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Biomedical subjects

V Raina

Publications and source records attributed to V Raina.

At least 37 records · Page 2Linked to original sources

Lipid peroxidation, free radical production and antioxidant status in breast cancer.

Reactive oxygen metabolites (ROMs), including superoxide anion (O2*-), hydrogen peroxide (H2O2) and hydroxyl radical (*OH), play an important role in carcinogenesis. There are some primary antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) which protect against cellular and molecular damage caused by the ROMs. We conducted the present study to determine the rate of O2*- and H2O2 production, and concentration of malondialdehyde (MDA), as an index of lipid peroxidation, along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients. Forty-two age- and sex-matched patients with minor surgical problems, who had no history of any neoplastic or breast disorders, were taken as controls. The rate of O2*- production was significantly higher (p < 0.001) in BC patients than controls, irrespective of clinical stages and menopausal status. Similarly, H2O2 production was significantly higher in BC patients, especially in stage III and postmenopausal groups, as compared to the respective controls. MDA concentration was also observed significantly elevated in stage II (p < 0.001), stage III (p < 0.01), postmenopausal (p < 0.005), and premenopausal (p < 0.02) group as compared to their corresponding controls. SOD and GPx activities were found significantly raised in all the groups (p < 0.001), except the GPx activity was found a smaller alteration in stage IV (p < 0.02). On the contrary, CAT activity was found significantly depressed in all the study groups. The maximum depression was observed in stage II (-61.8%). Lower CAT activity in our study may be the effect of higher production of ROMs, particularly O2*- and *OH. SOD and GPx, however, were less effected by these higher ROMs production. The results of our study have shown a higher ROMs production and decreased CAT activity, which support the oxidative stress hypothesis in carcinogenesis. The relatively higher SOD and GPx may be due to the response of increased ROMs production in the blood. However, the higher SOD and GPx activities may be inadequate to detoxify high levels of H2O2 into H2O leading to the formation of the most dangerous *OH radical followed by MDA. Therefore, administration of CAT may be helpful in the management of BC patients. However, further elaborate clinical studies are required to evaluate the role of such antioxidant enzymes in BC management.

Adult↗

Undifferentiated leukemia following treatment of gastric cancer with 5 fluorouracil, doxorubicin, mitomycin C chemotherapy.

Secondary leukemias are an increasingly well recognized complication of cancer chemotherapy. We report on the development of undifferentiated leukemia in a forty one year lady, eighteen months after treatment of gastric cancer with 5-fluorouracil (5 FU), doxorubicin and mitomycin C. She developed progressive weakness and pancytopenia over a period of few months. Leukemic blasts which were undifferentiated by immunophenotyping were seen in her peripheral blood. She died of intracranial haemorrhage during induction chemotherapy for the leukemia. Undifferentiated leukemia is a rare complication of FAM chemotherapy for gastric cancer.

Adenocarcinoma↗

Prognostic utility of silver stained nucleolar organiser region counting in non Hodgkin's lymphoma.

Silver stained Nucleolar Organiser Region (AgNOR) counting is a well established method of estimating the proliferative activity of a tumour. Their utility in prognostication in Non Hodgkin's Lymphoma (NHL) has not been fully investigated. We analysed hundred cases of NHL, all of which had a minimum of two and a half years of follow up, using histology by International Working Formulation (IWF) and their AgNOR scores. We found the IWF grading to have a good correlation with the outcome. The two and a half year survival for low grade NHL was 90 percent, for intermediate grade NHL was 47 percent and for high grade NHL was 30 percent. AgNOR scores correlated well with IWF grading and classification, with average AgNOR score of 1.82 (SD 0.34) in low grade NHL; 4.47 (SD 2.25) in intermediate grade NHL and 7.07 (SD 4.40) in high grade NHL. Over histology, AgNOR counting yielded additional prognostic information only in the diffuse small cleaved cell NHL (DSC), where finely dispersed NORs were seen. Of the 22 case of DSC included, 11 cases with AgNOR scores less than three had a much better outcome with 75 percent survival at two and a half years. Cases of DSC with AgNOR scores greater than three had a significantly worse outcome with only 25 percent survival at two and a half years (p=0.0103). Such sub-stratification could not be done in any other catergory of NHL using AgNOR scores. Thus, counting of AgNORs in lymphomas with finely dispersed NORs as in DSC is of prognostic value.

Adult↗

Alpha-interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses.

