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Dr. Parameswaran Venugopal, MD
Internist, Hematology Specialist, Oncology Specialist (cancer)
36 years of experience
Accepting new patients
Video profile

Credentials

Education ?

Medical School
University of Kerala Medical College (1976)
Foreign school

Awards & Distinctions ?

Awards  
Patients' Choice 5th Anniversary Award (2014)
Patients' Choice Award (2010 - 2014)
Compassionate Doctor Award - 5 Year Honoree (2014)
Compassionate Doctor Recognition (2010 - 2014)
Associations
American Society of Hematology
American Society of Clinical Oncology

Affiliations ?

Dr. Venugopal is affiliated with 2 hospitals.

Hospital Affiliations

Score

Rankings

  • Rush Oak Park Hospital
    520 S Maple Ave, Oak Park, IL 60304
    •  
    Top 25%
  • Rush University Medical Center
    Medical Oncology
    1653 W Congress Pkwy, Chicago, IL 60612
    •  
    Top 50%
  • Publications & Research

    Dr. Venugopal has contributed to 239 publications.
    Title Measurement of Renal Dimensions in Vivo: A Critical Appraisal.
    Date November 2011
    Journal Indian Journal of Urology : Iju : Journal of the Urological Society of India
    Excerpt

    Kidney volume is regarded as the most precise indicator of kidney size. However, volume assessment is not widely used clinically because its measurement is difficult due to the complex kidney shape. Apart from the conventional methods of measurement of renal dimensions from X-rays, ultrasound scan, computed tomography scan and magnetic resonance imaging have evolved as the three best modalities for this purpose currently. Assessment of kidney size should also be made individually since many factors like body mass index, height, gender, age, position of kidneys, sex, stenoses and number of renal arteries influence the measurements. In this paper, we have critically analysed the advantages and disadvantages of the various methods of renal morphometry, by reviewing the literature spanning over the period of 1976 - 2009.

    Title Efficacy and Safety of Clofarabine in Relapsed And/or Refractory Non-hodgkin Lymphoma, Including Rituximab-refractory Patients.
    Date May 2011
    Journal Cancer
    Excerpt

    Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients.

    Title Optimization and Scale-up of Wharton's Jelly-derived Mesenchymal Stem Cells for Clinical Applications.
    Date January 2011
    Journal Stem Cell Research
    Excerpt

    MSCs are promising candidates for stem cell therapy and regenerative medicine. Umbilical cord is the easiest obtainable biological source of MSCs and the Wharton's jelly of the umbilical cord is a rich source of fetus-derived stem cells. However, the use of MSCs for therapeutic application is based on their subsequent large-scale in vitro expansion. A fast and efficient protocol for generation of large quantities of MSCs is required to meet the clinical demand and biomedical research needs. Here we have optimized conditions for scaling up of WJ-MSCs. Low seeding density along with basic fibroblast growth factor (bFGF) supplementation in the growth medium, which is DMEM-KO, resulted in propagation of more than 1 x 10(8) cells within a time period of 15 days from a single umbilical cord. The upscaled WJ-MSCs retained their differentiation potential and immunosuppressive capacity. They expressed the typical hMSC surface antigens and the addition of bFGF in the culture medium did not affect the expression levels of HLA-DR and CD 44. A normal karyotype was confirmed in the large-scale expanded WJ-MSCs. Hence, in this study we attempted rapid clinical-scale expansion of WJ-MSCs which would allow these fetus-derived stem cells to be used for various allogeneic cell-based transplantations and tissue engineering.

    Title Complete Atrioventricular Septal Defect: Outcome of Pulmonary Artery Banding Improved by Adjustable Device.
    Date January 2011
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    We sought to evaluate pulmonary artery banding in infants with complete atrioventricular septal defects.

    Title Increased Proliferation and Analysis of Differential Gene Expression in Human Wharton's Jelly-derived Mesenchymal Stromal Cells Under Hypoxia.
    Date December 2010
    Journal International Journal of Biological Sciences
    Excerpt

    Multipotent mesenchymal stromal cells (MSCs) from Wharton's jelly (WJ) of umbilical cord bear higher proliferation rate and self-renewal capacity than adult tissue-derived MSCs and are a primitive stromal cell population. Stem cell niche or physiological microenvironment plays a crucial role in maintenance of stem cell properties and oxygen concentration is an important component of the stem cell niche. Low oxygen tension or hypoxia is prevalent in the microenvironment of embryonic stem cells and many adult stem cells at early stages of development. Again, in vivo, MSCs are known to home specifically to hypoxic events following tissue injuries. Here we examined the effect of hypoxia on proliferation and in vitro differentiation potential of WJ-MSCs. Under hypoxia, WJ-MSCs exhibited improved proliferative potential while maintaining multi-lineage differentiation potential and surface marker expression. Hypoxic WJ-MSCs expressed higher mRNA levels of hypoxia inducible factors, notch receptors and notch downstream gene HES1. Gene expression profile of WJ-MSCs exposed to hypoxia and normoxia was compared and we identified a differential gene expression pattern where several stem cells markers and early mesodermal/endothelial genes such as DESMIN, CD34, ACTC were upregulated under hypoxia, suggesting that in vitro culturing of WJ-MSCs under hypoxic conditions leads to adoption of a mesodermal/endothelial fate. Thus, we demonstrate for the first time the effect of hypoxia on gene expression and growth kinetics of WJ-MSCs. Finally, although WJ-MSCs do not induce teratomas, under stressful and long-term culture conditions, MSCs can occasionally undergo transformation. Though there were no chromosomal abnormalities, certain transformation markers were upregulated in a few of the samples of WJ-MSCs under hypoxia.

    Title Management of a Pulsatile Mass Coming Through the Sternum. Pseudoaneurysm of Ascending Aorta 35 Years After Repair of Tetralogy of Fallot.
    Date August 2010
    Journal Interactive Cardiovascular and Thoracic Surgery
    Excerpt

    We describe a case of an ascending aortic pseudoaneurysm during long-term follow-up after repair of tetralogy of Fallot (TOF). The patient had a complex cardiac surgical history with multiple operations for the correction of TOF. The aneurysm was located at the presumed site of previous aortic cannulation. It was initially treated percutaneously with an Amplatzer septal occluder device, with limited early success. After 12 months it was found to have migrated into the sac and open surgical repair was undertaken successfully.

    Title The Abcd (autologous Bone Marrow Cells in Dilated Cardiomyopathy) Trial a Long-term Follow-up Study.
    Date June 2010
    Journal Journal of the American College of Cardiology
    Title Delayed Presentation of a Post-traumatic Left Ventricular Pseudoaneurysm in a Child.
    Date June 2010
    Journal The Annals of Thoracic Surgery
    Excerpt

    Left ventricular pseudoaneurysms can occur after myocardial infarction or trauma, but are extremely rare in pediatric patients. We present a case of post-traumatic left ventricular pseudoaneurysm, in whom the causative event was some time before the acute clinical deterioration. The 9-year-old boy had repeated presentations for chest pain and lethargy for some months prior to admission. The report describes an effective primary suture repair.

    Title Late Embolization to the Aortic Arch of an Amplatzer Device Used to Occlude a Baffle Leak.
    Date March 2010
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title Retrograde Cerebral Perfusion for Brain Protection in Aortic Aneurysm Surgery.
    Date September 2009
    Journal Journal of Cardiovascular Medicine (hagerstown, Md.)
    Excerpt

    Retrograde cerebral perfusion is used as an adjunct to deep hypothermic circulatory arrest (DHCA) for cerebral protection while dealing with complex aortic lesions.

    Title Clofarabine: a New Treatment Option for Patients with Acute Myeloid Leukemia.
    Date August 2009
    Journal Expert Opinion on Pharmacotherapy
    Excerpt

    Clofarabine is a rationally designed, second-generation deoxyadenosine analog that incorporates characteristics of two other purine analogs, fludarabine and cladribine. It has shown efficacy in hematologic malignancies such as acute lymphoblastic leukemia, acute myeloid leukemia and myelodysplastic syndrome. It has already been approved for use in pediatric acute lymphoblastic leukemia after two lines of previous therapy. Clinical trials have also shown clofarabine to have activity both as a single agent and in combination with other cytotoxic drugs in adult myeloid leukemia. This compound seems to have efficacy in older patients, as well as those with adverse cytogenetics.

    Title Specific Issues After Surgical Repair of Partial Atrioventricular Septal Defect: Actuarial Survival, Freedom from Reoperation, Fate of the Left Atrioventricular Valve, Prevalence of Left Ventricular Outflow Tract Obstruction, and Other Events.
    Date April 2009
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    Our aim was to define the prevalence of specific sequelae after repair of partial atrioventricular septal defect.

    Title Primary Repair of D-transposition with Complete Atrioventricular Canal Defect.
    Date April 2008
    Journal Asian Cardiovascular & Thoracic Annals
    Excerpt

    A 4-month-old boy underwent successful single-stage anatomic repair of d-transposition of the great arteries with complete balanced atrioventricular canal defect, using the arterial switch procedure and two-patch repair of the atrioventricular canal defect. He had associated persistent left superior vena cava draining to the coronary sinus, and a patent ductus arteriosus.

    Title Efficacy and Safety of Rituximab Combined with Eshap Chemotherapy for the Treatment of Relapsed/refractory Aggressive B-cell Non-hodgkin Lymphoma.
    Date March 2008
    Journal Clinical Lymphoma & Myeloma
    Excerpt

    BACKGROUND: We evaluated the efficacy and safety of adding rituximab to nonanthracycline ESHAP (etoposide/methylprednisolone/cytarabine/cisplatin) chemotherapy for relapsed/refractory aggressive non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: Patients with intermediate- or high-grade NHL were to receive 6 rituximab doses and 6 ESHAP cycles. Rituximab 375 mg/m(2) was administered 1 week and 1 day before cycle 1 of standard ESHAP (etoposide 40 mg/m(2) on days 1-4; methylprednisolone 500 mg/m(2) on days 1-5; cytarabine 200 mg/m(2) on day 5; and cisplatin 25 mg/m(2) on days 1-4). Rituximab was repeated before the third and fifth 21-day ESHAP cycles (on days 48 and 90 of protocol, respectively), followed by 2 additional rituximab doses after cycle 6 (on days 134 and 141 of protocol). Use of growth factors was permitted. Thirteen patients were enrolled (median age, 56 years); all had previously treated NHL, 12 (92%) had diffuse large B-cell lymphoma, 10 (77%) had stage III/IV disease, and 2 (15%) had chemotherapy-refractory disease. RESULTS: The most common grade 3/4 toxicities were neutropenia and thrombocytopenia, with 3 cases of febrile neutropenia. Seven patients exhibited complete response (CR) and 3 had partial response, for an objective response rate of 77%. Median duration of response for all responders was 14 months (range, 2-51 months). Among 6 patients completing all 6 cycles, 4 (67%) had a CR, 1 had a partial response, and 1 had progressive disease. Three of the 4 CRs have remained for a median of 48 months (range, 46-51 months). CONCLUSION: Rituximab plus ESHAP led to durable responses with acceptable toxicity in patients with relapsed/refractory aggressive NHL, most of whom had advanced disease.

    Title Histopathologic Changes in Ascending Aorta and Risk Factors Related to Histopathologic Conditions and Aortic Dilatation in Patients with Tetralogy of Fallot.
    Date February 2008
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: The purposes of this study were to evaluate the histologic characteristics of the aortic wall and the risk factors related to histopathology and aortic dilatation in patients undergoing intracardiac repair of tetralogy of Fallot. METHODS: Operatively excised full-thickness aortic wall tissue from 98 consecutive patients undergoing intracardiac repair of tetralogy of Fallot aged 6 months to 47 years (mean 104.5 +/- 102.8 months; median 72 months) were studied by light microscopy. The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of loss of lamellar counts and multiple logistic regression models. RESULTS: Twenty-five (25.5%) aortic tissue specimens were indicated as histologically normal and were used as normal controls. The incidence of elastic fragmentation, increased ground substance, medionecrosis, smooth muscle disarray, and fibrosis was 74.5%, 54%, 39.8%, 26.5%, and 57.1%, respectively. A lamellar count of less than 60 was associated with a sensitivity of 80% and a specificity of 87.67%. Area under the receiver operating characteristic curve indicated that 93.37% (standard error +/- 0.039) of the time the value of lamellar count was lower for the abnormal histopathology group than for the normal group (P < .001). The risk of aortic dilatation was 15.97 times higher in patients with histopathologically abnormal aorta. CONCLUSIONS: The majority of aortic media of the ascending aorta in cyanotic tetralogy of Fallot indicates significant loss of lamellar units and pre-existing intrinsic aortopathy. The changes are present since infancy and are more pronounced in older patients subjected to long-standing cyanosis and volume overload and may account for or may coexist with the higher incidence of aortic dilatation encountered in these patients.

    Title Mixed Total Anomalous Pulmonary Venous Connection: Anatomic Variations, Surgical Approach, Techniques, and Results.
    Date February 2008
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: The purpose of this study was to identify the morphologic characteristics and other risk factors that may predispose patients with mixed totally anomalous pulmonary venous connection to continuing high mortality after surgery. METHODS: Fifty-seven consecutive patients aged 15 days to 18 years (median, 6 months) underwent rechanneling of mixed totally anomalous pulmonary venous connection. Twenty-three patients had "2+2" pattern (I category), 29 had "3+1" pattern (II category), and 5 patients had pulmonary venous connections of different combinations (III category). Obstructive patterns involving one or more pulmonary veins were present in 19 (33.3%) patients. RESULTS: Operative and late mortality rates were 19.3% and 4.3%, respectively. At a mean follow-up of 63.26 +/- 58.47 months, actuarial survival was 86.9% +/- 0.07% in category I, 86.2% +/- 0.06% in category II, and 20.0% +/- 0.18% in category III (log-rank, P = .001), respectively. At their last follow-up, all survivors (n = 43) had a Ross clinical heart failure score of 0 to 2. CONCLUSIONS: Patients with a "2+2" pattern of mixed totally anomalous pulmonary venous connection constitute the safe anatomic category for rechanneling, followed by the "3+1" variety. Cross-sectional echocardiography and/or computed tomographic angiography are mandatory to provide necessary diagnostic information and define the anatomy. Patients aged 2 months or younger, obstructive totally anomalous pulmonary venous connection, and perioperative pulmonary hypertensive crises were significant risk factors for death by logistic regression analysis. The risk of death was 5.85 times higher (95% confidence interval: 1.46-35.68; P = .02) in patients with category III of mixed TAPVC. The precise technique adopted in an individual patient depends on the pattern of anatomic drainage, and an individualized surgical approach is recommended.

    Title A Novel Percutaneously Adjustable Device for Ligature of the Vertical Vein in the Setting of Obstructive Totally Anomalous Pulmonary Venous Connection.
    Date December 2007
    Journal Cardiology in the Young
    Excerpt

    BACKGROUND: A patent vertical vein might be desirable in patients with obstructive totally anomalous pulmonary venous connection with pulmonary hypertension, in order to decrease perioperative pulmonary arterial pressure and avoid pulmonary hypertensive crises. A subset of patients with an unligated vertical vein requires interruption of the vein due to the development of significant left-to-right shunt and right heart failure. We describe here a new device, permitting adjustable ligation of the vertical vein, which permits us to avoid multiple reoperations. PATIENTS AND METHODS: In five patients, aged 2, 4, 3, 4, and 3 months respectively, and undergoing rechannelling of totally anomalous pulmonary venous connection with an unligated vertical vein, were treated with a device permitting adjusted ligation of the vertical vein over the course of postoperative congestive cardiac failure. RESULTS: There was no early or late death. Postoperatively, all ligatures were tightened gradually over a period of 24 to 96 hours, maintaining stable haemodynamics. At a mean follow-up of 55.40 months, there was no evidence of congestive heart failure in any patient, the clinical risk score varying from zero to 2, and no requirement of anti-failure medications. Computed tomographic angiograms during follow-up revealed absence of flow through the vertical vein, and ruled out distortion of the left upper pulmonary and left brachiocephalic veins. CONCLUSION: Use of a percutaneously adjustable device to ligate the vertical vein allows gradual tightening or loosening of the ligature under optimal physiologic conditions, without re-opening the sternum, or having to resort to another thoracotomy once the reactive components of pulmonary hypertension disappear.

    Title A Suggested New Surgical Classification for Mixed Totally Anomalous Pulmonary Venous Connection.
    Date December 2007
    Journal Cardiology in the Young
    Excerpt

    The morphologic variations of mixed totally anomalous pulmonary venous connection are many and varied. In this review, we give an account of all cases previously described as mixed totally anomalous pulmonary venous connection, analyzing in detail those cases where an accurate anatomical description was provided. We identified 182 suitable cases, from 54 investigations, and reviewed the clinical presentation, anatomic variations, diagnostic features, and management of the patients described.Cross-sectional echocardiography, and cardiac catheterization, provided the necessary diagnostic information, and defined the anatomy before surgery in 139 patients. Magnetic resonance imaging and computerized tomographic angiography had been used for further clarification of the pulmonary venous anatomy. An obstructive pattern of drainage, involving one or more pulmonary veins, had been described in over half of the patients. We then grouped the lesions into categories that have a bearing on the appropriate surgical approach, discussing the appropriate repair for each group. For the overall group, the operative mortality remains high, at 22.9%. We submit that an increased appreciation of various types of mixed totally anomalous pulmonary venous connection may well contribute to improved future surgical management.

    Title Sinus of Valsalva Aneurysm Masquerading As Coronary Artery Disease.
    Date December 2007
    Journal The Annals of Thoracic Surgery
    Title Autologous Stem Cell Transplantation Following Induction Therapy with an Anthracycline-based Regimen Including Interferon-alpha for Low-grade Non-hodgkin's Lymphoma.
    Date September 2007
    Journal Clinical Advances in Hematology & Oncology : H&o
    Excerpt

    The role of upfront autologous stem cell transplantation (ASCT) in low-grade non-Hodgkin's lymphoma (LGNHL) continues to be an area of investigation. After undergoing this novel anthracycline-based induction regimen including interferon (IFN)-alpha, a group of LGNHL patients received high-dose chemotherapy followed by ASCT. The induction regimen was based on the concept of regrowth resistance in which patients received nonmyelotoxic agents mid-cycle to slow tumor proliferation between courses of cytotoxic therapy. In addition, IFN-alpha was given at the end of the cycle because studies have shown that it has a 50% response rate in treating LGNHL. We treated 44 consecutive patients between August 1993 and February 1999 with an induction regimen containing cyclophosphamide, mitoxantrone, and teniposide intravenously on day 1 with oral prednisone given on days 1-5. On day 15, patients received vincristine and bleomycin IV. IFN-alpha-2b subcutaneously was administered on days 22-26. In this phase II single-institution study, there were 2 main patient groups. Nineteen patients received the chemotherapy induction regimen and 17 patients received chemotherapy followed by upfront ASCT. For the chemotherapy group, 58% had follicular histology and 84% had stage IV disease. For the ASCT group, 76% had follicular histology, and 71% had stage IV disease. Of the patients treated with chemotherapy, the overall response rate was 95% with 58% complete responses and 37% partial responses. Of the patients treated with chemotherapy and later ASCT, the overall response rate was 100% with 82% complete responses and 18% partial responses. In analyzing progression-free curves for these 2 groups of patients, there was evidence that the upfront autologous group fared better, log-rank test X(2)=4.6028, P < .0319.

    Title Lymphomatoid Granulomatosis Treated with Rituximab and Chemotherapy.
    Date September 2007
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Long-term Remission of Extramedullary Relapse from Acute Promyelocytic Leukemia After Treatment with Arsenic Trioxide, Intrathecal Chemotherapy, and Brain Irradiation.
    Date August 2007
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Application of Stem Cell Technology for Coronary Artery Disease at the All India Institute of Medical Sciences, New Delhi, India.
    Date July 2007
    Journal The Heart Surgery Forum
    Excerpt

    Stem cell technology is rapidly gaining popularity as a way to improve the prognosis of patients with coronary artery disease and heart failure. In this review, we systematically analyze the basis, methods, and results of stem cell technology for coronary artery disease at the All India Institute of Medical Sciences, New Delhi, India.

    Title Stem Cells As a Therapeutic Modality in Pediatric Malformations.
    Date July 2007
    Journal Transplantation Proceedings
    Excerpt

    AIM: The aim of this study was to explore stem cell use in congenital anomalies. PATIENTS AND METHODS: During July 2005 through July 2006, autologous stem cells were used in 29 patients: 12 with liver cirrhosis and 17 with meningomyelocele. Stem cells were injected into the hepatic artery and the portal vein or into the hepatobiliary radicals for liver cirrhosis, or into the spinal cord and caudal space for meningomyelocele. Preoperative status served as the control condition. OBSERVATIONS AND RESULTS: The ages of patients with liver cirrhosis ranged between 1.5 and 9 months (mean, 4.12 months). The etiology was extra hepatic biliary atresia (EHBA) versus neonatal cholestasis and choledochal cyst in 8; 2 and 2 patients, respectively. Five patients died due to ongoing cirrhosis. Follow-up at 3 to 12 months (N = 7) showed absence of cholangitis (4/7), yellow stools (5/7), decreased liver firmness (3/7), improved liver function (6/7), and better appetite (6/7). Hepatobiliary scan was excretory in 6 of 7 with improved uptake in 4 of 7. Histopathology demonstrated comparative improvement in fibrosis among 3 patients. Meningomyelocele patients were between 0 and 1 month, 1-5 months, and 1-4 years in 5, 8, and 2 cases respectively. Five had a history of rupture. Three had undergone meningocele repair in the past with neurological deficits. Redo surgery for a tethered cord was performed in 1 patient. Follow-up at 3 to 11 months in 14 cases showed improved power in 7 with dramatic recovery in 3 (22%) and status quo in 7 (50%). CONCLUSION: Initial stem cell use in liver cirrhosis and meningomyelocele has suggested beneficial results. However, long-term evaluation in randomized controlled trials is essential to draw further conclusions.

    Title Sensitivity of Patient-specific Numerical Simulation of Cerebal Aneurysm Hemodynamics to Inflow Boundary Conditions.
    Date July 2007
    Journal Journal of Neurosurgery
    Excerpt

    OBJECT: Due to the difficulty of obtaining patient-specific velocity measurements during imaging, many assumptions have to be made while imposing inflow boundary conditions in numerical simulations conducted using patient-specific, imaging-based cerebral aneurysm models. These assumptions can introduce errors, resulting in lack of agreement between the computed flow fields and the true blood flow in the patient. The purpose of this study is to evaluate the effect of the assumptions made while imposing inflow boundary conditions on aneurysmal hemodynamics. METHODS: A patient-based anterior communicating artery aneurysm model was selected for this study. The effects of various inflow parameters on numerical simulations conducted using this model were then investigated by varying these parameters over ranges reported in the literature. Specifically, we investigated the effects of heart and blood flow rates as well as the distribution of flow rates in the A1 segments of the anterior cerebral artery. The simulations revealed that the shear stress distributions on the aneurysm surface were largely unaffected by changes in heart rate except at locations where the shear stress magnitudes were small. On the other hand, the shear stress distributions were found to be sensitive to the ratio of the flow rates in the feeding arteries as well as to variations in the blood flow rate. CONCLUSIONS: Measurement of the blood flow rate as well as the distribution of the flow rates in the patient's feeding arteries may be needed for numerical simulations to accurately reproduce the intraaneurysmal hemodynamics in a specific aneurysm in the clinical setting.

    Title A Simplified Circuit of Modified Ultrafiltration.
    Date June 2007
    Journal Heart, Lung & Circulation
    Excerpt

    A simplified circuit of modified ultrafiltration (MUF) is described. The technique described is simple, inexpensive, allows both conventional ultrafiltration (CUF) and modified ultrafiltration with minimum manipulation of the circuit, allows re-institution of cardiopulmonary bypass (CPB) in an emergency, reduces the risk of air embolism and air cavitation and can be used in adults as well as children.

    Title Rechanneling of Total Anomalous Pulmonary Venous Connection with or Without Vertical Vein Ligation: Results and Guidelines for Candidate Selection.
    Date May 2007
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: This study investigated whether postoperative low cardiac output and mortality in obstructed total anomalous pulmonary venous connection could be reduced by selective vertical vein patency. METHODS: Fifty-eight patients undergoing rechanneling of total anomalous pulmonary venous connection between 1997 and 2006 were studied. The vertical vein was left patent in 27 patients (group I) and ligated in 31 (group II). Mean ages were 1.49 +/- 1.63 and 4.37 +/- 3.38 months for groups I and II, respectively. RESULTS: Operative mortalities were 29.1% and 7.4% for ligated and unligated groups, respectively (relative risk 1.75, 1.16-2.64, P = .036). Age younger than 1 month, obstructive total anomalous pulmonary venous connection, hypoplastic pulmonary veins, pulmonary hypertensive crisis, low cardiac output, and vertical vein ligation were significant risk factors for death according to logistic regression analysis. Patients with obstructed total anomalous pulmonary venous connection undergoing vertical vein ligation demonstrated predominant right ventricular dysfunction (relative risk 2.93, 1.28-6.73, P = .011), pulmonary hypertensive crisis (relative risk 2.90, 1.25-6.75, P = .013), and 3.28 times the risk of death (95% confidence interval 1.08-9.99, P = .032) relative to the unligated group. CONCLUSIONS: In a subset of patients with obstructed total anomalous pulmonary venous connection, an unligated vertical vein reduces pulmonary arterial pressure, decreases perioperative pulmonary hypertensive crises, provides a temporary pop-off valve during pulmonary hypertensive crisis, and improves survival by providing superior hemodynamics. The high mortality in the ligated group suggests that patients with obstructed total anomalous pulmonary venous connection with postbypass moderate pulmonary hypertension possibly should not undergo vertical vein ligation. We propose routine use of an adjustable ligature around the vertical vein in all patients with more than moderate post-bypass pulmonary hypertension, allowing gradual tightening in increments without multiple reoperations.

    Title Novel Techniques for Tumor Thrombectomy for Renal Cell Carcinoma with Intraatrial Tumor Thrombus.
    Date May 2007
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Radical nephrectomy with tumor thrombectomy in patients with renal cell carcinoma and level I to III thrombus extension is directly associated with an improved prognosis. However, radical surgery in patients with level IV thrombus extension is associated with high perioperative mortality, even if long-term survival is possible. In this report, we describe an alternative technique of vena caval and intraatrial tumor thrombectomy to decrease perioperative mortality and morbidity. METHODS: A cohort of 6 patients aged 46, 50, 53, 56, 54, and 52 years underwent radical nephrectomy with tumor thrombectomy from the vena cava and right atrium under mild hypothermic cardiopulmonary bypass and intermittent cross-clamping of the supraceliac abdominal aorta. Intraatrial tumor thrombectomy was performed on a beating, perfused heart in 4 patients and a hypothermic, cardioplegia-perfused heart in 2 patients. RESULTS: There were no early or late deaths. The aortic cross-clamp time was 12 and 15 minutes for patients 5 and 6, respectively. The cumulative hepatic and renal ischemic time was 16 minutes (range, 14 to 22 minutes) at 32 degrees C. The mean cardiopulmonary bypass time was 53.3 +/- 8.9 minutes (range, 40 to 65 minutes). At a mean follow-up of 43 +/- 24.6 months (range, 10 to 70 months), all patients are active and remain disease-free. CONCLUSIONS: We conclude that radical nephrectomy and tumor thrombectomy in patients with level IV thrombi can be safely performed with cardiopulmonary bypass, mild hypothermia. and intermittent supraceliac abdominal aortic occlusion, avoiding potential hematologic, hepatic, renal, neurologic, and septic complications associated with circulatory arrest.

    Title Anomalous Right Subclavian Artery Proximal to Juxtaductal Coarctation.
    Date January 2007
    Journal International Journal of Cardiology
    Excerpt

    Two patients with anomalous right subclavian artery proximal to aortic coarctation are reported for their rarity. The embryological basis and surgical implications are briefly discussed. The major surgical implication of this anomaly relates to the risk of spinal cord ischemia and in these cases, the repair was performed safely.

    Title Percutaneous Intracoronary Cellular Cardiomyoplasty for Nonischemic Cardiomyopathy: Clinical and Histopathological Results: the First-in-man Abcd (autologous Bone Marrow Cells in Dilated Cardiomyopathy) Trial.
    Date January 2007
    Journal Journal of the American College of Cardiology
    Title Criterions for Selection of Patients For, and Results Of, a New Technique for Construction of the Modified Blalock-taussig Shunt.
    Date January 2007
    Journal Cardiology in the Young
    Excerpt

    BACKGROUND: We describe alternative surgical techniques for construction of systemic-to-pulmonary arterial shunts, and propose criterions for their application in selected patients. PATIENTS AND METHODS: We constructed a variety of modified systemic-to-pulmonary arterial shunts, using polytetrafluoroethylene grafts, in 92 selected patients with cyanotic congenital heart disease and anomalies of the aortic arch and systemic veins. Their age ranged from 7 days to 3.6 years, with a mean of 7.08 months. We performed 88 operations through a thoracotomy. Of this cohort, 60 patients underwent a second-stage operation, with 15 receiving a superior cavopulmonary connection, 16 a total cavopulmonary connection, and 29 proceeding to biventricular repair after a mean interval of 15.6 months. We have 21 patients awaiting their second or final stage of palliation. RESULTS: There were five early (5.4%) and six late deaths (6.8%), two of which were related to construction of the shunts. At a mean follow-up of 45.29 months, the increase in diameter of pulmonary trunk and its right and left branches was uniform and significant (p value less than 0.001). Pulmonary arterial distortion requiring correction at the time of second-stage operation was observed in 5 patients (6.1%). Adequate overall palliation was achieved in 98% of the cohort at 8 months, 91% at 12 months, and 58% at 18 months. CONCLUSIONS: Patients with a right- or left-sided aortic arch and right-sided descending thoracic aorta, those with anomalies of systemic venous drainage masking the origin of great arterial branches, and those with disproportionately small subclavian arteries, constitute the ideal candidates for our suggested modification of the construction of a modified Blalock-Taussig shunt. The palliation provided by these shunts was satisfactory, with predictable growth of pulmonary arteries, insignificant distortion in the great majority, and easy take-down.

