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Biomedical subjects

A S Kumar

Publications and source records attributed to A S Kumar.

At least 37 records · Page 2Linked to original sources

Effect of Inoue balloon mitral valvotomy on severe pulmonary arterial hypertension in 315 patients with rheumatic mitral stenosis: immediate and long-term results.

BACKGROUND AND AIMS OF THE STUDY: Despite advances in surgical techniques, mitral valve surgery in patients with severe pulmonary arterial hypertension (PAH) causes considerable mortality and morbidity. Balloon mitral valvotomy (BMV) is an established alternative to treat high-risk surgical patients with mitral stenosis (MS). The study aims were to evaluate immediate and long-term efficacy of BMV in patients with MS and severe PAH, compared to those with mild/moderate PAH. METHODS: Among 1,125 patients who underwent Inoue BMV, 315 had severe PAH (mean pulmonary artery (PA) pressure > or = 50 mmHg (group I; 79 of these patients had suprasystemic PAH). Results from this group were compared with those of patients with mild/moderate PAH (group II). RESULTS: Group I patients were younger and more symptomatic (mean PA pressure 62 +/- 10.6 mmHg versus 32.6 +/- 8.2 mmHg in group II). Before BMV, mean transmitral gradient (17.8 +/- 6.5 versus 14.4 +/- 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP) (31.6 +/- 6.1 versus 22.8 +/- 6.2 mmHg) were significantly higher, while mitral valve area (MVA) (0.66 +/- 0.2 versus 0.85 +/- 0.2 cm2) was significantly lower in group I. After BMV, PA mean pressure was significantly reduced (34.8 +/- 11.2 and 21.1 +/- 8.4 mmHg), transmitral gradient (8.0 +/- 3.9 and 6.9 +/- 3.2 mmHg) and mean PCWP (12.8 +/- 5.8 and 11.0 +/- 5.1 mmHg) in groups I and II, respectively, with a comparable increase in MVA (1.77 +/- 0.4 and 1.84 +/- 0.5 cm2). Group I patients had worse baseline hemodynamic parameters than group II, but the former had a higher absolute gain in hemodynamic parameters. Residual severe PAH after BMV was seen in 9.8% of patients, with PA pressures normalized in 9.5%. Among 79 patients with suprasystemic PA pressure (mean PA systolic pressure 116.6 +/- 28.2 mmHg), 16.5% normalized their PA pressures and 25.3% had residual severe PAH. At mean follow up of 33 months, 80.4% were in NYHA class I. Mean PA systolic pressure in 161 patients was 39.0 +/- 14.2 mmHg compared with a post-BMV value of 55.0 +/- 16.9 mmHg; thus, a sustained fall in pressure was demonstrated at follow up. CONCLUSION: Inoue BMV is safe and effective in patients with MS and severe PAH. Although these patients have worse clinical and hemodynamic parameters before BMV, they achieve a greater absolute gain in terms of improvement in all hemodynamic parameters.

Adult↗

Bentall operation with valved homograft conduit.

Lesions of the ascending aorta associated with aortic valve disease are usually treated by implanting a prosthetic valved conduit (Bentall procedure). In this report, we present our experience in which a valved homograft conduit was used for the procedure. Six patients underwent a Bentall procedure with the use of a cryopreserved valved homograft conduit. Two of the patients had annuloaortic ectasia, 2 had Marfan syndrome, and 1 had an atherosclerotic aneurysm of the aorta. One patient had severe aortic stenosis due to a bicuspid aortic valve, along with an aneurysm and localized dissection of the ascending aorta. In all of the patients, the aortic annulus was substantially dilated, with accompanying moderate-to-severe aortic regurgitation. A standard procedure was performed with moderate hypothermia, cardiopulmonary bypass, and aortic and bicaval cannulation. The ascending aorta and the aortic valve were replaced with a cryopreserved valved homograft conduit (aortic in 5 patients and pulmonary in 1). The native coronary ostia were anastomosed directly to the homograft. Echocardiography, which was performed intraoperatively, before discharge from the hospital, and at follow-up visits (1 to 36 months), revealed good valve function without dilatation of the homograft conduits. There was 1 late death due to Aspergillus fumigatus endocarditis, 6 months postoperatively. In 1 patient, magnetic resonance imaging performed at 24 months revealed normal caliber of the homograft conduit. We conclude that the Bentall procedure can be performed, safely and with excellent results, using cryopreserved homograft conduits.

