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Biomedical subjects

R S Iyer

Publications and source records attributed to R S Iyer.

At least 19 recordsLinked to original sources
PubMed1997

Outcomes after delayed sternal closure in pediatric heart operations: a 10-year experience.

BACKGROUND: Open heart operations in young children may lead to myocardial swelling and increased lung water. Decreased intrathoracic space may then make sternal closure difficult. Delayed sternal closure may be beneficial in this setting. Potential risks of delayed sternal closure are sepsis and sternal instability. METHODS: To assess these risks, we reviewed retrospectively 150 consecutive children who underwent delayed sternal closure after repair of complex congenital cardiac defects. RESULTS: Diagnoses included transposition of the great arteries (66), total anomalous pulmonary venous drainage (11), and complete atrioventricular septal defects (10). Age at operation was 229 +/- 51 days (mean +/- standard error of mean). Sixteen patients required extracorporeal membrane oxygenation. Survival was 88% (133 patients). The sternum was left open for 3.86 +/- 0.29 days. Fifteen patients had minor wound infections requiring antibiotics. No patient required reexploration for mediastinitis and no patient had an unstable sternum. CONCLUSIONS: Delayed sternal closure with sternal stenting and silicone membrane skin closure is a safe procedure in infants and children with compromised cardiac output after repair of congenital cardiac defects.

Cardiac Surgical Procedures↗
PubMed1996

A viral genome containing an unstable aflatoxin B1-N7-guanine DNA adduct situated at a unique site.

A problem that has hindered the study of the biological properties of certain DNA adducts, such as those that form at the N7 atoms of purines, is their extreme chemical lability. Conditions are described for the construction of a single-stranded genome containing the chemically and thermally labile 8,9-dihydro-8- (N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct, the major DNA adduct of the potent liver carcinogen aflatoxin B1 (AFB1). A 13mer oligonucleotide, d(CCTCTTCGAACTC), was allowed to react with the exo-8,9-epoxide of AFB1 to form an oligonucleotide containing a single AFB1-N7-Gua (at the underlined guanine). This modified 13mer was 5'-phosphorylated and ligated into a gap in an M13 bacteriophage genome generated by annealing a 53mer uracil-containing scaffold to M13mp7L2 linearized by EcoRI. Following ligation, the scaffold was enzymatically removed with uracil DNA glycosylase and exonuclease III. The entire genome construction was complete within 3 h and was carried out at 16 degrees C, pH 6.6, conditions determined to be optimal for AFB1-N7-Gua stability. Characterization procedures indicated that the AFB1-N7-Gua genome was approximately 95% pure with a small (5%) contamination by unmodified genome. This construction scheme should be applicable to other chemically or thermally unstable DNA adducts.

Aflatoxin B1↗
PubMed1996

Mutational properties of the primary aflatoxin B1-DNA adduct.

The mutagenic activity of the major DNA adduct formed by the liver carcinogen aflatoxin B1 (AFB1) was investigated in vivo. An oligonucleotide containing a single 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-N7-Gua) adduct was inserted into the single-stranded genome of bacteriophage M13. Replication in SOS-induced Escherichia coli yielded a mutation frequency for AFB1-N7-Gua of 4%. The predominant mutation was G --> T, identical to the principal mutation in human liver tumors believed to be induced by aflatoxin. The G --> T mutations of AFB1-N7-Gua, unlike those (if the AFB1-N7-Gua-derived apurinic site, were much more strongly dependent on MucAB than UmuDC, a pattern matching that in intact cells treated with the toxin. It is concluded that the AFB1-N7-Gua adduct, and not the apurinic site, has genetic requirements for mutagenesis that best explain mutations in aflatoxin-treated cells. While most mutations were targeted to the site of the lesion, a significant fraction (13%) occurred at the base 5' to the modified guanine. In contrast, the apurinic site-containing genome gave rise only to targeted mutations. The mutational asymmetry observed for AFB1-N7-Gua is consistent with structural models indicating that the aflatoxin moiety of the aflatoxin guanine adduct is covalently intercalated on the 5' face of the guanine residue. These results suggest a molecular mechanism that could explain an important step in the carcinogenicity of aflatoxin B1.

Aflatoxin B1↗
PubMed1996

Expanded PTFE membrane to prevent cardiac injury during resternotomy for congenital heart disease.

BACKGROUND: Resternotomy for repair of congenital cardiac defects can result in cardiac injury. Closure of the pericardium during the initial operation may prevent this, and several pericardial substitutes have been tried, with variable results, in patients in whom primary pericardial closure is not possible. We conducted a multicenter observational study of the use of the expanded polytetrafluoroethylene membrane (Preclude Pericardial Membrane, formerly called the Gore-Tex Surgical Membrane; W. L. Gore & Associates, Flagstaff, AZ) in patients likely to undergo reoperation for treatment of congenital heart disease. METHODS: Data were collected retrospectively on all patients in whom the expanded polytetrafluoroethylene membrane was inserted at the initial operation for congenital heart disease at 12 centers in 1984 to 1993. RESULTS: A total of 1,085 patients (mean age, 55 +/- 2.5 months) received the membrane. During follow-up ranging from 1.3 to 10.5 years, 105 reoperations were performed. Injury during resternotomy occurred in only 1 patient (1% of reoperations). There were no membrane-related deaths or complications in the entire series of 1,085 patients. CONCLUSIONS: The expanded polytetrafluoroethylene membrane was safe and effective in helping to prevent cardiac injury during resternotomy for treatment of congenital heart disease.

