Turnover of HeLa ribosomal RNA. The characterization of a class of RNA in HeLa cytoplasm derived from 28S RNA.

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.

Clinico-hematological profile in biphenotypic acute leukemia.

BACKGROUND: We present a clinico-hematological profile and treatment outcome of Biphenotypic Acute Leukemia (BAL). AIM: Study incidence and subtypes of BAL, correlate with age, morphology, and cytogenetic findings and correlate the clinico-hematological data with the treatment response. St Jude's and the EGIL's criteria have been compared for their diagnostic and clinical relevance. MATERIAL AND METHODS: Diagnosis was based on WHO classification, including clinical details, morphology, cytochemistry, immunophenotyping, and molecular genetics. We included those cases, which fulfilled the European Group for the Immunological Characterization of Acute Leukemia's (EGIL's) scoring system criteria for the diagnosis of BAL, as per recommendation of the WHO classification. RESULTS: There were 32 patients diagnosed with BAL, based on EGIL's criteria. Incidence of BAL was 1.2%. B-Myeloid (14 cases) followed by T-Myeloid BAL (13 cases) were the commonest subtypes. Polymorphous population of blasts (16 cases) was commonly associated with T-Myeloid BAL (10 cases). BCR ABL fusion positivity was a common cytogenetic abnormality (seven cases). Fifteen patients received chemotherapy; eight achieved complete remission (CR) at the end of the induction period. CONCLUSIONS: Pediatric BAL and T-B lymphoid BAL have a better prognosis. A comprehensive panel of reagents is required, including cytoplasmic markers; to diagnose BAL. St Jude's criteria is a simple, easy, and cost-effective method to diagnose BAL. The outcome-related prognostic factors include age, HLA-DR, CD34 negativity, and subtype of BAL. BCR-ABL expression is an important prognostic factor, as these cases will be labeled as Chronic myeloid leukemia (CML) in blast crisis with biphenotypic expression and treated accordingly.

Bone marrow morphological changes in patients of chronic myeloid leukemia treated with imatinib mesylate.

BACKGROUND: Imatinib mesylate has shown promising results in chronic myeloid leukemia (CML) in all phases. This drug is an effective treatment for patients with CML in chronic phase as it induces hematological remission in nearly all patients and cytogenetic responses in many. The bone marrow changes produced by this drug are different from the treatment modalities used earlier in CML. MATERIALS & METHODS: We studied 80 patients of CML on treatment with Imatinib at doses of 400-800 mg per day. Morphological and cytogenetic evaluation (Ph analysis) of bone marrow aspirates was done at six months of treatment. RESULT: In our study, 95% (76 out of 80) patients showed complete hematological response and 63.3% showed major cytogenetic response at the end of six months of treatment. The most commonly observed changes in the bone marrow aspirates at the end of six months of therapy were in the form of reduction in the cellularity, reduction in the M: E ratio to a mean of 2:1, presence of relative erythroid hyperplasia, normalization of megakaryocytic morphology and variable increase in the bone marrow lymphocytes. None of these changes had significant correlation with the patient's Ph status. CONCLUSION: We advise study of trephine biopsies to overcome the often-faced problem of hemodiluted aspirates in these cases and evaluation of sequential bone marrows to check the durability of these morphological changes and their correlation with the cytogenetic response with emphasis on cytogenetic changes other than Ph positivity.

Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

[Binge eating disorder in a population of morbid obese candidates to bariatric surgery at the Oswaldo Cruz University Hospital in Recife, PE]. / Transtorno da compulsão alimentar periódica em uma população de obesos mórbidos candidatos a cirurgia bariátrica do Hospital Universitário Oswaldo Cruz, em Recife--PE.

OBJECTIVES: To analyze the frequency of binge eating disorder (BED) and of the main psychiatric disorders associated with morbid obesity in individuals on the waiting list for bariatric surgery. METHOD: Cross sectional study. Interviews with patients from the Surgery for Obesity Program of Oswaldo Cruz University Hospital were conducted evaluating socio-demographic profile, quality of life (SF-36 scale), BED (Binge Eating Scale BES) and psychiatric disorders (M.I.N.I./DSM-IV). RESULTS: 67 out of 400 patients enrolled in the program were interviewed (16.8%). The BMI varied from 36.1 to 81.8 kg/m(2) (average 48.5 +/- 8.8). All have associated diseases, the most frequent being systemic arterial hypertension, sleeping disorders and osteopathies. The most frequent psychiatric disorders were: 47.8% generalized anxiety disorder, 29.9% major depressive disorder, single episode, 34.3% recurrent major depressive disorder. In this group 56.7% showed BED (25.4% moderate and 31.3% severe) and the worse scores in all the domains of quality of life (SF-36 scale). CONCLUSIONS: High prevalence of BED. The compulsive eaters showed a higher number of obesity treatments, higher prevalence of actual major depression, and the worse scores in all the domains of the SF-36 scale. Considering the ample range of psychopathology associated with BED and the greater probability of jeopardizing the surgery results it is very important to improve the detection of these disorders in order to provide adequate treatment.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

Total body irradiation in chronic myeloid leukemia.

