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Biomedical subjects

V Kochupillai

Publications and source records attributed to V Kochupillai.

At least 19 recordsLinked to original sources
PubMed2005

Common cancers in India: knowledge, attitudes and behaviours of urban slum dwellers in New Delhi.

RESEARCH QUESTIONS: What is the level of knowledge and awareness of common cancers? What are the prevalent attitudes and behaviours relating to common cancers? OBJECTIVES: To assess knowledge, attitudes and behaviours regarding common cancers amongst urban slum dwellers in New Delhi. STUDY DESIGN: Field-based cross-sectional survey of an urban slum cluster. SETTING: Slum clusters along Pankha Road, West New Delhi. PARTICIPANTS: Slum dwellers of selected slums. STUDY VARIABLES: Independent variables were sociodemographic factors. Dependent variables were knowledge, attitudes and behaviours regarding preventive and curative aspects of common cancers. STATISTICAL ANALYSIS: Proportions, confidence intervals, tests of significance and multiple logistic regression. RESULTS: Only 13% (10.6-15.7%) of the study participants were aware of Pap smears, and only 2% (1.1-3.3%) were able to identify all the common signs of cancer. However, 87% (84.4-89.5%) of the study participants knew that tobacco is a risk factor for cancer. Overall, 51% (47.2-54.7%) had some knowledge pertaining to cancer. CONCLUSION: A focused, concerted and effective information, education and communication drive is urgently needed for all aspects of common cancers in India.

Adolescent↗
PubMed2003

Colony-stimulating activity of fetal liver cells: synergistic role of stem cell factor in bone marrow recovery from aplastic anemia.

Previously, we and others have shown that fetal liver infusion (FLI) leads to autologous hematopoietic improvement in 40-54% of patients with aplastic anemia. However, whether this recovery was spontaneous or the effect of the infused liver cells was not clear. To dissect the role of FLI in autologous hematopoietic recovery, the colony-supporting potential of fetal liver-conditioned medium (FLCM) was evaluated in bone marrow (BM) cells of normal adult and aplastic anemia patients. In both cases, each sample of FLCM supported the growth of colony-forming cells in semi solid culture medium. The FLCM was assayed for the presence of four principal colony-stimulating cytokines, namely stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo). While GM-CSF, IL-3, and Epo were present in insignificant amounts or were altogether absent, 50-635 pg/ml of SCF was found in 8 of the 13 FLCM samples tested. Preliminary results of bioneutralization assay indicated the possible role of SCF, secreted by the FL cells, in colony-supporting activity of aplastic anemia and normal BM cells. Overall, our in vitro study implicates the paracrine role of infused FL cells in regenerating autologous hematopoiesis in aplastic anemia patients.

Anemia, Aplastic↗
PubMed2002

Reconstitution of naïve T cells and type 1 function after autologous peripheral stem cell transplantation: impact on the relapse of original cancer.

BACKGROUND: Phenotypic and functional reconstitution of T cells after peripheral blood stem cell transplantation (PBSCT) and its influence on posttransplant immune status is important in terms of immune surveillance and relapse of original cancer. We investigated the relationship between the dominant immune reconstitution pathway and the immune surveillance. We also tested the cytokine bias acquired by T cells after transplantation and its possible influence on relapse of original malignancy. METHODS: Immunophenotyping of naïve and memory T cells was performed by flow cytometry on patients who underwent PBSCT for various cancers. Cytokine production by peripheral memory helper (CD4) and cytotoxic (CD8) T cells was investigated at various pretransplant and posttransplant time points with fluorescein isothiocyanate-based intracellular cytokine assay after short-term in vitro mitogenic stimulation (phorbol myristate acetate + ionomycin). Data on T-cell subsets and polarized cytokines gamma-interferon (Ifn) and interleukin 4 produced by memory T cells were compared with that of healthy controls. RESULTS: The reconstitution of naïve T cells and gamma-Ifn-producing memory cells was significantly lower in patients who experienced relapse of original cancer within 1 year of PBSCT compared to those who showed no signs of relapse even after 2 years and compared to normal subjects. The results indicate that efficient reconstitution of naïve T cells and type 1 function of memory T cells are important in maintaining T-cell repertoire diversity after PBSCT. It also confers appropriate levels of immune surveillance against diverse neoantigens that evolve from residual tumor burden. The data reveal that chemotherapy-induced thymic injuries may impair regeneration of naïve cells that result in a naivopenic state in a susceptible host. CONCLUSIONS: The study highlights the importance of naïve T-cell reconstitution and points towards cell replacement strategies for improving immune surveillance after PBSCT.

