Search

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.

Thirty patients of myelodysplastic syndrome (MDS) were treated over a period of 2 yr using 3 different treatment regimens. Twelve patients received hydroxyurea, 4 were given low dose cytosine arabinoside and 14 others were treated with an aggressive acute myeloid leukaemia (AML) induction regimen. A low complete remission was obtained in the first 2 groups (17 and 25% respectively), whereas 9 (64%) patients attained complete remission with the AML induction regimen. Remission in the latter group was associated with prolonged and severe pancytopenia requiring intensive support. Patients in all the 3 groups had a short duration of remission culminating in death with progressive marrow failure or evolution to AML, indicating the limitations of the current treatment strategies for MDS and highlighting the need for exploring newer therapeutic approaches.

Two hundred and nine children (20 years and below) diagnosed as acute lymphoblastic leukemia between January 1980 and December 1983 were retrospectively analysed to evaluate the clinical features, prognostic factors and the results of therapy. One hundred and eighty one evaluable patients were treated with three different chemotherapy regimens consisting of vincristine and prednisolone (Group-A), vincristine, prednisolone and L-asparaginase (Group B-60 patients), and vincristine, prednisolone and adriamycin (Group C-81 patients). Complete remission was achieved in 152 (84%) patients, remission induction being 75 percent, 85 percent and 88 percent in Group A, B and C respectively. At a median follow-up of 36 months the disease free survival for complete responders was 35.5 patient. The disease-free survival for Group A, B and C was 20 percent, 47 percent 34 percent respectively indicating the superiority of a three drug regimen over the conventional two drug regimen. Patients at standard risk in each group had significantly better survival when compared to those at high risk. A 3-drug treatment regimen was superior to the 2-drug regimen and a low initial leucocyte count was an important favourable prognostic factor.

We report the first outbreak of Acinetobacter species meningitis in a group of children with acute leukaemia following the administration of intrathecal chemotherapy. Eight of twenty patients receiving methotrexate injections on a single day developed signs and symptoms of meningitis within 18 h of treatment, and cases were clustered by time of administration. A cohort study comparing case and non-case patients did not identify any specific host factor associated with meningitis. Acinetobacter calcoaceticus var anitratus was isolated from the cerebrospinal fluid (CSF) of five patients; three patients died. Our investigation determined that the methotrexate was extrinsically contaminated by reused needles, used for reconstitution and administration, which had been inadequately sterilized. Acinetobacter calcoaceticus var anitratus was isolated from an autoclaved needle and a vial of methotrexate used for chemotherapy; these and the clinical isolates had similar antibiograms. After introduction of single-use disposable needles no subsequent cases occurred.

Twenty-eight patients with pure or predominantly endodermal sinus tumor were studied for their clinical behavior, relation with serum alpha-fetoprotein (AFP), and response to intensive postoperative combination chemotherapy. Eight percent of the patients were younger than 20 years of age. One patient was a pseudohermaphrodite. Serum AFP was estimated in 17 patients and was elevated in all. Seven patients were treated with adjuvant chemotherapy following surgery with a cisplatin-containing combination. Five patients (71%) are alive and continue to remain free of disease, with a median survival of 28 months after treatment and an overall median survival of 34 months. Two patients treated with adjuvant chemotherapy experienced early recurrence of the disease, which was detected with a rise in serum AFP before the clinical manifestation of recurrence.

The records of 458 patients with acute lymphoblastic leukemia (ALL) have been reviewed. The diagnosis of ALL was based on clinical examination and morphological, cytochemical and immunophenotypic characteristics (20% or more blasts reacting with lymphoid monoclonal antibodies) of blood and/or bone marrow. Blast cells of 6 (1.3%) patients showed positive reaction with Sudan black B (SBB) in the absence of reactivity to any other myeloid markers. Positive reaction with SBB stain cannot be considered specific for myeloid series.

Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.

Avascular necrosis of bone (AVNB) is a known complication of systemic adrenocorticosteroid therapy and is thought to be dose related. However, despite the large amount of prednisolone that has been used in the standard treatment of acute lymphoblastic leukemia (ALL), AVNB has rarely been reported with this disease. We have described our experience with an adolescent girl with ALL who developed multifocal AVNB after aggressive chemotherapy, which included high cumulative doses of corticosteroids along with other cytotoxic drugs, some of which have been associated with AVNB. Five similar cases from literature are reviewed. The occurrence of AVNB may become more common in the future with the increasing use of aggressive chemotherapy. Awareness of this possibility will lead to a more rapid diagnosis and early treatment of AVNB.