Adolescent↗

Pulmonary autograft: should it be used in young patients with rheumatic disease?

BACKGROUND: Although pulmonary autograft is being increasingly used to replace the diseased aortic valve with excellent long-term results, its use in the population with rheumatic disease still needs careful evaluation. PATIENTS AND METHODS: From October 1993 through March 1998, 102 patients underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The mean age was 27.9 +/- 4.2 years (range, 0.8-56 years). The cause was rheumatic disease in 75 patients (73%), bicuspid aortic valve in 26 patients (26%), and myxomatous aortoarteritis in 1 patient (1%). The root replacement technique was used in all. In addition, 31 patients had 33 associated procedures: mitral valve repair (n = 15 patients), open mitral commissurotomy (n = 15 patients), tricuspid repair (n = 2 patients), and homograft mitral valve replacement (n = 1 patient). RESULTS: Operative mortality was 6.9% (7 patients). Late mortality was 7.8% (8 patients). Follow-up ranged from 1 to 60 months (mean, 25.3 +/- 15.4 months) and was 98% complete. Two patients required reoperation for failed mitral valve repair, and 2 other patients underwent reoperation for failure of both the autograft and mitral valve repair. Echocardiographic assessment showed moderate to severe aortic regurgitation in 13 patients, along with thickening of the autograft. All of these patients had rheumatic disease and were young (<30 years). Ten of these patients had undergone associated mitral valve procedure. Morphologic and histopathologic examination of explanted autografts showed features compatible with rheumatic valvulitis. CONCLUSION: Pulmonary autograft is susceptible to rheumatic involvement. Young age (<30 years) and associated mitral valve disease are significant risk factors for autograft failure in patients with rheumatic disease. Use of pulmonary autograft in this subgroup of patients requires a cautious approach.

Adolescent↗

Analysis of mutations in the pore-forming region essential for insecticidal activity of a Bacillus thuringiensis delta-endotoxin.

The Bacillus thuringiensis insecticidal delta-endotoxins have a three-domain structure, with the seven amphipathic helices which comprise domain I being essential for toxicity. To better define the function of these helices in membrane insertion and toxicity, either site-directed or random mutagenesis of two regions was performed. Thirty-nucleotide segments in the B. thuringiensis cry1Ac1 gene, encoding parts of helix alpha4 and the loop connecting helices alpha4 and alpha5, were randomly mutagenized. This hydrophobic region of the toxin probably inserts into the membrane as a hairpin. Site-directed mutations were also created in specific surface residues of helix alpha3 in order to increase its hydrophobicity. Among 12 random mutations in helix alpha4, 5 resulted in the total loss of toxicity for Manduca sexta and Heliothis virescens, another caused a significant increase in toxicity, and one resulted in decreased toxicity. None of the nontoxic mutants was altered in toxin stability, binding of toxin to a membrane protein, or the ability of the toxin to aggregate in the membrane. Mutations in the loop connecting helices alpha4 and alpha5 did not affect toxicity, nor did mutations in alpha3, which should have enhanced the hydrophobic properties of this helix. In contrast to mutations in helix alpha5, those in helix alpha4 which inactivated the toxin did not affect its capacity to oligomerize in the membrane. Despite the formation of oligomers, there was no ion flow as measured by light scattering. Helix alpha5 is important for oligomerization and perhaps has other functions, whereas helix alpha4 must have a more direct role in establishing the properties of the channel.

Animals↗

Isolated congenital anterior mitral leaflet cleft: a rare cause of mitral insufficiency.