Total body irradiation (TBI), given as 10 rad daily for five days a week for a total dose of 150 rad has been used in an attempt to control the chronic phase of chronic myeloid leukemia (CML). Thirteen patients with CML received fractionated TBI leading to rapid and good control of WBC count without any adverse reaction. The chronic phase of CML could also be controlled with TBI, even in three patients who were resistant to busulfan. Following TBI, WBC count remained under control for a period of 32 weeks as compared to 40 weeks following busulfan alone. Repeat TBI was also well tolerated with good response. It appears that TBI is an effective and safe therapy for controlling the chronic phase of CML.

Head and neck extranodal non-Hodgkin's lymphomas in Indian patients.

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.

Calla positive acute lymphoblastic leukemia after etoposide-based therapy for Ewing's sarcoma.

This is an unusual and interesting case report concerning a 10 year old boy with an initial diagnosis of Ewing's sarcoma of the right tibia. He was successfully treated with a chemotherapy regimen consisting of vincristine, cyclophosphamide (cumulative dose 7200 mg/m2), doxorubicin, etoposide (cumulative dose 2700 mg/m2) and cisplatin and local radiotherapy to the tibia. After an interval of 37 months he developed CALLA positive acute lymphoblastic leukemia with 11q23 chromosomal abnormality. The possible roles of etoposide and cyclophosphamide are discussed.

Sezary cells with hairy projections.

A case of sezary syndrome where the sezary cells showed cytoplasmic hairy projections is reported. The patient had typical exfoliative erythematous dermatitis, high white cell count, atypical lymphocytes of T-phenotype with folded nuclei and bone marrow involvement. The ultra structure study showed cerebriform nucleus and cytoplasmic projections.

Pattern of subtypes of acute lymphoblastic leukemia in India.

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.

Karyotypic findings as an independent prognostic marker in chronic myeloid leukaemia blast crisis.

Fifty-three patients with Ph positive chronic myeloid leukaemia in blastic phase were studied. Additional abnormalities were found in 29 (55%) patients and were more common in myeloid (64%) than lymphoid (45%) blast crisis. The most frequent were +Ph (32%), +8 (28%), +19 (19%), +20 (9%) and +21 (9%). i(17q) (9%) was associated with thrombocytopenia (5/5) and basophilia (2/5). The incidence of additional abnormalities was higher in patients treated with busulphan (70%) than hydroxyurea (44%). No significant differences were noted in the mean values of the clinical and haematological findings recorded at blast crisis between patients with only Ph positive (PP) cells and those with additional abnormalities (AP + AA). Univariate analysis identified karyotypic findings as an independent prognostic marker indicating its significance in assessing the response to therapy and survival after the onset of transformation.

Hairy cell leukemia--an unusual presentation.

Hairy cell leukemia is a chronic lymphoproliferative disorder affecting middle-aged adults, with the median age of 50-55 years. The majority of the patients present with cytopenia. A high count is usually a feature of the hairy cell leukemia variant. We report a case of a 23-year-old male who presented with fever and cough of 15 days duration. His peripheral blood count was 63 x 10(9)/l. His peripheral blood and bone marrow smear showed hairy cells which were positive for tartarate-resistant acid phosphatase stain. Surface markers and electron microscopic study on peripheral blood ruled out hairy cell leukemia variant as a differential diagnosis.

Trisomy 12 in chronic lymphocytic leukemia--geographical variation.

Incidence of trisomy 12 was studied in 60 cases of chronic lymphocytic leukemia (CLL) with chromosome 12 specific alpha-satellite DNA probe by fluorescence in situ hybridization (FISH). Trisomy 12 was observed in 37 (61.8%) patients. Cells with trisomy 12 were detected in a varying proportion, ranging from > 2% to 86%. Patients with trisomy 12 were predominantly observed with total white blood cell (WBC) count > 80 x 10(9) l(-1) (P < 0.001). In addition, the percentage of trisomy 12 positive lymphocytes correlated with the high WBC counts. Trisomy 12 was observed equally in typical and atypical CLL. 90% of our patients were in the intermediate and high risk groups. It was seen that there was significantly higher percentage of trisomy 12 positive lymphocytes ( > 10%) in the high risk groups (P < 0.05). A higher incidence of FMC7 positivity in atypical CLL was seen in our study. However, there was no significant relationship found between trisomy 12 positivity and expression of either FMC7 or CD23 in our cases. It appears that the CLL that we see at our centre is at a different phase of evolution and perhaps biologically different compared to the CLL seen in the West.

Incidence of 5' bcl-2 rearrangement in patients with B cell chronic lymphocytic leukemia from India.

The incidence of B cell chronic lymphocytic leukemia (B-CLL) is lower in Asian countries, including India, when compared with Western countries. The bcl-2 gene rearrangement was restricted to the 5' region and seen in only one of the 20 Indian patients analyzed. The incidence remains similar to that reported from Western and Japanese institutions.