    Title Serial Radionuclide Angiographic Assessment of Left Ventricular Ejection Fraction and Regional Wall Motion After Mitral Valve Replacement in Patients with Rheumatic Disease.
    Date January 2007
    Journal American Heart Journal
    Excerpt

    BACKGROUND: This study was designed to prospectively investigate the effects of total or partial chordal-sparing and chordal-nonsparing mitral valve replacement (MVR) procedures on regional and global ventricular function in a rheumatic population using sequential multiple-gated acquisition scan. METHODS: One hundred five consecutive patients undergoing different techniques of chordal preservation procedures during MVR are included in this prospective study. Fifteen patients had complete excision of the chordopapillary apparatus (group 1), 34 had total chordal preservation (group 2), and 56 had preservation of the posterior chordopapillary apparatus (group 3). Radionuclide-derived left ventricular ejection fraction (LVEF) and regional wall motion (RWM) studies on 99 survivors were performed preoperatively, at discharge, at 1 year, and at 2 years. RESULTS: At discharge, there was a decline in LVEF in all the 3 groups. Statistically significant improvement in ejection fraction occurred in the chordal preservation groups (2 and 3) (P < .05) as compared with the nonchordal group immediately and late postoperatively. Only the total chordal group (2) demonstrated complete recovery of LVEF by 2 years postoperatively. Significant and persistent RWM abnormalities were noted in both the nonchordal and posterior chordal groups. CONCLUSIONS: We conclude that complete retention of the chordopapillary apparatus during MVR provides superior results compared with nonchordal and partial chordal preservation in terms of preservation of LVEF and reduced incidence of abnormal postoperative RWM.

    Title Durable Remission of Intravascular Lymphoma with Central Nervous System Involvement Following Chemotherapy and Rituximab.
    Date December 2006
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Posttransplant Lymphoproliferative Disorder: Extranodal Marginal Zone Lymphoma Occurring After Renal Transplantation.
    Date December 2006
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Mitral Stenosis After Duran Ring Annuloplasty for Non-rheumatic Mitral Regurgitation--a Foreign Body Response?
    Date November 2006
    Journal Heart, Lung & Circulation
    Excerpt

    We report two cases of mitral stenosis after Duran ring annuloplasty for myxomatous mitral regurgitation. Simple explantation of the ring provided relief of mitral stenosis.

    Title Recurrent Thrombotic Thrombocytopenic Purpura Treated Repeatedly and Successfully with the Monoclonal Antibody Rituximab.
    Date October 2006
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Total Transatrial Correction of Tetralogy of Fallot: No Outflow Patch Technique.
    Date October 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The aim of this study was to analyze the feasibility and early results of transatrial total correction of tetralogy of Fallot (TOF). METHODS: Of the 860 patients undergoing total correction for TOF between January 2000 and July 2005, 334 patients were considered morphologically suitable for transatrial total correction. The ventricular septal defect (VSD) closure, infundibular resection, and pulmonary valvotomy were performed through the right atrium without a right ventriculotomy. Age ranged from 6 months to 40 years (median, 2.8 years), and weight ranged from 5.5 to 70 kg (median, 14 kg). RESULTS: Peroperatively, 34 patients required right ventriculotomy and transannular patch; hence, they were excluded from the study. In addition, pulmonary arteriotomy was required in 71 patients (22.9%). There were 4 hospital deaths. There were 4 early reoperations (residual/additional VSD in 3 and tricuspid regurgitation in 1). Two patients had complete heart block requiring permanent pacemaker. Echocardiography at discharge showed a peak right ventricular outflow tract gradient of 20 +/- 5.2 mm Hg. Mean follow-up was 26.8 +/- 4.2 months (range, 1 to 52 months). The right ventricular outflow tract gradients reduced to 13 +/- 4.2 mm Hg after a mean interval of 18.8 +/- 5.2 months. Follow-up New York Heart Association class was I in 240 cases (82%), II in 49 (16%), and III in 7 (2%). There were no late deaths or reoperations. CONCLUSIONS: Transatrial total correction of TOF can be accomplished in selected patients with good early results. In 300 cases (90%), the feasibility of transatrial total correction could be predicted accurately.

    Title Histopathology of the Right Ventricular Outflow Tract and Its Relationship to Clinical Outcomes and Arrhythmias in Patients with Tetralogy of Fallot.
    Date September 2006
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVES: The purposes of this study were to evaluate the myocardial histopathology and ultrastructure in patients with tetralogy of Fallot and to identify the histopathologic characteristics that may predispose patients to postoperative myocardial dysfunction and arrhythmias. PATIENTS AND METHODS: Operatively resected crista supraventricularis muscle from 183 patients undergoing intracardiac repair of tetralogy of Fallot aged 12 months to 42 years (mean, 106.84 +/- 79.35 months) were studied by light and electron microscopy. Biventricular function and cardiac rhythm were assessed by 2-dimensional echocardiography and electrocardiography. RESULTS: The incidence of moderate or severe cellular hypertrophy, endocardial thickening, and interstitial fibrosis was 36%, 68.3%, and 65%, respectively. Logistic regression analysis demonstrated age greater than 4 years, systemic arterial desaturation, higher hematocrit values, and elevated ventricular end-diastolic pressures as the major predisposing risk factors for pathologic changes. Twenty-seven (81.8%) patients more than 15 years of age and 29 (29.3%) patients between 4 and 15 years of age had predominant right ventricular dysfunction and low cardiac output (chi(2) [1 degree of freedom (df)] = 27.95; P < .001; odds ratio [OR] = 10.86 [3.75-33.10]). Ventricular arrhythmia was detected in 11 patients in whom repair was performed between 4 and 15 years of age and in 13 patients whose age at operation was 15 years or older. According to an additive logistic model, the effect of age at repair on the influence of ventricular arrhythmia was significant (chi(2) [1 df] = 24.4; P < .001; OR = 8.21 (2.96-23.11]). CONCLUSIONS: The great majority of myocardial tissues in cyanotic tetralogy of Fallot indicates pre-existing ultrastructural hypertrophic and degenerative changes. The changes are more pronounced in older patients subjected to long-standing cyanosis and pressure overload and may account for or may coexist with the higher incidence of myocardial dysfunction and ventricular arrhythmia.

    Title Specific Issues After Extracardiac Fontan Operation: Ventricular Function, Growth Potential, Arrhythmia, and Thromboembolism.
    Date September 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The purpose of this study was to define the prevalence of specific sequelae after extracardiac Fontan operation. METHODS: Sixty-five consecutive patients undergoing extracardiac Fontan operation were studied for mortality, Fontan failure, systemic ventricular function, supraventricular arrhythmias, thromboembolism, and growth potential. Age was 3 to 31 years (mean +/- standard deviation, 9.4 +/- 1.8; median, 7 years). The conduits were constructed of polytetrafluoroethylene (n = 50), and "viable" in situ pericardium (n = 15). The patients underwent serial echocardiogram, dynamic radionuclide studies, and cardiac catheterization. RESULTS: Operative mortality was 3%, and the incidence of conduit thrombosis was 4.6%. There was paradoxic filling of the right lung after femoral injection of the radiotracer in all cases of conduit obstruction. Perioperative and late postoperative supraventricular arrhythmias were observed in 9.2% and 4.7% of patients, respectively. Risk factors for supraventricular arrhythmias included systemic ventricular dysfunction (p = 0.000), heterotaxy syndrome (p = 0.008), systemic venous anomalies (p = 0.015), and previous bidirectional Glenn operation (p = 0.017). At a mean follow-up of 77 +/- 2 months (range, 8 to 79 months), there were no late deaths (actuarial survival at 79 months, 96.9% +/- 0.02%). Serial echocardiograms demonstrated evidence of growth of the viable tunnels. Postoperatively, there was transient depression of ejection fraction in all patients (p = 0.000). CONCLUSIONS: Supraventricular arrhythmias after extracardiac Fontan are more common in patients with heterotaxy syndrome, bilateral superior venae cavae, systemic ventricular dysfunction, and those undergoing completion Fontan operation. The viable tunnel may emerge as an optimal alternative by virtue of reduction of supraventricular arrhythmias, elimination of the need for anticoagulation, and addressing the issue of growth potential in selected patients.

    Title Pericardiectomy for Constrictive Pericarditis: a Clinical, Echocardiographic, and Hemodynamic Evaluation of Two Surgical Techniques.
    Date August 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: This study was designed to compare the outcomes after total versus partial pericardiectomy clinically, echocardiographically, and hemodynamically. METHODS: Three hundred ninety-five patients undergoing pericardiectomy for constrictive pericarditis between January 1985 and December 2004 were studied. Age was 10 months to 71 years (mean, 25.1 +/- 13.4 years). Three hundred thirty-eight patients (85.6%) underwent total pericardiectomy (group I), and 57 patients (14.4%) underwent partial pericardiectomy (group II). RESULTS: Operative and late mortality rates were 7.6% and 4.9%, respectively. Preoperative high right atrial pressure, hyperbilirubinemia, renal dysfunction, atrial fibrillation, pericardial calcification, thoracotomy approach, and partial pericardiectomy were significant risk factors for death. The risk of death was 4.5 times higher (95% confidence interval: 2.05 to 9.75) in patients undergoing partial pericardiectomy. At a mean follow-up of 17.9 +/- 0.3 years (95% confidence interval: 17.3 to 18.6), actuarial survival was 83.8% +/- 0.04% in group I and 73.9% +/- 0.06% in group II (p = 0.004). At their last follow-up, 96.3% survivors of group I and 79.1% survivors of group II were in New York Heart Association class I/II (p < 0.001). CONCLUSIONS: Total pericardiectomy is associated with lower perioperative and late mortality, and confers significant long-term advantage by providing superior hemodynamics that appear to be independent of the etiology of constrictive pericarditis.

    Title Mitral Valve Replacement with and Without Chordal Preservation in a Rheumatic Population: Serial Echocardiographic Assessment of Left Ventricular Size and Function.
    Date August 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The aim of this study is to investigate the feasibility of chordal-sparing mitral valve replacement procedures in a rheumatic population, and to determine the early and late effects of different chordal preservation procedures on the clinical outcome and left ventricular mechanics. METHODS: Various techniques of chordal preservation during mitral valve replacement for rheumatic heart disease in 451 patients between 1996 and 1999 are described. The mean age was 35.6 +/- 19.0 years (range, 15 to 55 years). Seventy patients had complete excision of the subvalvular apparatus (group I), 124 had preservation of the posterior chordopapillary apparatus (group II), and 257 had total chordal preservation (group III). Echocardiography was performed preoperatively, at discharge, at 1 year, and at 4 years. RESULTS: Chordal preservation groups (II and III) demonstrated significant improvement (p < 0.05) in left ventricular function immediately and late postoperatively. Reduction of left ventricular end-systolic and end-diastolic volume was significant in the chordal preservation groups (II and III) as compared to the nonchordal group (group I; p < 0.005). The total chordal group demonstrated greater fractional change of left ventricular end-systolic volume as compared to the posterior chordal and nonchordal group. The left ventricular ejection fraction and fractional shortening continued to decline over time in the nonchordal cohort (p = 0.05 and p = 0.001, respectively) and did not improve by 4 years. Statistically significant change in ejection fraction occurred in the chordal preservation groups as compared to the nonchordal group. CONCLUSIONS: We conclude that total chordal preservation is possible in the large majority of rheumatic patients and confers significant long-term advantage by preserving left ventricular function. The surgical technique should be individualized.

    Title Right Pulmonary Artery-to-left Atrium Communication: Report of 5 Cases.
    Date August 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    Five patients of right pulmonary artery-to-left atrium communication presented with special emphasis on the clinical presentation, anatomic variations, diagnostic considerations, and management options. An individualized management algorithm is recommended.

    Title Right Pulmonary Artery to Left Atrium Communication.
    Date August 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    This is a collective review of 59 published cases of right pulmonary artery to left atrium communication in the English-language literature. In this article, we review the literature on the clinical presentation, anatomic variations, diagnostic features, and management considerations of previously reported cases. Two-dimensional echocardiography and cardiac catheterization including selective angiography provided the necessary diagnostic information and defined the anatomy before surgery in all patients. Various management options including medical, surgical, and transcatheter closure have been reported. The lesions have been classified into four types (I, II, III, and IV) that have a bearing on the appropriate surgical approach and techniques of repair that are discussed in the text. Use of extracorporeal circulation may be considered in selected instances. The operative mortality rate during the earlier era (1950 to 1979) was high, at 22%. More recently, the mortality rate has approached zero. An individualized surgical approach depending on the type of surgical connections is recommended.

    Title Successful Management of a Case of Massive Air Embolism from Cardiopulmonary Bypass with Retrograde Cerebral Perfusion in a Child.
    Date June 2006
    Journal Journal of Cardiothoracic and Vascular Anesthesia
    Title Noninvasive Assessment of Repaired Tetralogy of Fallot by Magnetic Resonance Imaging and Dynamic Radionuclide Studies.
    Date June 2006
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: This study was designed to validate the diagnostic accuracy of magnetic resonance imaging (MRI) in evaluating biventricular ejection fraction and to quantify pulmonary regurgitant fraction (PRF) in patients after repair of tetralogy of Fallot. METHODS: Two hundred and eighty survivors of repaired tetralogy of Fallot aged 42 months to 40 years (mean, 142.2 +/- 85.3 months) underwent cardiac MRI, first-pass and gated radionuclide ventriculography (RNV) for the assessment of biventricular function, and PRF after 89.26 +/- 42.40 months. The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of MRI. RESULTS: There was statistically significant agreement between MRI and RNV in evaluating right and left ventricular function. An MRI-derived right ventricular ejection fraction 47.2% or greater than normal was associated with a sensitivity of 92.3% and a specificity of 92.3%. An MRI-derived left ventricular ejection fraction 53.9% or greater than normal was associated with a sensitivity of 93.2% and a specificity of 93.3%. Area analysis indicated that 97.34% (standard error [SE] = 0.0118) and 98.56% (SE = 0.0052) of the time values of right and left ventricular ejection fraction were higher for patients with normal right and left ventricular functions, respectively, compared with abnormal. There was a strong agreement between velocity-encoded and stroke volume-derived PRF [(r = 0.886, p < 0.001; d = 2.62 +/- 1.12, p < 0.0001; r' = 0.121, p = 0.051; b = 0.96 (SE = 0.012); p < 0.0001; ICC = 0.98, p < 0.0001). Higher PRF was associated with increased indexed right ventricular dimensions and inversely correlated with biventricular ejection fractions. CONCLUSIONS: The MRI-derived ejection fraction values predictably separate patients with normal ventricular function from abnormal. Velocity-encoded MRI can accurately quantitate PRF in tetralogy of Fallot.

    Title Severe Mitral Regurgitation After Percutaneous Transmitral Commissurotomy: Underestimated Subvalvular Disease.
    Date June 2006
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title A New Technique of Percutaneously Adjustable Pulmonary Artery Banding.
    Date May 2006
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: Pulmonary artery banding is associated with a high morbidity and mortality. We describe a new technique of adjustable pulmonary artery banding to prevent these problems. METHODS: Between December 2003 and May 2005, 32 patients aged 18 days to 2 years (mean age, 2.5 +/- 0.5 months) and weighing 2.1 to 6.3 kg (mean, 3.6 +/- 1.3 kg) underwent adjustable pulmonary artery banding. RESULTS: All patients survived the operation. There were 2 deaths, one caused by meningitis and another caused by aspiration pneumonitis. Satisfactory band gradients were achieved between 3 and 10 days (7.2 +/- 2.6 days) in 3 to 6 sittings. Mean follow-up was 7.5 +/- 3.8 months (1-16 months). One patient required reoperation for unsatisfactory band gradient 2 weeks after discharge. There were no late deaths. Follow-up computed tomographic angiograms (n = 4) demonstrated proper band placement and ruled out distortion of the pulmonary arteries. Four patients underwent uneventful definitive operations after an interval of 7 to 13 months. CONCLUSION: This technique of percutaneously adjustable pulmonary artery banding is simple and inexpensive and allows easy band adjustments without the need for multiple reoperations.

    Title A Massive Pulsatile Chest Wall Mass.
    Date March 2006
    Journal The New Zealand Medical Journal
    Title The Evolving Role of Alemtuzumab in Management of Patients with Cll.
    Date January 2006
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    New insights into prognostic markers and the pathophysiology of chronic lymphocytic leukemia (CLL) are beginning to change the concept of CLL treatment. Alemtuzumab has evolved as a potent and effective therapeutic option for patients with CLL. Specifically, alemtuzumab has demonstrated substantial efficacy in fludarabine-refractory patients and has shown impressive responses when administered subcutaneously in first-line therapy. A group of experts gathered to discuss new data related to the use of alemtuzumab in CLL and to assess its place in the rapidly changing approach to treating patients with this disease. The main goals of this program were to update the management guidelines that were previously developed for alemtuzumab-treated patients and to provide community oncologists with guidance on the most effective way to integrate alemtuzumab into a CLL treatment plan.

    Title Univentricular Repair in Children Under 2 Years of Age: Early and Midterm Results.
    Date January 2006
    Journal Heart, Lung & Circulation
    Excerpt

    BACKGROUND: Encouraging results have been obtained from early univentricular repair. Our study was designed to assess the impact of young age (less than 2 years) on the outcome of univentricular repair. PATIENTS AND METHODS: Between January 1992 and December 1998, 65 out of 311 patients undergoing univentricular repair at the All India Institute of Medical Sciences, New Delhi, were less than 2 years of age. We compared these 65 carefully selected patients (group 1) with the 246 patients who were more than 2 years of age (group 2). Since 1994, all patients of both groups had a fenestration of the intra-atrial baffle. RESULTS: The early mortality rate was 9.2% in group 1 and 7.7% in group 2. The overall Fontan failure rate was 12.3% in group 1 and 12.2% in group 2. In group 1, a higher incidence of Fontan failure was noted in patients with suboptimal weight, non-tricuspid atresia morphology, nonfenestrated Fontan and those who did not comply with more than two of Choussat's criteria, but the values were not statistically significant. Aortic cross-clamp time of more than 60 min was the only and highly significant predictor of Fontan failure (P < 0.01). The overall effusion rate was 24.05% in group 1 and 27.98% in group 2. In group 1, patients weighing less than 10 kg (P = 0.0007), without fenestration of the atrial baffle (P < 0.05) and with systemic ventricular dysfunction (P < 0.001), systemic ventricular end-diastolic pressure of more than 12 mmHg (P < 0.001), mean pulmonary artery pressure of more than 15 mmHg (P < 0.001) and aortic crossclamp time of more than 60 min (P < 0.01), were all found to be significant risk factors of pleural effusion. Pulmonary artery distortion needing reconstruction did not increase the Fontan failure or effusion rates. Oxygen saturation ranged from 85 to 94% (mean 89%) in patients having a functioning fenestration at a mean follow-up period of 30 months. The actuarial survival at 84 months was 90 +/- 0.04% in group 1 and 88 +/- 0.02% in group 2. CONCLUSIONS: Our results suggest that carefully selected patients under 2 years of age are suitable candidates for one-stage univentricular repair and that survival is not significantly different from that of older patients. Routine fenestration of the intra-atrial baffle is an option available to ameliorate morbidity and obviate mortality. Non-compliance with more than two of Choussat's criteria appears to be additive in unsatisfactory outcome.

    Title Subaortic Membrane Excision: Mid-term Results.
    Date January 2006
    Journal Heart, Lung & Circulation
    Excerpt

    BACKGROUND: Subaortic membrane (SAM) is a form of fixed subaortic obstruction in which a fibrous membrane is located below the aortic valve. Aim: To determine the role of surgical treatment for patients with a discrete SAM. PATIENTS AND METHODS: The hospital records of 45 patients (age range: 2-23 years; median 8 years) undergoing surgery for SAM between 1990 and 1998 at the All India Institute of Medical Sciences, New Delhi, India, were analysed. Preoperative echocardiographically calculated gradients across the left ventricular outflow tract ranged from 50 to 154 mmHg (mean: 86.5 +/- 33.2 mmHg). Nine patients had trivial aortic regurgitation (AR), 10 had mild AR and five had moderate-severe AR. The left ventricular ejection fraction (LVEF) ranged from 20 to 68% (mean 48 +/- 15%). Nineteen patients had significant left ventricular dysfunction (LVEF <50%). Transaortic resection of SAM was done in all patients along with excision of a wedge-shaped segment of septal muscle underlying the membrane. RESULTS: There were no early or late postoperative deaths. On follow up (up to 113 months), only four patients had gradients >30 mmHg. LVEF improved to 45-70% (mean 58 +/- 7.7%). AR reduced to mild in four patients and trivial in four patients, and did not progress further. CONCLUSION: Resection of SAM carries long-term benefits. Routine septal myectomy appears to be associated with a low risk of recurrence.

    Title One and One-half Ventricle Repair: Results and Concerns.
    Date December 2005
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The study was designed to assess the long-term results of one and one-half ventricular repair on systemic and pulmonary circulation, right ventricular growth and function, and the prevalence of arrhythmias. METHODS: Eighty-four patients undergoing one and one-half ventricular repair between January 1990 and December 2003 were studied. Age was 4 to 504 months (mean, 47.9 +/- 57.3 months). Sixty-nine survivors underwent serial echocardiography, radionuclide studies, cardiac magnetic resonance imaging, and cardiac catheterization. RESULTS: Operative and late mortality were 10.7% and 8%, respectively. Perioperative and postoperative supraventricular arrhythmias were observed in 14.3% and 15.9% of patients, respectively. Risk factors for supraventricular arrhythmias included systemic ventricular dysfunction, heterotaxy syndrome, and Ebstein's anomaly. Mean late postoperative superior vena caval pressure was 14.2 +/- 1.52 mm Hg and right atrial pressure was 6.6 +/- 0.74 mm Hg. At a median follow-up of 87 months, actuarial survival was 81.9% +/- 0.04%, and 89.8% were in New York Heart Association class I or II. Serial cine-magnetic resonance imaging demonstrated significant growth of tricuspid valve and right ventricular cavity in 45% of patients. CONCLUSIONS: One and one-half ventricular repair can be performed with an acceptable risk. The operation maintains a low pressure in the inferior vena caval tributaries, and reverses the Fontan paradox. Patients with tripartite right ventricles demonstrated a tendency toward enlargement of the pulmonary ventricular chamber commensurable with somatic growth.

    Title Relapsed Non-hodgkin Lymphoma in Fraternal Twins Managed Successfully with Rituximab Maintenance Therapy.
    Date October 2005
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title The Combination of Fludarabine, Cyclophosphamide, and Granulocyte-macrophage Colony-stimulating Factor in the Treatment of Patients with Relapsed Chronic Lymphocytic Leukemia and Low-grade Non-hodgkin's Lymphoma.
    Date October 2005
    Journal Clinical Lymphoma
    Excerpt

    PURPOSE: The goal of this study was to evaluate the efficacy of the fludarabine/cyclophosphamide combination in patients with relapsed chronic lymphocytic lymphoma (CLL) and low-grade non-Hodgkin's lymphoma (NHL) and to assess the impact of adding granulocyte-macrophage colony-stimulating factor (GM-CSF) to this regimen in a randomized fashion. PATIENTS AND METHODS: Thirty-four patients (CLL, n=16; low-grade NHL, n=18) were enrolled. The median number of previous treatments was 2. Patients received <or=6 cycles of fludarabine at 30 mg/m2 per day and cyclophosphamide at 300 mg/m2 per day on days 1-3 of a 28-day cycle. Patients were randomized to supportive care or to receive GM-CSF at 250 mg/m2 per day, starting 24 hours after completion of chemotherapy and continuing up to 48 hours before the next cycle. Those who had received >6 months of previous therapy with an alkylating agent or had preexisting cytopenias received a 25% dose reduction. Twenty-two patients (65%) were randomized to receive GM-CSF. Patients completed a median of 5 cycles of treatment (range, 1-6 cycles). Twenty-seven patients (80%) received >or=3 cycles of treatment and were evaluated for response. RESULTS: Seven patients (26%) exhibited a complete response; 6 of the 7 had low-grade NHL. Fourteen patients (52%) exhibited a partial response, and 6 patients (22%) had stable disease. Notably, 6 of the 7 patients who exhibited complete response and 9 of 14 patients with partial responses were randomized to the GM-CSF arm. The duration of response ranged from 4 months to 26 months. The toxicities were mainly hematologic. Nineteen patients (70%) experienced >or=1 episode of grade 3/4 neutropenia, but only 4 (15%) experienced febrile neutropenia; 3 of those patients were assigned to the GM-CSF arm. CONCLUSIONS: The combination of fludarabine and cyclophosphamide is a well-tolerated and effective treatment regimen for patients with relapsed CLL and low-grade NHL. A higher percentage of complete responses were noted in patients with low-grade NHL compared with patients with CLL. Granulocyte-macrophage colony-stimulating factor did not seem to decrease the incidence of febrile neutropenia. However, the higher number of complete and partial responses noted on the GM-CSF arm is intriguing and warrants further investigation.

    Title Interruption of Aortic Arch in Adults: Surgical Experience with Extra-anatomic Bypass.
    Date October 2005
    Journal Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital
    Excerpt

    We reviewed our 3-year experience in treating interruption of the aorta in adult patients. Clinical profiles, surgical management, and results of early and mid-term follow-up are presented. From August 2001 through June 2003, 7 adult patients underwent an extra-anatomic bypass procedure to repair interruption of the aortic arch. Five patients underwent ventral aortic repair through a mid-sternotomy and an upper midline laparotomy, and 2 patients underwent repair through a left posterolateral thoracotomy. A bovine collagen-impregnated polyester fiber graft was used in 6 patients, and a Gore-Tex graft was interposed in 1 patient. All repairs were performed without cardiopulmonary bypass. Follow-up was complete in all patients. The mean follow-up was 1728 +/- 1 months (range, 9-31 months). No neurologic, renal, or gastrointestinal complications were noted in any patient. There was no in-hospital or late mortality or need for re-intervention. All patients were asymptomatic; however, 5 patients had mild residual hypertension. Graft patency in all the patients was confirmed by computed tomographic angiography. Interruption of the aorta is rare in adults. Ventral aortic repair through a midline approach is our preferred technique for surgical repair of this entity, because it avoids the extensive network of collateral vessels on the chest wall, enables simultaneous treatment of associated lesions, and in all likelihood reduces morbidity and mortality.

    Title Fibrinolytic Treatment for Recurrent Left Sided Prosthetic Valve Thrombosis.
    Date July 2005
    Journal Heart (british Cardiac Society)
    Title Postoperative Assessment of the Univentricular Repair by Dynamic Radionuclide Studies.
    Date May 2005
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The purpose of this investigation was to determine the role of radionuclide studies in evaluating postoperative Fontan hemodynamics and to quantify its diagnostic accuracy. METHODS: One hundred five patients (105), aged 11 months to 35 years old, who had undergone univentricular repair, underwent first-pass and multigated acquisition scan 1 month to 10 years after univentricular repair. Forty-five patients with evidence of Fontan failure underwent radionuclide studies using Technetium-99 m as well as cardiac catheterization (group 1). The remaining sixty randomly selected patients with excellent functional status received radionuclide studies alone (group 2). The receiver operating characteristic curve analysis was done to quantify the diagnostic accuracy of the first-pass study. RESULTS: There was paradoxical filling of the right lung after femoral injection in all cases of tunnel or conduit obstruction. A first-pass transit time of 16 to 25 seconds (mean +/- standard deviation [SD] = 18.82 +/- 2.69) was always associated with Fontan failure and high right atrial pressure (range = 20 to 24 mm Hg, mean +/- SD = 22.02 +/- 1.58). A first-pass transit time of 16 seconds was associated with a sensitivity of 100% and a specificity of 93.33%. The predictive accuracy of a positive or negative result was 91.8% and 100% respectively. The area measured under the receiver operating characteristic curve indicates that 99.41% (SE +/- 0.0035) of the time, the value of first-pass time is higher for the Fontan failure group (group 1) compared to the normal group (group 2; p = 0.000). CONCLUSIONS: Our data indicate that Fontan circuit can be reliably evaluated for both anatomic and functional flaws by radionuclide studies; radionuclide first-pass time may be used to predict the chances of Fontan failure postoperatively as well as its presence; and in the presence of atrial fibrillation with fast ventricular rate, analysis using first-pass radionuclide may be impossible and gated equilibrium radionuclide angiocardiography may be the preferred method. Inspection of the systemic ventricular time-activity curve is of crucial importance in this regard.

    Title Total Arterial Revascularization in a Child with Familial Homozygous Hypercholesterolemia.
    Date May 2005
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title Congestive Heart Failure in Unoperated Tetralogy of Fallot: Can Hypoxia Be a Cause?
    Date May 2005
    Journal Indian Heart Journal
    Excerpt

    A 10-year-old boy with tetralogy of Fallot and congestive heart failure underwent a right-sided modified Blalock-Taussig anastomosis because of severe biventricular dysfunction and repeated hypercyanotic spells. Postoperatively, there was improvement in systemic oxygen saturation and myocardial function. We postulate that congestive heart failure occurred because of severe myocardial hypoxia and its elimination resulted in markedly improved cardiac performance.

    Title Remicade As Tnf Suppressor in Patients with Myelodysplastic Syndromes.
    Date April 2005
    Journal Leukemia & Lymphoma
    Excerpt

    Remicade, a chimeric human-murine monoclonal antibody capable of neutralizing tumor necrosis factor alpha was given to 37 low-risk myelodysplastic syndromes (MDS) patients in two cohorts; 5 and 10 mg/kg intravenously every 4 weeks for 4 cycles. Median age was 68 years, 33 had primary MDS, 14 had refractory anemia (RA), 14 RA with ringed sideroblasts, 9 RA with excess blasts. Nine patients stopped therapy prior to completing 4 cycles, 3 from cohort 1 and 6 from cohort 2 and response was evaluated using the International Working Group criteria in 28 patients who completed the 4 cycles. Six patients showed disease progression, 14 had stable disease and 8 showed hematologic responses, 3/15 (20%) in cohort 1 and 5/13 (38%) in cohort 2. Two patients had multi-lineage responses, 2 had > 100% increase in absolute neutrophils, 1 had > 1 gm/dl increase in hemoglobin, 1 had reduction in blasts from 7% to 1%, and 2 had minor cytogenetic responses (> 50% reduction in + 8 and 20q-metaphases respectively). We conclude that Remicade may have a variety of activities in low risk MDS patients, is well tolerated with a high patient compliance, and may be considered for combination therapy in the future.