Child, Preschool↗
PubMed1995

Changes in the concentration of endothelin-1 during development of hypertensive rats.

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 +/- 43 pg/g tissue) rats was lower than that of WKY (452 +/- 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 +/- 33 pg/g tissue) rats were higher compared to WKY (439 +/- 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 +/- 33 pg/g tissue) compared to WKY rats (260 +/- 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY rats.

Animals↗
PubMed1994

Pilot study of sequential combination chemotherapy in advanced and recurrent retinoblastoma.

Eight patients with advanced/recurrent retinoblastomas were treated with sequential combination chemotherapy incorporating cyclophosphamide, cisplatin, adriamycin, and etoposide. All patients achieved complete clinical response (CR) at the end of the first 75 day cycle. Three patients developed recurrence of which 2 patients had recurrence in the central nervous system and 1 patient had local recurrence. Median time to treatment failure was 30 weeks. Two patients succumbed to chemotherapy related neutropenic sepsis. One patient is alive and disease free for 72 weeks from start of treatment. This combination chemotherapy shows promise in patients with advanced/recurrent retinoblastoma and merits further study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Brain tumors following cure of acute lymphoblastic leukemia.

The majority of children with acute lymphoblastic leukemia can be cured with effective modern day therapy. However, more and more long term sequelae including carcinogenic potential of the treatment are being recognised. We report two children who developed acute lymphoblastic leukemia at the age of 4 and 5 years respectively and were successfully treated. They developed meningioma and astrocytoma at 9 and 3 years respectively after completion of therapy. Both were treated surgically and the patient with astrocytoma also received radiotherapy. Both are now free of disease 19 months after diagnosis of second neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia.

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2-11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.

Blast Crisis↗
PubMed1993

Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin.

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.

Adolescent↗
PubMed1993

Ewing's sarcoma.

Between 1984-1987, 50 patients with Ewing's sarcoma of the bone were entered on combined modality protocol at Tata Memorial Hospital. Protocol treatment involved induction therapy consisting of 6-week therapy with vincristine, Adriamycin (doxorubicin), and cyclophosphamide (VDC) followed by local radiotherapy 50 Gy to the involved bone. This was followed for six more cycles of VDC. Five patients had metastatic disease at presentation. Seventy-six percent (38/50) of patients had disease either at axial or proximal site. With a median follow-up of 48 months (range 14-87) 21 patients remained alive with disease-free survival of 38.0% +/- 2.5% at 5 years and overall survival of 36.0% +/- 2.6% at 5 years. Twenty-five patients relapsed with five patients developing local failure and four local and distant metastasis. Using Lee-Desu statistical methods, only response to therapy was a significant factor for survival. We conclude that more aggressive therapy with proper selection of local treatment modality including surgery and/or radiotherapy is required to produce more long-term survival in high-risk Ewing's sarcoma.

Actuarial Analysis↗
PubMed1993

Myelodysplastic syndrome. A clinical and pathological analysis of 88 patients.

Eighty eight patients with myelodysplastic syndromes were studied to determine the clinical and pathological features and the prognosis. All the patients had anemia. Neutropenia was seen in 44% and thrombocytopenia in 78% patients. The subtypes included refractory anemia in six, refractory anemia with ringed sideroblasts in three, refractory anemia with excess blasts in 30, refractory anemia with excess blasts in transformation in 32 and chronic myelomonocytic anemia in 17 patients. Forty four patients who received chemotherapy were evaluable for response. Three of the 15 patients treated with hydroxyurea achieved partial remission. Eighteen patients were treated with low dose cytosine arabinoside and complete remission was achieved in five and partial response in six patients. Aggressive chemotherapy was given to 11 patients at the onset of the illness resulting in complete remission in six and partial response in two patients. Nineteen of the 88 patients transformed to acute myeloid leukemia. The crude survival of all the patients ranged from 15 days to 22.5 months. The mortality was due to hemorrhage in 15% and septicemia in 85%. Our data reveals ineffectiveness of the current therapy and emphasizes on the need to develop newer therapeutic approaches.

Adolescent↗
PubMed1993

L-asparaginase related hyperglycemia.