Adult↗
PubMed2001

Chemopreventive activity of Withania somnifera in experimentally induced fibrosarcoma tumours in Swiss albino mice.

The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.

Administration, Oral↗
PubMed2001

Redefining 'self': the role of microflora (commensals) mismatch in the development of GvHD after allogeneic stem cell transplantation and some possible remedies.

The discovery of human leukocyte antigen (HLA) molecules and their role in allorecognition has facilitated the initiation of allogeneic stem cell transplantation in human beings. HLA mismatch to a large extent explains the phenomenon of graft rejection and graft versus host disease (GvHD). Incidence of GvHD even in syngeneic transplants suggests a role for extra genetic factors in the causation of GvHD. We hereby propose a hypothesis that the definition of 'self' (in the immunological sense) should be broadened to include both genetically determined molecules (e.g. HLA) and the microbial flora that colonize an individual. This hypothesis explains several observations about GvHD which can not fully be accounted for by the HLA mismatch theory and gives some clues towards circumventing GvHD.

Age Factors↗
PubMed2001

Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the toxicity of etoposide, a topo-isomerase II inhibitor.

Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm(3) in volume. Liposomal etoposide (10 mg/m(2)/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.

Animals↗
PubMed2000

Infections in acute leukemia: an analysis of 240 febrile episodes.

Infections are the major cause of morbidity and mortality in acute leukemia patients. Case records of 91 consecutive patients (AML-48, ALL-40, RAEB-t/AML-3) treated between January 1997 and July 1999 were studied to determine the type, frequency and severity of infections. Patients' median age was 36 y (range 6-66) and male to female ratio was 2.5:1. A total of 240 febrile episodes were recorded; of them, 162 were associated with neutropenia (absolute neutrophil count, ANC<500/mm3) and 78 were without neutropenia. Among the neutropenic episodes, an infectious etiology could be documented in 52%; the remainder (48%) were defined as isolated febrile episodes. Chest was the most common site of infection (35. 7%) followed by skin, soft tissue (13%), GIT (7%) and genitourinary tract (6%) infections in order of decreasing frequency. Microbiologically, gram positive organisms (staphylococcus aureus, coagulase negative staphylococcus, streptococcus, enterococcus) were the most common isolates (52.8%) followed by gram negative organisms (E. coli, klebsiella, pseudomonas) in 42.8% of isolates. Two patients had pulmonary tuberculosis and three patients had fungal infections (candida-2, aspergillus-1). Among non-neutropenic patients, infection could be documented in 36%; the remaining 64% were isolated febrile episodes. Gram negative infections were documented in 50%, gram positive in 30% and fungal infections (candida-4, aspergillus-1, mucormycosis-1) in 20% of them. A combination of third generation cephalosporin and an aminoglycoside were used in 79% of episodes initially; a combination of a newer penicillin and aminoglycoside (4.6%), double betalactums (4.1%), oral antibiotics (9.8%) and others were used in the remaining episodes. Fever resolved in 38% of episodes using the above combinations; in the remainder second line antibiotics (mainly vancomycin) and antifungals (amphotericin-B) were added empirically or depending on culture and sensitivity. In 52.5% of episodes fever resolved after addition of second line antibiotics and antifungals. 11 of 91 patients died of infectious complications in this study. There is a need for improvised diagnostic tests to detect infections early as well as for new therapies to overcome antimicrobial resistance.

Adolescent↗
PubMed2000

Chemotherapy in recurrent epithelial ovarian cancer (EOC): an analysis of prognostic factors.