    Title Histopathology and Morphometry of Radial Artery Conduits: Basic Study and Clinical Application.
    Date February 2005
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The purpose of this study was to determine the pathohistology, morphometry, and risk factors for the development of intimal hyperplasia, calcification, and arteriosclerosis in the radial artery and to compare the morphometry of the distal and proximal radial arteries. METHODS: A total of 190 proximal and distal radial artery specimens obtained from patients who underwent myocardial revascularization were exposed to histopathologic and morphometric analysis. The severity of disease was evaluated on the basis of the percentage of luminal narrowing, intimal thickness index, and intima-to-media ratio. RESULTS: Sixty-two proximal (32.6%) and 22 distal (11.5%) radial artery segments were indicated as histologically normal. Morphometric analysis (Z test) revealed a lesser degree of intimal hyperplasia and luminal narrowing in the proximal segments compared with the distal segments (p < 0.001). The incidence of intimal hyperplasia, medial calcification, and arteriosclerosis in the distal radial arteries was 76.3%, 6.3%, and 5.78%, respectively. Using multivariate logistic regression, we have identified three significant predictors for intimal hyperplasia. Expressed as an odds ratio with a 95% confidence interval, these included (i) age greater than 50 years (1.052; 1.000-1.106, p = 0.052), (ii) smoking (14.073; 5.293-37.414, p = 0.000), and (iii) hypertension (2.777; 1.171-6.583, p = 0.020). Factors associated with an increased likelihood of medial calcification and arteriosclerosis included a history of smoking, diabetes, hypercholesterolemia, peripheral arterial disease, and chronic renal failure (p < 0.05). CONCLUSIONS: The great majority of radial artery conduits indicate preexisting intimal hyperplasia mostly affecting the distal portion. Therefore in cases of longer diseased segments of radial arteries, the discarded segments should be the distal end. Care should be taken when selecting radial artery as a conduit in myocardial revascularization, particularly in elderly males, diabetics, smokers, hypertensive patients, and in those with associated peripheral vascular disease.

    Title Mitral Valve Reconstruction: Early Results of a Modified Cooley Technique.
    Date February 2005
    Journal Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital
    Excerpt

    One hundred fifty consecutive patients (71 female, 79 male) underwent mitral valve reconstruction from February of 1987 through February of 1991 for mitral regurgitation, with or without mitral stenosis. Of these patients, 134 had rheumatic mitral disease and required 1 or more procedures for correction. One hundred twenty-eight patients were age 30 or under. A posterior semicircular annuloplasty was performed, with the repair buttressed by a collar of Teflon felt; in addition, commissurotomy, papillary muscle splitting, chordal shortening, chordal and papillary fenestration, and closure of acquired clefts were performed as needed. Pre- and postoperative assessment of mitral regurgitation was carried out with the aid of echocardiography. Operative mortality was 3.3% (5 patients), and late mortality was 1.3% (2 patients). There were 3 episodes of thromboembolism at follow-up (mean time of occurrence, 16 months).

    Title Surgical Outcome of Staged Univentricular-type Repairs for Patients with Univentricular Physiology and Pulmonary Hypertension.
    Date December 2004
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: There is no consensus about the most appropriate limits of pulmonary artery pressure and vascular resistance in case of patients undergoing univentricular or one and one-half ventricular repair. This study was conducted to analyze the mortality and morbidity of a heterogenous group of patients with a functionally univentricular heart and pulmonary artery hypertension, undergoing pulmonary artery banding followed by univentricular-type repairs. METHODS AND RESULTS: Out of 254 patients undergoing pulmonary artery banding for a functionally univentricular heart with increased pulmonary blood flow, 148 patients underwent definitive second stage surgery. Post-band hemodynamic evaluation revealed persistently high pulmonary artery pressure (> 18 mmHg), and pulmonary vascular resistance (>2.0 Woods units/m2) in 78.3% patients. Sixteen patients with moderate right ventricular hypoplasia were given a one and one-half ventricle repair (Group I), 82 patients a bidirectional Glenn connection (Group II), and 50 patients a fenestrated total cavopulmonary connection (Group III). The overall mortality following second stage surgery for the high pulmonary artery pressure group (n=116) was 30.17%, while none of the low pulmonary artery pressure group died (p=0.0009). Pulmonary hypertensive crises and/or systemic desaturation were the main causes of death at second stage repair. All mortality occurred in patients with mean pulmonary artery pressure > 18 mmHg and pulmonary vascular resistance > 3.5 Woods units/m2. Survivors from this group had persistent morbidity in the form of superior vena caval syndrome and suboptimal oxygen saturation (70-75%). CONCLUSIONS: It is advisable not to proceed with definitive second stage repair if post-pulmonary artery banding mean pulmonary artery pressure is over 25 mmHg and pulmonary vascular resistance exceeds 4.0 Woods units/m2. These patients may possibly be deemed to have undergone definitive palliation during their pulmonary artery banding.

    Title Redo Mitral Valve Surgery-a Long-term Experience.
    Date November 2004
    Journal Journal of Cardiac Surgery
    Excerpt

    BACKGROUND: Our experience with reoperative mitral valve (MV) surgery over a 27-year period is presented here. METHODS: From January 1975 to June 2002, 11,908 operations were performed for MV disease. Out of these 744 were reoperations. The mean age at primary operation was 23.6 +/- 10.1 years (range 2 to 53 years) and at reoperation was 36.0 +/- 11.0 years (range 6 to 65 years) with a mean interval of 11.5 +/- 2.5 years. Mitral valve replacement (MVR) was performed following previous closed mitral valvotomy (CMV) in 408 patients, open mitral commissurotomy (OMC) in 21 patients, and MV repair in 58 patients, MVR in 80 patients, homograft mitral valve replacement (HMVR) in 11 patients. The reasons for reoperation were mainly progression of lesions. Valve thrombosis and endocarditis were indications for reoperation following MVR. Twenty-eight patients underwent redo CMV, 53 patients underwent OMC, and 14 patients underwent MV Repair. RESULTS: Early mortality was 5.64% (n = 42). Hemorrhage and low cardiac output were the major causes. Follow-up was 124.8 +/- 30.5 months (2 to 300 months). Follow-up was 88%. There were no late deaths in the valve repair group. There were three episodes of thromboembolism in this group (0.3% per patient-year). In the valve replacement group there were six late deaths; three due to valve thrombosis, one due to infective endocarditis, and two due to anticoagulant-related hemorrhage. There were 13 episodes of thromboembolism in this group (0.6% per patient-year). CONCLUSION: Redo MV surgery is safe and can be undertaken with acceptable mortality and morbidity.

    Title Dose Comparison of Tranexamic Acid in Pediatric Cardiac Surgery.
    Date November 2004
    Journal Asian Cardiovascular & Thoracic Annals
    Excerpt

    To compare different doses of tranexamic acid, 150 consecutive children with congenital cyanotic heart disease were randomly assigned to one of 5 groups of 30 each. Group A served as a control. Group B received 50 mg.kg(-1) of tranexamic acid at induction of anesthesia. Group C received 10 mg.kg(-1) at induction followed by an infusion of 1 mg.kg(-1).h(-1). Group D had 10 mg.kg(-1) at induction, 10 mg.kg(-1) on bypass, and 10 mg.kg(-1) after protamine. Group E had 20 mg.kg(-1) at induction and again after protamine. The control group had the longest sternal closure time, the greatest blood loss in the first 24 hours, and the highest requirements for blood and blood products. Among the 4 groups given tranexamic acid, group D (triple dose) had the best results, followed by group E (double dose). Group B (single dose) had the worst results among the groups receiving tranexamic acid.

    Title Hemangioma of the Tricuspid Valve: a Report of Two Cases with Review of Literature.
    Date September 2004
    Journal Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
    Excerpt

    We describe two cases of hemangioma affecting the tricuspid valve (TV). One patient was a 47-year-old male who presented with recurrent episodes of dyspnea on exertion for 5 years. Echocardiography revealed an echo dense 1 x 1 cm mass attached to the chordae tendineae of the TV. Surgical excision was done and histopathology of the lesion showed features of hemangioma. The other case was a 1-day-old neonate with complex congenital abnormalities in whom multiple small hemangiomas affecting the TV were incidentally detected at autopsy.

    Title Arsenic Trioxide and Thalidomide Combination Produces Multi-lineage Hematological Responses in Myelodysplastic Syndromes Patients, Particularly in Those with High Pre-therapy Evi1 Expression.
    Date August 2004
    Journal Leukemia Research
    Excerpt

    Twenty-eight myelodysplastic syndromes (MDS) patients were treated with arsenic trioxide (ATO) and thalidomide. Seven patients responded including one complete hematologic and cytogenetic response and one with regression in spleen size. Two trilineage responses were seen in patients with inv(3)(q21q26.2). Three of five patients who had high pre-therapy EVI1 levels showed unexpectedly good responses while two died early in the first cycle. In vitro studies using 32Dcl3 cells forced to express EVI1 confirmed increased sensitivity of these cells to ATO. Both low/high risk MDS may benefit significantly from therapy with ATO/thalidomide, and those with high pre-therapy EVI1 expression may be uniquely sensitive.

    Title Minimally Invasive Pulmonary Artery Banding: a New Approach.
    Date May 2004
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: A variety of approaches have been described for banding of the pulmonary artery. The indications for this procedure are limited; however in developing countries, many patients still need pulmonary artery banding for a variety of reasons. We describe a new approach, minimally invasive, using only a split in the manubrium sterni to conduct the procedure. METHODS AND RESULTS: Between January 2000 and May 2002, 19 patients who had undergone pulmonary artery banding using a minimally invasive technique were compared with 20 cases of pulmonary artery banding performed by the conventional technique. The mortality was similar in the two groups (p=0.45). The period of intubation and duration of intensive care unit stay were significantly shorter in the minimally invasive group (p=0.015 and 0.002, respectively). The duration of hospital stay was not significantly different between the 2 groups (p=0.139). In the minimally invasive group, three patients underwent subsequent reoperation. CONCLUSIONS: Minimally invasive pulmonary artery banding is useful in babies with high-flow cardiac lesions and cardiac cachexia.

    Title Involvement of Cyclin D1 and E2f1 in Intramedullary Apoptosis in Myelodysplastic Syndromes.
    Date April 2004
    Journal Journal of Hematotherapy & Stem Cell Research
    Excerpt

    An unusually high incidence of apoptosis in S-phase cells is characteristically found in the bone marrow (BM) of patients with myelodysplastic syndromes (MDS). Previously, E2F1, c-myc, and Cyclin D1 have been shown to bring about both S-phase changes and/or apoptotic changes. We have already found a stoichiometric imbalance between pRb and E2F1 causing deregulated E2F1 activity in these disorders. In the present study, we investigated the status of Cyclin D1 in relation to E2F1 and apoptosis in 19 patients with a confirmed diagnosis of MDS in comparison with 6 healthy donors. Cyclin D1 was localized immunohistochemically using a specific monoclonal antibody (1:150 dilution) in plastic-embedded BM sections. The nuclear localization of Cyclin D1 graded on a subjective rating scale of 0 (negligible staining) to 8+ (highest), demonstrated negligible levels in normal marrows (median 1+), and in 11/19 evaluable MDS marrows. In contrast, 8/19 MDS biopsies showed an almost four-fold increase in Cyclin D1 localization (p< or =0.001). A western blot analysis of E2F1 in corresponding bone marrow (BM) aspirate mononuclear cells (MNC) demonstrated that the MDS patients with elevated Cyclin D1 expression also had a significant increase in E2F1 protein (p< or =0.03). Additionally, these patients revealed higher levels of mRNA of one of the E2F1 transcriptional target genes, dihydrofolate reductase (DHFR, p=0.01). Subsequently, the relationship of Cyclin D1 with apoptosis was elucidated in a colocalization experiment in BM biopsy sections using immunohistochemistry for Cyclin D1 and in situ end labeling of DNA (ISEL) for apoptosis. The percentage of ISEL-positive apoptotic cells was several fold higher in MDS as compared to normal BMs (p=0.009). Interestingly, 7-41% (median 20%) of the apoptotic cells in different MDS BMs revealed co-localization of Cyclin D1 in their nucleus, whereas in normal BMs co-localization was virtually absent (p=0.008). Thus, it is possible that in a subset of MDS patients, apoptotic death of bone marrow cells may involve Cyclin D1/E2F1 pathway.

    Title Radioactive Seed Localization Breast Biopsy and Lumpectomy: Can Specimen Radiographs Be Eliminated?
    Date February 2004
    Journal Annals of Surgical Oncology
    Excerpt

    BACKGROUND: Wire localization (WL) is the current standard for surgical diagnosis of nonpalpable breast lesions. Many disadvantages inherent to WL are solved with radioactive seed localization (RSL). This trial investigated the ability of RSL to reduce the need for specimen radiographs and operating room delays associated with WL. METHODS: A total of 134 women were entered onto an institutional review board-approved study. RSL was performed by placing a titanium seed containing.29 to 20 mCi of iodine-125 to within 1 cm of the suggestive breast lesion. The surgeon used a handheld gamma detector to locate and excise the iodine-125 seed and the lesion. RESULTS: Specimen radiographs were eliminated in 98 (79%) of 124 patients. Surgical seed retrieval was 100% in 124 patients. No seed migration occurred after correct radiographical placement. A total of 26 (21%) of 124 patients required a specimen radiograph; 22 (85%) of these 26 were performed for microcalcifications. CONCLUSIONS: After surgical removal, RSL can eliminate specimen radiographs when the radiologist accurately places the seed and the pathologist grossly identifies the lesion. If small microcalcifications are noted before surgery, then specimen radiographs may be necessary. RSL reduced requirements for specimen radiographs, decreased OR time, improved incision placement, and improved resections to clear margins.

    Title Cardiac Myxoma with Glandular Elements: a Histologic, Histochemical, and Immunohistochemical Evaluation.
    Date September 2003
    Journal Indian Heart Journal
    Excerpt

    Epithelial differentiation in cardiac myxoma is a rare phenomenon. Out of 104 surgically excised specimens, we studied 3 cases of cardiac myxoma with glandular differentiation. All the cases had well formed glands in addition to the myxoma cells lying in a myxoid background. Detailed histochemical and immunohistochemical studies suggest that the epithelial islands in cardiac myxoma show an enteric phenotype.

    Title Dissecting Aneurysms of the Interventricular Septum.
    Date August 2003
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Title Modified Circuit for Retrograde Cerebral Perfusion.
    Date August 2003
    Journal Asian Cardiovascular & Thoracic Annals
    Excerpt

    A modified circuit for delivery of retrograde cerebral perfusion during ascending aortic or aortic arch surgery is described. The technique was applied in 15 patients who showed good postoperative recovery.

    Title A Novel Method for Single Cell Detection of in Situ Telomerase or Histone H3 in Combination with Clonal Analysis by Fish.
    Date June 2003
    Journal Leukemia Research
    Excerpt

    A novel method for simultaneously detecting clonality by FISH, and presence of telomerase activity (telo+ cells) or histone H3 mRNA (H3+) in single cells from a mixed leukemic population is reported. The methods were validated using K562 cells mixed with peripheral blood granulocytes and bone marrow aspirate cells from newly diagnosed AML patients. Fifty patients with AML were analyzed for telo+ cells, while eight AML patients were analyzed for FISH-Telomerase and FISH-H3+ during remission induction therapy. Our results demonstrate that: (1). changes in the leukemic populations during therapy could be followed; (2). a favorable response to chemotherapy occurred when there was a reduction in both the cytogenetically abnormal cells along with reduction in telo+ cells within this abnormal population; (3). reduction of either telo+ cells or FISH+ cells alone did not correlate with good response. H3+ could be detected in only 4% of the leukemic population, most of which were cytogenetically abnormal. These newly established methods allow sub-populations of cells to be followed during disease progression and treatment and to elucidate factors that give a specific clone proliferative advantage.

    Title Ten-year Experience with the Arterial Switch Operation.
    Date April 2003
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: Arterial level repair is considered the most appropriate procedure for transposition of the great arteries. This report describes our experience with the arterial switch operation over the past decade. METHODS AND RESULTS: From January 1991 to January 2001, a total of 299 patients underwent an arterial switch operation for transposition of the great arteries or double-outlet right ventricle. Group I (n=169, 56.5%) comprised patients with transposition of the great arteries in whom the ventricular septum was essentially intact. Group II patients (n=130, 43.5%) had transposition of the great arteries with an additional significant ventricular septal defect or had double-outlet right ventricle with a subpulmonic ventricular septal defect. Of the total, 245 (82%) were males and 54 (18%) were females. In group I, the ages ranged from 2 days to 18 years (median 19 days) and weight ranged from 1.7 to 68 kg (median 2.5 kg). In group II, the ages ranged from 4 days to 4 years (median 90 days) and weight ranged from 2.5 to 17 kg (median 4 kg). Fifteen percent of the patients (25/169) in group I and 30% of the patients (39/130) in group II had features of bacteriologic infection. Arterial switch operation was performed on standard lines. In group I, 141 patients (83.4%) had a primary arterial switch operation while 28 (16.6%) underwent a rapid two-stage repair. Twenty-three patients required concomitant relief of associated anatomic left ventricular outflow tract obstruction. Operative mortality was 8.8% (15/169) in group I and 33% (44/130) in group II with an overall mortality of 19% (59/299). The major causes of operative mortality included pulmonary arterial hypertensive crisis (n=21), sepsis and related complications (n=16), and left ventricular failure (n=8). Coexisting arch anomalies, longer cross-clamp time, late presentation, and preoperative bacteriologic infections were incremental risk factors. Follow-up ranged from 1 to 10 years and was 87% complete. On follow-up, 91% of the patients were asymptomatic and off all medications. There were 3 late deaths and 5 patients required reoperation. CONCLUSIONS: Excellent long-term results are obtained in operative survivors following the arterial switch operation. However. operative mortality remains a concern in our set-up.

    Title Late Outcome After Arterial Switch Operation for Complete Transposition of Great Arteries with Left Ventricular Outflow Tract Obstruction.
    Date March 2003
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Long-term follow-up of patients who underwent arterial switch operation for complete transposition of great arteries with anatomic left ventricular outflow tract obstruction (LVOTO) has rarely been brought into the focus. METHODS: Of 299 patients who underwent an arterial switch operation between January 1991 and January 2001, 23 patients had anatomic LVOTO. Age ranged from 4 days to 18 years (median 90 days) and weight ranged from 2.6 to 35 kg (median 4.3 kg). Surgical management included arterial switch operation, closure of ventricular septal defect wherever indicated, and excision of LVOTO. RESULTS: Among patients with preoperative LVOTO there were 2 early deaths and 8 patients had mild neoaortic regurgitation at the time of discharge. Follow-up ranged from 8 months to 9 years (mean 60 +/- 12 months). In 4 patients who had mild neoaortic regurgitation at discharge, the regurgitation progressed to moderate or severe degree after a follow-up of 22 to 72 months. In 1 patient mild mitral regurgitation present at the time of discharge progressed to severe mitral regurgitation. This patient subsequently underwent double valve replacement. CONCLUSIONS: Presence of preoperative anatomical LVOTO in patients undergoing arterial switch operation predicts high incidence of postoperative neoaortic regurgitation.

    Title Medium-term Outcome of Anatomically Repaired Congenitally Corrected Transposition: the Double Switch Operation.
    Date February 2003
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: The double switch operation is emerging as the procedure of choice for congenitally corrected transposition of the great arteries. However, rhythm disturbances in the postoperative period are rarely discussed. METHODS AND RESULTS: Eighteen survivors who underwent corrective surgery for congenitally corrected transposition of the great arteries were followed up. Patients in group I (n=8), who also had a ventricular septal defect and pulmonary stenosis, had undergone the Senning plus Rastelli operation. Patients in group II (n=10), who did not have pulmonary stenosis, had undergone the Senning and arterial switch operation. The patients were followed up by periodical clinical examination, echocardiography and 24-hour Holter monitoring. In group I, follow-up ranged from 24 to 66 months (mean 44 months). There was no late death and all the patients are symptom free. There was no significant atrioventricular valve regurgitation and left ventricular function was normal. There were no rhythm disturbances. In group II, follow-up ranged from 2 to 72 months (mean 48 months). There were 2 late deaths due to atrial tachyarrhythmia and residual pulmonary hypertension 36 and 8 months after the procedure, respectively. One patient had significant mitral regurgitation and required mitral valve replacement. Three patients had recurrent atrial/junctional tachyarrhythmia: one of them was lost to follow-up after 1 year while another died of resistant atrial tachyarrhythmia. The third patient underwent mitral valve replacement for severe mitral regurgitation and developed complete heart block necessitating a permanent pacemaker implantation. CONCLUSIONS: Though good long-term results are obtained following the double switch operation, the problem of atrial arrhythmias still needs to be addressed suitably.

    Title Left Ventricle is Better Suited As Pulmonary Ventricle in Simple Transposition with Severe Pulmonary Hypertension.
    Date December 2002
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The conventional treatment of transposition of great arteries with prepared left ventricle is an arterial switch operation. This, in our experience, does not hold for patients with transposition of great arteries with intact ventricular septum where the left ventricle continues to be prepared secondary to severe pulmonary arterial hypertension without an immediately reversible cause. METHODS: Ten infants with D-transposition of the great arteries with essentially intact interventricular septum and severe pulmonary arterial hypertension underwent surgical treatment. Age ranged from 3 to 6 months (mean, 4.2 months). One of these patients had a large ductus with left to right shunting but the others had no intra- or extracardiac shunt to account for their pulmonary hypertension. All 10 had "prepared" left ventricles. The first 4 children underwent an arterial switch operation. Uneventful surgery was followed by prolonged ventilator dependence in all 4 with occurrence of severe pulmonary arterial hypertension every time weaning from ventilator was attempted. This was accompanied by metabolic acidosis and features of right heart failure. Only 1 patient with large ductus could be extubated and discharged from hospital. Subsequently, the other 6 infants underwent a Senning repair. RESULTS: There was no early mortality. All patients were separated from mechanical ventilation within 48 hours of surgery without blood gas derangement or heart failure despite elevated pulmonary artery pressure in all. The child with the arterial switch operation has pulmonary artery pressure of 50% systemic 4 years following repair; although among the Senning group, 2 patients continue to have pulmonary artery pressure more than 60% of systemic and 4 have normal pulmonary artery pressure at a mean follow-up of 1 year. CONCLUSIONS: Atrial level repairs seem to perform better than arterial level repairs in children having TGA with persistent pulmonary artery hypertension without a correctable cause. Better tolerance of pulmonary arterial hypertension in this group is probably consequent to the superior ability of the left ventricle to tolerate a pressure load in the early postoperative period.

    Title The Class Certification of Medical Monitoring Claims.
    Date November 2002
    Journal Columbia Law Review
    Excerpt

    The tort claim of medical monitoring has produced a disarrayed set of state and federal court opinions. The procedural dimensions of this claim are as vexing as the related substantive issues with which courts and commentators have long been grappling. Ordinarily, mass tort actions, typically involving claims for money damages, are certified under Rule 23(b)(3), which class category requires the right to notice and to opt out of a proceeding, and the fulfillment of "predominance" and "superiority" requirements. Such features are absent in Rule 23's mandatory classes. Nevertheless, this Note argues that it is appropriate for claims exclusively for medical monitoring to be certified as a mandatory class action under Rule 23(b)(2) of the Federal Rules of Civil Procedure or its state law counterparts. Given that a medical monitoring fund is an equitable remedy, nonpreclusive of a future damages claim, and groupwide in nature, the (b)(2) class category adequately protects the due process rights of class plaintiffs.

    Title Diaphragmatic Fenestration for Resistant Pleural Effusions After Univentricular Repair.
    Date September 2002
    Journal The Annals of Thoracic Surgery
    Excerpt

    A 12-year-old child with chronic pleural effusions for a month and a half after a fenestrated Fontan operation underwent bilateral diaphragmatic fenestrations with complete relief. We suggest this approach as an alternative treatment for chronic pleural effusions that may ensue after total cavopulmonary connection.

    Title Simplified Technique for Retrograde Cerebral Perfusion During Repair of Distal Aortic Arch and Proximal Descending Thoracic Aorta.
    Date September 2002
    Journal The Annals of Thoracic Surgery
    Excerpt

    Lesions of distal aortic arch and proximal descending thoracic aorta require a posterolateral thoracotomy approach and total circulatory arrest. Retrograde cerebral perfusion through the superior vena cava is technically difficult in such situations. We describe a simplified technique for delivery of retrograde cerebral perfusion through the left internal jugular vein.

    Title Retrograde Cerebral Perfusion.
    Date August 2002
    Journal The Annals of Thoracic Surgery
    Title Ventricular Septal Defect with Congenital Mitral Valve Disease: Long-term Results of Corrective Surgery.
    Date June 2002
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: A retrospective analysis of the mortality, morbidity and long-term follow-up of patients undergoing corrective surgery for ventricular septal defect and congenital mitral valve disease is presented. METHODS AND RESULTS: Between January 1991 and December 2000, 69 consecutive patients aged 2 months to 45 years (median 18 months) underwent repair of ventricular septal defect and associated mitral valve disease. In 52 patients (75%), the ventricular septal defects were located in the perimembranous and subarterial area. Forty-six patients had congenital mitral incompetence and 23 had congenital mitral stenosis. The ventricular septal defect was repaired through the right atrium in all. Sixty-five patients underwent reconstruction of the mitral valve and 4 underwent primary mitral valve replacement. Another 4 patients underwent mitral valve replacement after a failed repair. Associated procedures included: patent ductus arteriosus ligation (n=12), aortic valve replacement (n=6), coarctation repair (n=13), interrupted aortic arch repair (n=1), atrial septal defect closure (n=17) and Takeuchi repair (n=1). There were 6 early deaths (8.6%). Three deaths were due to pulmonary arterial hypertensive crisis and one due to residual mitral stenosis. One death was due to intractable congestive heart failure. Another patient died due to persistent low cardiac output. Follow-up ranged from 6 months to 120 months (mean 64.4+/-33.6 months). Reoperation was required in 22 patients, mainly for recurrent/residual mitral valve dysfunction or hemodynamically significant left ventricular outflow tract obstruction. There were 4 late deaths, 2 due to residual mitral stenosis and the other 2 as a result of a thrombosed prosthetic valve. At 10 years, the actuarial survival rate was 850+/-5.0%, and freedom from reoperation was 45%+/-10.0%. CONCLUSIONS: Reconstruction of the mitral valve along with closure of VSD is possible in most cases. However, careful follow-up is recommended to detect changes in the mitral valve status over a course of time.

    Title Special Clinical Concerns/problems in the Management of Mds and Secondary Acute Myeloid Leukemias.
    Date May 2002
    Journal Cancer Treatment and Research
    Title Infective Complications of Central Venous Catheters in Cardiac Surgical Patients.
    Date April 2002
    Journal Indian Journal of Pathology & Microbiology
    Excerpt

    Prospective randomised study was conducted over a 24 months period in a cardiac surgical intensive care unit to determine the incidence of infection associated with multilumen venous catheters. The influence of various factors including fever, peripheral blood culture, catheter site, catheter usage for monitoring central venous pressure and/inotrope therapy on infection rates were statistically evaluated. A total of 100 catheters submitted to the Microbiology laboratory were bacteriologically examined. Forty-nine of these were inserted into upper body sites, and 51 were inserted into the femoral vein. Twenty-one were triple-lumen catheters. Catheters were removed when a central line was no longer necessary. Catheter tips were cultured by semiquantitative technique for aerobic and anaerobic bacteria. Bacteremia occurred in 3% of catheter insertions; (Enterococcus faecalis, one; Enterobacter spp. One; Acinetobacter spp., one); and catheter colonisation developed in 24%. Neither catheter colonisation nor catheter related infection were associated with any of the risk factors evaluated. Our data indicates that central venous catheters are safe to use in our patients. The inability to identify "risk factors" for catheter infection emphasise the need to maintain a high index of suspicion.

    Title Total Anomalous Pulmonary Venous Connection: Surgical Experience in Indians.
    Date March 2002
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: We report a retrospective analysis of the demographic. morphological and clinical profiles of patients along with results of operative repair for total anomalous pulmonary venous connection. METHODS AND RESULTS: In the last 15 years, 248 patients (168 boys, 80 girls) underwent repair for total anomalous pulmonary venous connection. Their ages ranged from I day to 24 years (median 8 months) and 145 of them were < or = 1 year of age. The patients' weight ranged from 2 to 52 kg (median 5 kg). About 70% of patients (n = 174) were less than the 50th percentile of predicted weight for age and sex. The anomalous connection was supracardiac in 134 (54%), cardiac in 80 (32.2%), infracardiac in 9 (3.6%) and mixed in 25 (10.1%) patients. Fifty (20.2%) patients had obstructed drainage and 76 patients (30.2%) had moderate or severe pulmonary arterial hypertension. Forty-five patients (18.1%) had to be operated upon on an emergency basis. All the patients were operated upon using moderately hypothermic cardiopulmonary bypass. In 114 patients, circulatory arrest was used. There were 45 (19.1%) in-hospital deaths. The major causes of early death were pulmonary arterial hypertensive crisis in 19 (7.7%) and low cardiac output syndrome in 17 (6.9%) patients. Age < or = 1 year (odds ratio 2.16; 95% confidence interval: 1.22-3.82, p=0.008), severe pulmonary arterial hypertension (odds ratio 5.86; 95% confidence interval: 2-17, p=0.001), and need for emergency surgery (odds ratio 3.65; 95% confidence interval: 1.59-8.38, p=0.002) were independent risk factors for early death. Follow-up ranged from 1 to 180 months (median 48 months). There were 4 lake deaths. Actuarial survival at 12 years was 92.6% +/- 2.8%. CONCLUSIONS: In Indian circumstances, mortality continues to be high in infants with total anomalous pulmonary venous connection. Severe pulmonary arterial hypertension appears to be the most important predictor of operative mortality. Severe malnutrition, delayed diagnosis and late referrals possibly contribute to the high mortality.

    Title Juxtaductal Coarctation with Type B Dissection of the Aorta: a New Operative Technique.
    Date March 2002
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title The Clinical and Biological Effects of Thalidomide in Patients with Myelodysplastic Syndromes.
    Date March 2002
    Journal British Journal of Haematology
    Excerpt

    Thirty patients with myelodysplastic syndromes (MDS) were treated with thalidomide at 100 mg/d p.o., increased as tolerated to 400 mg/d for 12 weeks. Levels of apoptosis, macrophage number, microvessel density (MVD), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), interleukin 6 (IL-6), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were determined in the serum, bone marrow (BM) plasma and BM biopsies before and after therapy. Pretherapy biological characteristics of MDS patients were compared with similar studies performed in 11 normal volunteers. Ten patients demonstrated haematological improvement in the erythroid series, six becoming transfusion independent. Responders had a higher pretherapy platelet count (P < 0.048) and lower BM blasts (P < 0.013). Median time to response was 10 weeks, and four remain in remission beyond a year. Pretherapy MDS BMs showed higher MVD (P < 0.001) and TGF-beta (P < 0.03) and higher serum TNF-alpha (P < 0.008) compared with normal control subjects. After therapy, only BM TGF-beta decreased significantly (P < 0.002). Pretherapy haemoglobin was directly related to serum VEGF (P < 0.001) in responders and inversely related in non-responders (P < 0.05), suggesting the possibility that angiogenesis may be a primary pathology in the former and a consequence of anaemia-induced hypoxia in the latter. We conclude that thalidomide has important clinical and biological effects in at least a subset of MDS patients, but the precise mechanism of its action remains unknown and requires further study including a larger number of patients.

