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Biomedical subjects

R Gopal

Publications and source records attributed to R Gopal.

At least 163 records · Page 9Linked to original sources

Management of Hodgkin's disease in western India.

The authors report a retrospective analysis of 441 patients with Hodgkin's disease seen at the Tata Memorial Hospital, Bombay, over a 4-year period from 1975 to 1978. Clinicopathologic features seem to vary from those reported in the western literature, but are similar to the patterns observed in Africa and South America. Thirty-three percent of all malignant lymphomas were Hodgkin's disease. Histologically, the mixed cell (MC) type (40%) and the lymphocytic predominant (LP) type (24%) were the most common, with 52% of patients presenting in Stages III and IV. The nodular sclerosis (NS) variant occurred in only 11% of the cases. Systemic symptoms were present in 24% of clinical Stage I patients, and increased steadily to 85% in Stage IV patients. Bone marrow biopsies in 242 patients were found to be of little value in Stages I and II. Thirty of 34 patients with positive bone marrow biopsy were in clinical Stages III B and IV, whereas 24 of 34 patients showed MC and LD patterns. Lymphangiography in 104 patients altered the clinical staging of Stages I and II in 27% of the cases with accuracy of 80%. Staging laparotomy performed in 93 patients altered the stage in 45% of clinical Stage I and 62% of Stage II patients. Splenic involvement was common in the presence of systemic symptoms (67%) and MC/LD histology (82%). The incidence of liver involvement was 16% in 15 patients with all, but one, associated with splenic pathology. The clinical stage and histopathologic variants of the disease bear an excellent correlation with a significant impact on treatment responses and total survival. The survival rates for Stage I were 81%, Stage II 76%, Stage IIIA 71%, and Stage IIIB and IV 46% at 48 months. The LP type had the best prognosis with 85% survival at 48 months, whereas the survival in the depleted variety was only 56%. Surprisingly, the MC type did better with a 64% survival, while the nodular sclerosis group had 59% surviving at 48 months.

Adolescent↗

Single mutations at many sites within the DNA polymerase locus of herpes simplex viruses can confer hypersensitivity to aphidicolin and resistance to phosphonoacetic acid.

Aphidicolin, a tetracyclic diterpenoid which inhibits the DNA polymerase-alpha activities of many eukaryotic cells, inhibited herpes simplex virus growth and DNA synthesis in infected cultures and the activity of the virus DNA polymerase in vitro. A wide range of stable aphidicolin sensitivities was represented amongst a collection of virus strains with no prior exposure to this drug, but viruses with polymerase mutations selected for resistance to phosphonoacetic acid (PAA) or to acycloguanosine typically showed increased sensitivity to aphidicolin. Of 16 unrelated PAA-resistant variants, 7 were hypersensitive to aphidicolin. A number of mutants with temperature-sensitive (ts) lesions in the polymerase gene also showed increased aphidicolin sensitivity (e.g. HSV-1[mP17]tsH) or aphidicolin hypersensitivity (e.g. HSV-1[KOS]tsD9, tsC4). Resistance or hypersensitivity of virus growth and DNA synthesis in vivo were correlated with resistance or hypersensitivity of virus DNA polymerase reactions in vitro. Resistance phenotypes were closely linked to the polymerase gene during recombination with outside markers. Moreover, the selection of aphidicolin-resistant mutants from hypersensitive variants with independent PAA resistance or ts mutations in the polymerase gene could result in co-selection for PAA-sensitive and ts+ phenotypes. Confirmation that multiple independent mutations could determine aphidicolin hypersensitivity was obtained by studies of recombination between independent hypersensitive variants. Aphidicolin-resistant recombinant progeny were formed with recombination frequencies (0.4 to 2.6%) compatible with intragenic events. With parental hypersensitive variants which were products of limited PAA selection, or with the ts polymerase mutations, aphidicolin-resistant recombinants were PAA-sensitive and/or ts+. The segregation of other markers (ts, plaque morphology) amongst recombinant progeny permitted the orientation of multiple determinants of PAA resistance and aphidicolin hypersensitivity with respect to other markers in the polymerase gene and in other genes. The nature of residues determined at any one of a constellation of separate sites within the polymerase locus can determine resistance or sensitivity to antiviral drugs and aphidicolin hypersensitivity associated with changes at the polymerase locus facilitates high resolution genetic analysis of this locus.

Antiviral Agents↗

Circulating immune complexes in patients with lymphomas and leukemias.

Immune complexes (IC) were examined in the sera of 100 patients with histologically confirmed non-Hodgkin's lymphoma (NHL) and 80 leukemic patients by the EA-rosette forming cell inhibition assay. Sera from 55 healthy controls were also tested for the presence of IC. Using 9% rosette inhibition as a base-line, IC were observed to be present in 66 out of 100 sera from patients with NHL (66%), 35 out of 80 sera from patients with leukemia (43.7%) and 10 out of 55 control subjects (18%, p less than 0.001). The percentage of positive results was significantly lower in NHL patients with favorable prognosis (45%) than in patients with unfavorable prognosis (80%). IC from the sera of 7 ALL and 6 CML patients were investigated before chemotherapy, in remission and at relapse. The mean inhibitory rate of rosette inhibition was significantly higher in patients during the blastic stage of leukemia than during the complete remission (12.5%), and later it became higher again at the time of relapse. In CML patients, the previously normal serum rosette inhibition activity increased during the blastic crisis. These observations indicate that the follow-up studies of such patients may determine their prognosis accurately.

Acute Disease↗

Acute lymphoblastic leukemia: end-result analysis of treatment and prognostic factors in Indian patients.