BACKGROUND: Nearly 14% of non-alcoholic chronic liver disease in India is related to hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. There are no clear data available from the literature on the therapeutic management of these patients who often suffer an unfavourable course. METHODS: Fourteen consecutive cases of biopsy-proven chronic liver disease fulfilling the following criteria were included: Child's A or B liver disease, hepatitis B surface antigen positive, HBV-DNA positive, antibody to HCV positive and HCV-RNA positive. Seven patients had chronic liver disease (group I), while the remaining seven patients (group II) had additional disorders (non-Hodgkin's lymphoma (two), acute leukaemia (two), thalassaemia (two), chronic renal failure (one). Interferon alpha-2b (IFN) was given in a dose of 6 MIU thrice weekly for 6 months. Complete response was defined as loss of HBV-DNA and HCV-RNA at 6 months and sustained response (SR) as the sustained loss of HBV-DNA and HCV-RNA for more than 6 months during the follow-up period. RESULTS: At the end of 6 months, alanine aminotransferase (ALT) levels remained unchanged (120 +/- 40 vs 136 +/- 64 IU/L), but six of the seven (86%) patients in group I lost HBV-DNA. All three hepatitis Be antigen (HBeAg)-positive patients lost HBeAg with an early flare of ALT (at 45 +/- 12 therapy days). Two of these patients (29%) lost HCV-RNA. Thus, SR was seen in 29%, while HBV-DNA loss was found in 100% during the follow-up period. In group II patients, there was a significant decrease in ALT (308 +/- 14 vs 65 +/- 25 IU/L, P < 0.001), but only three (43%) patients lost HBV-DNA and two (29%) lost HCV-RNA. One patient with acute leukaemia and another with renal failure had a complete response to IFN, but none of the lymphoma patients showed any antiviral response. CONCLUSIONS: In chronic hepatitis due to dual infection with HBV and HCV, interferon therapy is: (i) safe; (ii) effective (more so in clearing HBV); (iii) often associated with early ALT flare; and (iv) may be less effective if non-Hodgkin's lymphoma is present.

Adult↗

Prevalence of hepatitis C virus antibody in healthy blood donors.

The present study was conducted to find the prevalence of HCV antibody in blood donors with an aim to provide safe blood for transfusion. A total of 44,086 blood samples from healthy blood donors was screened for HCV antibody by third generation ELISA assay and a prevalence of 0.53 per cent was found in our study. We suggest that routine screening of all donor blood should be done.

Adolescent↗

Expression of genes implicated in multidrug resistance in acute lymphoblastic leukemia in India.

In order to investigate the phenomenon of multidrug resistance as a possible mechanism for poor response to treatment in patients with acute lymphoblastic leukemia (ALL) from India, a series of 32 cases of de novo untreated ALLs were analyzed by a cDNA-PCR approach to estimate the relative mRNA levels of the MDR-associated genes encoding MDR1, MRP, GSTpi, and GSTmu. The expression of beta2 microglobulin served as an internal standard. Quantifiable transcripts were observed in 20 patients for MRP, in 5 for MDR1, in 24 for GSTpi, and in 19 for GSTmu. The values ranged from undetectable to 132% of the control A549 cell line for MRP, undetectable to 49% of the HL60/DNR control cell line for MDR1, undetectable to 268% of A549 control cell line for GSTpi, and undetectable to 247% of A549 control cell line for GSTmu mRNA. Increased MRP levels were associated with increased GSTpi and GSTmu levels (p<0.01 for both), and increased levels of MDR1 were associated with increased GSTpi levels (p<0.05). The present observations showed no correlation between the MDR1 and MRP values with treatment outcome, in terms of either achieving a complete remission or predilection to early relapse. In view of some recent studies that envisage MRP as an energy-dependent pump involved in the efflux of GSH conjugates, the simultaneous up-regulation of transcription of all these genes might well be part of an integrated detoxification response that has been switched on after exposure to an environmental stress.

ATP-Binding Cassette Transporters↗

Detection of BCR-ABL transcripts in acute lymphoblastic leukemia in Indian patients.

Thirty-three patients with acute lymphoblastic leukemia (ALL) from India were studied for the presence of BCR-ABL chimeric transcripts, by a seminested cDNA-PCR. We report the presence of BCR-ABL chimeric transcripts in 4/17 (24%) children (under 15 years) and 3/16 (19%) adults (15-50 years). This is in sharp contrast to the published literature from the West where the presence of BCR-ABL has been reported in only 2-5% children and 35% adults. Whether the presence of BCR-ABL fusion mRNA, which is generally an attribute of ALL in adults and of poorer prognosis, may contribute to chemo-incurability in young Indian patients, remains to be seen, as a larger number of patients are studied for treatment outcome and survival on uniform therapy protocols.