    Title P15ink4b Gene Methylation and Expression in Normal, Myelodysplastic, and Acute Myelogenous Leukemia Cells and in the Marrow Cells of Cured Lymphoma Patients.
    Date February 2002
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    P15INK4B methylation and expression was studied in bone marrow cells obtained from normal individuals, from patients who had been cured of lymphoma, and from patients with either MDS or AML. The level of p15 methylation was very low in normal BM cells and in CD34+ and CD34- subpopulations (0-6.5%; med, = 2.5%). P15INK4B transcripts were present in each of these cell populations. In contrast, methylation was the usual situation in MDS and AML marrows. The presence of methylation of the p15INK4B gene did not always indicate an absence of expression nor was expression always present if methylation was absent. P15INK4B methylation was studied in the marrows of nine patients (one studied twice) who had been cured of lymphoma and in whom hemopoiesis was believed to be normal. Increased methylaton was present in all 10 marrows. These data indicate that p15INK4B methylation is likely to be a very early event in the development of the secondary hematologic disorders.

    Title Effectiveness of Interferon-alfa and Mid-cycle Chemotherapy Added to an Anthracycline-based Regimen in the Treatment of Aggressive Non-hodgkin's Lymphoma.
    Date February 2002
    Journal Leukemia & Lymphoma
    Excerpt

    Interferon-alfa in combination with cytotoxic chemotherapy has been shown to be effective in treating certain types of non-Hodgkin's lymphoma (NHL) (1). However, there is no published data on upfront induction treatment of aggressive NHL with IFN-alfa containing regimens. Studies have also shown that one can overcome regrowth resistance by administering mid-cycle agents which slow tumor proliferation between courses of cytotoxic therapy (2). Based on this, we treated 32 consecutive patients between 1/93 and 9/96 with a regimen containing cyclophosphamide 750 mg/m2, mitoxantrone 12 mg/m2, and teniposide 60 mg/m2 IV on day 1 with prednisone 100 mg PO given on days 1-5. On day 15, patients received vincristine 1.4 mg/m2 (2 mg max.) and bleomycin 10 units/m2 IV. Interferon-alfa-2b 5x10(6) units/m2 SQ was administered on days 22-26. The median age was 55 (range 26-83), M:F ratio was 2.5:1, and the median International Prognostic Index was 2. 38% of patients had stages I-II and 62% had stages III-IV disease. Fifty-nine percent of the patients achieved a complete response, 22% a partial response, and 19% had progressive disease. The overall survival (OS) was 81% and the progression free survival (PFS) was 56% at 4.3 years. There were no severe (grade IV) hematologic, flu-like, GI and infectious toxicities from IFN-alpha. Leukopenia was the main severe toxicity related to the chemotherapy regimen (days 1-15), but not IFN-alpha. Severe infection secondary to the chemotherapy regimen occurred in one patient. Interferon-alfa-2b and mid-cycle chemotherapy added to an anthracycline based regimen is effective induction treatment for patients with aggressive NHL. The OS and PFS using this regimen, based on regrowth resistance, appears to be at least as or more effective than CHOP therapy for this group of patients. Severe toxicities were rare.

    Title Tubercular Pseudoaneurysms of Aorta.
    Date December 2001
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Tubercular pseudoaneurysm of aorta is a rare but important complication of tuberculosis. With worldwide resurgence of tuberculosis due to increasing incidence of drug-resistant tuberculosis and its association with acquired immunodeficiency syndrome, the tubercular pseudoaneurysm has become a real clinical entity. METHODS: In the past 3 years, 5 young patients (22 to 40 years) presented with tubercular pseudoaneurysm. Site of involvement included ascending aorta, distal aortic arch, proximal descending thoracic aorta, distal descending thoracic aorta, and infrarenal abdominal aorta. Two patients had macroscopic focus of tuberculosis in the nearby vicinity, and all 5 patients had evidence of active/treated pulmonary pericardial tuberculosis. All patients either had received antitubercular therapy previously or were receiving it at the time of presentation. Rapid deterioration in the clinical status was the most marked clinical feature. All patients underwent operation. Graft interposition was performed in 2, patch repair in 2, and direct closure of the rent was performed in 1 patient. All 5 patients received antitubercular therapy in the postoperative period. RESULTS: All patients survived the operation and were discharged from the hospital. One patient developed recurrence at the original site after 8 months and died at reoperation. The remaining patients are symptom free at 18 to 36 months postoperatively. CONCLUSIONS: A combination of chemotherapy and operation yields gratifying results for the treatment of tubercular pseudoaneurysm.

    Title Alterations in Irf1/irf2 Expression in Acute Myelogenous Leukemia.
    Date October 2001
    Journal American Journal of Hematology
    Excerpt

    The interferon response genes 1 and 2 have been shown to be involved in the regulation of differentiation and proliferation of cells of the myeloid series, with the former functioning as an anti-oncogene and the latter as an oncogene. In the study described here, the levels of expression of these two genes and the ratio of their expression were compared in AML and normal marrow. The ratio of gene expression was significantly less in AML marrow cells as compared to normal marrow cells [med ratio = 1.33 vs. 2.97, P = 0.003]. While the expression ratio was unaffected by the presence or absence of either ras or fms mutations, p53 mutations were associated with higher IRF1:IRF2 expression ratios that wt p53 genes [med = 1.701 vs. 1.135, P = 0.014]. Given the functional characteristics and the competitive nature of these two genes, it is possible that leukemic transformation is associated with a fall in IRF1:IRF2 ratios. Finally, the administration of IL4 can result in the normalization of the IRF1:IRF2 ratio in the marrow cells of some patients with AML.

    Title Thalidomide Produces Transfusion Independence in Long-standing Refractory Anemias of Patients with Myelodysplastic Syndromes.
    Date September 2001
    Journal Blood
    Excerpt

    Thalidomide was administered to 83 patients with myelodysplastic syndrome (MDS), starting at 100 mg by mouth daily and increasing to 400 mg as tolerated. Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy. International Working Group response criteria for MDS were used to evaluate responses. Intent-to-treat (ITT) analysis classified all off-study patients as nonresponders. Off-study patients belonged to a higher risk category (P =.002) and had a higher percentage of blasts in their pretherapy bone marrow than patients who completed 12 weeks of therapy (P =.003). No cytogenetic or complete responses were seen, but 16 patients showed hematologic improvement, with 10 previously transfusion-dependent patients becoming transfusion independent. Responders had lower pretherapy blasts (P =.016), a lower duration of pretherapy platelet transfusions (P =.013), and higher pretherapy platelets (P =.003). Among responders, 9 had refractory anemia (RA); 5 had RA with ringed sideroblasts; and 2 had RA with excess blasts. By ITT analysis, 19% of patients (16 of 83) responded, and when only evaluable patients were analyzed, 31% (16 of 51) responded. It was concluded that thalidomide, as a single agent, is effective in improving cytopenias of some MDS patients, especially those who present without excess blasts. (Blood. 2001;98:958-965)

    Title Surgical Experience with Dissecting and Nondissecting Aneurysms of the Ascending Aorta.
    Date September 2001
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: Patients who underwent replacement of the ascending aorta with a prosthetic graft for treatment of ascending aortic aneurysm and dissection between January 1992 and December 2000 were studied. METHODS AND RESULTS: Bentall's operation, using a composite aortic valve and prosthetic graft. was performed in 82 patients (70 males). Indications for the procedure included ascending aortic aneurysm (n=54 including 16 patients with Marfan's syndrome): DeBakey Type I or II aortic dissection (n=26 including 10 patients with Marfan's syndrome) and ascending aortic aneurysm with severe aortic stenosis (bicuspid aortic valve disease) (n=2). Bentall's procedure with the inclusion technique was performed in 72 patients and a Cabrol fistula created in 63 patients. In 10 other patients, coronary button transfer was done without a Cabrol fistula. There were 6 early deaths (7.3%) and 8 patients required re-exploration for excessive bleeding. Eighteen patients showed low cardiac output while the wound of 8 became infected. Postoperative arrhythmia and renal failure was seen in 26 and 6 patients, respectively. Four patients had pericardial effusion. Follow-up ranged from 1 month to 8 years. There were 8 late deaths, the causes of which include congestive heart failure (n=3). cerebral hemorrhage (n=3) and sudden cardiac death (n=2). Two patients reported back with dissection of the descending thoracic aorta and await surgery. CONCLUSIONS: Bentall's operation is a safe procedure with an acceptable mortality and morbidity.

    Title Poor Prognosis Acute Myelogenous Leukemia: 3--biological and Molecular Biological Changes During Remission Induction Therapy.
    Date August 2001
    Journal Leukemia Research
    Excerpt

    This is the third paper in a series which describes a new remission induction regimen for patients with 'poor prognosis' acute myelogenous leukemia (AML). Twenty-four patients were treated with two one day pulses of chemotherapy separated by 96 h. Each pulse consisted of two doses of cytarabine and a single dose of mitoxantrone. Amifostine was administered three times a week after the second pulse of chemotherapy until treatment outcome became known. The first paper described the outcome of treatment while the second described the relationship of treatment outcome to the pretherapy characteristics of the leukemia. This paper describes the changes in the leukemia cells which occur during remission induction therapy. While only a limited number of specimens were available for each post treatment study, the studies demonstrated a profound fall in blood counts, BM cellularity, and telomerase activity in leukemia cells after pulse #1 of treatment. This fall was usually accompanied by a coordinate rise in IL6, TNFalpha, and IL1beta transcripts within the AML cells which survived chemotherapy. High levels of telomerase activity in the day 5 marrow was correlated with high levels of IL1beta transcripts which in turn were associated with treatment failure ascribable to resistant disease.

    Title In Vivo Effects of Il-4, Il-10, and Amifostine on Cytokine Production in Patients with Acute Myelogenous Leukemia.
    Date August 2001
    Journal Leukemia & Lymphoma
    Excerpt

    Both IL-4 and IL-10 have been shown in vitro to inhibit leukemia cell secretion of IL-1beta, GM-CSF, and TNFalpha, and increase leukemia cell release of IL-1ra. In this study, we have investigated the in vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia (AML). Serum IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF levels were measured in AML patients who received IL-4, IL-10, or amifostine. No significant changes in the serum levels of IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF were found in AML patients who received amifostine. Both IL-4 and IL-10 were found to increase serum IL-1ra. This data is in accord with the in vitro studies. However, IL-4 increased serum GM-CSF levels and IL-10 increased serum IL-1beta and TNFalpha levels. These in vivo effects of the two cytokines differ from their in vitro effects. Despite the similar effects of IL-4 and IL-10 on cytokine production by AML cells in vitro, different effects were observed in AML patients in vivo. IL-4 increased serum SCF levels, whereas IL-10 decreased serum SCF levels. IL-4 increased serum GM-CSF levels, whereas IL-10 had no effect on them. Although IL-10 increased serum IL-1beta and TNFalpha levels, IL-4 had no effect on them. These findings indicate that the in vitro effects of IL-4 and IL-10 do not necessarily reflect their in vivo effects, and that the complex effects of the two cytokines on serum cytokine levels make it difficult to predict their therapeutic potential.

    Title High Remission Rate in Acute Myeloblastic Leukemia with Only Two Days of Chemotherapy.
    Date August 2001
    Journal Leukemia & Lymphoma
    Excerpt

    Twenty five patients with AML who had neither a history of toxic exposure or myelodysplasia were treated with a remission induction regimen consisting of two pulses of chemotherapy separated by 96 hrs. Each pulse consisted of cytarabine 2gm/m(2) (at t=0 and t=12 hrs) with mitoxantrone [30mg/m(2) ] administered immediately after the second cytarabine administration. Amifostine was administered three times a week [on Monday, Wednesday, and Friday] until the outcome of therapy was known. This regimen induced complete remissions in 15 of 17 patients less than 70 years of age and in 5 of 8 patients older than 70 years.

    Title Fatal Atypical Mycobacterial Infection in a Cardiac Transplant Recipient.
    Date August 2001
    Journal Indian Heart Journal
    Excerpt

    A 37-year-old female underwent heart transplantation for giant cell myocarditis. The patient died within three-and-a-half months of cardiac transplantation. Postmortem specimens from the heart and lung showed multiple necrotizing granulomas with numerous acid-fast bacilli. Polymerase chain reaction done on both the postmortem samples confirmed the presence of atypical mycobacterial infection. This fatal case of atypical mycobacteriosis in a cardiac transplant patient is reported for its rarity.

    Title Does Inhaled Nitric Oxide Improve Survival in Operated Congenital Disease with Severe Pulmonary Hypertension?
    Date August 2001
    Journal Indian Heart Journal
    Excerpt

    BACKGROUND: The present study aimed to assess the impact of inhaled nitric oxide on survival following correction of congenital heart defects with residual pulmonary arterial hypertension. METHODS AND RESULTS: Inhaled nitric oxide was utilized for the management of residual pulmonary hypertension in 24 children following surgical correction of their underlying heart defects. Their ages ranged from 15 days to 14 months (median 5 months). Pulmonary artery hypertension was diagnosed either by direct pulmonary artery pressure monitoring or by echocardiography. Inhaled nitric oxide was used electively in 22 patients when the ratio of the mean pulmonary arterial pressure and mean systemic arterial pressure exceeded 0.5. In the remaining 2 patients, nitric oxide was used only to manage a pulmonary hypertensive crisis. Inhaled nitric oxide was also used a second time in 2 patients who developed delayed pulmonary hypertensive crisis. Twenty-two patients showed an initial response to therapy and the pulmonary artery pressures dropped significantly. Of the patients on direct pulmonary artery pressure monitoring, a pulmonary artery to systemic artery pressure ratio below 0.3 on prolonged therapy was associated with a survival ratio of 4/6 (including 1 neurological death and one reoperation); that between 0.3 and 0.5 with a survival ratio of 3/4. Three out of four patients with sustained echocardiographic and clinical response also survived and were discharged from the hospital. All the patients who showed a lack of response to (n=2), tolerance to (n=1), or dependence on (n=6) the use of inhaled nitric oxide died. In addition, all 5 patients who had a pulmonary hypertensive crisis died, 3 in spite of successful resuscitation with nitric oxide. Thus, excluding one neurological death and one re-operation, only 9 (41%) out of 22 patients survived. CONCLUSIONS: Though inhaled nitric oxide is effective in lowering pulmonary pressure, it does not appear to improve the survival rate following repair of congenital heart disease in those with associated severe pulmonary hypertension. A randomized trial between the use and non-use of inhaled nitric oxide is warranted to determine its exact role in influencing survival in patients with residual pulmonary hypertension following surgical repair.

    Title One and a Half Ventricle Repair with Pulsatile Bidirectional Glenn: Results and Guidelines for Patient Selection.
    Date July 2001
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The guidelines for performing a one and a half ventricle repair with pulsatile bidirectional Glenn remains controversial. This retrospective report summarizes the experience of a single institution, with an attempt at providing an answer. METHODS: Fifty consecutive patients, aged 4 months to 42 years, underwent intracardiac repair along with a superior cavopulmonary connection. Twenty-seven of the patients had had previous surgical palliation. Repair consisted of patch closure of the ventricular septal defect (n = 25), tricuspid valve repair (n = 26), reconstruction of the right ventricular outflow tract (n = 34), transpulmonary annular patch (n = 34), right ventricle to pulmonary artery homograft conduit (n = 4), and concomitant repair of atrioventricular canal (n = 9). Ten patients were left with a fenestration in the atrial septum. RESULTS: There were six hospital deaths (12%) and two late deaths (4.5%). Forty-two survivors were followed from 8 months to 116 months. Eighty-eight percent are in functional class I. Actuarial survival at 97 months was 74%. CONCLUSIONS: Moderate right heart hypoplasia constitutes a safe anatomic category for a pulsatile bidirectional Glenn. It is advisable not to proceed with a one and a half ventricle repair if postoperative residual pulmonary artery hypertension is anticipated. Patients requiring an intricate intracardiac repair and those with concomitant right heart hypoplasia may be better suited for a Fontan type of repair to reduce the complexity of the procedure.

    Title Pretreatment of Human Myocardium with Adenosine.
    Date June 2001
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    OBJECTIVES: While the role of adenosine pretreatment in animals has been well established, the role in humans has been controversial. We performed this prospective, randomized study to find out the usefulness of adenosine pretreatment in humans. PATIENTS AND METHODS: Twenty patients undergoing coronary artery bypass surgery for severe triple vessel disease and left ventricular dysfunction (ejection fraction<35%) formed the study population. The adenosine group (n=10) received adenosine infusion (200 microg/kg) before aortic cross-clamp. The control group (n=10) received only normal saline injection. Cardiac function indices were assessed post-operatively. RESULTS: In the adenosine group there was a significant increase in cardiac output in the post-operative period from 3.46+/-1.06 to 4.46+/-0.92 l/min (P<<0.05). The cardiac index increased significantly in the adenosine group from 1.97+/-0.43 to 2.54+/-0.5 l/min per m2 (P<<0.05) and even when compared with the control group this increase was significant (adenosine group vs. control group, P=0.03). Systemic vascular resistance fell from 1898.8+/-558.4 to 1134.9+/-530.7 dyne/s per cm(-5) (P<<0.05) in the adenosine group. The pulmonary artery wedge pressure fell significantly in the adenosine group from 11.1+/-5.0 to 7.2+/-2.6 mmHg (P<<0.05). Patients in the adenosine group maintained a lesser increase in resting heart rate post-operatively (96.1+/-13.4 to 114.1+/-18.7 beats/min) (P=0.7), as compared to the control group where the increase in the heart rate was significant (77.1+/-8.3 to 109.7+/-14.9 beats/min) (P<<0.05). In the adenosine group only one patient (10%) had a raised creatine phosphokinase (MB) level at 12 h post-operatively as compared to three patients (30%) in the control group (P<0.05). CONCLUSIONS: Adenosine pretreatment appears to protect against reperfusion injury in human hearts and thus results in improved post-operative haemodynamics.

    Title Effect of Interferon-alpha on Cd20 Antigen Expression of B-cell Chronic Lymphocytic Leukemia.
    Date May 2001
    Journal Cytokines, Cellular & Molecular Therapy
    Excerpt

    Chimeric CD20 monoclonal antibody as alternative therapy in relapsed low-grade non-Hodgkin's lymphoma (NHL) has produced responses in nearly 50% of patients. Augmenting CD20 expression on tumor cells and/or inducing its expression may increase the cell kill and effectiveness of antibody therapy. Peripheral blood lymphocytes from 19 patients with B-cell chronic lymphocytic leukemia (B-CLL) were incubated in vitro in the presence of interferon-alpha (IFN-alpha) (500 U/ml and 1,000 U/ml) for 24 and 72 hours. The effect on CD20 expression was studied by flow cytometry. The differences in the percentage positivity, the mean fluorescence intensity (MFI), and the product of percentage positivity and MFI were used to assess upregulation. There was a significant upregulation of CD20 expression on B cells seen at both concentrations after 24-hour priming (p < 0.01). B-CLL cells cultured for 72 hours in the presence of IFN-alpha also showed upregulation of CD20 expression; however, the degree of upregulation was much lower than that seen at 24 hours. There was no statistically significant increase in CD20 antigen expression on normal lymphocytes following cytokine exposure. These results suggest that IFN-alpha priming may augment the effectiveness of antibody therapy by directly upregulating CD20 antigen expression in addition to its indirect action through effector cells of the host.

    Title Presence of Activation-related M-rna for Ebv and Cmv in the Bone Marrow of Patients with Myelodysplastic Syndromes.
    Date April 2001
    Journal Cancer Letters
    Excerpt

    The bone marrow (BM) in myelodysplastic syndromes (MDS) undergoes pathobiological changes that mimic an inflammatory process, and hence, an infectious etiology was suspected in these disorders. In the present report, we examined the bone marrow mononuclear cells (BMMNC) of 19 MDS patients and seven normal donors for the expression of one latency-related (Latency membrane protein 1 (LMP-1) and immediate early protein (IEP)) and one activation-related (BZLF and DNA-Pol) m-RNA each for two herpes viruses, Epstein-Barr virus (EBV) and cytomegalovirus (CMV), respectively. Reverse transcriptase polymerase chain reaction was used for this purpose. The latency-related transcripts (EBV-LMP-1 and CMV-IEP) were present in all the MDS and normal specimens. Intriguingly, 10/19 MDS specimens ( approximately 53%) and 2/7 normal donors ( approximately 28%) were positive for active EBV-BZLF (P=0.0067), while 2/19 MDS specimens ( approximately 11%) with 1/7 normal ( approximately 14%) showed active CMV-DNA-Pol (P=0.1588). Later, from another set of MDS patients (n=7) and normal donors (n=4), BM stromal cultures were established, which, at a 75% confluency, were overlaid with cord blood mononuclear cells (CBMNC). IEP was detectable in the CBMNC before and after co-incubation with MDS, as well as normal stroma. So, it was also present both in MDS and normal stromal cells. The other three were absent both in MDS and normal stromal layers. In CBMNC though, active EBV-BZLF and CMV-DNA-Pol m-RNA were detectable in one of seven MDS co-cultures each, albeit from different patients. None of the normal co-cultures showed active virus, either in stroma or CBMNC. Thus, the present report demonstrates, for the first time, the presence of active herpes viruses in the BMMNC of MDS patients and reveals the ability of the MDS stroma to support the viral activation.

    Title Detection of Coronary Artery Anomalies in Tetralogy of Fallot Using a Specific Angiographic Protocol.
    Date February 2001
    Journal The American Journal of Cardiology
    Excerpt

    Patients with tetralogy of Fallot were studied with a prespecified angiographic protocol aimed to delineate the types and incidence of coronary artery anomalies and to look for any correlation with other abnormalities detected by simultaneous detailed angiography. The incidence of coronary anomalies was found to be 7.0%; no association was found with these anomalies with any of the other abnormalities detected.

    Title Thrombolytic Therapy for Prosthetic Valve Thrombosis: Short- and Long-term Results.
    Date January 2001
    Journal American Heart Journal
    Excerpt

    BACKGROUND: Thrombolytic therapy (TT) has evolved as an alternative to surgery for prosthetic valve thrombosis (PVT), but its utility in patient management is still debated and the long-term results are not available. METHODS: From 1990 through 1999, we treated 110 consecutive patients (52 men, mean age 35.4 +/- 10.8 years) of left-sided obstructive PVT (96 mitral, 14 aortic) with TT (streptokinase in 108, urokinase in 2) according to a specified protocol of prolonged infusion. Serial echo Doppler parameters were monitored in all patients to guide the duration of TT and to quantify its efficacy. Ninety of the 102 survivors of the index episode were followed up for a mean period of 31.3 +/- 27.8 months (range 1-112 months). RESULTS: Complete hemodynamic response (on cinefluoroscopy and echo Doppler criteria) was seen in 90 (81.8%) episodes, partial response in 11 (10%), and failure in 9 (8.2%). The mean duration of TT was 42.8 +/- 20.4 hours. Five of the 7 patients who were initially seen in cardiogenic shock/overt pulmonary edema died during therapy. After these patients were excluded, the rate of complete response did not differ among patients with New York Heart Association class I/II (80%), class III (86.3%), or class IV (81.5%). The response rate also did not vary with the type, position of prosthesis, duration of symptoms, or time lag since surgery. There were 21 (19.1%) embolic episodes during therapy, including 6 strokes. These were significantly more frequent in patients with atrial fibrillation (AF) (odds ratio on multivariate analysis 2.3, 95% confidence interval 1.3-3.9, P =.01). On follow-up, there were 25 recurrences of PVT, of which 20 again received TT with a complete response in 14 (70%). At 5 years the actuarial survival was 85.2% and the event-free survival was 61.5%. The presence of chronic AF was a significant predictor of recurrence of PVT (odds ratio 2.2, 95% confidence interval 1.2-3.9, P =.008). CONCLUSIONS: TT is effective in the majority of patients with PVT but is associated with a high rate of embolism, especially in patients with AF. Excluding patients with cardiogenic shock/overt pulmonary edema (in whom TT is largely ineffective), the success of TT does not vary with the New York Heart Association class, duration of symptoms, or other patient variables. The recurrence rates of PVT are high after even successful TT, especially in patients with AF.

    Title Cardiac Arrhythmias in Surgically Repaired Total Anomalous Pulmonary Venous Connection: a Follow-up Study.
    Date December 2000
    Journal Indian Heart Journal
    Excerpt

    Twenty-five patients with diagnosis of total anomalous pulmonary venous connection, who had undergone corrective surgery, were studied at variable time period after surgery with 24-hour ambulatory electrocardiographic monitoring (Holter) and echocardiography. The aim of this study was to record arrhythmias, if any, and to correlate occurrence of arrhythmia with adequacy of repair and other related variables. All the patients were clinically asymptomatic. Twenty-four hours ambulatory electrocardiographic monitoring of these patients showed the presence of significant arrhythmias in 21 of the 25 patients. These included supraventricular ectopics in 19 patients, ventricular ectopics in 8, atrioventricular block in 2, right bundle branch block and atrial fibrillation 1 each and atrial tachycardia in 2 patients. There was no correlation between development of arrhythmia and age at repair, type of connection, operative approach and adequacy of repair. The study indicates that cardiac arrhythmias can occur in otherwise asymptomatic patients after correction for total anomalous pulmonary venous connection. Thus, these patients require long-term follow-up, even if they are asymptomatic.

    Title Surgical Considerations of Extracardiac Total Cavopulmonary Connection.
    Date December 2000
    Journal Indian Heart Journal
    Excerpt

    Extracardiac total cavopulmonary connection has been proposed as a rational alternative to the lateral intra-atrial tunnel for complex congenital cyanotic heart diseases undergoing univentricular repair. In five patients, aged 4 1/2 years to 27 years, an extracardiac lateral conduit was used for total cavopulmonary connection at our Institute. Extracardiac lateral conduits were constructed in all the five patients using polytetrafluoroethylene tube grafts. One child required reoperation because of graft thrombosis and an aortic homograft was used in him on the second occasion. Aortic cross clamp was completely avoided in all including reoperation. The results showed no early or late mortality. One child developed persistent hypoxemia and progressive hepatomegaly. Reoperation on 5th post-operative day revealed graft thrombosis with technically unrestricted anastomosis which was replaced by an aortic homograft. He also required embolectomy for inferior vena cava and hepatic veins thrombosis. Post-operative follow-up (range 3 months to 14 months) revealed all patients in functional class I and in normal sinus rhythm. Doppler echocardiography, magnetic resonance imaging and angiocardiography revealed unrestricted anastomoses and unobstructed pulmonary blood flow across the conduit. The technical advantages and haemodynamic benefits of this operation are encouraging. However, the lone incidence of graft thrombosis raises concern about the routine usage of synthetic grafts in extracardiac total pulmonary connection. Other inherent weakness appears to be the lack of growth potential of the synthetic tube.

    Title Efficacy of Aprotinin, Epsilon Aminocaproic Acid, or Combination in Cyanotic Heart Disease.
    Date November 2000
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Aprotinin and epsilon aminocaproic acid are antifibrinolytic agents used to reduce postoperative blood loss after cardiopulmonary bypass. We compared low dose aprotinin with epsilon aminocaproic acid and a combination of the two agents to reduce postoperative blood loss in infants with congenital cyanotic heart disease undergoing corrective surgical procedures. METHODS: This prospective study was conducted randomly on 300 children. Group I (n = 80) acted as the control and did not receive either of the study drugs. Group II (n = 100) received low dose aprotinin, group III (n = 60) received epsilon aminocaproic acid, and group IV (n = 60) received a combination of the two antifibrinolytic agents. RESULTS: The control group had the longest time for sternal closure, maximum blood loss at 24 hours, and greatest requirements for packed red blood cells and platelets. Fibrinogen levels were significantly lower, and levels of fibrin breakdown products were significantly higher compared with the groups given either or both of the antifibrinolytics. CONCLUSIONS: Epsilon aminocaproic acid is as efficacious as low dose aprotinin in reducing postoperative blood loss and packed red blood cell and platelet requirements in children with congenital cyanotic heart disease. The combination of the two was slightly more effective.

    Title Poor Prognosis Acute Myelogenous Leukemia 2--biological and Molecular Biological Characteristics and Treatment Outcome.
    Date October 2000
    Journal Leukemia Research
    Excerpt

    Biological and molecular biological studies were performed on the marrow cells of 25 patients with poor prognosis AML to both characterize this type of leukemia and to assess the relationship between the parameters which were measured and treatment outcome. Treatment failure associated with high levels of telomerase activity and low levels of IL6 transcripts. Studies of the effects of amifostine on these parameters demonstrated that this agent reduced telomerase activity in aspirates of AML marrows. These data suggest that the beneficial effect associated with the administration of amifostine after the end of chemotherapy is likely, to be due to a reduction in the rate at which the surviving leukemia cells repopulate the marrow.

    Title Right Ventricular Outflow Tract After Non-conduit Repair of Tetralogy of Fallot with Coronary Anomaly.
    Date October 2000
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: A total of 25 patients with tetralogy of Fallot and an important coronary artery crossing the right ventricular outflow tract underwent complete repair without use of an extracardiac conduit between January 1990 and December 1994. Repair was exclusively done by the transatrial or transatrial-transpulmonary approach. Age of these patients ranged from 1 to 12 years (mean 3.6 years). Three of the patients had already received a systemic to pulmonary artery shunt. METHODS: All patients reporting for follow-up (n = 18) were subjected to transthoracic echocardiography and, if required, cardiac catheterization and angiography. Right ventricle to pulmonary artery gradients were noted preoperatively, at discharge following repair and at follow-up study. RESULTS: Mean follow-up was 40.6 months (24 to 62 months). Mean early postoperative gradient was 23.5+/-13.4 mm Hg and 4 patients had significant (> 30 mm Hg) gradients. Mean late postoperative gradient was 20.6+/-12.4 mmHg and 2 patients had gradients greater than 30 mmHg. All the patients were in New York Heart Association functional class I at the time of last follow-up. CONCLUSIONS: Acceptable gradients across the right ventricular outflow tract are achievable following repair of tetralogy of Fallot in the presence of anomalous coronary artery across the right ventricular outflow tract using the transatrial or transatrial-transpulmonary approach. Most gradients were found not to vary significantly on subsequent follow-up.