BACKGROUND AND AIM OF THE STUDY: Isolated cleft of the anterior mitral leaflet is a rare cause of mitral insufficiency. Although an established entity, due to its rarity the exact anatomic diagnosis is difficult to establish unless sought specifically. METHODS: Four patients (age range: 16 to 26 years) with isolated cleft of the anterior mitral leaflet were treated at the authors' institute. Clinical symptoms were typical of mitral insufficiency; the exact anatomic diagnosis was not established preoperatively in any patient. The cleft was directly sutured in all four patients and additional annuloplasty was performed in three. RESULTS: Postoperative echocardiography confirmed satisfactory results. After a mean follow up of 46.7 months (range: 3 to 84 months), one patient had mild mitral insufficiency and the remaining patients had no mitral regurgitation. CONCLUSION: In severe mitral insufficiency with no obvious mitral valve pathology and an intact atrial septum, a cleft of the anterior mitral leaflet should be sought. Repair of the cleft can restore normal mitral valve function.

Adolescent↗

Valvular heart disease--repair or replacement?

An estimated 3 million patients in India need treatment for valvular heart disease. Rheumatic heart disease continues to be the major aetiologic factor. The mitral valve is best conserved with valvotomy or repair. The aortic valve is difficult to repair and is best replaced by a biological substitute (autograft or homograft). The tricuspid valve can be repaired in all patients. Prosthetic valves offer good long term durability but introduce additional risks to the patients. Experience over the past three decades suggests that conservation of natural valve mechanism is currently the best option.

Cardiovascular Surgical Procedures↗

Aneurysm of sinus of Valsalva dissecting into interventricular septum.

BACKGROUND: Dissection of interventricular septum by aneurysm of the sinus of Valsalva is extremely rare. We present our experience with the management of 10 patients with this condition. METHODS: Ten patients with aneurysm of the sinus of Valsalva dissecting into the interventricular septum were managed at All India Institute of Medical Sciences, New Delhi, between May 1987 and September 1996. Conduction abnormalities and aortic insufficiency dominated the clinical picture. Eight patients underwent surgical repair. Two patients refused operation, and only permanent pacemaker implantation was done for complete heart block in both these patients. RESULTS: There was no hospital mortality. Follow-up ranged from 1 to 9 years. There was one late death due to carcinoma of the larynx, and 1 patient required reoperation for persistent aortic insufficiency. All other patients who underwent operation are in New York Heart Association functional class I. CONCLUSIONS: We recommend surgical repair of this condition to deal with aortic regurgitation and to avoid the potential risk of rupture, thromboembolism, and infective endocarditis. However, surgical repair offers no guarantee against arrhythmias and conduction abnormalities.

Adolescent↗

Surgical experience with intracardiac myxomas: long-term follow-up.

BACKGROUND: Myxomas are the most common benign intracardiac tumors. This report summarizes our 20-year experience with these tumors. METHODS: Sixty-six patients (25 male) with a median age of 39 years (range, 6 to 70 years) underwent surgical excision of primary or recurrent intracardiac myxomas during the years 1976 to 1996. Symptom duration ranged from 2 to 8 months. There were 55 left atrial myxomas, 10 right atrial myxomas, and 1 biatrial myxoma. Three of the patients were in one family. The surgical approach comprised complete wide excision. RESULTS: There were two early deaths. Late follow-up is 89% (57/64) complete. There was one late death, which was not due to a cardiac cause. Echocardiography at a mean follow-up of 66.9 months (range, 7 to 241 months) showed no recurrence of sporadic myxomas. However, 2 of the 3 patients with familial myxomas had recurrence. CONCLUSIONS: Surgical excision of atrial myxoma gives excellent short-term and long-term results leading to eventual cure of nonfamilial myxomas. However, familial myxomas retain a strong tendency to recur even 20 years after excision.

Adolescent↗

Aortic valve replacement with biological substitute.