Adolescent↗

Plasmodium vivax causing pancytopenia after allogeneic blood stem cell transplantation in CML.

A 20-year-old male patient with chronic myeloid leukemia (CML), in chronic phase, underwent allogeneic blood stem cell transplantation in August 1996. Engraftment was well documented in the marrow on day 19, but pancytopenia and mild splenomegaly continued. On day +70, the patient developed severe anemia and had one pyrexial episode. He was detected to have malaria (Plasmodiium vivax). After chloroquin therapy, the pancytopenia reversed completely. We suggest that malaria should be considered as a possible cause of pancytopenia in the post-transplant period in endemic areas.

Adult↗

Mitoxantrone, mitomycin-C, methotrexate combination chemotherapy with radiotherapy and/or surgery in stage III (T4B, NO-2, M0) breast cancer.

Results of primary surgery with or without locoregional radiotherapy (LRRT) are poor in stage III (T4b, NO-2, M0) breast cancer. Combination of mitoxantrone, mitomycin-c and methotrexate (MMM) has been reported to be as efficacious as doxorubicin based protocols with advantages of reduced nausea, vomiting, alopecia and cardiotoxicity. We tested MMM chemotherapy with LRRT and surgery in locally advanced breast cancer (LABC) with a view to assess response, survival, breast conservation, cost and toxicity. Fifty two previously untreated patients were given Mitoxantrone: 8 mg/m sq by infusion on days 1 and 21, Mitomycin-C: 8 mg/m sq by infusion on day 1 and Methotrexate: 35 mg/m sq i.v. on days 1 and 21. Cycles were repeated every 42 days. After 3 cycles LRRT was given if lump reduced to less than 2 cms. Otherwise patients were subjected to modified radical mastectomy (MRM) or radical mastectomy (RM). Following this 3 more cycles of chemotherapy were given. Patients with soft tissue, skin or heavy nodal involvement also received LRRT. Tamoxifen 20 mg daily was prescribed at the end of chemotherapy to postmenopausal patients. Complete/partial responses were seen in 5 and 26 patients, respectively after chemotherapy giving an overall response of 59.5%. Twenty four patients each had LRRT and MRM/RM. Responses could be significantly enhanced by LRRT/and or surgery. Nineteen out of 25 relapses were at distant sites. Breast conservation was achieved in 24/52 (46%) patients. Three year disease free and overall survival was 54% and 65%, respectively. There was 1 toxic death. Severe prolonged myelosuppresion was seen in those who also received LRRT. Mucositis, alopecia, nausea and vomiting were minor problems. Overall, combination was less expensive than doxorubicin based protocols.

Adult↗

A prospective study on the incidence of hepatitis B & C infections amongst patients with lymphoproliferative disorders.

Fifty one patients with acute lymphoblastic leukaemia (ALL) and non-Hodgkins lymphoma (NHL) undergoing chemotherapy were studied prospectively to determine the incidence, aetiology and natural course of hepatitis. Of 51 patients (31 NHL and 20 ALL), 22 developed hepatitis. Hepatitis B (IgM anti HBc positive) was the cause in 11 patients (50%), hepatitis C in 4 patients, and septicaemia and cytotoxic drugs in 3 patients each. Malignant infiltration of the liver was the cause in the remaining 1 patient. Hepatitis was predominantly (75%) anicteric. Mean duration of hepatitis was 21 days. Of 51 patients, 21 acquired hepatitis B and/or C virus infection. They had received 6.4 (+/- 3.4) units of packed red cells and 5.3 (+/- 11) units of platelet concentrate as compared to 3.4 (+/- 4.8) units of red cells and 5.3 (+/- 12.1) units of platelet concentrate received by those who did not acquire virus infection (P < 0.05 for packed red cells). Only transient stoppage of chemotherapy was necessary following development of hepatitis and most of the patients who developed hepatitis could complete their chemotherapy schedule. None of the patients who developed viral B or C infection cleared the infection. We conclude that there was a high incidence of hepatitis B and C infection amongst patients with lymphoproliferative disorders with an increased carrier rate. Transfusion was a major risk factor for such infections.

Acute Disease↗

Whole blood harvested after granulocyte-colony stimulating factor (Neupogen) mobilization, and reinfused unprocessed after high-dose melphalan treatment, accelerates hematopoietic recovery in patients with multiple myeloma.