    Title Neurological Evaluation and Intelligence Testing in the Child with Operated Congenital Heart Disease.
    Date September 2000
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The immediate and intermediate-term neurodevelopmental outcome in infants undergoing open heart procedures using deep hypothermic cardiopulmonary bypass was assessed prospectively. METHODS: One hundred consecutive infants (age 2 to 174 days) were operated on using either deep hypothermic bypass only (group A, n = 28), or with associated circulatory arrest (group B, n = 72). Early neurological outcome was recorded. Survivors underwent mental development evaluation after 31 to 55 months. Fifty other children of similar demographic profile but without heart disease were also tested as controls. RESULTS: In group A, there were two neurological deaths. In group B, 5 patients had clinical seizures, 1 had monoparesis and 1 had hyperkinetic syndrome with decreased attention span. Mean mental performance quotient was 90.0+/-8.2 in group A, and 89.1+/-6.8 in group B, (group A vs. B, p = 0.60). Mean mental performance quotient in the control group was 101.4+/-8.4, which was significantly higher than the patient population (p << 0.001). No correlation was found between duration of circulatory arrest and postoperative mental performance quotient. CONCLUSIONS: There was significant retardation of mental development in infants operated with deep hypothermic cardiopulmonary bypass. However, use of total circulatory arrest and its duration did not affect clinical outcome up to preschool age.

    Title Non-myxomatous Cardiac Tumours: Twenty-year Experience.
    Date September 2000
    Journal Indian Heart Journal
    Excerpt

    Eighty-eight patients underwent surgery for various cardiac tumours from January 1978 to June 1998 at our Institute. Seventy-seven tumours were myxomas, 10 were non-myxomatous and one was secondary cardiac tumour. Case records of the patients with non-myxomatous primary cardiac tumours and one secondary tumour were reviewed. Six of these primary tumours were benign and four, malignant. Age of the patients ranged from 26 days to 47 years. Among patients (3 children, 8 adults) with non-myxomatous primary cardiac tumours, dyspnoea on exertion was the commonest symptom and was the cause of presentation in seven out of 11 patients. Of the eight adults, six were in New York Heart Association functional class II/III and two in class IV. Echocardiographic diagnosis was possible in all the patients. Complete excision of the tumour was possible in all benign and two of the four malignant tumours. Incomplete resection was done in the secondary tumour. Of the six benign tumours, three were rhabdomyomas and one each of fibroma, haemangioma and lipoma. The malignant tumours were one each of fibrosarcoma, angiosarcoma, unclassified sarcoma and malignant mesothelioma. The secondary tumour was a malignant thymoma. Follow-up ranged from 1 to 10 years (mean 7.2 years). Of the patients with benign tumours, four out of six are alive; one patient died on the first post-operative day and one lost to follow-up. Two of the four patients with malignant cardiac tumours died, one was lost to follow-up and one is alive two years after surgery. The patient with secondary malignant thymoma to the superior vena cava was lost to follow-up three months after an uneventful recovery from surgery.

    Title Multiple Fungal Mycotic Pulmonary Artery Aneurysms in an Infant.
    Date September 2000
    Journal Indian Heart Journal
    Title Poor Prognosis Acute Myelogenous Leukemia: 1 - Response to Treatment with High Dose Cytarabine/mitoxantrone/ethyol @ (amifostine).
    Date September 2000
    Journal Leukemia Research
    Excerpt

    Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.

    Title Cytokine Production by in Vitro Processed and Unprocessed Haematopoietic Cells.
    Date September 2000
    Journal Cytokine
    Excerpt

    The studies described here demonstrate that in vitro processing of cells before extraction of RNA has a major effect on the number and type of cytokine transcripts present within MDS and leukemia cells. Transcripts for GM-CSF, a cytokine whose production by leukemia cells is believed to play an important role in the pathogenesis of leukemia, was not detectable in 12/13 unprocessed AML specimens, in 12/12 MDS specimens, or in 7/7 CML specimens but once detected in many specimens after processing. These data strongly suggest that leukemia cell production of GMCSF rarely occurs in vivo.

    Title Tumor Necrosis Factor Modulates Cd 20 Expression on Cells from Chronic Lymphocytic Leukemia: a New Role for Tnf Alpha?
    Date August 2000
    Journal Microscopy Research and Technique
    Excerpt

    Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine that is constitutively produced by leukemic cells in B Chronic Lymphocytic Leukemia (B-CLL). It has been shown to have autocrine and paracrine functions in normal B cells and in B lymphoproliferative diseases. This study was conducted to determine the effect of TNF alpha (in vitro) on CD20 expression on cells from patients with B-CLL. Currently, anti-CD20 monoclonal antibody therapy is becoming a second line treatment in the management of B cell disorders like low-grade non-Hodgkin's lymphoma (NHL) and B-CLL. Our results demonstrate amply that very low doses of TNF alpha (0. 0125 ng/ml) can be used to significantly increase CD20 expression on cells from patients of B-CLL as evidenced by increases in both percentage positivity and mean fluorescence intensity. The upregulation is evident as early as 24 hours and is maintained for up to 72 hours. We propose that the upregulation is a direct result of in vitro differentiation stimulated by TNF alpha. The results presented can be exploited in the designing of priming protocols prior to antibody therapy and this is discussed.

    Title Scf, Il-1beta, Il-1ra and Gm-csf in the Bone Marrow and Serum of Normal Individuals and of Aml and Cml Patients.
    Date August 2000
    Journal Cytokine
    Excerpt

    This study compared cytokine transcript and protein levels in BM cells of normal individuals and leukemic patients. AML differed from normal in that: (1) AML marrow cells contain more IL-1beta protein than normal cells, (2) IL-1ra transcripts are absent from AML marrow cells, (3) AML marrow serum contains less IL-1ra protein than normal, (4) peripheral blood and marrow serum of AML patireents contains more SCF protein than normal serum, and (5) SCF transcripts have been detected in AML marrow biopsies and not in aspirate cells. These data suggest that unbalanced cytokine production may make a significant contribution to the abnormal behaviour of AML cells.

    Title Surgical Considerations of Univentricular Heart with Total Anomalous Pulmonary Venous Connection.
    Date August 2000
    Journal Indian Heart Journal
    Excerpt

    Out of the 600 patients undergoing univentricular repair during the last 11 years, 20 children had associated total anomalous pulmonary venous connection. The objective was to outline the clues to establish the diagnosis of this rare disease combination and the various surgical options available to manage the same. Bidirectional Glenn, bilateral bidirectional Glenn, total cavopulmonary connection and atriopulmonary connection were performed in combination with rechannelling of various types of total anomalous pulmonary venous connection in 20 children aged 6 months to 36 months (mean +/- SD 17.65 +/- 9.02 months). Diagnosis could be established pre-operatively in only 13 (65%) patients. Out of 6 early deaths (30%), 4 were directly attributable to missed diagnosis. No late deaths occurred over a follow-up period ranging from 1 month to 132 months. None of the surviving children required reoperation and all are in NYHA functional class I. Doppler echocardiography of the surviving children revealed unrestricted atrio/cavopulmonary anastomosis and pulmonary vein to atrium connection in all survivors. Our own experience, coupled with a review of the literature, indicates that a missed diagnosis increases the hospital mortality. Cross sectional 2D echocardiography is a superior method of detection of associated total anomalous pulmonary venous connection compared to angiocardiography. Exclusion of the diagnosis of anomalous pulmonary venous connection is imperative in all univentricular hearts pre-operatively and on operation table. Failure to recognise this disease combination results in formation of a closed systemic circuit after bidirectional Glenn or a modified Fontan of connection and is lethal as happened in our early experience. It is suggested that one-stage Fontan operation should be performed only if other criteria for Fontan procedure are satisfied.

    Title Harmonic Scalpel: a Word of Caution.
    Date July 2000
    Journal The Annals of Thoracic Surgery
    Title Univentricular Repair: is Routine Fenestration Justified?
    Date July 2000
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: A decade after the introduction of baffle fenestration, the outcome of Fontan-type repair for hearts with a functional single ventricle finally looks promising. Our study was designed to assess the impact of fenestration on the outcome of univentricular repairs. METHODS: From January 1988 to December 1997, 348 patients (104 with tricuspid atresia and 244 with other morphological diagnoses) underwent univentricular repair at our institute. Since 1994, routine fenestration of the atrial baffle was performed in all patients (n = 126). RESULTS: The overall Fontan failure rate was 14% (50 of 348) and included 45 early deaths and five Fontan take downs. Absence of fenestration was the only and highly significant predictor of Fontan failure (risk ratio [RR] 3.3, 95% confidence interval [CI] 1.49 to 7.31, p = 0.002). Significant pleural effusion was seen in 27% of patients. Absence of fenestration of the atrial baffle (RR 3.97, 95% CI 2.17 to 7.26, p < 0.001) and aortic cross-clamp time more than 60 minutes (RR 2.15, 95% CI 1.3 to 3.5, p = 0.002) were found to be significant risk factors. The follow-up ranged from 6 to 120 months (mean 46.0 +/- 18.0 months). There were 12 late deaths and 5 patients were lost to follow-up. Actuarial survival (Kaplan Meier) at 90 months was 81% +/- 4%. Two hundred and fifty-eight patients (90%) were in New York Heart Association class I at their last follow-up visit. Oxygen saturation in the fenestrated group ranged from 85% to 94% (mean 89%). Thirty patients (26%) had spontaneous closure of the fenestration over a mean period of 34 months, and there has been no incidence of late systemic thromboembolism. In no instance has there been a need to close the fenestration. CONCLUSIONS: Elective fenestration of the intraatrial baffle is associated with decreased Fontan failure rate and decreased occurrence of significant postoperative pleural effusions. Routine elective fenestration of the atrial baffle may, therefore, be justified in all univentricular repairs.

    Title Signal Antonymy Unique to Myelodysplastic Marrows Correlates with Altered Expression of E2f1.
    Date June 2000
    Journal British Journal of Haematology
    Excerpt

    Myelodysplastic syndromes (MDS) have previously been reported to show competitively high rates of apoptosis and proliferation in the bone marrow (BM). Using a double-labelling technique in the present study, we demonstrated that a significantly high number of S-phase cells were simultaneously apoptotic (signal antonymy; SA) in MDS (mean +/- s.e.m. 53.5 +/- 6.7%, n = 24, P < 0.001). In contrast, SA was negligible in all other specimens studied, including normal control BM (n = 13) from non-Hodgkin's lymphoma (NHL) patients, BM from patients with de novo acute myelogenous leukaemia (1'AML; n = 5), or secondary AML that had transformed from MDS (2'AML; n = 10), or the solid tumours from patients with NHL (n = 9) or head and neck squamous cell carcinoma (HNSCC; n = 10). Subsequently, the expression of a transcription factor, E2F1, was studied in density-separated BM aspirate mononuclear cells from MDS patients (n = 9) and a normal control. Two separate sets of primers were used that recognized the regulatory retinoblastoma (Rb) protein-binding region and the functional DNA-binding region of E2F1. Interestingly, although the latter manifested the expected band (280 bp) in all samples, the Rb-specific primers showed the expected band (380 bp) in the normal and in 4/9 MDS specimens. Two other MDS specimens also showed a smaller band ( approximately 325 bp), whereas 3/9 MDS patients showed exclusively the smaller band. The levels of SA were significantly higher in those MDS cases that showed the smaller Rb-specific band either alone or in addition to the expected band (median 19.5%, n = 4, P = 0.037) than in those showing exclusively the expected band (median 0.4%, n = 3). Our present studies show SA as a characteristic feature of MDS and, importantly, demonstrate its link with an altered expression of E2F1 in some MDS patients.

    Title Effects of Cytokines on Cd20 Antigen Expression on Tumor Cells from Patients with Chronic Lymphocytic Leukemia.
    Date June 2000
    Journal Leukemia Research
    Excerpt

    Anti-CD20 antibody is an established treatment for low-grade non-Hodgkin's lymphoma (NHL). Augmenting the expression of CD20 antigen on the tumor cells may increase the cell kill and therefore increase the effectiveness of the antibody. To study this, we incubated peripheral blood lymphocytes from CLL patients with the following cytokines: EPO, SCF, TNFalpha, TGFbeta, GMCSF, TPO, IL-1, IL-2, IL-3, IL-4, GCSF. CD20 expression was studied by flow cytometry at baseline, 24 and 72 h after exposure to these cytokines. Upregulation of CD20 antigen expression was observed with IL-4, TNFalpha and GMCSF.

    Title Epsilon Aminocaproic Acid in Paediatric Cardiac Surgery to Reduce Postoperative Blood Loss.
    Date June 2000
    Journal The Indian Journal of Medical Research
    Excerpt

    We have studied the efficacy of epsilon aminocaproic acid in reducing postoperative blood loss in infants and children with congenital cyanotic cardiac anomalies undergoing corrective operative procedures. This prospective study was carried out on 170 infants and children randomly divided into two equal groups. Group A acted as the control group and received normal saline as placebo while group B patients received epsilon aminocaproic acid (100 mg/kg body wt) intravenously slowly soon after anaesthetic induction followed by 100 mg/kg in the cardiopulmonary bypass pump at the time of starting of cardiopulmonary bypass and 100 mg/kg after weaning from bypass over a period of 3 h. In group A the time for sternal closure after separation from bypass and administration of protamine was 75.18 +/- 5.5 min and in group B 50.7 +/- 5.2, (P < 0.001). Blood loss at 24 h in group A was 42.6 +/- 6.9 ml/kg/24 h and in group B 23.7 +/- 5.8 ml/kg/24 h, (P < 0.001). The need for packed red cells in group A was 21.8 +/- 7.1 ml/kg/24 h and in group B 10.7 +/- 7.8 ml/kg/24 h, (P < 0.001). The need for platelet concentrate in group A was 22.0 +/- 6.7 ml/kg/24 h and group B 6.2 +/- 3.2 ml/kg/24 h, (P < 0.001). Fibrin degradation products (split) in group A was 8.2 +/- 0.8 micrograms/ml, and group B 3.8 +/- 1.3 micrograms/ml, (P < 0.001). Reexploration rate was also considerably reduced in group B, 5 of 85 (6%) compared to group A, 13 of 85 (15%), (P < 0.001). It was found that epsilon aminocaproic acid is effective in reducing postoperative blood loss, packed red cells and plasma product requirements in paediatric patients undergoing corrective surgical procedures for congenital cyanotic heart diseases.

    Title Management of Tetralogy of Fallot with Absent Pulmonary Valve: Early and Mid-term Results of a Uniform Approach.
    Date June 2000
    Journal Indian Heart Journal
    Excerpt

    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.

    Title Profound Hypothermic Circulatory Arrest in Management of Aortic Aneurysms.
    Date June 2000
    Journal Indian Heart Journal
    Excerpt

    A total of 15 patients having aneurysms of aorta were operated from June 1997 to December 1998 using deep hypothermic circulatory arrest as a modality of brain protection. There were 12 males and 3 females. The age ranged from 19 years to 74 years and the mean age was 44.9 years. Nine patients had aneurysms of ascending aorta (group I), one had aneurysm of ascending aorta and arch of aorta (group II), four had aneurysm of the distal aortic arch (group III) and one patient had thoracoabdominal aortic aneurysm (group IV). In group I, six patients underwent Bentall procedure, two underwent Wheat procedure and one patient had repair of pseudoaneurysm of ascending aorta. The only patient in group II had his ascending aorta and arch replaced, with reimplantation of left common carotid and innominate artery. In group III, three patients had interposition Gelseal graft and one had repair of the tear in distal aortic arch. The lone patient in group IV had interposition Gelseal graft of thoracoabdominal aorta. The hypothermic circulatory arrest was used in all of them for brain and/or spinal cord protection. Retrograde cerebral perfusion was used in two patients. There were two (13%) operative deaths. One patient died of cerebrovascular accident on eighth post-operative day and second died of inadequate surgical repair. There was one instance of left hemiparesis secondary to an infarct in right frontoparietal region. To conclude, hypothermic circulatory arrest could provide an adequate brain protection for aortic aneurysm surgery. Retrograde cerebral perfusion could be an adjuvant when the anticipated time of hypothermic circulatory arrest is likely to exceed 45 minutes.

    Title Suppression of Telomerase Activity and Cytokine Messenger Rna Levels in Acute Myelogenous Leukemia Cells in Vivo in Patients by Amifostine and Interleukin 4.
    Date May 2000
    Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
    Excerpt

    High levels of telomerase activity and high rates of cell proliferation are associated with a poor prognosis in acute myelogenous leukemia. Furthermore, cytokine production by leukemia cells is believed to play an important role in determining the proliferative characteristics of leukemia. The in vivo effects of two noncytotoxic agents on these parameters were determined in 33 acute myelogenous leukemia patients. Three daily doses of interleukin (IL) 4 or a single dose of amifostine reduced telomerase activity in the leukemia marrow cells in 7 of 9 and 11 of 13 patients, respectively. The administration of a single dose of amifostine resulted in a reduction in tumor necrosis factor alpha and IL-6 transcript levels in the marrow cells of 10 of 13 and 12 of 13 patients in which these transcripts were present. The administration of only three doses of IL-4 or a single dose of amifostine has a significant effect on leukemia cell parameters, which are believed to have a significant impact on the in vivo biology of the disease and on its response to remission induction therapy.

    Title Surgical Myocardial Revascularization Without Cardiopulmonary Bypass.
    Date May 2000
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Though coronary artery bypass grafting (CABG) without cardiopulmonary bypass is being performed with increasing frequency, in the absence of adequate angiographic follow-up, safety, reproducibility, and efficacy of the procedure remain doubtful. In this prospective study, we report the results obtained by 100% angiographic follow-up of 96 consecutive patients. METHODS: A total of 96 patients (age range 33 to 76 years) underwent CABG without cardiopulmonary bypass. Single vessel disease was present in 46 (47.9%) patients, double vessel disease in 31 (32.3%), and triple vessel disease in 19 (19.8%) patients. All patients were operated through a standard midsternotomy and an optimal combination of pharmacological and mechanical methods were used to restrict cardiac movements during anastomosis. All patients underwent coronary angiography before discharge from the hospital. RESULTS: A total of 160 grafts were placed (range 1 to 4 grafts per patient, average 1.7+/-0.3 grafts per patient). A single graft was placed in 46 patients, double grafts in 38, triple grafts in 10, and quadruple grafts in 2 patients. Various grafts included pedicled left internal mammary artery (LIMA) (n = 95), free LIMA (n = 1), right internal mammary artery (n = 14), radial artery (n = 24), right gastroepiploic artery (n = 5), and saphenous vein grafts (n = 21). Operative mortality was 1.0% (1 of 96). Two patients required reoperation for excessive bleeding. Mean hospital stay was 5.7+/-1.2 days. Overall angiographic patency was 95.0% with LIMA patency of 97.9% (93 of 95). One patient with block in midsegment of LIMA was reoperated using cardiopulmonary bypass. Follow-up ranged from 4 to 17 months (mean 8.2+/-3.1 months). Two patients (one with narrowed LIMA to left anterior descending artery anastomosis, and one with patent anastomosis) had residual angina. CONCLUSIONS: Coronary artery bypass grafting without cardiopulmonary bypass is a reproducible, effective, and safe option in selected group of patients. A conscientious approach in patient selection and route of operation is required.

    Title Supporting a Failing Heart: a Review.
    Date April 2000
    Journal Indian Heart Journal
    Title Post-infarction Ischaemic Mitral Regurgitation: What Determines the Outcome.
    Date April 2000
    Journal Indian Heart Journal
    Excerpt

    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.

    Title Patients with Myelodysplastic Syndromes Benefit from Palliative Therapy with Amifostine, Pentoxifylline, and Ciprofloxacin with or Without Dexamethasone.
    Date March 2000
    Journal Blood
    Excerpt

    Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M(2), 300 mg/M(2), and 400 mg/M(2)) to cohorts of 10 patients each. Therapy has been continued for 1 year in responders. Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secondary MDS. No differences were noted in response rates among the 3 dose levels. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%). Three had a triple lineage response, 10 had a double lineage response, and 9 had a single lineage response (8 of 9 in absolute neutrophil count [ANC] and 1 had more than a 50% reduction in packed red blood cell transfusions). Fifteen patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in blood transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond. This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered. (Blood. 2000;95:1580-1587)

    Title Adenosine for Cardioplegic Induction: a Comparison with St Thomas Solution.
    Date March 2000
    Journal Journal of Cardiothoracic and Vascular Anesthesia
    Excerpt

    OBJECTIVE: To determine if quicker cardiac standstill obtained by adding adenosine to potassium crystalloid cardioplegia translated into better myocardial preservation and cardiac function in the early postoperative period compared with the same cardioplegia without adenosine. DESIGN: A prospective study. SETTING: Cardiac center of a teaching institute. PARTICIPANTS: Sixty consecutive patients with left main vessel or triple-vessel disease undergoing coronary artery bypass surgery under moderate hypothermia. INTERVENTIONS: The study comprised two groups of patients. Group N (n = 15) was the control group, given St Thomas cardioplegic solution after aortic cross-clamping, without adenosine; whereas group A (n = 45) received 250 microg/kg of adenosine into the aortic root after aortic cross-clamping, followed by the same St Thomas cardioplegia as in group N. The two groups were otherwise similar in all aspects of perfusion management. MEASUREMENTS AND MAIN RESULTS: Time taken to achieve cardiac standstill after aortic cross-clamping was significantly greater, 18.7+/-3.1 seconds, in the control group compared with the adenosine group, 3.4+/-0.9 seconds (p<0.001). The quicker arrest of the adenosine group led to better postoperative function, in the form of higher cardiac index (p<0.01), lower filling pressures (pulmonary artery wedge pressure) (p<0.05), and lower mean pulmonary artery pressure (p<0.05) at 6 hours. In the adenosine group, only 3 of 45 (6.6%) patients had elevated creatine phosphokinase (CPK) (MB) values greater than 50 U/L over preoperative CPK values compared with 3 of 15 (20%) in the control group (p<0.01). CONCLUSIONS: Injection of 250 microg/kg of adenosine into the aortic root before administration of cold crystalloid St Thomas cardioplegia solution after cross-clamping, in patients with severe coronary artery disease, produces significantly faster cardiac standstill, better myocardial preservation, and better cardiac function in the early postoperative period.

    Title Cd20-negative Relapse After (131)i-anti-cd20 Therapy.
    Date January 2000
    Journal Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
    Title Ambulatory 24-hour Electrocardiographic Monitoring Following Total Cavopulmonary Connection.
    Date November 1999
    Journal Indian Heart Journal
    Excerpt

    A total of 72 patients (53 males, 19 females) in the age range 1-22 years (mean 6.4 years) who underwent univentricular repair between April 1990 and May 1997 at our institute were followed up from six months to seven years (mean 3.6 years). Twenty-four hours ambulatory electrocardiographic Holter monitoring was done in all the patients. Thirty-four out of 40 patients (85%) who underwent fenestrated total cavopulmonary connection and 25 out of 32 patients (78%) who underwent non-fenestrated total cavopulmonary connection had normal Holter recording; thus 59 out of 72 (82%) patients had normal findings. Among the fenestrated total cavopulmonary connections, three patients each had atrial tachycardia and sinus bradycardia. In the non-fenestrated group, two patients had atrial tachycardia, three had supraventricular tachycardia, one sinus bradycardia and one had intermittent ventricular tachycardia. No correlation was found between age at surgery, pre-operative morphology, cross clamp time or cardiopulmonary bypass time with post-operative arrhythmia. To conclude, post-operative arrhythmias following total cavopulmonary connection were not related to age at surgery, pre-operative morphology, cross clamp or cardiopulmonary bypass time. However, a larger patient pool and longer follow-up is required for evaluation of any definitive correlation.

    Title Spontaneous Down-regulation of Fas-associated Phosphatase-1 May Contribute to Excessive Apoptosis in Myelodysplastic Marrows.
    Date October 1999
    Journal International Journal of Hematology
    Excerpt

    In this study, we examined the role of Fas-signaling in the apoptotic pathway in myelodysplastic syndromes (MDS). Ficoll-separated mononuclear cells from 18 bone marrow aspirate specimens obtained from 17 MDS patients, 4 normal healthy donors, and 3 acute myeloid leukemia patients transformed from MDS (t-AML) were studied for mRNA expression of Fas-L, Fas, and the effectors of their signaling, Caspase 1 and Caspase 3, using reverse transcriptase polymerase chain reaction. Fas-L, Fas, and Caspase 1 were detectable in all of the samples in the three groups. Caspase 3 was detectable both in MDS and t-AML specimens but was negligible in normal cells. The apoptotic index (AI%) determined by in situ end labeling of fragmented DNA in 4-hour cultures of mononuclear cells was significantly higher in MDS cells compared to normal or t-AML cells (mean +/- SEM: 2.3% +/- 0.4% in MDS, n = 10 vs. 0.6% +/- 0.2%, n = 4, P = 0.014 in normal cells, and 0.2% +/- 0.2%, n = 3, P = 0.007 in t-AML cells). Treatment of MDS cells with anti-Fas-L antibody suppressed apoptosis (AI%: 2.1% +/- 0.6% in untreated vs. 1.37% +/- 0.5% in treated, n = 6, P = 0.02), indicating functional participation of Fas-signaling in MDS. Further, it was found that Fas-L, Fas, and Caspase 1 mRNA expression remained unchanged in 4 hours. Caspase 3 expression appeared in normal cells after 4 hours and was present at both 0 and 4 hours in MDS and t-AML cells. In contrast to persistent expression in normal and t-AML cells, cells from the 5 MDS patients studied consistently showed significantly lowered or undetectable expression of a negative regulator of Fas, called Fas-associated phosphatase-1 (Fap-1) after 4 hours. Thus, the high AI% in MDS corresponds to a rapid decline in Fap-1. Furthermore, in tumor necrosis factor alpha (TNF-alpha) treated HL60 promyelocytic cells, a definite periodicity in the expression of different mRNAs was observed with upregulation of TNF-alpha itself at 30 minutes, increased expression of Fas and the appearance of Fas-L after 2 hours, and a decrease in Fap-1 expression after 8 hours. These results suggest that TNF-alpha not only induces the effectors of Fas-signaling but also may downregulate the inhibitor. We conclude that a spontaneous and rapid down-regulation of Fap-1, possibly induced by TNF-alpha, a cytokine shown to be present in excess in MDS marrows, may underlie the increased apoptotic death of hematopoietic cells in these patients. Interference with Fap-1 turnover may provide a new therapeutic modality for MDS.

    Title Correlation of Tumor Necrosis Factor Alpha (tnf Alpha) with High Caspase 3-like Activity in Myelodysplastic Syndromes.
    Date August 1999
    Journal Cancer Letters
    Excerpt

    Increased intramedullary apoptotic death of hematopoietic cells is thought to contribute to the ineffective hematopoiesis in myelodysplastic syndromes (MDS). Furthermore, high amounts of tumor necrosis factor alpha (TNF alpha) have previously been correlated with apoptosis in MDS marrows. The present studies were undertaken to examine the status of two key downstream effectors of TNF alpha signaling, i.e. Caspase 1 and Caspase 3 enzymes, using a fluorometric assay in the bone marrow aspirate mononuclear cells (BMMNC) in relation to apoptotic DNA fragmentation detected by in situ end-labeling (ISEL) of DNA and with localization of TNF alpha in the corresponding biopsies from 14 MDS patients. Both Caspase 1 and 3 were detectable in freshly harvested BMMNC, albeit median Caspase 3 levels (47.5 units/mg protein) being almost 10 times higher than Caspase 1 (4.0 units/mg protein). Upon short-term culture for 4 h in a serum-supplemented medium in vitro a significant increase was seen in Caspase 3 activity (58.8 +/- 13.9 at 0 h vs. 177.8 +/- 55.2 units/mg protein at 4 h, n = 14, P = 0.017) and in percent cells labeled by ISEL (apoptotic index or AI%: 0.76% +/- 0.25% vs. 3.99% +/- 1.1%, n = 14, P = 0.004, respectively). Caspase 1 activity increased after 15 min in culture. Interestingly, TNF alpha levels measured by immunohistochemistry correlated with the net increase in Caspase 3 activity after 4 h (p = 0.517, n = 13, P = 0.07) and the starting levels of Caspase 1 at 0 h correlated with the Caspase 3 levels attained at 4 h (p = 0.593, n = 13, P = 0.033). Additionally when TNF alpha-positive bone marrows (8/14) were compared with the negative marrows (6/14) the Caspase 3 levels were significantly higher in the TNF alpha-positive marrows (189.6 +/- 66.2 vs. 25.0 +/- 14.6 units/mg protein, respectively, P = 0.043). The increase in AI%, though not statistically significant, was also higher in the TNF alpha-positive marrows. Finally in HL60 cells the effects of different Caspase inhibitors and pentoxifylline (PTX) (interferes with lipid signaling of cytokines) on TNF alpha-induced apoptosis were evaluated. TNF alpha treatment significantly increased AI% (P < 0.003) as compared to the untreated controls. A co-treatment with three Caspase inhibitors, zVAD.FMK (inhibitor of Caspases 1 and 3, 10 microM/l), Ac.YVAD.FMK (Caspase 1 inhibitor, 1 microM/l), Ac.DEVD.FMK (Caspase 3 inhibitor, 10 microM/l) as well as PTX (250 microM/l) significantly curtailed the AI% induced by TNF alpha. The present studies thus identify the downstream effectors of TNF alpha-inducible apoptosis in MDS and so also the suppressors of TNF alpha apoptotic signaling. These results may have significant clinical implications in the therapy of MDS in the future.

    Title Adult Cyanotic Congenital Heart Disease: Surgical Experience.
    Date August 1999
    Journal Indian Heart Journal
    Excerpt

    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.

    Title Repair of Total Anomalous Pulmonary Venous Connection in Infancy: Experience from a Developing Country.
    Date August 1999
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: Corrective surgery for total anomalous pulmonary venous connection in infancy still carries high morbidity and mortality rates in developing countries. The present study evaluates the factors responsible for it. METHODS: Seventy-three infants were operated on for total anomalous pulmonary venous connection from January 1987 through October 1997. Age ranged from 5 days to 12 months (mean, 3.9+/-0.24 months), with 10 (13.7%) patients younger than 1 month old. Patient weight varied from 2.0 to 5.2 kg (mean, 3.7+/-0.27 kg). Most (90.5%) patients were small for their ages (< 50th percentile). Anomalous connection was supracardiac in 42 (57.5%), cardiac in 18 (24.7%), infracardiac in 4 (5.5%), and mixed in 9 (12.3%) patients. Thirty-five patients had obstructed drainage. Preoperatively, 30 patients received antibiotic therapy for respiratory tract infection, 3 patients had balloon atrial septostomy, and 4 patients required mechanical ventilation. Fifteen patients (20.5%) were operated on as an emergency procedure. For supracardiac and infracardiac connections, a posterior approach was used for anastomosis. In cardiac type, coronary sinus was unroofed and the resultant defect along with atrial septal defect was closed with a single patch. RESULTS: The operative mortality rate was 23.3% (17 of 73). Pulmonary hypertensive crisis was the cause of death in 10 patients. Emergency operation and weight less than the 25th percentile were the important risk factors for operative mortality. Young age (< 1 month) and type of drainage did not affect the mortality. Follow-up ranged from 1 to 108 months (mean, 56.4+/-26.0 months). There were two late deaths. The actuarial survival (Kaplan Meier) at 9 years was 72.87%+/-5.39%. CONCLUSION: Failure of early recognition, and thus delayed referral, accounted for onset of cardiac cachexia, respiratory tract infection, and severe pulmonary hypertension, which had a major effect on unfavorable outcome.