In the quest for an ideal aortic valve substitute, homografts and autografts are well-established options. We reviewed our results with homografts and autografts for aortic valve replacement during the last 5 years. From March 1992 through July 1997, 189 patients (138 male and 51 female), age 8 months to 68 years (mean 31.0+/-4.2 years), underwent aortic valve replacement with a human biological substitute. Of these, 93 patients received a cryopreserved or antibiotic-preserved aortic/pulmonary homograft, whereas 96 patients underwent a Ross procedure. Etiology was rheumatic in 143 (75.6%) patients, bicuspid aortic valve in 40 (21.2%), Marfan's disease in 5 (2.6%), and myxomatous aortitis in 1 (0.5%). Among the homograft group, a scalloped subcoronary implantation technique was used in 54 patients, whereas 32 patients underwent root replacement. Five patients required aortic root and ascending aortia replacement for annuloaortic ectasia. In all patients undergoing the Ross procedure, a root replacement technique was used. Operative mortality was 7.4% (14 patients). Late mortality was 5.3% (10 patients). Follow-up ranged from 1 to 46 months postoperatively. In patients with homograft aortic valve replacement, 76 patients (91.5%) had trivial to mild aortic regurgitation, while 7 patients (8.4%) had important aortic regurgitation. In patients with the Ross procedure, 78 patients (89.6%) had trivial to mild regurgitation. Moderate to severe aortic regurgitation was present in 9 patients (10.3%), all of whom had rheumatic heart disease and were young (< 30 years at surgery). We conclude that homografts and autografts provide an excellent substitute for the diseased aortic valve. Young age (< 30 years) with rheumatic etiology is a major risk factor for early progressive aortic regurgitation in patients undergoing the Ross procedure.

Adult↗

Management of annuloaortic ectasia in association with aortic regurgitation.

Annuloaortic ectasia associated with severe aortic regurgitation is usually managed by implanting a composite graft that comprises both valve and conduit. Synthetic valved conduits have been used by most cardiovascular surgeons, with various modifications in the technique. Yet prosthetic valves carry the risks associated with anticoagulation therapy, together with an increased risk of infective endocarditis. We report a case in which a cryopreserved aortic homograft was used for a Bentall procedure in a patient who had annuloaortic ectasia with severe aortic regurgitation. To the best of our knowledge, there are no prior published reports of homograft insertion in treatment of annuloaortic ectasia.

Aorta↗

Experience with homograft mitral valve replacement.

BACKGROUND AND AIMS OF THE STUDY: Homograft mitral valve replacement may offer a superior alternative to replacement with a prosthetic valve. The authors' early experience with this technique is reported. METHODS: Between May 1994 and May 1995, 24 patients (19 males, five females; age range 17 to 49 years) underwent homograft mitral valve replacement (HMVR) at the authors' institution. The etiology was rheumatic in all patients; 22 had severe calcific mitral stenosis (MS) and two had combined MS and severe mitral regurgitation (MR). RESULTS: There were three early deaths (12%) and two late deaths (8%). In three patients the homograft had to be explanted due to severe MR at six weeks, 10 weeks and 12 months, respectively. Mean follow up was 18 months (range: 12 to 25 months). Postoperative echocardiography showed trivial or mild MR in 12 patients and moderate MR in four. Mitral stenosis was absent in all patients (mean mitral valve area 2.5 cm2). Sixteen patients showed satisfactory homograft valve function at follow up. The valve explanted after six weeks showed normal cusp architecture, endothelial growth and incorporation of the pericardial strip and complete healing of the papillary muscle junction. Magnetic resonance imaging in 12 patients showed normal appearance and function of the homografts. CONCLUSIONS: The authors' experience suggests that homograft mitral valve replacement can be performed with good early results.

Adolescent↗

Normothermic cardiopulmonary bypass & post-operative blood loss.

Normothermic cardiopulmonary bypass (CPB) has been shown to have less disruptive effects on coagulation factors and platelet function. Ninety patients undergoing valvular heart surgery were randomly divided into two groups of 45 patients each to undergo normothermic (35 degrees C-37 degrees C) or hypothermic (28 degrees C) bypass. We found normothermic bypass to significantly reduce bypass time and requirements of fluid and blood post-operatively. However, there was no reduction in post-operative blood loss, re-exploration rate or blood product requirements by use of normothermic cardiopulmonary bypass.

Adolescent↗

Small aortic annulus: a functional definition.