Clinical trials of a new anthelmintic, 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), for the cure of hookworm infection.

A new compound, 4-isothiocyanato-4'-nitrodiphenylamine (C.9333-Go/CGP 4540), was tried in 39 hospitalized patients with hookworm infection, using several treatment schedules. At effective dose schedules (125 mg X 3 given 4-hourly; 250 mg X 3, 8-hourly; 1,000 mg X 3, 12-hourly), the egg reduction was 96% to 100%; the zero egg-counts were confirmed by coproculture for larvae. The compound was very well tolerated. Transient and mild side effects--giddiness, diarrhea and sweating--were observed in only three patients. No toxic effects were seen as judged by serial organ function tests, except a transient and mild asymptomatic elevation of transaminases in one patient.

Translocation (11;14)(q13;q32) and overexpression of cyclin D1 protein in a CD23-positive low-grade B-cell neoplasm.

We describe a case of low-grade B-cell neoplasm with features overlapping between B-chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The patient presented with a 10-year history of stable CLL without any treatment. The peripheral-blood picture was consistent with atypical mixed CLL (French-American-British criteria), whereas the lymph-node histology was more consistent with MCL. Neoplastic cells were strongly positive for surface immunoglobulin M, kappa, CD5, CD20, CD23, and cyclin D1. Expression of CD11c was weak. Translocation (11;14) and der(10)t(10;?)(p11;?) were the primary cytogenetic changes observed in both peripheral blood (47%) and lymph node (7%). Trisomy 12 was absent. Deletion 6q21 and rearrangements involving 1p/q, consistently associated with progression in lymphomas, also were noted in the peripheral blood but were nonclonal. The present case and similar cases with features overlapping between CLL and MCL most likely represent hybrids. In cases with features of typical CLL, t(11;14) is probably associated with gradual progression and may precede clinical and histologic transformation.

Cytogenetic studies in patients from India with T-acute lymphoblastic leukemia.

Cytogenetic analysis was performed in 30 patients with T cell acute lymphoblastic leukemia (11 adults, 19 children) at initial presentation and analysis was also repeated in clinical and hematological remission in 15 patients. At initial presentation, chromosomal abnormalities were detected in 27 cases (90%) and hypodiploidy was detected in 19 patients (63.3%), followed by pseudodiploidy in six patients (20%) and hyperdiploidy in two patients (6.6%). Other karyotypic abnormalities detected were deletion 6q (40%), deletion 11 q (16.6%), deletion 7q (10%), abnormalities of chromosome 9 in (13.3%) and translocation t(11;14)(p13;q11) in 6.6% and der(12)t(12;?)(p13;?) in (3.3%). In complete remission, nine out of 15 cases (60%) showed chromosomal aberrations. Original abnormalities were detected in two cases (13.3%) and new abnormalities were detected in seven cases (46.6%).

Rhabdomyosarcoma. A cytogenetically interesting case report.

Chromosomal analysis was performed on the tumor tissue in a case of ocular rhabdomyosarcoma. Cytogenetic analysis revealed multiple clonal abnormalities. Derivative(5)t(1;5)(q21;q35) and t(2;11) (q21;q23) were present in all the metaphases analyzed (100%). Translocation(1;19)(q21;q13) was observed in 61% of the metaphases. Other clonal abnormalities present included +i(6p)(85%),i(17q)(38%),18q+(57%), 4p+ (38%), loss of the Y chromosome (33%), and presence of double minutes (12.8%).

All trans retinoic acid with low dose cytosine arabinoside in the treatment of myelodysplastic syndrome.

The demonstration of synergistic interaction between differentiation inducing agents and DNA synthesis inhibitors suggests that these two groups act by two different mechanisms. We prospectively studied the response rate, response duration, survival, and toxicity in 10 patients with myelodysplastic syndrome (MDS) treated with all trans retinoic acid (ATRA) and low dose cytosine arabinoside (ara-C). These patients diagnosed between October 1993 and May 1995 were treated with ATRA (45 mg/M2/day) for 90 days followed by 90 mg/M2 on alternate day till Day 275; together with Ara-C (10 mg/m2) subcutaneously twice daily for 21 days for a total of 6 cycles. These patients were analyzed for response after 3 cycles of LD Ara-C and at the time of completion of therapy. Toxicity was recorded at the end of each cycle of Ara-C. There were 6 male and 4 female patients in the age range of 24 to 76 years. The morphological diagnosis was chronic myelomonocytic leukemia in 2, refractory anemia with excess blasts in 4 and refractory anemia with excess blasts in transformation in 4. Only 1 patient achieved a complete remission and 1 patient achieved a partial response. Four patients had progressive disease on treatment. One patient died of neutropenic sepsis and 1 of resistant thrombocytopenia and intracranial hemorrhage while on treatment. One patient refused further treatment after a minor clinical response and in 1 patient treatment was stopped due to toxicity. This data in a pilot study with a limited number of patient suggests that ATRA in combination with Ara-C has little effect in MDS.