    Title Left Superior Vena Cava in a Distal Arch Aneurysm: Could It Be of Any Advantage?
    Date August 1999
    Journal The Annals of Thoracic Surgery
    Title Tyrosine Phosphorylation of Shc Proteins in Normal Cd34+ Progenitor Cells and Leukemic Cells.
    Date July 1999
    Journal Blood
    Title Radial Artery in Cabg: Could the Early Results Be Comparable to Internal Mammary Artery Graft?
    Date July 1999
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND: The accidental detection of patency of radial artery grafts, by Acar, which had been labeled as blocked 18 years earlier, has led to its revival as a conduit in coronary artery bypass surgery. We used radial artery as one of the grafts in 287 patients from February 1996 to June 1998. Here we present our early clinical experience and the midterm angiographic follow up of the initial 62 patients. METHODS: A no touch, atraumatic harvesting technique coupled with gentle hydrostatic and pharmacological dilatation of the radial artery graft was employed. Radial artery was used to revascularize coronary vessels with >80% proximal stenosis. Postoperatively, the patients were administered a low dose nifedipine that was continued for 6 months thereafter. The patients were followed up clinically after discharge from the hospital and angiographic evaluation of the grafted radial artery by selective injection was done at a mean interval of 16.2 +/- 5.1 months (3-24 months) postoperatively. RESULTS: There was no perioperative or late myocardial infarction or mortality. No significant complications related to the harvesting of radial artery were encountered. Angiographically, the radial artery grafts were found to be patent in 96.8% of patients (60/62). Mild distal anastomotic narrowing was seen in angiogram of one patient with good filling of the target vessel. Another patient showed diffuse spasm of radial artery graft. The patency of the pedicled left internal mammary grafts was also 98.2% (56/57). All the patients were asymptomatic. CONCLUSIONS: Radial artery seems to be an excellent alternate arterial conduit for myocardial revascularization with early and midterm patency rates equivalent to that of pedicled internal mammary artery, and it should be used more often for myocardial revascularization as an adjunct to pedicled internal mammary artery graft.

    Title Double Switch for Congenitally Corrected Transposition of the Great Arteries.
    Date June 1999
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Excerpt

    OBJECTIVE: To evaluate the early and medium term results of operations for congenitally corrected transposition of the great arteries (CCTGA) wherein the left ventricle becomes the systemic ventricle. METHODS: Fourteen patients with CCTGA who underwent anatomic repair from 1994 to 1998 were placed in one of two groups: those without pulmonic stenosis (PS) (N = 7) and those with PS (N = 7). Main associations in the group without PS were: severe left atrioventricular (AV) valve regurgitation (N = 4), ventricular septal defect (VSD) (N = 4), criss-cross AV connection (N = 1), and hypoplasia of the morphologic RV (N = 1). Main associations in the group with PS were: VSD (N = 7), anomalous pulmonary venous drainage (N = 2) and major aorto-pulmonary collaterals (N = 1). All patients in the group without PS underwent an arterial switch operation and all except one had a modified senning repair for atrial rerouting for anatomic correction. All seven patients with PS underwent a Rastelli repair and all except one needed a modified senning repair. RESULTS: Early survivorship in both groups was 6/7. Follow-up ranges from 1 month to 48 months. The mean left ventricular ejection fraction (LVEF) in the arterial switch and senning patients was 65% and in the Rastelli and atrial rerouting was 52%. None of the survivors except one have any significant mitral regurgitation (MR). The one exception resulted from iatrogenic damage to a chorda during VSD closure. All except two patients are class I symptomatic and all are in normal sinus rhythm. CONCLUSION: Satisfactory early and mid term results of anatomic repair support the double switch option as the procedure of choice for patients of CCTGA amenable to biventricular repair.

    Title Biologic Characteristics of 164 Patients with Myelodysplastic Syndromes.
    Date June 1999
    Journal Leukemia & Lymphoma
    Excerpt

    Rates of proliferation, apoptosis and cytokine expression were measured in bone marrow (BM) biopsies of 164 myelodysplastic syndrome (MDS) patients. There were 107 males and 57 females. Median age was 69 years and 101 had refractory anemia (RA), 17 RA with ringed sideroblasts (RARS), 38 with RA and excess blasts (RAEB) and 8 with RAEB in transformation (RAEB-t). Apoptosis measured by in-situ end labeling (ISEL) was directly related to the number of macrophages (p = 0.028, n = 83). Mean tumor necrosis factor alpha (TNF-alpha) and ISEL positivity were higher in RAEB + RAEB-t patients (p = 0.0554 and p = 0.06 respectively) while hemoglobin was higher for RA + RARS group (p = 0.0472). Patients with high apoptosis had lower white blood cell counts (p = 0.0009), lower percentage of blasts (p = 0.0009) and higher number of macrophages (p = 0.0086). We conclude that measurements of apoptosis, proliferation and cytokine expression provide important biological information which helps to distinguish RA + RARS patients from RAEB + RAEB-t patients, and may be of additive prognostic significance.

    Title Mixed Variety of Total Anomalous Pulmonary Venous Connection: Diagnosis by 2d Echocardiography and Doppler Colour Flow Imaging.
    Date June 1999
    Journal Indian Heart Journal
    Excerpt

    Of the many types of total anomalous pulmonary venous connection, mixed type is the least common. Its accurate non-invasive diagnosis by echocardiography poses a diagnostic challenge. We report our experience of echocardiography in 21 infants with mixed type of total anomalous pulmonary venous connection aged 25 days to one and half years. Multiple windows were used to identify individual pulmonary veins and various sites of drainage. Cardiac catheterisation and angiography were performed for 17 cases. In 11 of 21 cases, the left upper pulmonary vein was seen draining into vertical vein and the left lower and right-sided pulmonary veins were draining into the coronary sinus. Cardiac and supracardiac combinations of other types were seen in eight more cases. Both drainage sites were supracardiac in one case and supracardiac and infracardiac in another. On comparing echocardiographic findings with those obtained at cardiac catheterisation and/or surgery (carried out in 18 cases), there were three instances of error. In two cases (echocardiography performed without the use of colour flow imaging) the second site of drainage could not be defined. These patients were catheterised as all four pulmonary veins were not delineated by echo. The third error occurred in a case where although two sites of drainage were picked up by echo but at surgery, the right lower pulmonary vein was noted to have a double connection, both to coronary sinus and to vertical vein. We conclude that mixed type of total anomalous pulmonary venous connection can be accurately diagnosed by echocardiography and Doppler colour flow imaging. The diagnostic errors are rare and would not alter the surgical management.

    Title Appraisal of Histogenesis of Cardiac Myxoma: Our Experience of 78 Cases and Review of Literature.
    Date June 1999
    Journal Indian Heart Journal
    Excerpt

    Cardiac tumours are uncommon. Of these, myxomas have generated significant interest, not only because it is the commonest cardiac neoplasm but also because of controversial theories regarding its histogenesis. We encountered 78 cases of cardiac myxoma in our centre between 1976 and 1997. These included 73 sporadic cases and five cases from a single family of mother, daughter and son. The familial cases had recurrent, biatrial cardiac myxomas. Histopathologic analysis, immunohistochemical study, electron microscopic evaluation and DNA ploidy analysis done in some of these cases revealed evidence in support of the neoplastic nature of this entity. This communication sums up our observations and literature related to the histogenesis of cardiac myxoma.

    Title Biologic Characteristics of Patients with Hypocellular Myelodysplastic Syndromes.
    Date May 1999
    Journal Leukemia Research
    Excerpt

    Rates of proliferation and apoptosis as well as expression of tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and the number of macrophages were measured in bone marrow (BM) biopsies of 33 patients who presented with hypocellular (cellularity < 30%) myelodysplastic syndromes (MDS). Results showed that 2/3 of the patients had high apoptosis, high cytokine levels and large number of macrophages in their biopsies while 1/3 did not. Apoptosis and TNF-alpha levels were directly related (r = 0.583, P = 0.003, n = 24) as was apoptosis and the degree of anemia (P = 0.033, n = 18). A subgroup of patients with abnormalities of chromosomes 5 or 7 had higher platelets (P = 0.026) and higher apoptosis (P = 0.038) when compared with the rest of the group. Eight patients had no evidence of apoptosis and almost no detectable TNF-alpha in their biopsies. We conclude that within the hypocellular variant of MDS, there may be two distinct sub-groups of patients, one who present with high cytokine-mediated intramedullary apoptosis and the other who may be better characterized as having a stem-cell failure defect since they showed no evidence of apoptosis.

    Title The Relative Extent and Propensity of Cd34+ Vs. Cd34- Cells to Undergo Apoptosis in Myelodysplastic Marrows.
    Date May 1999
    Journal International Journal of Hematology
    Excerpt

    The paradox of peripheral cytopenias despite cellular bone marrow (BM) observed in myelodysplastic syndromes (MDS) has been associated with excessive intramedullary apoptosis of hematopoietic cells. Since MDS is regarded as a stem cell disorder, the present studies were undertaken to examine the relative susceptibility and propensity of early progenitor CD34+ cells to undergo apoptosis as compared to more maturing/matured CD34- cells. Five serial studies were performed on 4 independent groups of 36 newly diagnosed MDS patients. First, in 2 separate groups of 16 and 8 patients each, measurement of the extent of apoptosis in CD34+ and CD34- fractions of the BM aspirate mononuclear cells was carried out using independent biparametric flow cytometry methods, CD34 labeling/terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (n = 16), and CD34 labeling/reduced uptake of nucleic acid staining dye LDS751 (n = 8). The difference in the median degrees of apoptosis in CD34+ vs. CD34- cells was not statistically significant by either technique (P = 0.583 and P = 0.674 for TUNEL and LDS751, respectively). In the next group of 4 MDS patients, a double-labeling was performed on plastic embedded marrow biopsy sections, to detect CD34 antigen with specific monoclonal antibody and apoptosis by in situ end labeling (ISEL) of fragmented DNA. Despite high overall apoptosis (56.2% +/- 18.4%), only an occasional CD34+ cell was found to be simultaneously labeled with ISEL. Finally, in the last group of 8 MDS patients, CD34+ cells were separated from CD34- cells on affinity column and cultured in serum containing medium for 4 hours. At 0- and 4-hour time points, ISEL was carried out to label apoptotic cells. In addition, a fluorometric assay was employed to estimate the activity of a proapoptotic enzyme, Caspase 3. Both the net increase in % ISEL labeled cells (apoptotic index or AI) and Caspase-3 activity were significantly lower in CD34+ cells as compared to CD34- cells (AI, 0.87% +/- 0.5% vs. 3.97% +/- 1.4%, n = 6, P = 0.028 and Caspase-3 Units/mg protein, 46.9 +/- 25.0 vs. 71.7 +/- 23.03, n = 5, P = 0.042, respectively). We conclude that when estimated in a total population of mononuclear cells, CD34+ cells and CD34- cells show comparable degrees of apoptosis. However, once separated the CD34+ fraction demonstrates lower propensity to undergo apoptosis, thereby suggesting the CD34- fraction as being a possible source for proapoptotic signaling.

    Title Prostaglandin E1 in Infants with Congenital Heart Disease: Indian Experience.
    Date May 1999
    Journal Indian Pediatrics
    Excerpt

    BACKGROUND: E-type prostaglandins (PGE1) can effectively maintain the patency of the ductus arteriosus in neonates. Its use, therefore and be life saving in infants born with ductus dependent congenital heart disease. Although PGE1 is available for over two decade in western world, it has been introduced in India only since April, 1995. OBJECTIVE: To assess the efficacy of PGE1 at our center. SETTING: Hospital based. METHOD: 65 infants with ductus dependent congenital heart disease were included. Age at time of starting PGE1 infusion ranged from 18 hours to 39 days. Forty two of these were more than a week of age, 19 were more than 14 days, and two were above one month. PGE1 was started in an initial dose of 0.05 microgram/kg/min, decreased to 0.005-0.01 microgram/kg/min for maintenance. The indications for use of PGE1 were to increase pulmonary blood flow in 33 cases with pulmonary atresia, tricuspid atresia or critical pulmonic stenosis (Group I); to increase systemic blood flow in 15 cases with coarctation of aorta, hypoplastic left heart and interruption of aortic arch (Group II); to improve mixing in 13 cases of transposition of great arteries (Group III) and for improving the left ventricular volumes by keeping the duct open in 4 cases of transposition of great arteries with intact ventricular septum (Group IV). The efficacy of the drug was assessed by a rise on PaO2 and SaO2% determined for Group I & III, and by appearance of lower limbs pulses in Group II. Left ventricular volumes were serially measured by echocardiography in Group IV cases. RESULTS: The drug was successful in 62 of the 65 cases. There were two failures. One was a 39 days old baby with Ebstein's anomaly of tricuspid valve and pulmonary atresia and other was an eight days old baby with coarctation of aorta and renal failure. In addition, PGE1 could not be continued in another baby due to development of a linear skin rash locally. Side effects included apnea in 5 (9%) of 56 spontaneously breathing patients. Necrotizing enterocolitis, hyperpyrexia and jitteriness was sent in one case each. Six patients died. Two were related to PGE1, one due to failure, another due to its side effects. Definitive procedure were performed in 51 cases electively. PGE1 was used upto 13 days with sustained benefit. CONCLUSIONS: PGE1 is an effective drug for keeping the ductus open in infants with ductus dependent congenital heart disease. It can be used for neonates beyond the first week of life with efficacy. Apnea is a major side effect and close monitoring is essential.

    Title Aortic Valve Replacement with Biological Substitute.
    Date March 1999
    Journal Journal of Cardiac Surgery
    Excerpt

    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.

    Title Routine Cleft Closure in Repair of Complete Atrioventricular Septal Defects.
    Date March 1999
    Journal Indian Heart Journal
    Excerpt

    Thirty patients with complete atrioventricular septal defect were operated upon between 1989 and 1996 at our institute. Their ages ranged from two months to 24 years (mean age 2.81 years). All patients had severe pulmonary arterial hypertension except one who had associated pulmonic stenosis. Four patients had severe atrioventricular valve regurgitation and another six had moderate regurgitation. Five patients had Down's syndrome. The cleft in the left atrioventricular valve was closed in all but seven patients. There were five (16.66%) in-hospital deaths which included two patients in whom the cleft was left open. Follow-up ranged from three months to eight years. All patients were evaluated by 2D echocardiography in the immediate post-operative period and three to six monthly subsequently. One patient progressed to moderate and another to severe left atrioventricular valve regurgitation during follow-up. In both the patients the cleft had been left open. All other patients continue to have stable left atrioventricular valve status, that is, none or trivial to mild regurgitation. In view of late deterioration of the left atrioventricular valve regurgitation only in those patients where the cleft was left open, we suggest complete closure of the cleft in all complete atrioventricular canal defects.

    Title Dna Ploidy and Proliferative Index of Cardiac Myxoma.
    Date March 1999
    Journal Indian Heart Journal
    Excerpt

    Cardiac myxoma is the commonest tumour of heart. The histogenesis of this lesion is controversial as its origin has often been debated between the thrombogenic and neoplastic theories. We analysed DNA ploidy and proliferation indices of 30 cardiac myxomas which include 25 sporadic and five familial cases by image cytometry and proliferating cell nuclear antigen immunostaining. Of the 25 cases, 18 were aneuploid, three diploid and four tetraploid. Four of the five familial cases including the recurrent lesions were aneuploid. Poor tissue preservation precluded ploidy analysis in one familial case. The proliferation index of the sporadic cases ranged from 0.4 to 36.1 percent. The familial cases showed proliferation index between 10.2 and 22 percent. In addition to cardiac myxoma, proliferation index was assessed in 10 cardiac thrombi where it ranged from three to 58 percent. This study suggests that cardiac myxoma can be best interpreted as a neoplasm with a slow growth potential.

    Title Biological Characteristics of Myelodysplastic Syndrome Patients Who Demonstrated High Versus No Intramedullary Apoptosis.
    Date March 1999
    Journal European Journal of Haematology
    Excerpt

    Spontaneous intramedullary apoptosis was measured in bone marrow (BM) biopsies of 175 patients with myelodysplastic syndromes (MDS) using in situ end-labeling (ISEL) of fragmented DNA. Two groups of high (n=71) versus low (n =43) levels of apoptosis were identified while 61 patients were ISEL-negative. Semiquantitative assessment of 3 cytokines, the number of macrophages and in vivo labeling indices (LI) were also determined from consecutive sections of the biopsy. Patients with high apoptosis levels tended to have a high LI (p=0.013), more macrophages in their BM biopsies (p=0.006) and higher tumor necrosis factor alpha (TNF-alpha) levels (not significant) compared to patients with no apoptosis. In addition, low risk MDS patients had significantly lower rates of apoptosis (p = 0.047) and lower levels of TNF-alpha (p = 0.055) compared to high-risk MDS patients. We conclude that the genesis of cytopenias in MDS is of multifactorial origin and that cytokine-associated apoptosis clearly identifies a distinct biological subgroup of patients who may benefit selectively by use of anti-cytokine therapies.

    Title Recurrent Pseudoaneurysm of the Left Ventricle with Subcutaneous Herniation into the Chest Wall. A Case Report.
    Date March 1999
    Journal Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital
    Excerpt

    Pseudoaneurysm of the left ventricle is rare, and recurrence is extremely rare. We report the case of a 62-year-old man who presented at our hospital with a painless pulsatile swelling in the left breast. He had undergone coronary artery bypass grafting and left-ventricular aneurysmectomy 14 years earlier. On investigation, the swelling was diagnosed to be a pseudoaneurysm of the left ventricle with subcutaneous herniation. The extreme rarity of this condition prompted us to report the case. The investigative techniques and the surgical strategy are discussed.

    Title Evidence for Involvement of Tumor Necrosis Factor-alpha in Apoptotic Death of Bone Marrow Cells in Myelodysplastic Syndromes.
    Date January 1999
    Journal American Journal of Hematology
    Excerpt

    We previously reported excessive apoptosis and high levels of tumor necrosis factor-alpha (TNF-alpha) in the bone marrows of patients with myelodysplastic syndromes (MDS), using histochemical techniques. The present studies provide further circumstantial evidence for the involvement of TNF-alpha in apoptotic death of the marrow cells in MDS. Using our newly developed in situ double-labeling technique that sequentially employs DNA polymerase (DNA Pol) followed by terminal deoxynucleotidyl transferase (TdT) to label cells undergoing apoptosis, we have characterized DNA fragmentation patterns during spontaneous apoptosis in MDS bone marrow and in HL60 cells treated with TNF-alpha or etoposide (VP16). Clear DNA laddering detected by gel electrophoresis in MDS samples confirmed the unique length of apoptotic DNA fragments (180-200 bp). Surprisingly, however, phenotypically heterogeneous population of MDS cells as well as the homogenous population of HL60 cells showed three distinct labeling patterns after double labeling--only DNA-Pol reaction, only TdT reaction, and a combined DNA Pol + TdT reaction, albeit in different cohorts of cells. Each labeling pattern was found at all morphological stages of apoptosis. MDS mononuclear cells, during spontaneous apoptosis in 4 hr cultures, showed highest increase in double-labeled cells (DNA Pol + TdT reaction). Interestingly, this was paralleled by TNF-alpha-induced apoptosis in HL60 cells. In contrast, VP16 treatment of HL60 cells led to increased apoptosis in cells showing only TdT reaction. The double-labeling technique was applied to normal bone marrow and peripheral blood mononuclear cells after treatment with known endonucleases that specifically cause 3' recessed (BamHI), 5' recessed (PstI), or blunt ended (DraI) double-stranded DNA breaks. It was found that the DNA-Pol reaction in MDS and HL60 cells corresponds to 3' recessed DNA fragments, the TdT reaction to 5' recessed and/or blunt ended fragments, and a combined "DNA Pol + TdT reaction" corresponds to a copresence of 3' recessed with 5' recessed and/or blunt ended fragments. Clearly, therefore, apoptotic DNA fragments, in spite of a unique length, may have differently staggered ends that could be cell (or tissue) specific and be selectively triggered by different inducers of apoptosis. The presence of TNF-alpha-inducible apoptotic DNA fragmentation pattern in MDS supports its involvement in these disorders and suggests that anti-TNF-alpha (or anticytokine) therapy may be of special benefit to MDS patients, where no definitive treatment is yet available.

    Title Septal Course of the Left Main Coronary Artery from Right Aortic Sinus and Ventricular Tachycardia.
    Date January 1999
    Journal International Journal of Cardiology
    Excerpt

    A 42-year-old man with resistant ventricular tachycardia was found to have an anomalous origin of the left main coronary artery from the right aortic sinus that pursued an intramyocardial course through the ventricular septum. The tachycardia resolved after coronary artery bypass graft to otherwise normal left anterior descending and circumflex coronary arteries. Septal course of an anomalous left main coronary artery from right aortic sinus should not always be considered benign.

    Title Magnetic Resonance Imaging Features of Submitral Left Ventricular Aneurysm.
    Date December 1998
    Journal Indian Heart Journal
    Title Surgery for Aortic Valve Endocarditis.
    Date November 1998
    Journal Indian Heart Journal
    Excerpt

    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.

    Title Surgical Experience with Intracardiac Myxomas: Long-term Follow-up.
    Date October 1998
    Journal The Annals of Thoracic Surgery
    Excerpt

    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.

    Title Sinus of Valsalva Aneurysms: 20 Years' Experience.
    Date August 1998
    Journal Journal of Cardiac Surgery
    Excerpt

    BACKGROUND: Aneurysms of sinus of Valsalva are rare. Here, we analyze retrospectively patients operated on at our center during the last 20 years. PATIENTS AND METHODS: One hundred four cases of congential aneurysm of sinus of Valsalva were operated upon between January 1977 and April 1996. Only 12 aneurysms were unruptured. The majority (76.9%) arose from the right coronary sinus. The right ventricle was the most common chamber of rupture (58.6%). Ventricular septal defect was associated in 46 patients (44.2%), of which 28 (60.9%) were supracristal. Ventricular septal defect was more common in aneurysms arising from the right coronary sinus (91.3%). Aortic incompetence was found in 45 patients (43.3%). The defect was closed through the aortic root alone in 24 patients (23.1%) and through both the aortic root and the chamber of rupture in the remaining 80 patients. Six patients underwent aortic valve repair, and 21 an aortic valve replacement. RESULTS: There were two hospital deaths (1.92%). Morbidities were few. Follow-up ranged from 1 to 20 years (mean 8.2 +/- 1.1). There was one late noncardiac death, and in the majority, the long-term follow-up was uneventful. CONCLUSION: Surgery for aneurysm of sinus of Valsalva yields gratifying results, and it should be undertaken as soon as the condition is diagnosed.

    Title Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass.
    Date August 1998
    Journal Annals of Thoracic and Cardiovascular Surgery : Official Journal of the Association of Thoracic and Cardiovascular Surgeons of Asia
    Excerpt

    Coronary artery bypass surgery on a beating heart is now an accepted modality to treat selected patients of ischaemic heart disease. From June '92 through Sep '97, 162 patients underwent this procedure. There was no mortality and none of the patients had any respiratory or neurological morbidity, though 24% of the patients form a high risk group for conventional coronary bypass surgery. It is definitely cost effective in comparison to any other modalities for treatment of ischaemic heart disease. We conclude that continous use of this technique is justified and all cardiac surgeons should have exposure to this procedure.

    Title Cytokine Gene Activity in Aml Cells in Vivo in Patients.
    Date July 1998
    Journal Leukemia Research
    Excerpt

    The proliferation of acute myelogenous leukemia cells is dependent upon cytokine stimulation. Additionally, there is a body of literature which reports that leukemia cells produce GMCSF, IL6, and other cytokines. The study reported here, using an rt-multiplex polymerase method, determined the presence or absence of transcripts in freshly obtained AML cells for the following cytokine or cytokine-related genes: IL 1beta, IL1ra, TNF alpha, GMCSF, IL6, flt 3, and hSCF. This demonstrated that leukemia cell populations usually contain transcripts for IL1beta, TNF alpha, flt 3 and flt 3 ligand in vivo and that transcripts for the other cytokines only appear after the leukemia cells are processed in vitro. The presence of TNF alpha transcripts appears to be associated with resistance to remission induction therapy. Furthermore, the transcript profile of the leukemia cells can change during remission induction therapy. The data also demonstrate the assessment of cytokine production by leukemia cells after in vitro manipulation should not be extrapolated to the in vivo situation.

    Title Total Correction of Tetralogy of Fallot in Adults--surgical Experience.
    Date May 1998
    Journal International Journal of Cardiology
    Excerpt

    A total of 100 patients of tetralogy of Fallot aged 13 years and over were operated upon at the All India Institute of Medical Sciences, New Delhi, India between January 1991 and December 1996. There were 69 males (69%) and 31 females (31%). Age ranged from 13 years to 43 years (mean 19.66 years). Twenty % of patients had preoperative complications like haemoptysis, cerebrovascular accidents, brain abscess and infective endocarditis. Twenty-two patients had previous palliative shunts. Fifteen patients had coil embolisation of major collaterals prior to surgery. In hospital mortality rate was 4%. Follow-up ranged from 1 month to 5 years (mean 3.4 years). There was one late death due to infective endocarditis. Postoperatively 93.6% patients were in NYHA class I. Significant residual defects warranting re-operation were present in three patients. Total correction of tetralogy of Fallot in older patients can be performed with acceptable results.

    Title Aneurysm of Sinus of Valsalva Dissecting into Interventricular Septum.
    Date April 1998
    Journal The Annals of Thoracic Surgery
    Excerpt

    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.

    Title Pathology of Cardiac Transplantation--the Initial Experience.
    Date March 1998
    Journal The National Medical Journal of India
    Excerpt

    BACKGROUND: Cardiac transplantation has recently been started in India at the All India Institute of Medical Sciences, New Delhi. All transplants are monitored by right ventricular endomyocardial biopsies. This study describes our initial experience with the histopathological assessment of post-transplant endomyocardial biopsies. METHODS: Fifty-four endomyocardial biopsies from 8 transplanted hearts were reviewed. At least 3 haematoxylin-eosin and Masson trichrome stained sections were available on each biopsy. Special stains and immunohistochemistry were done as required. Biopsies were graded for rejection using the grading system of the International Society for Heart and Lung Transplantation. Infection, 'Quilty' effect, biopsy site, ischaemia and reperfusion injury were also assessed. RESULTS: There was no evidence of rejection in 34 biopsies. Eleven biopsies showed mild rejection. Only 9/54 biopsies from 4 of the transplant recipients had clinically significant grades of rejection. Biopsy sites were present in 13/54 biopsies. Ischaemia was present in the first biopsy after transplantation in 4 recipients. There was no evidence of viral or parasitic infection. 'Quilty' lesions were seen in 14/54 biopsies from 5 transplant recipients. Four of these 5 recipients had 'Quilty' lesions on more than 1 biopsy. CONCLUSIONS: The low rejection rate at our centre is consistent with reports from around the world. Endomyocardial biopsy has been a safe, convenient and useful method for diagnosing rejection and monitoring the postoperative course of cardiac transplants at our centre.

    Title Aortic Valve Replacement with a Homovital Valve.
    Date December 1997
    Journal Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital
    Excerpt

    "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.

    Title Severe Hypoxic Biventricular Dysfunction in Tetralogy of Fallot: is Blalock Shunt the Answer?
    Date November 1997
    Journal International Journal of Cardiology
    Excerpt

    In a 4-year-old boy with tetralogy of Fallot, a right modified Blalock-Taussig anastomosis was created because of severe myocardial dysfunction and repeated hypercyanotic spells. Post-operatively, systemic oxygen saturation improved and also myocardial function. It is postulated that hypoxia was responsible for myocardial dysfunction previously, and its elimination has resulted in markedly improved cardiac performance.

    Title Aortic Atherosclerosis and Perioperative Stroke in Patients Undergoing Coronary Artery Bypass: Role of Intra-operative Transesophageal Echocardiography.
    Date October 1997
    Journal International Journal of Cardiology
    Excerpt

    Intra-operative transesophageal echocardiography was performed in 126 patients undergoing coronary artery bypass grafting. Significant protruding atheromas (grade IV and V; Katz et al., 1992) were present in 12 patients (9.5%). Protruding atheromas had significantly higher incidence in patients above 60 years in age. Preoperative assessment with chest roentgenography and angiography, as well as intra-operative assessment by surgical palpation proved to be insensitive in detecting aortic atheromas. Out of four patients with grade V atheromas, two (50%) developed right hemiplegia postoperatively. For the rest, patients with grade V atheromas and eight patients with grade IV atheromas, surgical technique was modified and that helped in preventing occurrence of perioperative stroke.

    Title Serial Echocardiography in Transplanted Heart: an Initial Report of Five Cases.
    Date September 1997
    Journal Indian Heart Journal
    Excerpt

    Role of echocardiography including Doppler is established in selection of donor and in the care of patients after cardiac transplantation. Its value for recognition of transplant rejection is however still evolving. We present here, serial echocardiographic findings in five male patients, aged 22 to 46 years who underwent cardiac transplantation at our institution. There was no appreciable change on follow-up in the left ventricular dimensions, thickness of left ventricular posterior wall and interventricular septum and left ventricular systolic function. Transient pericardial effusion was noted in two patients. Trivial to mild mitral and tricuspid regurgitation was observed. The diastolic function of the left ventricle, as assessed by mitral valve inflow wave pattern, was normal in four patients. However in the fifth patient, there was evidence of diastolic dysfunction of the left ventricle and this change was accompanied by rejection episode (IIIB changes) in the endomyocardial biopsy. With resolution of rejection in biopsy, the diastolic function by Doppler also returned to normal. We conclude that echocardiography has a definite role in the general care of patients after cardiac transplantation. Transient small pericardial effusion and mild atrioventricular valve regurgitation are common after the operation. Echocardiography may also be of use in recognition of rejection episode by demonstrating evidence of diastolic dysfunction of the left ventricle. Currently, endomyocardial biopsy remains the gold standard for diagnosis of rejection.