Though radiotherapy has traditionally been the treatment of the choice for the patients with localised extranodal lymphomas of the head and neck areas, its adequacy as the sole modality of treatment has come to be questioned. The disease is shown to relapse in other distant extranodal sites especially the gastrointestinal tract. The addition of systemic chemotherapy has been suggested. Fifty-five patients with localised head and neck extranodal lymphomas were treated at the Tata Memorial Hospital during the period 1976-1982, 35 with radiation therapy alone and 20 with combination therapy. The total survival at 5 years was 65% for patients treated with radiation alone and 85% for those treated with combination therapy. The 5 year disease-free survival dropped to 45% for the former group but was 74% for the latter group. This difference was statistically significant (p less than 0.01). We infer that localised extranodal lymphomas be regarded as a systemic disease and be treated by a multimodal approach.

Repeated treatment with guinea pig or rabbit serum, but not with human serum, was found to eliminate mycoplasma contaminants from mammalian cell cultures as judged by staining with the fluorescent dye Hoechst 33258. Following treatment with rabbit serum and several passages, M. hyorhinis could not be detected by staining, isolation on agar, or specific immunofluorescence in a human prostate carcinoma cell line heavily contaminated with this organism. There was no evidence for the involvement of antimycoplasma antibodies in the bactericidal activity of rabbit serum. Mycoplasmacidal activity of rabbit serum was associated with a heat-labile component(s) which could be inactivated by incubation of the serum with goat antirabbit complement component C3.

A research trial was conducted at in-patient level to compare the efficacy of Sahacharadi taila with that of Nirgundi taila in Saisaveeyavata (Poliomyelitis). Forty cases were selected for the trial and grouped into two at random and treated with Sahacharadi taila and Nirgundi taila respectively. Results in both groups were highly encouraging and statistically significant. The study also revealed that 25% of patients had undergone Polio vaccination and it was not helpful to prevent the disease.

60 patients studied at the Tata Memorial Hospital from January 1976 to December 1982 were diagnosed as having T-cell acute lymphoblastic leukemia (ALL) by nonimmune rosette formation with sheep red blood cells. The analysis revealed a high incidence of mediastinal mass (50%) and extramedullary infiltration at presentation. The majority of patients (62%) presented with a high WBC count (greater than 50,000/mm3). Unipolar acid phosphatase activity was observed in 90% of patients. The remission rate with a combination treatment of adriamycin, vincristine and prednisolone was found to be 95%. Long-term survival was around 30%. More aggressive or innovative treatments will be needed to improve the results in T-cell ALL.

Front loading chemotherapy using methotrexate (200 mg/m2) alone or methotrexate (200 mg/m2) with cisplatin (20 mg/m2 daily for 5 days) was used in epidermoid carcinoma of esophagus. Evaluation after two courses showed objective response of 50% or greater in 48% of patients with methotrexate alone. Response rate was increased to 76.2% with addition of cisplatin to methotrexate. Small lesions (less than 10 cm) showed better response as compared to advanced cases. Therapy was generally well tolerated and good palliation was obtained even after the first course. Postchemotherpy treatment either with surgery or radiotherapy was tolerated without any major complications. The data confirm the short-term usefulness of initial chemotherapy with methotrexate and cisplatin in esophageal cancer. Results of prolonged follow-up will help to evaluate the role of front loading chemotherapy on long-term survival.

Fifty patients of multiple myeloma have been studied. Seventy eight per cent of the patients were in the 5th, 6th and 7th decades of life. Commonest presenting feature was bone pains (76%). 8%, 20% belonged to stage I, II and III respectively. Skull (58%), ribs (52%) and pelvis (24%) were most commonly involved. Immunoelectrophoresis revealed IgG type of myeloma in 76% and IgA type in 10% cases. Bence-Jones proteinuria was seen in 60% of patients; Kappa specificity was commoner than lambda. Overall survival at 30 months was 50%. The survival was adversely influenced by advanced stage, higher plasma cell count in the bone marrow, low haemoglobin and high serum creatinine values.

The polyadenylate [poly(A)] content of the genome RNA of human rhinovirus type 14 (HRV-14) is nearly twice as large as that of the genome RNA of poliovirus type 2. The poly(A) content of viral RNA was determined to be the RNase-resistant fraction of 32P-labeled viral RNA extracted from purified virions. Polyacrylamide gel electrophoresis indicated that the poly(A) sequences of HRV-14 are more heterogenous and on an average larger than those of poliovirus RNA. On the basis of susceptibility to micrococcal polynucleotide phosphorylase the rhinovirus genome terminates in poly(A). Replication of both viruses is almost totally inhibited by cordycepin at 50 mug/ml. At lower concentrations, rhinovirus replication is more sensitive to cordycepin than poliovirus replication. Addition of cordycepin (75 mug/ml) to infected culture prior to or during viral RNA replication results in more or less complete inhibition of virus-specific RNA synthesis. The results do not indicate that cordycepin sensitivity of either virus is due to preferential inhibition of viral poly(A) synthesis by this antibiotic.

