Evaluation of target mRNA cleavage by Aurorakinase B specific siRNA in prostate and hepatic cancer cells and its therapeutic potential in mouse models of liver cancer.

The anti proliferative potential of siRNA26, targeted to Aurora kinase B, in prostate cancer cells is known from a previous study from our laboratory. Here we first show that siRNA26 cleaves at the same position of the target mRNA in the prostate cancer and hepatocellular carcinoma cell lines, PC3 and HepG2 respectively. Aurorakinase B specific siRNA, but not a control siRNA, inhibited PC3 and HepG2 cell proliferation and cell migration. These effects correlated to RNA silencing of Aurorakinase B in both the cell lines. Intra-tumoral administration of HiPerfect complexed siRNA26 inhibited the growth of HepG2 xenografts in SCID mice. In an orthotopic setting, intravenous administration of HiPerfect encapsulated siRNA26 appeared to reduce the severity of multifocal lesions.

Liver ultrasound and faecal copper estimation in oral submucous fibrosis.

There is no evidence of an increased quantity of ingestion of copper in areca nut chewers by way of habitually swallowing the 'quid juice' allegedly contain 'appreciable quantity' of soluble copper. Our experimental findings are favour of assuming that the amount of copper ingested, if at all, is well within the threshold limit of tolerance and therefore of no clinical significance. In conjunction with our earlier observation this study again proved the absence of visible and clinically/diagnostically detectable fibrosis in visceral organs, that includes liver, in patients suffering from advanced oral submucous fibrosis.

Acute reversible left ventricular dysfunction following general anesthesia.

Acute reversible left ventricular dysfunction due to myocardial stunning is a known phenomenon during acute myocardial infarction, coronary angiography, coronary angioplasty or after coronary artery bypass surgery. We report a rare case of acute reversible dysfunction of the myocardium as a complication of general anesthesia in a patient with normal coronary arteries. This is a potentially fatal complication unless recognized early and treated aggressively.

Management of tetralogy of Fallot with absent pulmonary valve: early and mid-term results of a uniform approach.

The operative management of absent pulmonary valve syndrome remains controversial regarding palliative or one-stage correction, the need for pulmonary valve implantation and pulmonary arterioplasty. This retrospective report summarises the experience of a single centre with a view to provide some answers to this controversy. Forty-six consecutive patients including five infants, aged 2 months to 43 years, underwent primary surgical correction during the last 8.5 years. All the patients underwent two-dimensional echocardiography and cardiac catheterisation. Nine patients had mild and 10 moderate pulmonary artery hypertension. Repair consisted of patch closure of the ventricular septal defect and reconstruction of the right ventricular outflow tract. A valve was incorporated in the pulmonary position in 19 patients. Pulmonary arterioplasty was performed only in infants. Overall hospital mortality was 4 out of 46 patients (8.6%). Two out of five infants died accounting for 40 percent mortality. Forty-two survivors were followed up from 4 to 101 months; 40 patients are in functional class I and two in class II. Actuarial survival at 8.5 years was 91 percent. It is concluded that reconstruction of the right ventricular outflow tract with a transannular patch is sufficient in majority of patients. A selective approach to pulmonary valve insertion is recommended in patients with pulmonary hypertension or other anomalies. Pulmonary arterioplasty should be performed as the primary treatment in infants.

Intraoperative transoesophageal echocardiography in aortic valve surgery.

From January 1994 to May 1998, 272 patients underwent homograft aortic valve replacement (n = 139), Ross procedure (n = 100) and aortic valve repair (n = 33). Transoesophageal echocardiography was performed intraoperatively before and after cardiopulmonary bypass. Aortic valve morphology, aortic root diameter, pulmonary valve morphology, pulmonary annulus diameter and mitral valve morphology were assessed by two-dimensional imaging. Colour flow mapping was used for assessing severity of aortic regurgitation before and after the procedure. There were no complications related to the procedure. The accuracy of aortic annular diameter measured in the long axis view was confirmed at surgery. The aortic valve morphology was thought suitable for repair and a satisfactory repair was performed in 33 patients as assessed by transoesophageal echocardiography. Post-operative transoesophageal echocardiography showed a competent aortic valve in all but four of the remaining 239 patients. Intraoperative transoesophageal echocardiography is easy to learn and provides the surgeon additional information necessary to decide a particular procedure. In addition, intraoperative transoesophageal echocardiography provides accurate assessment of the results of surgery on the table.