OBJECTIVE: Prognosis of patients with recurrent epithelial ovarian cancer (EOC) is generally poor. Cisplatin is the most effective drug. We used three cisplatin based chemotherapeutic (CT) regimens and retrospectively analyzed the data to determine the response rate, toxicity, survival and the impact of various prognostic factors on the outcome. PATIENTS AND METHODS: Between August, 1989 and September, 1997, 102 patients were diagnosed to have recurrent EOC. Sixty-five of 102 patients received CT every 3 weeks using cisplatin 75 mg/m2 i.v. day 1 plus cyclophosphamide 750 mg/m2 i.v. day 1 (CP, Group A, n = 29), cisplatin 75 mg/m2 i.v. day 1, plus adriamycin 40 mg/m2 i.v. day 1 and cyclophosphamide (CAP, Group B, n = 22) and paclitaxel 135 mg/m2 i.v. day 1 plus cisplatin 75 mg/m2 i.v. day 1 (TP, Group C, n = 14). Twelve patients received single agent CT and were not analyzed. Remaining 25 patients refused CT treatment and were followed for survival. RESULTS: The overall response rate (complete and partial) was 59.2% for patients receiving CP (Group A), 45% for CAP (Group B) and 76.9% for those receiving TP (Group C), p = ns. Response rate was significantly higher for patients with platinum sensitive disease compared to those with platinum resistant disease; 55.76 vs 39%, p < 0.007. CT was generally tolerated well; 2 patients died of CT toxicity, one each in Group A (CP) and C (TP), respectively. The median survival from the date of relapse for patients receiving chemotherapy was 15 months compared to 4 months for those who did not receive chemotherapy, p < 0.001. Chemotherapy responders had a significantly higher median survival than chemotherapy non-responders, 24 months vs 10 months, p < 0.01. The median overall survival was not significantly different in the 3 groups; Group A--15 months, Group B--12 months and 15 months in Group C, p = 0.738. On univariate analysis--time since last CT (< 6 months vs > 6 months, p < 0.037, response to previous CT, p < 0.0183, cisplatinum sensitivity vs resistance, p < 0.032, number of sites (< 2 vs > 2) of recurrence, p < 0.004 and response to salvage CT, p < 0.01 were associated with survival benefit. On multivariate analysis, 2 factors--platinum sensitivity and response to salvage CT attained significance. CONCLUSIONS: Our study confirms the benefit of platinum based chemotherapy in recurrent EOC. Patients with platinum sensitive disease, and those responding to salvage chemotherapy benefit most.

Adult↗
PubMed1999

High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy.

Numerous articles and several reviews have been published on the role of antioxidants, and diet and lifestyle modifications in cancer prevention. However, the potential role of these factors in the management of human cancer have been largely ignored. Extensive in vitro studies and limited in vivo studies have revealed that individual antioxidants such as vitamin A (retinoids), vitamin E (primarily alpha-tocopheryl succinate), vitamin C (primarily sodium ascorbate) and carotenoids (primarily polar carotenoids) induce cell differentiation and growth inhibition to various degrees in rodent and human cancer cells by complex mechanisms. The proposed mechanisms for these effects include inhibition of protein kinase C activity, prostaglandin E1-stimulated adenylate cyclase activity, expression of c-myc, H-ras, and a transcription factor (E2F), and induction of transforming growth factor-beta and p21 genes. Furthermore, antioxidant vitamins individually or in combination enhance the growth-inhibitory effects of x-irradiation, chemotherapeutic agents, hyperthermia, and biological response modifiers on tumor cells, primarily in vitro. These vitamins, individually, also reduce the toxicity of several standard tumor therapeutic agents on normal cells. Low fat and high fiber diets can further enhance the efficacy of standard cancer therapeutic agents; the proposed mechanisms for these effects include the production of increased levels of butyric acid and binding of potential mutagens in the gastrointestinal tract by high fiber and reduced levels of growth promoting agents such as prostaglandins, certain fatty acids and estrogen by low fat. We propose, therefore, a working hypothesis that multiple antioxidant vitamin supplements together with diet and lifestyle modifications may improve the efficacy of standard and experimental cancer therapies.

Animals↗
PubMed1998

Outbreak of nosocomial Acinetobacter baumannii bacteremia in a high risk ward.

Acinetobacter baumannii is emerging as a major cause of nosocomial infections particularly in high risk patients. Being resistant to adverse environmental conditions, it can stay for prolonged periods in the hospital environment. We report an outbreak in the medical oncology ward where nine patients suspected of bacteraemia were blood culture positive for A. baumannii from the two samples each, one collected through the i.v. cannula and another through the peripheral veneous puncture. The bacteria was also isolated from the environmental sources from the various samples collected. The biotype, antibiogram, cellular protein profiles on SDS-PAGE and the restriction enzyme analysis patterns of the patient isolates and the environmental isolates were similar. This points to the environment as a source of infection. With reinforcement of proper barrier nursing and use of disposable heparine ampoules it was possible to control the outbreak.

Acinetobacter Infections↗
PubMed1998

Foetal liver infusion in a chronic myeloid leukemia patient with busulphan toxicity.

A 36-year-old man suffering from chronic myeloid leukemia (in chronic phase) was initially treated with busulphan. At the end of 6 months of follow-up he developed bone marrow aplasia. He was given single foetal liver infusion therapy. The patient recovered fully from aplasia. He continued in chronic phase for more than 7 years with intermittent busulphan therapy.

Adult↗
PubMed1998

Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.

Adult↗