BACKGROUND & OBJECTIVE: Small aortic annulus is conventionally associated with poor outcome after aortic valve replacement (AVR). Contrarily, several patients have excellent follow-up results after AVR with 19, 20 or 21 size Medtronic Hall (MH) or Sorin Carbocast (SC) prostheses. This disparity prompted a relook at the semantics of a small aortic annulus. METHODS: Available survivors of isolated AVR with #19, #20 or #21 prostheses - 13 with 19 SC or 20 MH valves (Group A) and 29 with 21 SC or MH valves (Group B) were studied. Disparity between actually implanted prostheses versus predicted prosthetic size (tissue annulus diameter) was analysed according to nomograms of Rowlatt et al, NIH Plehn, Kishimoto formula and Sievers composite criteria. Preoperative and follow-up echocardiographic assessments were used for hemodynamic and prosthetic function indices. RESULTS: Both groups were similar in age, height, weight, BSA, BMI, mean NYHA class, CTR, preoperative peak gradient (PG) (92. 0 +/- 29.55 vs 102.88 +/- 33.65), mean gradient (MG) (56.8 +/- 24.6 vs 61.55 +/- 16.56), LVEDD (50.75 +/- 10.92 vs 56.0 +/- 13.5), LVESD (34.37 +/- 13.32 vs 38.52 +/- 13.85) and LVEF (67.5 +/- 12.5 vs 63.9 +/- 14.3). By developmental indices of Rowlatt et al. and NIH, no valve annulus could be designated as narrow. By Sievers composite nomogram all implanted valves were undersized by echocardiographic parameters, in normal range by angiographic criteria and oversized by anatomic autopsy data. Implanted valves in both groups were bigger than Plehn-predicted size (18.16 +/- 1.48 in GrA, 19.46 +/- 1. 10 in GrB). Valve size indices (VSI) (GrA 16.16 +/- 2.85 GrB 14.24 +/- 1.64) and geometric orifice area indices (VAI: valve area index) (GrA 1.50 +/- 0.28 vs 1.41 +/- 0.19) and postoperative rest PG (GrA 47.2 +/- 18.6 GrB 33.8 +/- 9.9) and MG (GrA 27.2 +/- 12.9 vs 19.0 +/- 9.9) were acceptable. LVEDD and LVESD regressed in both groups. LV mass indices regressed from 218.56 +/- 100.85 to 128.17 +/- 27.7 in GrA and 238.94 +/- 102.5 to 134.22 +/- 34.72 in GrB. Performance indices of implanted valves and postoperative aortic valve resistances were correlative. CONCLUSIONS: The size of the implanted prostheses per se does not denote narrowness. Patient-prosthesis mismatch may be considered if predicted prosthesis has VSI <12 mm/m2, VAI <1.31 cm2/m2 or prosthesis orifice diameter <19 mm which may indicate annular enlargement.

Adult↗

Phorbol ester down-regulation of lung surfactant protein B gene expression by cytoplasmic trapping of thyroid transcription factor-1 and hepatocyte nuclear factor 3.

The lung-specific surfactant protein B (SP-B) is essential for surfactant function and normal respiration. We investigated the role of thyroid transcription factor-1 (TTF-1) and hepatocyte nuclear factor 3 (HNF3) in the down-regulation of SP-B gene expression by phorbol ester in pulmonary adenocarcinoma H441 cells. Responsiveness to 12-O-tetradecanoylphorbol-13-acetate (TPA) localized to the SP-B proximal promoter (-140/-65 bp) and specifically to binding sites for TTF-1 and HNF3, which act as cell-specific enhancers of SP-B expression. Treatment of cells with TPA (10 nM) caused a time-dependent decrease in both TTF-1 and HNF3 in nuclear extracts and accumulation of both factors in the cytoplasm as assessed by electromobility shift, Western, Southwestern, and immunofluorescence assays. Treatment did not alter the mRNA content or DNA binding activity for either transcription factor. We conclude that down-regulation of SP-B gene expression by phorbol ester involves cytoplasmic trapping and loss of TTF-1 and HNF3 from the nucleus. This mechanism of action is independent of AP-1 and other transcription factors known to be influenced by phorbol ester.

Animals↗

Aortic valve replacement with a homovital valve.

"Homovital" allografts (viable homografts) are a good substitute for native aortic valves. A case of aortic valve replacement with a homovital aortic allograft is reported along with the results of immunologic investigations. Postoperatively, there was no clinical or echocardiographic evidence of valve dysfunction, and immunologic tests did not show evidence of graft versus host reaction.

Aortic Valve↗