Post-infarction ischaemic mitral regurgitation: what determines the outcome.

Ischaemic mitral regurgitation is an important determinant of survival in patients with coronary artery disease. A retrospective analysis was performed to evaluate the overall outcome and its determinants in patients with ischaemic mitral regurgitation. Over a period of 10 years, 72 patients underwent operations for mitral regurgitation of ischaemic origin. Age ranged from 37 to 68 years (mean 54.6 +/- 10.4 years), and 62 (86.1%) were male. Thirteen (18%) patients had acute and 59 (82%) had chronic ischaemic mitral regurgitation. Twenty-one patients were in New York Heart Association class II, 32 in class III and 19 in class IV. Moderate to severe left ventricular dysfunction was present in 42 patients. Valve prolapse was present in 35 (48.6%) patients and restricted leaflet motion secondary to myocardial dysfunction was present in 37 (51.4%) patients. All the patients were operated using standard cardiopulmonary bypass technique. Mitral valve was replaced in 33 patients and repaired in 39. Repair included a combination of techniques: chordal transposition (n = 2), chordal shortening (n = 18), leaflet resection (n = 2), posterior collar annuloplasty (n = 35) and annuloplasty with flexible Duran's ring (n = 3). Operative mortality was 18.1 percent (13/72). Low cardiac output was the cause of death in the majority (n = 10). Acute presentation and presence of restricted leaflet motion were the significant predictors of early mortality. Follow-up ranged from 3 to 84 months (mean 41.6 +/- 10.2 months). Late mortality was 46.2 percent. Actuarial survival in operative survivors at five years was 44.4 +/- 8.8 percent. To conclude, ischaemic mitral regurgitation carries a poor early and late outcome, with left ventricular dysfunction and presence of restricted leaflet motion being important contributors to it. In addition, acute presentation also reflects greater early mortality.

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.

Adult cyanotic congenital heart disease: surgical experience.

Cyanotic congenital heart diseases constitute about 10 percent of total congenital heart disease cases in adults in the developing world. Prolonged cyanosis and old age adversely affect the outcome of surgery, thus posing a challenge to the cardiac surgeons. This study was conducted to assess the feasibility, safety and outcome of surgery in this group of patients. From January 1991 to December 1997, a total of 303 patients, aged 14 to 54 years (mean 19.8 +/- 1.5 years) with diagnosis of various cyanotic congenital heart diseases were operated at our institute. There were 210 males (69.3%). Two hundred and forty-seven patients (81.5%) had tetralogy of Fallot's physiology, 51 patients (16.8%) had single ventricle physiology and five (1.6%) had other lesions. Sixty-six patients (21.7%) had pre-operative complications such as haemoptysis, epistaxis, cerebrovascular accidents, brain abscess and infective endocarditis. Sixty patients (19.8%) had previous palliative shunts and 26 patients (8.5%) had coil embolisation of major aortopulmonary collaterals prior to surgery; 229 patients (75.5%) underwent biventricular repair, 52 (17.1%) had univentricular repair, 22 (7.7%) had palliative shunts and one patient had open ligation of a major aortopulmonary collateral in addition. In-hospital mortality was 3.3 percent. Follow-up period ranged from five months to seven years (mean 4.2 +/- 1.8 years). There were two late deaths. Of the 291 survivors, 11 were lost to follow-up. Two hundred and fifty-eight patients (92.1%) are in New York Heart Association class I. Significant residual defects warranting reoperation were present in four patients (1.3%). It is concluded that congenital heart surgery in older cyanotic patients can be performed safely with satisfactory results.

