta-Peptides↗
PubMed2004

Ascending aortic origin of a branch pulmonary artery--surgical management and long-term outcome.

OBJECTIVE: Ascending aortic origin of a branch pulmonary artery (AOPA, hemitruncus arteriosus) is a rare congenital malformation. While there have been isolated case reports, larger series, relating to long-term outcomes following surgery are few. This article analyses the surgical results of a series of nine patients, over a period of 29 years. METHODS: Between 1974 and 2003, nine patients [neonates, 6; infants, 3; male, 5; female, 4] were operated on for AOPA. Median age at presentation was 14 days (range birth to 231 days). Six [corrected] patients (group 1) had associated simple lesions like patent ductus arteriosus or right aortic arch. Three patients (group 2) had complex lesions with right ventricular outflow tract obstruction. One patient (group 2) had DiGeorge syndrome. All patients except group 2 presented with congestive cardiac failure and, in addition one had pre-operative coronary ischemia. Diagnosis was established by angiocardiography in two patients and by echocardiography in seven [corrected] The median age at operation was 28 days (range 7-365). Follow-up period ranged from 7 months to 20.5 years (median 9 years). RESULTS: All nine patients had an anomalous right pulmonary artery (RPA) arising from the proximal ascending aorta, while the left branch was of right ventricular origin. All had evidence of pulmonary hypertension or elevated right ventricular pressure pre-operatively. There was no operative mortality. Of eight patients who had direct anastomosis of the RPA to the main pulmonary artery, one required patch enlargement and another required stenting of an anastomotic stenosis. One patient had a RV-RPA conduit, which required replacement 8, 13, and 14 years later. At follow-up, all patients were alive. All patients in group 1 had normal haemodynamic function and were in NYHA class I. In group 2, all were in NYHA class II with evidence of right ventricular hypertrophy. Four patients had post-operative ventilation-perfusion scans which showed satisfactory perfusion to both lungs. CONCLUSIONS: Early surgery is indicated in this lesion and is compatible with good long-term outlook. Surgical repair should not be deferred for corrective procedures of associated cardiac anomalies.

Analysis of Variance↗
PubMed2004

False positive computed tomography findings in aortic dissection.

Dissection is the commonest acute catastrophe involving the aorta. Computed tomography (CT) is increasingly used in evaluating patients with suspected aortic dissection. Occasionally normal anatomic structures may be misconstrued as pathologic due of lack of familiarity with anatomical variations. In scanning two patients with suspected dissection, we encountered pitfalls that led to an erroneous diagnosis of dissection. The subsequent clinical course and evaluation confirmed that the CT findings were artefactual. This report illustrates these potential errors and discusses the mechanisms.

Journal Article↗
PubMed2004

Structure of A beta(25-35) peptide in different environments.

The fragment A beta(25-35) of the Alzheimer's amyloid beta-peptide, like its full-length peptide A beta(1-42), has shown neurotoxic activities in cultured cells. The conformational preference of this important peptide is examined here in solution, gel, and film states (obtained with organic and aqueous solvents) by vibrational circular dichroism spectroscopy for the first time. For comparative studies, vibrational absorption and electronic circular dichroism measurements were also carried out under identical conditions. The peptide was found to adopt beta-sheet and beta-turn structures, with their relative proportions changing in different environments.

Amyloid beta-Peptides↗