    Title Aortoaortic Bypass: Indications, Techniques and Results.
    Date September 1997
    Journal Indian Heart Journal
    Excerpt

    The standard surgical treatment of complex cases of aortic obstructions is difficult and sometimes even hazardous, thus necessitating the use of alternative surgical methods to manage these cases. Between 1986 and 1995, nine such patients underwent ascending aorta to descending/abdominal aorta bypass graft as an alternative procedure at a premier medical institution. There was no hospital death nor any significant morbidity. Preoperative systolic blood pressure in right upper limb ranged from 150 mm Hg to 230 mm Hg (mean 180.5 mm Hg) while postoperative systolic blood pressure in right upper limb ranged from 126 mm Hg to 150 mm Hg (mean 134 mm Hg), thereby showing marked improvement. Preoperative pressure gradient across the aortic obstruction ranged from 50 mm Hg to 120 mm Hg (mean 87.2 mm Hg). It was relieved in all except two patients who had resting gradients of 10 mm Hg and 12 mm Hg respectively. All the patients were relieved of their symptoms. After a mean follow-up of 33.3 months (range 6 to 108 months), all the patients are in New York Heart Association (NYHA) class I with evidence of good distal perfusion. This technique of bypassing the aortic obstruction has the added advantage of avoiding the complications associated with standard technique.

    Title A Case of Prosthetic Valve Endocarditis Caused by Cryptococcus Neoformans Var. Neoformans.
    Date July 1997
    Journal Journal of Medical and Veterinary Mycology : Bi-monthly Publication of the International Society for Human and Animal Mycology
    Excerpt

    A case of prosthetic valve endocarditis caused by Cryptococcus neoformans var. neoformans is described. The infection followed closed mitral valvotomy and insertion of a valvular prosthesis. Infection was manifested 2 weeks after the operation. The diagnosis was based on direct demonstration of the yeast with characteristic morphology in clinical material, isolation from an arterial thrombus and detection of cryptococcal antigen in the serum. The patient's infection could not be resolved despite institution of antifungal therapy.

    Title Cell Cycle Kinetic Studies in 68 Patients with Myelodysplastic Syndromes Following Intravenous Iodo- And/or Bromodeoxyuridine.
    Date July 1997
    Journal Experimental Hematology
    Excerpt

    Sixty-eight patients with myelodysplastic syndromes (MDS) received sequential infusions of iodo- and/or bromodeoxyuridine for cell kinetic analysis. Bone marrow biopsy sections were treated by appropriate antibodies and a labeling index (LI), duration of S-phase (Ts), and total cell cycle time (Tc) of myeloid cells were determined. The mean LI was 28.4%, Ts was 11.8 hours and Tc was 40.7 hours. The %LI decreased as the disease evolved from refractory anemia toward transformation to acute leukemia (p = 0.04). Double-labeling of biopsy sections for apoptosis and proliferation showed that 30-90% of S-phase cells in MDS patients were simultaneously apoptotic or "antonymous." We conclude that MDS are highly proliferative disorders in which the ineffective hematopoiesis is probably the result of excessive apoptosis rather than slow proliferation.

    Title Cytokines, Molecular Biological Abnormalities, and Acute Myelogenous Leukemia.
    Date June 1997
    Journal Leukemia Research
    Excerpt

    Leukemia cell proliferation is dependent upon cytokines produced by the leukemia cells or by the microenvironment under stimulation by leukemia cells. Abnormal expression of the p53, rb, and ras genes is associated with cytokine production, suggesting that abnormal expression can affect leukemia cells by affecting intracellular growth controls and by stimulating cytokine production. While these observations suggest that cytokines can be used to stimulate leukemia proliferation during cytotoxic therapy increasing the sensitivity to treatment, they also suggest that inhibition of cytokine affects could increase clinical responses by reducing leukemia cell regrowth between courses of therapy.

    Title Right Ventricle to Pulmonary Artery Connections.
    Date May 1997
    Journal Indian Heart Journal
    Excerpt

    From March 1988 through June 1995, 80 patients underwent repair for right ventricle (RV) to pulmonary artery (PA) discontinuity. Of these, 30 patients received homograft conduits, while the remaining 50 underwent repair without the use of a homograft. Handmade pericardial valved vascutek conduits (n = 18), non-valved vascutek tubes (n = 13) and non-conduit procedures like the rev operation (n = 12) and extended pericardial gusset (n = 5) were mainly used. The indications for repair for RV-PA discontinuity included ventricular septal defect with pulmonary atresia (VSD PA) (n = 36), truncus arteriosus (n = 18), ventricular septal defect with pulmonary and major aorto-pulmonary collaterals (VSD PA MAPCA) with staged repair (n = 5), congenitally corrected transposition of the great arteries with ventricular septal defect and pulmonic stenosis (CCTGA VSD PS) (n = 5) and double outlet left ventricle with ventricular septal defect and pulmonic stenosis (DOLV VSD PS) (n = 5). The choice of the procedure was governed by various factors, including type of cardiac defect, pulmonary artery pressure and morphology, previous operation, socio-economic constraints and availability of appropriate sized homografts. Non-circuit operations may prevent future reoperations in these patients.

    Title Giant Left Ventricular Inferior Wall Aneurysm.
    Date May 1997
    Journal Indian Heart Journal
    Title Measurement of Apoptosis, Proliferation and Three Cytokines in 46 Patients with Myelodysplastic Syndromes.
    Date February 1997
    Journal Leukemia Research
    Excerpt

    Extensive apoptosis or programmed cell death (PCD) of both hematopoietic (erythroid, myeloid, megakaryocytic) and stromal cells in myelodysplastic syndromes (MDS) cancels the high birth-rate resulting in ineffective hematopoiesis and has been demonstrated as the probable basis for peripheral cytopenias in MDS by our group. It is proposed that factors present in the microenvironment are inducing apoptosis in all the cells whether stromal or parenchymal. To investigate this hypothesis further, bone marrow biopsies from 46 MDS patients and eight normal individuals were examined for the presence of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and granulocyte macrophage-colony stimulating factor (GM-CSF) and one cellular component, macrophages, by the use of monoclonal antibodies immunohistochemically. Results showed the presence of TNF-alpha and TGF-beta in 41/46 and 40/46 cases of MDS respectively, while only 15 cases showed the presence of GM-CSF. Further a significant direct relationship was found between the degree of TNF-alpha and the incidence of PCD (p= 0.0015). Patients who showed high PCD also had an elevated TNF-alpha level. Thus, the expression of high amounts of TNF-alpha and TGF-beta and low amounts of the viability factor GM-CSF may be responsible for the high incidence of PCD leading to ineffective hematopoiesis in MDS. Future studies will be directed at attempting to reverse the lesion in MDS by using anti-TNF-alpha drugs such as pentoxifylline.

    Title Transesophageal Echocardiography During Surgical Closed Mitral Commissurotomy.
    Date February 1997
    Journal Cardiology
    Excerpt

    We report a case of a 28-year-old woman with severe mitral stenosis for which surgical closed commissurotomy was done. Intraoperative transesophageal echocardiography was performed to assess its utility during this surgical procedure. It was helpful in instant confirmation of the adequacy of the surgery, detecting residual mitral regurgitation, and in visualisation of the Tubbs dilator that is used to accomplish mitral commissurotomy.

    Title Surgical Experience with Total Correction of Tetralogy of Fallot in Infancy.
    Date February 1997
    Journal International Journal of Cardiology
    Excerpt

    Fifty two patients less than one year old with tetralogy of Fallot underwent primary repair between January 1991 and December 1994. Age range was three to twelve months (mean 10.09 +/- 2.01 months) and body weight ranged from 4.5 to 9 kg (mean 8.38 +/- 2.79 kg). Transatrial-transpulmonary repair was performed in 36 patients and the classical transventricular approach was used in 16 patients. Six patients underwent emergency surgery for severe cyanosis and spells. Five patients had left pulmonary artery plasty for pulmonary artery bifurcation stenosis and two out of the five patients who had anomalous coronary arteries needed a right ventricle to pulmonary artery conduit. Mean post repair peak right ventricular/systemic pressure ratio was 0.74 +/- 0.18 in the transventricular group and 0.71 +/- 0.26 in the transatrial-transpulmonary group. There were three hospital deaths. Follow-up ranged from 3 to 46 months (mean 21.18 months). Forty patients underwent echocardiography and twenty patients underwent cardiac catheterisation six to eighteen months after surgery. Mean right ventricular outflow tract gradient on echocardiography was 20.35 +/- 10.12 and, at cardiac catheterisation, 17.51 +/- 13.49 mmHg with mean post repair peak right ventricle/left ventricle pressure ratio of 0.44 +/- 0.11. These were significantly less than the values obtained in the operating room. Only one patient had residual ventricular septal defect with left to right shunt of 1.6:1 at cardiac recatheterisation. There was one late death after reoperation for residual obstruction. Encouraging results with primary repair of tetralogy of Fallot in infancy prompt us to continue this policy in suitable cases.

    Title Improved Exposure for Tapvc Repair by Posterior Approach.
    Date January 1997
    Journal The Annals of Thoracic Surgery
    Title Phenotypic Characterization of Cellular Components of Cardiac Myxoma: a Light Microscopy and Immunohistochemistry Study.
    Date December 1996
    Journal Human Pathology
    Excerpt

    Cardiac myxoma is the most common primary tumor of the heart. A detailed evaluation of cell types in 41 cardiac myxomas by light microscopy and in 30 cases by immunohistochemistry was made. Reactivity to the various antisera were observed in the surface lining cells, the stromal myxoma cells and the cells in the perivascular location. Factor VIII-related antigen (FVIIIR-Ag) and Ulex europaeus agglutinin (UEA-1), both endothelial markers, were positive in 23 cases each. UEA-1 was found to be a more sensitive marker than factor VIII. Desmin and myoglobin were positive in 16 and 24 cases, respectively. Reactivity for cytokeratin was noted in ten cases, one of which showed glandular differentiation. Vimentin and S-100 positivity was obtained in 16 and 14 cases respectively. Thus, cardiac myxoma appears to arise from multipotent cells which have the potential to differentiate along several mesenchymal cells or epithelial cells and may also concurrently exhibit reactivity for both mesenchymal and epithelial markers.

    Title Extended Use of Pulse Oximetry in Harvesting Radial Artery.
    Date December 1996
    Journal The Annals of Thoracic Surgery
    Title Indication of an Involvement of Interleukin-1 Beta Converting Enzyme-like Protease in Intramedullary Apoptotic Cell Death in the Bone Marrow of Patients with Myelodysplastic Syndromes.
    Date November 1996
    Journal Blood
    Excerpt

    Our previous studies using in situ end labeling (ISEL) of fragmented DNA revealed extensive apoptotic cell death in the bone marrows (BM) of patients with myelodysplastic syndromes (MDS) involving both stromal and hematopoietic cells. In the present report we show greater synthesis of interleukin-1 beta (IL-1 beta) in 4 hour cultures of density separated BM aspirate mononuclear (BMAM) cells from MDS patients as compared to the cultures of normal BM from healthy donors or lymphoma patients (1.7 +/- 0.37 pg/10(5) cells, n = 29 v 0.42 +/- 0.24 pg/10(5) cells, n = 11, respectively, P = .049). Further, these amounts of IL-1 beta in MDS showed a significant correlation with the extent of apoptosis detected by ISEL in corresponding plastic embedded BM biopsies (r = .480, n = 30, P = .007). In contrast normal BMs did not show any correlation between the two (r = .091, n = 12, P = .779). No significant correlation was found between the amounts of IL-1 beta and % S-phase cells (labeling index; LI%) in MDS determined in BM biopsies using immunohistochemistry following in vivo infusions of iodo- and/or bromodeoxyuridine. Neither anti-IL-1 beta antibody nor IL-1 receptor antagonist blocked the apoptotic death of BMAM cells in 4 hour cultures (n = 5) determined by ISEL (apoptotic index; AI%), although the latter led to a dose-dependent accumulation of active IL-1 beta in the culture supernatants. On the other hand, a specific tetrapetide-aldehyde inhibitor of ICE significantly retarded the apoptotic death of BMAM cells at 1 mumol/L in 5/6 MDS cases studied (AI% = 2.99 +/- 0.30 in controls v 1.58 +/- 0.40 with ICE-inhibitor, P = .05) and also reduced the levels of active IL-1 beta synthesized (5.59 +/- 2.63 v 2.24 +/- 0.93 pg/10(6) cells, respectively). In normal cells, neither IL-1 blockers nor the ICE inhibitor showed any effect on the marginal increase in apoptosis observed in 4 hour cultures. Our data thus suggest a possible involvement of an ICE-like protease in the intramedullary apoptotic cell death in the BMs of MDS patients.

    Title Interpretation of Calcifications in Screen/film, Digitized, and Wavelet-enhanced Monitor-displayed Mammograms: a Receiver Operating Characteristic Study.
    Date October 1996
    Journal Academic Radiology
    Excerpt

    RATIONALE AND OBJECTIVES: The acceptance of filmless digital mammography is currently limited by digitization and display drawbacks, as well as bias toward hard-copy interpretation. In the current study, we evaluated a wavelet-based image enhancement method for the filmless interpretation of breast calcifications. METHODS: A set of 100 mammograms (58 with calcification clusters) was digitized at 105 microns and 4,096 gray levels per pixel and was processed with nonlinear filters and wavelets. Standard receiver operating characteristic analysis was performed by four radiologists, who independently read the films, the unprocessed digital images, and unprocessed and wavelet-enhanced digital images presented simultaneously. RESULTS: Statistical differences were observed between screen/film and unprocessed digitized mammography displayed on monitors. Differences were not significant when wavelet enhancement was included in the monitor display. Interobserver variation in the digitized reading was greater than in film reading, but the wavelet enhancement reduced the difference. CONCLUSION: Wavelet-enhanced digital mammograms may assist radiologists in diagnosing calcifications directly from computer monitors and may compensate for current technologic limitations. A study with a larger data-base is needed before this method is accepted for clinical use.

    Title A Paradigm Shift in Myelodysplastic Syndromes.
    Date October 1996
    Journal Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.k
    Excerpt

    A poorly defined transforming event(s) affects the pluripotential bone marrow (BM) stem cell in myelodysplastic syndromes (MDS), conferring a growth advantage upon it which leads eventually to monoclonal hematopoiesis. The progeny of this transformed ancestor undergo recognizable albeit dysplastic maturation. We propose that this picture is further complicated by a variety of cytokines, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta) and interleukin 1beta (IL-1beta) which exert a dual effect on the diseased cells. The immature CD34+ cells are stimulated to proliferate, while their later differentiated daughters are induced to undergo apoptosis accounting for the clinical syndrome of pancytopenia despite hypercellular BMs. Studies directed at measuring the rates of proliferation and apoptosis as well as the levels of TNF-alpha, TGF-beta and IL-1beta confirm this hypothesis and are presented in greater detail. A novel approach towards MDS therapy emerges as a result of this paradigm shift based upon the premise that anti-cytokine therapy would prevent excessive intramedullary apoptosis and result in improved cytopenias as well as cause a slowing down of the diseased precursor cell proliferation resulting in resumption of polyclonal hematopoiesis. Because a number of cytokines function through common lipid second messengers, interruption of this pathway should theoretically cause disruption in the signalling of a cascade of cytokines.

    Title Chronic Constrictive Pericarditis Presenting As Mass Lesion in Infancy.
    Date October 1996
    Journal Indian Heart Journal
    Title Coronary Sinus Size As a Determinant of Outcome in Cardiac Tapvc.
    Date October 1996
    Journal The Annals of Thoracic Surgery
    Title Novel Insights into the Biology of Myelodysplastic Syndromes: Excessive Apoptosis and the Role of Cytokines.
    Date September 1996
    Journal International Journal of Hematology
    Excerpt

    The paradox of myelodysplastic syndromes (MDS) which present with pancytopenias despite cellular bone marrows (BM) was investigated by conducting detailed studies of proliferation and apoptosis in 89 MDS patients. Our results demonstrated a rapid rate of both proliferation as well as apoptosis. Levels of three cytokines, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta) and interleukin-1 beta (IL-1 beta) were measured in the same patients. High levels of TNF-alpha were found to correlate with high levels of apoptosis in 83 MDS patients (P = 0.0045). We propose a dual role for TNF-alpha (or other cytokines) in the pathogenesis of MDS. On the one hand, TNF-alpha induces apoptosis in the maturing cells causing pancytopenia while on the other, it stimulates the proliferation of the primitive progenitors accounting for the hypercellular BM frequently seen in MDS. A new model for MDS is presented. The initial abnormality probably affects a primitive hemopoietic progenitor which acquires a growth advantage leading to monoclonal hemopoiesis, which in turn makes these cells susceptible towards acquiring additional mutations and appearance of cytogenetically marked (or unmarked) clones. Cytokines such as TNF-alpha whose source is presently unknown, then contribute towards the clinical syndrome of pancytopenia and hypercellularity.

    Title Orthotopic Pulmonary Valve Replacement with a Homograft.
    Date February 1996
    Journal The Journal of Heart Valve Disease
    Excerpt

    Eight pulmonary valve replacements (PVR) have been performed from January 1992 to October 1994. Three patients (mean age 7.7 years, range two to 16 years) had absent pulmonary valve with tetralogy of Fallot and underwent primary PVR at the time of surgical correction. Five other patients, who had correction of tetralogy of Fallot (four cases) and of double outlet right ventricle with ventricular septal defect and pulmonary stenosis (one case), were reoperated for pulmonary regurgitation with progressive right ventricular dysfunction. Mean age at the time of reoperation was 18 years (range seven to 34 years). There was no early death. Early postoperative recovery was satisfactory in all of them. The follow up ranges from six to 35 months (mean 19 months). Seven patients were in functional class I and one in functional class II when they were last evaluated in the out-patient department and five of them were off diuretics and vasodilator. In the presence of right ventricular dysfunction pulmonary regurgitation is poorly tolerated. A competent and non-obstructive pulmonary valve is often life saving in these critically ill patients.

    Title Univentricular Repair. Early and Midterm Results.
    Date January 1996
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    A total of 202 patients (62 with tricuspid atresia and 140 without tricuspid atresia) underwent univentricular repair at our unit from January 1990 to September 1994. Of these patients, 182 had nonfenestrated and 20 had fenestrated interatrial baffles. Early mortality was 15.9% (29/182) in the group with nonfenestrated baffles and 5% (1/20) in the group with fenestrated baffles. The follow-up period ranged from 2 to 58 months. Seven late deaths occurred, and five patients were lost to follow-up. Of 160 patients who have been evaluated in the outpatient department in the past 3 months, 142 (88.75%) required no cardiac medicines and were in functional class I. Risk factors analyzed for early mortality and significant effusion were age, preoperative diagnosis, type of Fontan modification, cardiopulmonary bypass time, aortic crossclamp time, pulmonary artery size, associated pulmonary arterioplasty, takedown of systemic-pulmonary artery shunt, and pulmonary artery debanding, along with the Fontan operation. Bypass time exceeding 120 minutes was associated with a higher early mortality (12/47 vs 18/155; p = 0.0187). Bypass time exceeding 120 minutes (p = 0.0456) and aortic crossclamp time exceeding 60 minutes (p = 0.0278) were associated with significant postoperative effusion. Other factors were not associated with any significantly increased risk for early mortality or postoperative effusions. Fenestration of the interatrial baffle appeared to decrease early mortality, although the numbers are too small to be statistically significant. The prevalence of effusions did not differ significantly between the group with fenestrated baffles and the group without fenestrated baffles.

    Title Tree Structured Wavelet Transform Segmentation of Microcalcifications in Digital Mammography.
    Date December 1995
    Journal Medical Physics
    Excerpt

    A novel multistage algorithm is proposed for the automatic segmentation of microcalcification clusters (MCCs) in digital mammography. First, a previously reported tree structured nonlinear filter is proposed for suppressing image noise, while preserving image details, to potentially reduce the false positive (FP) detection rate for MCCs. Second, a tree structured wavelet transform (TSWT) is applied to the images for microcalcification segmentation. The TSWT employs quadrature mirror filters as basic subunits for both multiresolution decomposition and reconstruction processes, where selective reconstruction of subimages is used to segment MCCs. Third, automatic linear scaling is then used to display the image of the segmented MCCs on a computer monitor for interpretation. The proposed algorithms were applied to an image database of 100 single view mammograms at a resolution of 105 microns and 12 bits deep (4096 gray levels). The database contained 50 cases of biopsy proven malignant MCCs, 8 benign cases, and 42 normal cases. The measured sensitivity (true positive detection rate) was 94% with a low FP detection rate of 1.6 MCCs/image. The image details of the segmented MCCs were reasonably well preserved, for microcalcification of less than 500 microns, with good delineation of the extent of the microcalcification clusters for each case based on visual criteria.

    Title Coronary Angioplasty in High Risk Patients: Comparison of Elective Intraaortic Balloon Pump and Percutaneous Cardiopulmonary Bypass Support--a Randomized Study.
    Date November 1995
    Journal Journal of Interventional Cardiology
    Excerpt

    Forty patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with severely impaired left ventricular ejection fraction (LVEF) < 30% were randomized between prophylactic intraaortic balloon pump (IABP) support (N = 20) and percutaneous cardiopulmonary bypass (PCPB) support (N = 20). The indications for both groups were left ventricular (LV) dysfunction and a large area of myocardium (> 50%) being perfused by the target vessel. The IABP and PCPB supported groups were comparable in LVEF (20% +/- 6.4% vs 22.8% +/- 8.1%), mean pulmonary artery pressure (46.5 +/- 10.5 mmHg vs 42.6 +/- 12.6 mmHg), average number of vessels dilated (1.4 vs 1.3), mean inflation time (2.8 +/- 0.3 min vs 3.1 +/- 0.5 min), and hospital stay after PTCA (5.6 +/- 1.2 days vs 5.2 +/- 1.4 days). The primary success rate (95% vs 95%) and hospital mortality (5% vs 5%) were also similar in the two groups. Two patients required surgical exploration of the femoral artery and eight patients required blood transfusion in the PCPB group. IABP patients had no vascular complications and did not require blood transfusion. High risk PTCA is equally effective whether using prophylactic IABP or PCPB support. PCPB support, however, has a higher rate of vascular complications and need for blood transfusions. IABP has the additional advantage of ease of insertion and the support can be used for a longer period after PTCA, if required.

    Title Late Rhythm Abnormalities After Surgical Repair of Tetralogy of Fallot: Noninvasive and Invasive Evaluation.
    Date November 1995
    Journal Indian Heart Journal
    Excerpt

    Twenty five patients aged 6 to 35 years (mean +/- SD: 14.2 +/- 7.1 years), surgically corrected for tetralogy of Fallot (TOF) more than one year ago, were assessed for rhythm abnormalities by resting electrocardiogram (ECG), twenty-four hours ambulatory ECG monitoring, signal averaged ECG and electrophysiological studies. An X-ray chest for assessing heart size, two dimensional and Doppler echocardiography for residual defects and radionuclide angiography for resting left ventricular ejection fraction were also done. Eight out of 25 (32%) patients were found to have significant rhythm abnormalities. Ventricular arrhythmias were detected in four patients. In two, ventricular tachycardia was induced during electrophysiologic studies, being sustained in one. Multiform ventricular ectopics were observed in two other patients. All these patients were operated, after the age of 10 years, and three of them are presently more than 20 years old. Cardiomegaly was present in the chest X-ray in three patients, and significant residual pulmonary stenosis was seen in one patient. Left ventricular ejection fraction was reduced in two, while signal averaged ECG was positive in one of the three cases subjected to this investigation. Supraventricular tachycardia (SVT) was observed in three patients. This was diagnosed by ambulatory ECG monitoring in all but in addition, was also inducible in one patient on electrophysiologic testing. There was no correlation of the occurrence of SVT with age or age at correction for TOF. None of these patients had any residual defect, cardiomegaly or subnormal left ventricular ejection fraction. Transient complete heart block requiring temporary pacing was documented in one patient with a large residual ventricular septal defect.(ABSTRACT TRUNCATED AT 250 WORDS)

    Title Nonsyndrome Familial Atrial Myxoma in Two Generations.
    Date October 1995
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Title Serial Echocardiography for Decision Making in Rapid Two-stage Arterial Switch Operation.
    Date October 1995
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND. Rapid two-stage arterial switch operation is advocated in infants with simple transposition presenting late. Accurate assessment of left ventricular preparation is crucial to successful outcome. The role of echocardiography alone in surgical decision making remains unclear. METHODS. Seventeen patients with simple transposition (mean age, 4 months) underwent pulmonary artery banding and modified Blalock-Taussig shunt (first stage) to prepare the left ventricle for the arterial switch operation (second stage). Serial echocardiography was performed in the interval phase to assess left ventricular growth. Sixteen patients underwent arterial switch operation after a mean interval of 10.4 +/- 4 days, with 14 successful conversions. There was one mortality (5.9%) and two conversions to a Senning repair. RESULTS. In all patients a mean increase in left ventricular mass (40.8 +/- 17.8 g/m2 to 81.4 +/- 25.4 g/m2) and posterior wall thickness (3.37 +/- 0.47 mm to 4.63 +/- 0.58 mm) was recorded. Left ventricular end-diastolic internal diameter increased in all except the two switch failures. In all the successful cases the left ventricle had assumed a circular shape on cross-section with the interventricular septum contracting in synergy with the left ventricular mass. In the two failures, however, the interventricular septum had remained flat. CONCLUSIONS. Echocardiography can be used reliably in surgical decision making in rapid two-stage arterial switch operation. Increase in left ventricular mass, left ventricular posterior wall thickness, and left ventricular end-diastolic internal diameter toward normal combined with an acquisition of circular left ventricular configuration with the interventricular septum contracting in synergy with the left ventricular mass appear to best predict successful outcome.

    Title Regrowth Resistance in Cancer: Why Has It Been Largely Ignored?
    Date September 1995
    Journal Cell Proliferation
    Excerpt

    In drug-sensitive malignancies, treatment failure is a complex phenomenon resulting from both drug resistance and the rapid regrowth of malignant cells in between cycles of chemotherapy. This phenomenon has been referred to as regrowth resistance, and has been identified as a common impediment to the successful treatment of many neoplastic diseases. This phenomenon has received little attention in the past. The administration of maximally tolerated individual dosages of chemotherapeutic agents, combined with the use of biological response modifiers to slow the regrowth between courses of therapy, would be an effective approach to reduce the regrowth resistance. This also could reduce the emergence of drug resistant clones.

    Title Systemic-to-pulmonary Artery Collateral Vessels and Surgical Shunts in Patients with Cyanotic Congenital Heart Disease: Perioperative Treatment by Transcatheter Embolization.
    Date June 1995
    Journal Ajr. American Journal of Roentgenology
    Excerpt

    OBJECTIVE. Systemic-to-pulmonary collateral vessels can develop in patients with obstruction of the right ventricular outflow tract or the pulmonary artery. Occlusion of these vessels is necessary before surgical correction of the primary disease. We report the results of transcatheter coil embolization in the treatment of 56 patients. MATERIALS AND METHODS. Seventy-four procedures were done in the perioperative period for treatment of 67 aortopulmonary collateral arteries, five modified Blalock-Taussig shunts, and two enlarged veins. RESULTS. In the "aortopulmonary collateral" group, occlusion was complete in 51 patients (76%), subtotal in seven (10%), partial in four (6%), and failed in five (8%). Inadvertent embolization to the aorta occurred in two procedures, but both coils were retrieved nonsurgically. During follow-up of 1-12 months (n = 32; mean, 6.3 months), the coils remained in position, without any migration. Follow-up angiograms in 14 embolized vessels showed no recanalization (mean, 5.3 months; range, 2-12 months). In the "shunt" group, occlusion was complete in four patients and failed in one. Distal embolization to the pulmonary artery occurred in one patient. This coil was retrieved during surgery. During follow-up of 3-6 months, coils remained in position in all patients. In one patient, a follow-up angiogram at 3 months showed no recanalization. In the "venous embolization" group, occlusion was complete in one patient. The coils were in position 5 months later. The procedure was unsuccessful in the other patient. CONCLUSION. We conclude that transcatheter coil embolization is useful in the treatment of abnormal systemic-to-pulmonary vessels and shunts in patients with obstruction of the right ventricular outflow tract or the pulmonary artery. Homemade coils are safe and effective in obliterating antegrade flow.

    Title The First Successful Heart Transplant in India.
    Date February 1995
    Journal The National Medical Journal of India
    Title Magnetic Resonance Imaging (mri) in Evaluation of Left Atrial Masses: an in Vitro and in Vivo Study.
    Date October 1994
    Journal The Journal of Cardiovascular Surgery
    Excerpt

    Thirty patients, 15 each of suspected of left atrial myxoma and clot were studied in a prospective study to assess the role of magnetic resonance imaging (MRI) in evaluation of left atrial masses. Upon clinical and echocardiographic suspicion of a left atrial mass, patients were subjected to ECG-gated MRI (in vivo study) and subsequently all of them underwent surgery for the removal of mass and/or mitral valve replacement/repair. Within 6 hours of its removal the mass was subjected to in vitro MRI study and subsequently to histopathological examination. During the study T1, T2 gated images were obtained and tissue characterization was done. A magnetic dye Gd-DTPA was used for contrast enhancement. Cine-display of the images was obtained to demonstrate dynamic movement of the mass across the mitral valve. MRI was found to be highly useful in delineating the exact anatomical details of left atrial masses. Results of MRI diagnosis with illustrations are discussed.

    Title Life-threatening Arterial Haemorrhage: Results of Treatment by Transcatheter Embolization Using Home-made Steel Coils.
    Date May 1994
    Journal Clinical Radiology
    Excerpt

    Major arterial haemorrhage can be fatal. Its management by percutaneous embolization using commercially available embolizing agents is well established. We describe the use of home-made steel coils in the treatment of five patients. These coils were designed during the procedure in order to conform to the dimension of the bleeding artery. The group included two patients with life-threatening haemoptysis after surgical correction for tetralogy of Fallot; one patient each with exsanguinating haemorrhage from a branch of the left profunda femoral artery following violent trauma; massive haematuria due to an inoperable hypernephroma; and haemoptysis due to post-tubercular bronchiectasis. The bleeding vessel was evaluated by selective angiography in each patient. After assessing its length and diameter, steel coils of desired dimensions were made by utilizing a conventional 0.032-in wide guidewire and these were released into the bleeding artery. Occlusion of the bleeding vessel was obtained in all patients, without complication. Fabrication of coils of desired length and diameter can be done within a few minutes during the procedure. These coils provide an effective method of treating life-threatening arterial haemorrhage in selected cases.