Defective cell-mediated immunity (CMI) occurs early in the course of Hodgkin's disease (HD) and may persist even two years after successful treatment. This has been confirmed by in vivo and in vitro tests performed on 51 untreated and 52 treated patients of HD. The grading of skin reponse in vivo to dinitrochlorobenzene (DNCB) correlated very well with the in vitro leukocyte migration inhibition (LMI) response against phytohemagglutinin (PHA). An inhibitory influence of HD patients' sera was demonstrated by LMI tests in vitro. The response of peripheral leukocytes from HD patients in the LMI tests could be augmented in vitro by addition of levamisole (an immuno-potentiator) to the culture medium, thus pointing to an intrinsic defect in Lymphocytes. The data indicate that defect at multiple sites in the immune system is responsible for persistent anergy in HD.

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have described a comparison of four regimens (three of isoniazid alone and one of isoniazid plus PAS) in the treatment of pulmonary tuberculosis and an investigation of the serum isoniazid levels in the patients concerned. The present report studies the emergence of isoniazid-resistant organisms in these patients during treatment. All patients with an unsatisfactory response to treatment yielded resistant cultures, showing that the isoniazid dosage was never too low to inhibit sensitive organisms. From the degree of resistance of the first resistant cultures and of the six-month cultures from the patients treated with isoniazid alone it was concluded that resistance emerged in two stages. In the first stage, very earlyin treatment, highly resistant mutant bacilli grew freely whatever the isoniazid dosage, but mutants of lower resistance were prevented from growing to an extent dependent on the peak isoniazid concentration in the serum. Consequently, when the isoniazid dosage was increased the proportion of patients with resistant organisms decreased, since fewer low-resistance strains were able to develop. In the second stage, organisms with relatively low resistance continued to multiply, though still partially inhibited by isoniazid, and became more resistant, particularly in slow inactivators. The first-stage events determined the results of treatment since, once resistance had emerged, its extent was unrelated to the patient's eventual progress. These findings emphasize the importance of early intensive chemotherapy and adjustment of the isoniazid dosage according to peak serum concentrations rather than concentrations measured three or six hours after the dose. Concomitant administration of PAS prevented emergence of isoniazid resistance in many patients and in others delayed its emergence and reduced its degree, possibly because growth in the second stage was slow.

A class of RNA in HeLa cytoplasm with a sedimentation value of 22S is described. This RNA is a true cytoplasmic component and is not an artifact of cell rupture or of the method of RNA preparation. The 22S RNA sediments in a sucrose gradient with those ribosomal structures containing 28S ribosomal RNA (60S and 74S particles and polyribosomes). It has a base composition and methyl content similar to those of 28S RNA. The kinetics of formation of 22S suggest that it is not a direct product of transcription but is derived in vivo from "old" molecules of 28S RNA.

A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis in a 1-year comparison of four domiciliary chemotherapeutic regimens-three of isoniazid alone, either in moderate (HI-1 and HI-2 regimens) or in low (H regimen) dosage, and one of isoniazid in low dosage plus p-aminosalicylic acid (PAS) (PH regimen) -has recently been undertaken by the Tuberculosis Chemotherapy Centre, Madras. This paper-the third of the series-presents information on the length of time during which inhibitory concentrations of isoniazid (0.2 mug/ml or more) were maintained in the serum and on the estimated peak serum concentrations of isoniazid produced by the four regimens and relates these factors to the therapeutic effectiveness of the different regimens.THE RESULTS SUGGESTED THAT: (a) the therapeutic superiority of the PH regimen over the isoniazid-alone regimens was only in part due to the effect of PAS in enhancing the serum levels of isoniazid; (b) the therapeutic superiority of the HI-1 regimen (moderate dosage, given in one dose a day) over the HI-2 and H regimens (moderate and low dosage, respectively, given in two doses a day) was due to the higher peak serum concentration of isoniazid produced rather than to the period minimal inhibitory concentrations of isoniazid were maintained in the serum; and (c) there was a possibility that raising the peak serum concentration of isoniazid above a critical concentration of about 3 mug/ml had a greater therapeutic effect than similar proportional increases below this concentration. It also appeared that the slightly better therapeutic response observed in the slow inactivators of isoniazid than in the rapid inactivators was due to the higher peak serum concentrations of isoniazid produced; the enhanced therapeutic effect was approximately the same as would be expected from a 50% increase in isoniazid dosage.