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Biomedical subjects

P Venugopal

Publications and source records attributed to P Venugopal.

At least 37 records · Page 2Linked to original sources
PubMed2001

High remission rate in acute myeloblastic leukemia with only two days of chemotherapy.

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.

Adult↗
PubMed2001

Infective complications of central venous catheters in cardiac surgical patients.

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.

Adolescent↗
PubMed2000

Tumor necrosis factor modulates CD 20 expression on cells from chronic lymphocytic leukemia: a new role for TNF alpha?

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.

Antibodies, Monoclonal↗
PubMed2000

Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone.

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)

Adult↗
PubMed2000

Cytokine production by in vitro processed and unprocessed haematopoietic cells.

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.

Bone Marrow Cells↗
PubMed2000

SCF, IL-1beta, IL-1ra and GM-CSF in the bone marrow and serum of normal individuals and of AML and CML patients.

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.

Biopsy↗
PubMed2000

Univentricular repair: is routine fenestration justified?

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.

Actuarial Analysis↗
PubMed2000

Neurological evaluation and intelligence testing in the child with operated congenital heart disease.

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.

Brain Damage, Chronic↗
PubMed2000

Right ventricular outflow tract after non-conduit repair of tetralogy of Fallot with coronary anomaly.

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.

Child↗
PubMed2000

Efficacy of aprotinin, epsilon aminocaproic acid, or combination in cyanotic heart disease.

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.

Adolescent↗
PubMed2000

Surgical myocardial revascularization without cardiopulmonary bypass.

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.

Adult↗
PubMed2000

Poor prognosis acute myelogenous leukemia 2--biological and molecular biological characteristics and treatment outcome.

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.

Amifostine↗
PubMed2000

Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine).

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.

Adult↗
PubMed2000

Effects of cytokines on CD20 antigen expression on tumor cells from patients with chronic lymphocytic leukemia.

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.

Antigens, CD20↗
PubMed2000

Adenosine for cardioplegic induction: a comparison with St Thomas solution.

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.

Adenosine↗
PubMed2000

Signal antonymy unique to myelodysplastic marrows correlates with altered expression of E2F1.

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.

Apoptosis↗