    Title Coil Embolization of a Blalock-taussig Shunt.
    Date March 1994
    Journal Indian Heart Journal
    Title Leiomyosarcoma of Urinary Bladder: a Case Report.
    Date March 1994
    Journal Indian Journal of Pathology & Microbiology
    Title High-risk Coronary Angioplasty Using Percutaneous Cardiopulmonary Bypass Support.
    Date June 1993
    Journal The National Medical Journal of India
    Excerpt

    BACKGROUND. Balloon angioplasty has a high success rate but results in abrupt closure of the vessel in 2% to 6% of patients. This can lead to haemodynamic collapse and death, particularly if the patient has poor left ventricular function. In the event of abrupt closure of the coronary vessels, such patients may not survive long enough to undergo emergency bypass surgery. The prophylactic use of cardiopulmonary bypass to support patients at high-risk for angioplasty has been reported recently. We describe our initial experience with this technique. METHODS. Eighteen high-risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high-risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < 25% in 13 patients). Triple-vessel disease was present in all of them. Angioplasty of the only remaining vessel was done in 12 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flow ranged from 2.8 to 4.5 litres and was discontinued after a mean of 35 minutes. Haemostasis was achieved by external clamp compression in 16 patients. RESULTS. The angioplasty was successfully performed in all the patients and was well tolerated. During the bypass period, the pulmonary artery diastolic pressure ranged from 0 to 8 mmHg. There was no hospital death. Two patients required surgical exploration of the femoral artery puncture site--one because of poor distal perfusion and the other for continued bleeding. During the follow up period of 1 to 10 months, 11 patients were free of angina and 1 had died. CONCLUSION. Our experience confirms that percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty is safe and effective.

    Title Congenital Asymptomatic Absence of Pericardium.
    Date June 1993
    Journal The Indian Journal of Chest Diseases & Allied Sciences
    Excerpt

    An interesting congenital anomaly of the pericardium is its absence. One such case is reported here. Recent literature is reviewed also.

    Title High Risk Coronary Angioplasty Using Percutaneous Cardiopulmonary Bypass Support.
    Date December 1992
    Journal Indian Heart Journal
    Excerpt

    Twenty high risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < or = 25% in 15 patients). Three vessel disease was present in all. Angioplasty of the only remaining vessel was done in 14 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flows ranged from 2.8-4.5 litres. Bypass was discontinued after a mean bypass time of 35 min. Haemostasis was achieved by external clamp compression in 16 patients. The angioplasty was successfully performed in all the patients and the procedure was well tolerated. During the bypass period the pulmonary artery diastolic pressures ranged from 0-8 mm Hg. There was 1 hospital death due to abrupt vessel closure. Two patients required surgical help to repair femoral artery. During the follow up period of 1-12 months, 67% patients have no angina and only 1 has died. Our experience demonstrates the safety and efficacy of percutaneous bypass support in selected patients undergoing high risk coronary angioplasty.

    Title Comparison of Immediate Hemodynamic Response to Closed Mitral Commissurotomy, Single-balloon, and Double-balloon Mitral Valvuloplasty in Rheumatic Mitral Stenosis.
    Date December 1992
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    The hemodynamic response to closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty was compared using 20 patients in each group. All patients had symptomatic rheumatic mitral stenosis with a mitral valve area < 1 cm2, without any left atrial clot, mitral valve calcification, or mitral regurgitation. There was a significant improvement in hemodynamics following intervention in all three groups. The mean pulmonary artery pressure decreased from 49.1 +/- 17.5 to 28.6 +/- 8.3 mm Hg (p < 0.001), 48.8 +/- 12.3 to 34.0 +/- 13.9 mm Hg (p < 0.001), and 46.7 +/- 18.0 to 26.3 +/- 13.7 mm Hg (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The mitral valve area increased from 0.62 +/- 0.27 to 1.5 +/- 0.5 cm2 (p < 0.001), 0.68 +/- 0.24 to 1.5 +/- 0.4 cm2 (p < 0.001), and 0.68 +/- 0.25 to 1.9 +/- 0.8 cm2 (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The increase in the mitral valve area was maximum in the group with double-balloon mitral valvuloplasty. In the closed mitral commissurotomy group there was a significant rise in left ventricular end-diastolic pressure, from 6.8 +/- 3.9 to 9.3 +/- 3.1 mm Hg (p < 0.001), but this remained unchanged in the single-balloon and double-balloon mitral valvuloplasty groups. Our study shows that single-balloon and double-balloon mitral valvuloplasty are comparable to closed mitral commissurotomy in the immediate hemodynamic response, with a larger valve area in the double-balloon mitral valvuloplasty group.

    Title Prospective Controlled Study of Post-transfusion Hepatitis After Cardiac Surgery in a Large Referral Hospital in India.
    Date September 1992
    Journal Liver
    Excerpt

    We studied the risk of post-transfusion hepatitis (PTH) in recipients of blood collected from voluntary donors screened for HBsAg. Two hundred and fifty patients without any previous history of liver disease or transfusion were followed up for 12 months subsequent to cardiac surgery. Thirty-five of them had closed-heart surgery without receiving transfusion and served as controls. The remaining 215 patients received single-point transfusions (mean 4 +/- 2.4 units). None of the controls and 15 (6.9%) blood recipients developed PTH. Three (20%) patients had hepatitis-B-virus-induced hepatitis while the remainder (80%) had non A, non B (NANB) hepatitis. The number of units of blood transfused and surrogate markers for development of PTH (donor alanine aminotransferase, anti-HBc and anti-HBs antibody) were not associated with the occurrence of PTH (p greater than 0.05). Nine (60%) of the 15 patients developing PTH were asymptomatic. All the patients recovered from the PTH, except one who died of fulminant hepatitis. At the end of 1 year of follow-up, none of the patients had evidence of chronic hepatitis. Only three (25%) of the patients with NANB-PTH developed anti-hepatitis C virus (HCV) antibody during the follow-up. We conclude that the incidence of PTH in India is similar to other parts of the world and NANB virus was the major cause of the PTH. The absence of chronicity and lack of seroconversion to anti-HCV antibody in the majority of the patients after 1 year of follow-up may suggest the possibility of a NANB virus other than HCV as the major cause of PTH in India.

    Title Left Ventricular Pseudoaneurysm Following Infective Endocarditis--a Case Report.
    Date August 1992
    Journal Indian Heart Journal
    Excerpt

    A patient with pseudoaneurysm involving anterolateral border of left ventricle following infective endocarditis of aortic valve with severe aortic incompetence is reported. He showed clinical improvement after aneurysmectomy and aortic valve replacement.

    Title Thrombolytic Therapy for Prosthetic Valve Thrombosis: a Study Based on Serial Doppler Echocardiographic Evaluation.
    Date July 1992
    Journal American Heart Journal
    Excerpt

    Sixteen patients with echocardiographic and cinefluoroscopic evidence of Björk-Shiley prosthetic valve obstruction (13 mitral valves and 3 aortic valves) were treated with intravenous streptokinase. Streptokinase was administered as an initial bolus of 250,000 units for 30 minutes, followed by an infusion of 100,000 units/hr. Serial cinefluoroscopy and echocardiography (M-mode, two-dimensional, and Doppler) were performed at 0, 24, 48, and 72 hours of treatment. The end point of treatment was defined as near normalization of clinical, echocardiographic, and fluoroscopic parameters. Successful thrombolysis was achieved in all patients. The average duration of streptokinase therapy was 43 hours (range 2 to 72 hours). Two of 16 patients had minor systemic embolism during therapy. Short-term follow-up has shown sustained benefit in 14 of 16 patients. Two patients have had rethrombosis of the mitral prosthetic valves and have undergone thrombectomy. Our study demonstrates the feasibility, safety, and efficacy of thrombolytic therapy in the treatment of prosthetic valve thrombosis. It also emphasizes the role of serial Doppler echocardiography in guiding the duration of therapy and assessing its efficacy.

    Title Carcinoma of the Rectal Pouch Following Restorative Proctocolectomy. Report of a Case.
    Date March 1992
    Journal Diseases of the Colon and Rectum
    Excerpt

    A case of adenocarcinoma developing in the pouch following restorative proctocolectomy is presented. This seems to be the third reported in the literature. The carcinoma developed from the remnants of precancerous rectal mucosa left in the muscular rectal cuff. The patient had been suffering from ulcerative colitis for 17 years prior to the development of the malignancy. He presented with features of subacute intestinal obstruction. Diagnosis was by sigmoidoscopic examination of the pouch and biopsy. He was treated with abdominoperineal resection of the pouch and rectum, followed by chemotherapy.

    Title Comparison of Left Coronary and Laevo-phase Pulmonary Angiograms in Detecting Left Atrial Thrombi in Rheumatic Mitral Stenosis.
    Date September 1991
    Journal Clinical Radiology
    Excerpt

    We have compared the diagnostic accuracy of left coronary and laevo-phase pulmonary angiograms in detecting left atrial thrombi in 27 consecutive patients with rheumatic mitral stenosis who underwent both these procedures prior to open-heart surgery. In 10 patients, both procedures were 'positive' for thrombus, confirmed at subsequent surgery in all instances (true positive). Both procedures were negative for thrombus in 11 patients, and none of these patients showed thrombi at subsequent surgery (true negative). Left coronary angiography only was positive for thrombus in one patient in whom no thrombus was found at surgery. Laevo-phase pulmonary angiography only was positive for thrombus in five patients, two of whom had thrombus at subsequent surgery. The sensitivity, specificity and predictive accuracy of left coronary angiogram were 83.3% and 93.3% and 90.9% and that of laevo-phase pulmonary angiogram 100%, 80% and 80% respectively. Laevo-phase pulmonary angiograms showed higher sensitivity and left coronary angiograms showed higher specificity for angiographic diagnosis. However, the differences were found to be statistically insignificant. Angiography is a reliable method for detecting left atrial thrombi if both left coronary and pulmonary angiograms are performed and both procedures are positive or negative for thrombus.

    Title Profile of Coronary Arterial Disease in Diabetic Patients Undergoing Coronary Arterial Bypass Grafting.
    Date September 1991
    Journal International Journal of Cardiology
    Excerpt

    Diabetics are believed to have more extensive and diffuse lesions of the coronary arteries in presence of coronary arterial disease. We studied prospectively 52 diabetics with coronary arterial disease who underwent coronary arterial bypass grafting and evaluated their pre-operative symptomatology, angiographic appearance of coronary arteries, coronary arterial dimensions as assessed at surgery, and the post-operative complications. These were compared to 52 age and sex matched non-diabetic controls undergoing surgery during the same period. There was no statistically significant difference in the incidence of pre-operative symptomatology or frequency of myocardial infarction in the two groups. Left ventricular angiographic findings were also comparable, as was the observation on the extent and severity of coronary arterial disease as assessed by angiography and at surgery. Hence, we recommend coronary arterial bypass grafting to diabetics with the same criteria as are applied to non-diabetics, confident that there will be no added morbidity and mortality.

    Title Immunohistochemical Characterization of Aschoff Nodules and Endomyocardial Inflammatory Infiltrates in Resected Left Atrial Appendages.
    Date July 1991
    Journal Indian Heart Journal
    Excerpt

    Presence of Aschoff nodules and other chronic inflammatory cells in the left atrial appendage even in the absence of rheumatic activity has been reported in a high percentage of patients with chronic rheumatic valvular heart disease. This study was conducted on 37 left atrial appendages resected at the time of closed mitral valvotomy. Aschoff nodules were present in 61.2 percent of resected appendages, positivity being 71.4 percent in the age group of 20 years of less and 53.3 percent in patients more than 20 years of age. The histological findings did not change significantly in the presence of activity. The frequency of Aschoff nodules and chronic inflammatory cells and their subtypes also did not show any correlation with age, sex, duration of symptoms or severity of mitral stenosis.

    Title Chest Radiographs Are Unreliable in Predicting Thrombi in the Left Atrium or Its Appendage in Rheumatic Mitral Stenosis.
    Date June 1991
    Journal Clinical Radiology
    Excerpt

    We have assessed the diagnostic accuracy of a flat or concave left mid-cardiac border (the region of the left atrial appendage) on conventional postero-anterior chest radiographs as a predictor of the presence of thrombi in the left atrium or its appendage in 80 patients with rheumatic mitral stenosis who subsequently underwent open-heart surgery. Forty-six patients (Group I) were found to have left atrial thrombus at surgery whereas 34 patients (Group II) showed no evidence of thrombosis. Only 22 of 46 patients in Group I showed a flat or concave left mid-cardiac border (sensitivity, 48%; specificity, 53%; positive predictive value, 58%). Furthermore in Group 1, the thrombus involved the left atrial appendage in 33 patients. In this subgroup only 14 patients showed a flat or concave left mid-cardiac border (sensitivity, 42%; specificity, 49%; positive predictive value, 37%). The presence of flatness or concavity in the left mid-cardiac border on conventional posterior-anterior chest radiographs in patients with rheumatic mitral stenosis is an unreliable indicator of the presence of thrombi in the left atrium or its appendage.

    Title Intravenous Digital Subtraction Angiography in the Pre-operative Evaluation of Coarctation of the Thoracic Aorta.
    Date May 1991
    Journal Indian Heart Journal
    Excerpt

    Many authors have previously advocated the use of intravenous digital subtraction angiography (IV-DSA) in the pre-operative evaluation of coarctation of aorta with excellent results and good surgical correlation. We have studied 20 patients with coarctation of aorta by IV-DSA and compared the angiographic findings with those seen at surgery in nine patients. The IV-DSA examinations were performed by utilizing small-volume (25 ml), bolus injections of an ionic, iodinated water soluble contrast medium delivered in the mid-right atrium. Good quality diagnostic arterial images were obtained in 14 patients (70 per cent). Associated cardiac decompensation and inability to profile the coarct segment due to overlap by surrounding dilated blood vessels were responsible for the unsuccessful examinations. Whereas most IV-DSA findings were confirmed at surgery, the calibre and length of the coarct segment at IV-DSA were found to be unreliable predictors of the actual severity of the coarctation. The IV-DSA images failed to detect a localized diaphragm at the coarct site in two patients. Even though IV-DSA is useful for the diagnosis of aortic coarctation, the surgeon must be aware of its pitfalls in assessing the calibre and length of the coarct segment.

    Title Mitral Valve Repair: Techniques and Results.
    Date January 1991
    Journal Indian Heart Journal
    Excerpt

    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.

    Title Left Coronary Angiography in the Pre-operative Diagnosis of Thrombosis of the Left Atrium or Its Appendage in Rheumatic Mitral Stenosis.
    Date November 1990
    Journal Clinical Radiology
    Excerpt

    We studied the utility of pre-operative selective left coronary angiograms for detecting thrombosis in the left atrium or its appendage in 81 patients with rheumatic mitral stenosis, who subsequently underwent open-heart surgery. Thrombus was predicted by the angiographic demonstration of neovascularity seen as a bunch of small vessels arising from the circumflex branch of the left coronary artery coursing superiorly to the region of the left atrial appendage and terminating in a network of smaller vascular channels with a blush of contrast medium coalescing into small 'lakes'. This pooling of contrast medium was considered essential for positive angiographic diagnosis. Based on these criteria, the angiographic diagnosis of thrombus was made in 27 patients. Thrombus was found in 33 patients at surgery. Selective left coronary angiography had a sensitivity of 72.7%, specificity of 92.7% and predictive value of 88.8% for detecting thrombi in the left atrium or its appendage. Coronary angiography should be performed in all the patients with mitral stenosis who are undergoing cardiac catheterization especially if balloon mitral valvoplasty or closed mitral valvotomy are planned.

    Title Effect of Hydroxyurea on Foetal Haemoglobin in Myeloproliferative & Myelodysplastic Syndromes.
    Date August 1990
    Journal The Indian Journal of Medical Research
    Excerpt

    The effect of hydroxyurea on foetal haemoglobin (HbF) levels was evaluated in 36 patients of myeloproliferative and myelodysplastic disorders. In 17 (47.2%) patients, HbF levels increased from 1.40 +/- 1.17 to 3.03 +/- 1.97 per cent after 4 wk therapy with hydroxyurea. In the responders this increase was highly significant (P less than 0.001). The rise in the HbF levels after hydroxyurea therapy was significant in patients with chronic myeloid leukaemia but not in the other groups.

    Title Efficacy of Pre-operative Levo-phase Pulmonary Angiograms in Detecting Left Atrial Thrombi.
    Date February 1990
    Journal Indian Heart Journal
    Excerpt

    We have studied the efficacy of levo-phase pulmonary angiograms in detecting thrombosis of the left atrium or its appendage in 33 patients with rheumatic mitral stenosis who subsequently underwent open-heart surgery. Left atrial thrombi had been suspected in all these patients due to the presence of atrial fibrillation and/or history of systemic embolization. The angiographic criteria for the presence of thrombus included mobile or persistent fixed filling defects of constant size in the contrast shadow of the left atrium or its appendage, partial or complete non-visualization of the left atrial appendage, irregular outline of the left atrium or its appendage and an atrial chamber which appeared smaller than the atrial shadow. 19 patients showed one or more angiographic features of thrombosis. All the patients subsequently underwent open-heart surgery for mitral valve disease, and thrombi were found in 17 patients. The angiogram was false positive in three patients, and false negative in one patient. The angiographic diagnosis of left atrial thrombosis by levo-phase pulmonary angiography has a sensitivity of 94%, specificity of 81.3%, and predictive value of 84.2%. Non-visualization of left atrial appendage as the only feature of thrombus formation was seen in five patients, and thrombi were subsequently formed at surgery in four patients (80%). Levo-phase pulmonary angiograms are safe and reasonably accurate for preoperatively detection of left atrial thrombi, and should be performed in all the patients of mitral stenosis if left atrial thrombi are clinically suspected.

    Title Multiple Myeloma. Analysis of Fifty Cases.
    Date January 1990
    Journal The Journal of the Association of Physicians of India
    Excerpt

    Fifty patients of multiple myeloma have been studied. Seventy eight per cent of the patients were in the 5th, 6th and 7th decades of life. Commonest presenting feature was bone pains (76%). 8%, 20% belonged to stage I, II and III respectively. Skull (58%), ribs (52%) and pelvis (24%) were most commonly involved. Immunoelectrophoresis revealed IgG type of myeloma in 76% and IgA type in 10% cases. Bence-Jones proteinuria was seen in 60% of patients; Kappa specificity was commoner than lambda. Overall survival at 30 months was 50%. The survival was adversely influenced by advanced stage, higher plasma cell count in the bone marrow, low haemoglobin and high serum creatinine values.

    Title Functional, Malignant Intrathoracic Paraganglioma.
    Date December 1989
    Journal Postgraduate Medical Journal
    Excerpt

    This paper describes a case of functional, malignant branchiomeric paraganglioma, the third such to be reported. The patient presented with malignant hypertension and symptoms suggestive of excessive catecholamine secretion.

    Title Congenital Systemic Mastocytosis.
    Date September 1989
    Journal Indian Pediatrics
    Title Secondary Acute Leukemia--review of 15 Cases.
    Date May 1989
    Journal Indian Journal of Cancer
    Title Castleman's Disease--an Unusual Cause of Mediastinal Mass.
    Date March 1989
    Journal The Indian Journal of Chest Diseases & Allied Sciences
    Title Central Nervous System Involvement in Adult Acute Myeloblastic Leukaemia.
    Date December 1988
    Journal The Journal of the Association of Physicians of India
    Title Supportive Care in the Management of Acute Myeloid Leukaemia.
    Date June 1988
    Journal The Journal of the Association of Physicians of India
    Title Prosthetic Mitral Valve Mucormycosis Caused by Mucor Species.
    Date January 1988
    Journal International Journal of Cardiology
    Excerpt

    We report, to the best of our knowledge the first case of prosthetic mitral valve mucormycosis caused by Mucor species in an 18-year-old female after mitral valve replacement. She was successfully treated with surgery and antifungal treatment. Mucormycosis was documented by direct demonstration, isolation and histopathological findings of the fungus from embolus and prosthetic mitral valve thrombus.

    Title Nephrotic Syndrome of Amyloid Etiology in Hodgkin's Disease.
    Date October 1987
    Journal Indian Journal of Cancer
    Title Assessment of Rest and Exercise Ventricular Function Following Coronary Artery Bypass Surgery by Radionuclide Ventriculography.
    Date October 1986
    Journal Indian Heart Journal
    Title Permanent Pacemaker Complications: a 16 Years Experience.
    Date September 1986
    Journal The Journal of the Association of Physicians of India
    Title Cine-fluororadiographic Evaluation of the Björk-shiley Prosthesis--a Serial Post-operative Follow-up in 400 Patients.
    Date August 1986
    Journal Australasian Radiology
    Title Thrombosis of Björk-shiley Valve Prostheses. Evaluation by Cineradiography.
    Date March 1984
    Journal Acta Radiologica: Diagnosis
    Excerpt

    Cineradiography is the most accurate and rapid method in evaluation of the function of Björk-Shiley prosthetic valves manufactured after late 1975 and which incorporate a tantalum foil hoop into the disc. This helps in demonstration of the disc and in the calculation of the opening angle of the disc. In the present series 8 cases with valve dysfunction have been correctly diagnosed by conventional cineradiography, 7 in the mitral and one in the aortic position. In all 8 cases and also in the group of 300 postoperative cases having no symptoms, the opening angle has been measured by the method described by Venkataraman et coll. in 1980. It is recommended that in accordance with the suggestions of these authors, the opening angle should be established for each patient in the immediate postoperative period in order to provide a basis for possible future examinations.

    Title In Vitro Susceptibility of Pseudomonas Pyocyanea Strains to a New Antimicrobial Agent Derived from Almond (prunus Amygdalis) Shells.
    Date June 1973
    Journal The Indian Journal of Medical Research
    Title Pentoxifylline, Ciprofloxacin and Dexamethasone Improve the Ineffective Hematopoiesis in Myelodysplastic Syndrome Patients; Malignancy.
    Date
    Journal Hematology (amsterdam, Netherlands)
    Excerpt

    Twenty-five patients with a diagnosis of myelodysplastic syndromes (MDS) were randomized to either begin therapy with pentoxifylline, ciprofloxacin and dexamethasone (PCD) immediately (10 patients) or after a 12 week observation period (control arm, 15 patients). PCD was administered with the goal of suppressing cytokine-induced excessive intramedullary apoptosis of hematopoietic cells. No marked fluctuations of blood counts were noted during the period of observation. Twenty-two patients completed at least 12 weeks of therapy: 18/22 showed some type of hematologic response, 9/18 showing an improvement in absolute neutrophil count only (p = < 0.001) and 9/18 showing multi-lineage responses. No unique category of MDS responded better, however 19/25 patients had refractory anemia (RA)/RA with ringed sideroblasts. The median time to response was 6 weeks and 3/18 responding patients maintained their responses beyond a year. We conclude that hematologic improvement in response to PCD therapy supports the validity of this unique anti-cytokine approach. Future trials should combine PCD therapy with established approaches (growth factors/chemotherapy) and also should focus on identifying more effective ways of suppressing the pro-apoptotic cytokines in MDS.

    Title Results Of Open Heart Surgery In The First Year Of Life.
    Date
    Journal Cardiovascular Diseases
    Title Troponin-i Release After Cardiac Surgery with Different Surgical Techniques and Post-operative Neurological Outcomes.
    Date
    Journal Mcgill Journal of Medicine : Mjm : an International Forum for the Advancement of Medical Sciences by Students
    Excerpt

    Cerebral hypoperfusion during cardiopulmonary bypass surgery has been thought to be a factor in the aetiology of brain damage with evidence of post-operative neurological deficits. Cardiac-specific biomarkers such as troponin-I, troponin-T and CK-MB have been used extensively to predict myocardial injury and ischaemia. This prospective study investigateed the level of troponin-I release in both off-pump and CPB-technique CABG surgery, as well as postulated a relationship of troponin release and post-operative neurological outcome. A total of 44 adult patients undergoing coronary artery bypass graft (CABG) were enrolled into either an off-pump or on-pump groups, with 22 patients participating in each. Group A (on-pump) underwent myocardial revascularisation with CPB and cardioplegic arrest, while Group B (off pump) underwent beating heart surgery. The measurement of troponin-I is a 1-step enzyme immunoassay method, with specificity and sensitivity set at 0.4 ug/mL. Neurological assessment was done using the NIH Stroke Scale, and neuropsychologic assessment was assessed on cognitive function using modified Weschler Memory Scale, for which scores were standardized to achieve a composite measure of concentration. A set of statistical analysis was done to correlate troponin-I release with different surgical techniques of CPB and OPCAB. Although each independent technique showed a marked rise of troponin-I from baseline to 6 hours post-operatively, the difference in troponin release was not significant between the 2 groups at specified time intervals (p=0.124). There was however a significant correlation of troponin-I release with the number of grafts used in the surgery, irrespective of the type of grafts or surgical technique. None of the patients in either group showed any neurological or cognitive deficits presenting at day 3 and day 7 post-operatively. The findings of this study demonstrate that there is no significant short-term cognitive or neurological dysfunctions post-operatively, as indicated by troponin-I release in assessing the severity of myocardial injury.

    Title Gm-csf Plus Rituximab Immunotherapy: Translation of Biologic Mechanisms into Therapy for Indolent B-cell Lymphomas.
    Date
    Journal Leukemia & Lymphoma
    Excerpt

    Historically, patients with indolent non-Hodgkin lymphomas (NHL) have been treated with radiotherapy, chemotherapy or a combination of these therapies. The introduction of biologic agents, most notably rituximab, a monoclonal antibody targeting cell-surface CD20 present on B-cell NHL cells, has enhanced patient response rates; however, relapse continues to limit long-term disease-free survival. Recent advances in the treatment of patients with indolent B-cell NHL have taken two directions--combining rituximab with chemotherapy or enhancing rituximab-mediated mechanisms of action. The combination of rituximab with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) takes the second approach and appears to lead to improved patient responses over rituximab monotherapy without compromising its tolerability profile. GM-CSF functions by increasing the numbers and cytotoxic activity of effector cells, perhaps in part by increasing the expression of some cell surface molecules (i.e., receptors, antigens). The combined biologic effects of GM-CSF and rituximab appear promising in that they might enhance a patient's inherent immune response against malignant cells. The biologic effects of these individual and combined immunotherapeutic agents, with or without chemotherapy, and their translation into patient outcomes are reviewed here.

    Title Idiopathic Hemophagocytic Syndrome with a Fulminant Clinical Course.
    Date
    Journal Clinical Advances in Hematology & Oncology : H&o
    Title Strategies for Prostate Cancer Prevention: Review of the Literature.
    Date
    Journal Indian Journal of Urology : Iju : Journal of the Urological Society of India
    Excerpt

    The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing treatment-related adverse events, cost of treatment of the disease and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its high incidence and prevalence, increased disease-related mortality, long latency and molecular pathogenesis and epidemiological data indicating that modifiable environmental factors may decrease risk. Various agents have been suggested to prevent prostate cancer and many clinical trials are currently on. Ultimately the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used. This article is aimed to examine the experimental and epidemiological data spanning a period of 1998 to 2007, demonstrating the chemopreventive activity, safety and toxicity of various nutritional elements and other agents that can help prevent prostate cancer and/or slow disease progression.

    Title A Letter.
    Date
    Journal Indian Journal of Urology : Iju : Journal of the Urological Society of India
    Title Bovine Jugular Vein Valved Conduit: Up to 10 Years Follow-up.
    Date
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: The present study evaluated the mortality and conduit failure in bovine jugular vein (BJV) conduits. METHODS: Between October 1999 and February 2009, 193 patients (mean age, 6.7 ± 5.8 years; range, 5 days to 18 years; mean weight, 23.9 ± 21.0 kg; range 2.4-105.4 kg) had been discharged after BJV implantation. The reason for BJV implantation was right ventricular outflow tract reconstruction in 117 conduit replacement in 44, and the Ross procedure in 32. The diameter of the BJV was 12 mm in 18 patients (9.3%), 14 mm in 16 (8.3%), 16 mm in 42 (21.7%), 18 mm in 37 (19.2%), 20 mm in 15 (7.8%), and 22 mm in 65 (33.7%). RESULTS: At a mean ± SD follow-up of 4.6 ± 2.3 y/patient (range, 8 months to 10 years), 5 late deaths (2.6%) had occurred, all unrelated to conduit failure. Conduit-related problems required an interventional procedure as the first treatment in 10 patients (5.2%) within a mean interval of 2.5 ± 1.4 years (range, 8 months to 5.3 years) or surgical revision in 5 patients (2.6%) after 2.1 ± 1.9 years (range, 19 days to 4.1 years). Late deaths occurred in 5.9% (2/34) of patients with a BJV size of 12 to 14 mm versus 1.9% (3/159) in patients with a size of 16 to 22 mm (P = NS). An interventional procedure or surgical revision was required in 29.4% (10/34) of patients with a BJV size of 12 to 14 mm versus 3.1% (5/159) in patients with a size of 16 to 22 mm (P < .0005). CONCLUSIONS: After 10 years of experience with the BJV, this conduit has remained a reliable alternative to pulmonary homografts with respect to survival and freedom from conduit failure. However, the incidence was greater and the presentation of conduit failure was earlier in patients with a smaller size BJV conduit (12-14 mm).

    Title Efficacy and Safety of Clofarabine in Relapsed And/or Refractory Non-hodgkin Lymphoma, Including Rituximab-refractory Patients.
    Date
    Journal Cancer
    Excerpt

    BACKGROUND:: Currently, no standard therapy exists for patients with relapsed and/or refractory non-Hodgkin lymphoma (NHL) who are ineligible for transplantation or who have failed after bone marrow transplantation. The authors of this report investigated the safety and efficacy of clofarabine (CLO) in these patients. METHODS:: In a 2-step, open-label study, CLO (as a 1-hour intravenous infusion given daily for 5 days) was given every 28 days (maximum, 6 cycles). In the phase 1 portion (n = 7; standard 3 + 3 study design), the dose was escalated by 2 mg/m(2) to determine the maximum tolerated dose (MTD). The phase 2 study (n = 26) was initiated at the MTD, and patients were followed until disease progression. RESULTS:: Of 33 patients who were enrolled, 31 patients (median age, 69 years) were evaluable; 24% failed after previous stem cell transplantation, and 72% were rituximab-refractory. The MTD for CLO was 4 mg/m(2). The overall response rate was 42%. Seven patients (23%) achieved a complete response, and 6 patients (19%) achieved a partial response. The median response duration was 5 months. Among the rituximab-refractory patients, the overall response rate was 47% (complete response rate, 28%), and the median response duration was 7 months. At a median follow-up of 14 months, 45% of patients remained alive (median overall survival, 10 months). Toxicity was mainly hematologic (≥60% of patients had neutropenia or thrombocytopenia). Nonhematologic toxicity included tumor lysis syndrome, infection, and renal insufficiency (in 6% of patients each). No treatment-related mortality was observed. CONCLUSIONS:: Single-agent CLO was active and was tolerated well in patients with refractory NHL, including patients in a rituximab-refractory subset. Reversible myelosuppression was the major toxicity. Study is registered at www.clinicaltrials.gov (NCT00156013). Cancer 2010. © 2010 American Cancer Society.

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