BACKGROUND: High-dose melphalan (HDM) is now a standard treatment for multiple myeloma (MM). Stem cell transplants are fast evolving as an alternative to bone marrow transplants because they are less traumatic and easier to perform. A study was undertaken to test if whole blood harvested after mobilizing peripheral blood stem cells with granulocyte-colony stimulating factor (G-CSF) reinfused as such (without stem cells being processed or concentrated through a cell separator) for rescue after HDM (dose 140-180 mg/m2) in MM accelerates hematopoietic recovery. METHODS: Eight consecutive patients with MM were given HDM after receiving 4-5 courses of infusional vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy. Approximately 6 weeks after the last course of chemotherapy, at the start of the procedure, G-CSF (Neupogen) was given at a dose of 10 microgram/kg subcutaneously daily for 4 days to mobilize stem cells. All of the patients had brisk leukocytosis (18.4-64.6 x 10(9)/L). On day 0 (fifth day after G-CSF), 1 L of blood was removed by phlebotomy and kept at room temperature for 24 hours. This was followed by a rapid intravenous (i.v.) bolus of melphalan at a dose of 140 mg/m2 in the first three patients, 155 mg/m2 in the 4th, 170 mg/m2 in the 5th, and 180 mg/m2 in the 6th, 7th, and 8th patients, applies to all patients along with hydration and diuresis. Twenty-four hours later, I L of blood previously removed was transfused back to the patient without any processing through the cell separator. The numbers of mononuclear cells reinfused was between 0.76 and 3.2 x 10(8)/kg (mean: 1.82 x 10(8)/kg). The number of CD 34+ cells infused in 4 patients ranged from 1.9 to 2.8 x 10(6)/kg (mean: 2.35 x 10(6)/kg). G-CSF was restarted on day 2 at a dose of 5 microgram/kg and given daily until the granulocyte count was 0.5 x 10(9)/L or more for 3 consecutive days. Antibiotics were given whenever a patient developed pyrexia. Platelets were transfused if below 20 x 10(9)/L or for incidences of overt bleeding. RESULTS: Granulocyte counts touched 0 between Days 6 and 10, lasting for an average of 3.4 days. Duration of granulocyte count below 0.5 x 10(9)/L was 6.5 days (range: 5-9), and these rose to 1.0 or more x 10(9)/L by Day 13.7 (range: 13-16). The number of platelet transfusions given per patient was 2.5 (range: 0-4). Intravenous antibiotics were used for 9 days (range: 4-12), and patients were discharged on Day 19 (range: 16-22). Follow-up ranged from 45 to 380 days. CONCLUSIONS: Hematopoietic recovery was rapid in all patients, including those who received doses of melphalan higher than 140 mg/m2. This resulted in less need for platelet transfusions or antibiotics, and hospitalization was short. Our results are historically similar to conventional peripheral blood stem cell transplants but much better than autologous bone marrow transplants, indicating that whole blood after G-CSF provided sufficient progenitor cels for early engraftment. The procedure is less labor intensive insofar as it does not require separation and concentration of stem cells. It has the potential of becoming an alternative to autologous marrow and peripheral blood stem cell transplantation in patients with MM.

Adult↗

Male breast cancer: a retrospective study from a regional cancer center in northern India.

Over a 7-year period from 1987 to 1993, 41 male breast cancer patients were seen in the breast cancer clinic of the Institute Rotary Cancer Hospital (IRCH) at the All India Institute of Medical Sciences (AIIMS). Their mean age was 54.2 years; and duration of symptoms ranged from 1 to 84 months with a mean of 15.1 months. Breast lump was the commonest presenting symptom. Fine needle aspiration cytology (FNAC) was the commonest diagnostic procedure. The TNM stage distribution was stage I, 5; stage II, 13; stage III, 17; and stage IV, 6. Radical mastectomy (25/36) was the commonest surgical procedure. Locoregional radiotherapy was given in 15 patients. Thirty patients received systemic adjuvant therapy (chemotherapy or tamoxifen, or a combination of the two). Local or distant recurrence occurred in 8 patients (8/31, 28.3%). Actuarial overall and disease-free survival was 100% and 80.1% at 2 years and 91.7% and 66.7% at 4 years, respectively. On univariate analysis, axillary lymph node status and age were found to affect disease-free survival significantly. Advanced stage of disease at presentation is common in Indian patients and will continue to influence treatment policies. Neoadjuvant chemotherapy needs to be evaluated for locally advanced tumors to improve outcome. Multicentric studies are necessary to define the relative roles of tamoxifen and chemotherapy for adjuvant treatment.