Acute Lymphatic Leukemia (ALL) patients seen during the period 1974-1978 at the Tata Memorial Hospital. Bombay, are analyzed retrospectively to evaluate the clinical features at presentation, results of sequential therapy, and prognostic factors. A total of 301 patients were registered during the study period. There were 153 evaluable patients. Of these 73 patients received induction therapy with vincristine and prednisolone (VP) followed by cranial prophylaxis (cranial radiotherapy, 2,400 rads, and 10 weekly intrathecal injections of methotrexate 7.5 mg/m20 and continuous oral maintenance with daily 6-mercaptopurine and weekly methotrexate (group A). Another 39 patients (group B) received pulse therapy with vincristine and prednisolone during maintenance therapy. Finally 41 patients (group C) received L-asparaginase during induction and pulse therapy in addition to drugs as in group A. Of the 153 patients, 88 (58%) achieved complete response after induction treatment. Induction remission was 53% with vincristine and prednisolone (group A and group B), whereas it was 70% in group C. The difference in complete response rate in group C was statistically significant (P less than 0.05). The 3-year survival in our series was 22%, with median survival of 11 months. Group C patients receiving L-asparaginase along with vincristine and prednisolone showed 41% 3-year survival compared to 16% for group B. The 3-year survival in group A patients was only 7%, probably owing to lack of pulse therapy during maintenance treatment. The prognostic factors such as age, sex, WBC count, and mediastinal node were compared for induction remission and total survival. Possible factors relating to poor results in our series as compared to developed countries are discussed.

Adolescent↗

Immunity in esophageal carcinoma.

In carcinoma of the esophagus, response to in vivo sensitization with recall antigens and DNCB was markedly depressed with 13% and 16% positivity respectively. Similarly, the number of T-cells was found to be significantly low (24 +/- 14) as compared to normal control (61 +/- 23). Blastogenesis index with PHA was only 1.75 +/- 1.04 in contrast to normal of 6.79 +/- 2.57. This depression was independent of serum albumin level and body weight. Cell-mediated immunity was further depressed following radiotherapy and did not improve following enteral alimentation for 3 weeks. In untreated patients, there was a significant rise in levels of IgA (298 +/- 184 mg/100 ml) as compared to normal (154 +/- 54 mg/100 ml). Levels of IgA did show a downward trend following enteral hyperalimentation. Circulating immune complexes and serum CEA level were elevated in almost 50% of patients. These data confirm the influence of tumor-related impairment of cell-mediated immunity while nutrition appears to affect IgA levels.

Adult↗

Bullous pemphigoid and multiple autoimmune diseases. Alopecia universalis, bullous pemphigoid, hypothyroidism, rheumatoid arthritis, and neutropenia in one patient.

A 57-year-old white man developed Hashimoto's thyroiditis, bullous pemphigoid, and autoimmune neutropenia during the last year of his life. In addition, he had alopecia universalis since the age of 21 and rheumatoid arthritis since the age of 38. This unique constellation of autoimmune diseases has not been reported previously. Its significance is discussed in relation to the polyglandular failure syndrome and thymoma-related autoimmune disease.

Alopecia↗

Therapy-related leukemia. A report of five patients and a review of the literature.

5 patients developed acute nonlymphocytic leukemia (ANLL) 2-4 years following the use of various cytotoxic agents for other primary disease. Alkylating agents were responsible for development of ANLL in 3 patients while mitomycin-C and methotrexate appear to be linked with leukemia transformation in the remaining 2 patients. 3 patients had a prolonged preleukemic phase preceding ANLL. Pancytopenia observed in 4 of 5 patients favors drug-induced stem cell damage leading to relatively resistant leukemia. Although the incidence of secondary leukemia is not very high, careful use of cytotoxic agents is needed to minimize therapy-linked neoplasms.

Aged↗

Moderate-dose methotrexate in head and neck cancer.

200 mg/m2 methotrexate given intravenously in a running drip for 6 h has been used as an initial adjuvant therapy in 38 patients with advanced head and neck cancer. The response rate is as high as 80%, with 21% achieving complete remission. Histologically, specimens were tumor free in 3 patients. Toxicity in 38 patients included leukopenia (4), mucositis (6) and diarrhea (1). This particular dose of methotrexate appears to be safe and usually does not need leucovorin rescue. Also, when given as initial treatment, it is effective in reduction of tumor bulk. A prolonged randomized trial is essential to determine its role in improving long-term survival.

Adult↗

Immune dysfunction in non-Hodgkin's lymphoma.

Immune dysfunction seems to be more common in lymphoproliferative disorders wherein the malignant cells originate from the immune system itself. The reaction of Dinitrochlorobenzene (DNCB) and six recall antigens were found to be diminished in patients with non-Hodgkin's lymphomas as compared to control subjects (P less than 0.005). The skin reactivity was lost in increasing order in well differentiated, poorly differentiated, and histiocytic types. The depression in delayed hypersensitivity was greater with generalized as compared to localized disease. In angioimmunoblastic lymphadenopathy (AIL), skin tests also showed negative response in 7 of 8 patients. This T-cell dysfunction in a preneoplastic condition (AIL) suggests early appearance of immunodeficiency and probably a prerequisite for the development of a lymphoma. The serum immunoglobulin levels failed to show any relation with respect to histology or extent of disease. Presumably, the alteration of IgG is secondary to a malignancy.

Adolescent↗

Uhl's anomaly.

Uhl's anomaly of the heart is a rare condition. Another well-documented case is presented with a review of the published reports outlining the main clinical features and the bad overall prognosis. Right atriotomy should be avoided if closure of the atrial septal defect is attempted.

Adult↗