L-asparaginase is a valuable chemotherapeutic agent used in the induction of remission and improvement of long term survival in patients with acute lymphoblastic leukemia. Hyperglycemia is a well known side effect of L-asparaginase. Fourteen patients developed hyperglycemia during induction therapy of acute lymphoblastic leukemia with L-asparaginase, prednisolone, vincristine and daunorubicin. Hyperglycemia was observed after a mean of five doses of L-asparaginase (range 2-10). Seven of fourteen patients had neutropenic related infective episodes. Hyperglycemia resolved in all patients within 12 days (range 4-25) and two patients died of neutropenic septicemia. During reinduction therapy with the same drugs, only one out of ten patients developed hyperglycemia E-coli-L-asparaginase was replaced by Erwinia asparaginase in two patients one of who had recrudescence on further therapy. Close monitoring during L-asparaginase therapy for hyperglycemia will enable prompt recognition and early correction and prevent delay in therapy of acute lymphoblastic leukemia.

Adolescent↗
PubMed1993

Infantile neuroblastoma: 10 year TMH experience.

The results of 19 children with neuroblastoma under one year of age treated at the Tata Memorial Hospital between 1981-1990 were analysed. Biologically, neuroblastomas in children under the age of 12 months have an entirely different prognosis as compared to older children. There were four children less than six months of age and 15 children between six and 12 months. All patients with stage II (2/2) disease are alive; 3/4 patients with stage IV-S disease are disease free; 3/5 stage III patients are disease free and 2/8 patients with stage IV disease are disease free. The survival of infants with stage II and IV-S is better than for those with stage III and IV disease.

Female↗
PubMed1993

Prognostic significance of myeloperoxidase containing blast cells in acute myelogenous leukaemia.

Fifty three newly diagnosed patients of de novo acute myelogenous leukaemia (AML) received treatment consisting of remission induction with daunorubicin 60 mg/m2 on day one and continuous infusion of cytosine arabinoside 200 mg/m2/day over 24 h from day one to 7. Thereafter patients in complete remission received consolidation chemotherapy with two identical courses. Complete remission (CR) could be achieved in 40 patients (75.5%). Seven patients (13.2%) died with complications during aplasia phase following remission induction therapy while six patients (11.3%) had resistant disease. Twenty seven patients (67.5%) developed relapse while eight patients (15.1%) continue to remain in complete remission ranging from 51 to 68 months (median 62.5). The projected event free survival and disease free survival at 60 months is 15 per cent (SE + 11.9%) and 21 per cent (+6%) respectively. Evaluation of the prognostic significance of pretherapy characteristics showed that infection at presentation and low number of myeloperoxidase (MPO) containing blasts affected the achievement of complete remission adversely on univariate analysis. Similarly age at diagnosis, of more than 45 yr, total leucocyte count of 50,000/cumm or more and low number of MPO containing blasts affected the remission duration (disease free survival) adversely on univariate analysis. On multivariate analysis, MPO positivity of blast cells, remained the only significant independent characteristic. High MPO positivity affected the remission duration favourably (P < 0.01). Patients with high MPO positivity also achieved CR with one induction cycle in 32 out of 40 instances while only 2 out of 5 patients with low MPO positivity, achieved CR with one chemotherapy cycle (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Four-agent induction/consolidation therapy for childhood acute lymphoblastic leukemia: an Indian experience.

During 1984-1986, a total of 128 children with acute lymphoblastic leukemia (ALL) were treated with an induction-consolidation regimen consisting of doxorubicin, vincristine, cytosine-arabinoside, and prednisolone. One hundred two (80%) patients belonged to high-risk group. The complete remission rate for all the patients was 91%. The event-free survival at 5 years was 32.0% +/- 23%. On multivariate analysis the event-free survival and disease-free survival was not altered by age, sex, WBC count, platelet count, LDH level, and surface phenotype. Infection due to prolonged marrow aplasia was a common complication, leading to mortality of 8 patients during induction and 33 patients during first remission. The relapse rate has been 36% (42 patients). The predominance of high-risk ALL in the Indian population underscores the need for intensive therapy. Improved supportive care during induction and remission seems essential to decrease therapy-related mortality, leading to improved survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Long-term right atrial catheters in patients with malignancies: an Indian experience.

Ninety-eight single lumen and two double lumen silicone right atrial Hickman/Broviac catheters inserted in 91 patients with various malignancies over a period of 36 months were prospectively studied. The average duration of use for all Hickman/Broviac catheters was 7,460 days with an average of 74.6 days. A total of 41 episodes of catheter-related infections were documented in all patients (0.5 per 100 access days). Catheter related bacteremia was the most frequent type of infection (31 out of 41, 75%). Majority of the bacteremias could be controlled with routine antimicrobial therapy. Exit site infections were seen in 5 Hickman/Broviac catheters. Two catheters had to be removed because of catheter tunnel infections. Gram negative bacteremic infections were the most common, with Pseudomonas aeruginosa being the major pathogen. Silicone rubber Hickman/Broviac catheters proved to be convenient, reliable, and easily manageable devices in our experience.

Adolescent↗