Adult↗

Cytogenetic and molecular genetic studies on Indian patients with chronic lymphocytic leukemia.

This is the first cytogenetic and molecular genetic study to find any specific genetic abnormalities in Indian patients with chronic lymphocytic leukemia (CLL). Cytogenetic studies on 18 patients indicated that their karyotypes were relatively simple and trisomy 12 was seen on karyotype evolution in one patient. Fluorescence in situ hybridization (FISH) revealed abnormal clones of trisomy 12 in nine cases and RB gene deletion in 14 of the 29 cases analyzed. Three patients had both clones. Immunoglobulin genes were rearranged in all the cases and TCR beta in none of the 18 cases Southern blotted. BCL-1 was rearranged in one case. No rearrangement of BCL-2 gene was seen in any case. Genetic changes in Indian CLL were more similar to Western CLL than to Japanese CLL, even though India is supposed to be a low incidence area. Therefore, factors (such as HLA and other genetic markers) other than these routine parameters must be studied to explain the low incidence of CLL in India.

Aged↗

Multicentric liposarcoma: report of two cases.

We present herein two unusual cases of multicentric liposarcoma which highlight the problems associated with the management of this disease entity. When the surgeon is confronted with multicentric liposarcomas, it is necessary to define whether they are secondary tumors or independently arising multicentric liposarcomas, since the latter situation merits a more aggressive approach. Guidelines for this differentiation are suggested in the discussion following the case reports. Surgery, which is often multiple, remains the mainstay of treatment, although adjuvant chemotherapy and radiotherapy are also usually required.

Abdominal Neoplasms↗

Primitive neuroectodermal kidney tumor: 2 case reports and review of the literature.

Peripheral neuroectodermal tumors are uncommon cancers arising from outside the central nervous system. The urinary system is rarely involved. The differentiation of these tumors from other small cell cancer and neuroblastoma is based on immunohistochemical differences. We report 2 cases of such tumors arising from the renal parenchyma. Tumor behavior and treatment modalities are discussed.

Adult↗

Germ cell tumours in uncorrected cryptorchid testis at Institute Rotary Cancer Hospital, New Delhi.

Twenty-four out of 164 (14%) adult patients with primary germ cell tumours of testis seen over the last 6 years at the Institute Rotary Cancer Hospital (IRCH) of the All India Institute of Medical Sciences (AIIMS), New Delhi, were found to have cryptorchidism. Only one patient had undergone correction. As a result the testes were intra-abdominal in the vast majority, and patients presented late. Twenty-two patients presented with stage IIb or more advanced disease. Twelve patients had seminoma and the others had mixed or non-seminomatous germ cell tumour (NSGCT), i.e. 50% each. The earlier patients were managed by initial resection followed by radiation and/or chemotherapy. As experience grew the seven patients who presented late were given initial chemotherapy followed by resection in those with residual tumours. The probability of overall survival was 0.65 at 36 months and, was not significantly different from survival in 114 patients with tumours of normally descended testis. Early orchipexy facilitates the detection, but whether it reduces the incidence of tumours is controversial. Uncorrected cryptorchidism is now rarely seen in the West, but in India and many other developing countries tumours of uncorrected cryptorchid testes continue to be seen.

Actuarial Analysis↗

Brain metastasis as the site of relapse in germ cell tumor of testis.

BACKGROUND: Brain metastases occur in approximately 8-15% of patients with testicular germ cell tumors and invariably are associated with relapse at other sites, most commonly the lungs, or as a terminal event. METHODS: The authors, from the Institute Rotary Cancer Hospital, a regional cancer center in northern India, did a retrospective analysis to determine how many previously treated patients had isolated cerebral metastasis develop. RESULTS: Three of 123 patients with testicular germ cell tumor seen during a 6-year period starting in January 1986 had isolated cerebral metastasis develop during remission after initial treatment. Two patients who had pure seminoma were treated with radiation therapy and are alive and symptom free at 15 and 18 months. The third patient had a combined tumor, the major component of which was embryonal cell carcinoma, that required debulking surgery and radiation therapy, and the patient died with recurrent cerebral metastases. CONCLUSIONS: Review of the literature reveals that although cerebral metastasis is well recognized in testicular cancer, particularly nonseminomatous germ cell tumor (NSGCT), it is invariably preceded by systemic metastasis. Cerebral metastasis is extremely rare as the sole and presenting feature of relapse. This complication must be recognized and treatment defined because it may become more frequent as patients survive for longer periods with modern disease management.

Adult↗