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.

Surgery for aortic valve endocarditis.

From March 1994 to March 1997, 36 patients with aortic valve endocarditis were managed surgically. Of these, 30 patients had native valve endocarditis and six had prosthetic valve endocarditis. In patients with native valve endocarditis, surgical procedures included aortic valve repair (n=6), homograft aortic valve replacement (n=9), Ross procedure (n=5) and prosthetic aortic valve replacement (n=10). There were three early and two late deaths in this group. In patients with prosthetic valve endocarditis, aortic valve replacement with a homograft was performed in all. Active infection and prosthetic valve endocarditis were the most important predictors of early mortality. The availability of a homograft valve provides an alternative to prosthetic valve replacement in patients with aortic valve endocarditis.

Furazolidone in typhoid fever--correlation of clinical efficacy with serum bactericidal activity.

Treatment of typhoid fever with furazolidone produces a high cure rate. This is a clinical curiosity, as furazolidone is described to be poorly absorbed. The present study examined whether furazolidone could produce unequivocal clinical response and, if so whether this was due to the drug producing bactericidal levels in the serum. Twenty one patients selected by defined criteria were treated with furazolidone and evaluated for definite clinical response in 5-7 days. Bactericidal activity of pre dose and post dose sera were estimated in seven patients showing definite clinical response. All the seven patients had a clinical cure without the drug producing significant bactericidal levels in the blood. Hence we concluded that the major site of action of furazolidone was in the intestine. It is our postulate that the organisms reaching the intestine in large numbers from bile are prevented from gaining re-entry into the circulation by the action of furazolidone in the intestine. After repeated cycles of entry of organisms into the intestine from bile and the simultaneous prevention of its re-entry into the circulation, the number of organisms remaining in circulation comes down considerably, thus helping the immune system to bring about a cure.

Mitral valve repair: techniques and results.

From January 1986 to December 1989, seventy patients underwent mitral valve repair. Sixty-four patients had severe mitral stenosis (MS) and mitral regurgitation (MR), while six patients had severe mitral regurgitation (MR) only. The technique used was a combination of posterior semicircular annuloplasty, mitral commissurotomy and chordal shortening. There were two operative deaths. All except three of the surviving patients are asymptomatic. There has been no episode of thromboembolism. One patient has required valve replacement and two others have had a revision of the repair in the follow up period. Predischarge and late (3 months to 3 years) echocardiography suggests that the repair is satisfactory.

Our experience with surgical management of patients with diffuse coronary artery disease.

During a follow up period of 5 years (January 1983-December 1988), 145 consecutive patients (14% of all patients undergoing coronary artery bypass surgery) underwent multiple coronary artery bypass grafting combined with endarterectomy whenever necessary for treatment of severe diffuse triple-vessel coronary artery disease. Fifty-one patients (35%) had poor left ventricular ejection fraction (less than 35%). Associated left main coronary artery disease was present in 30 (21%) patients. All coronary arteries and branches with greater than 50% obstructive disease were bypassed, using saphenous vein conduit; average grafts per patient were 5.5. Endarterectomies were done in 137 patients in 210 vessels. Right coronary artery was the commonest site (132 patients). Multiple vessel endarterectomy (greater than 2 vessels) was done in 44 patients (30%). The peri-operative mortality was 3.5%. Pre-operatively, 75% patients had class III and 14% class IV (Canadian Cardiovascular Society angina criteria). During the mean follow up period of 2 years, 86% patients have class 1 symptoms, and 14% have class II symptom. Thirty of these 145 patients have undergone resting and exercise radionuclide ventriculographic studies which have shown a significant improvement in the ejection fraction response to exercise (p less than 0.05). Thus, patients with severe diffuse coronary disease can undergo multiple bypass grafting procedure, along with endarterectomies with low mortality rates and improved exercise tolerance and functional classification.