Effects of cancer, radiotherapy and cytotoxic drugs on intestinal structure and function.
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Biomedical subjects
Publications and source records attributed to M T Shaw.
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In an attempt to improve remissions and survivals in previously treated patients with adult acute leukemia, we gave Adriamycin, vincristine, and prednisone for induction therapy, followed by 6-mercaptopurine and methotrexate for maintenance therapy to patients attaining complete remission (CR). The study group consisted of 18 patients with acute myeloblastic leukemia (AML), ten with acute lymphoblastic leukemia, and one with acute undifferentiated leukemia. Only one patient had previously received Adriamycin. Overall, there were ten CRs and two partial remissions. The five CRs and one partial remission in patients with AML occurred among those with one prior induction attempt; none of the eight AML patients with more than one prior induction attempt responded. The actuarial median duration of CR was 15 weeks and was similar for AML and acute lymphoblastic leukemia patients. Responders had a longer median survival (30 weeks) than nonresponders (9 weeks). Thus, although a reasonable number of responses in previously treated patients were obtained with this program, improvements in maintenance therapy are clearly needed.
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Acute monocytic leukemia is an uncommon form of acute leukemia. Distinctive clinical features include gingival hypertrophy, lymphoadenopathy, coagulation disorders, and lysozymuria. Blast cell morphology and cytochemistry are diagnostic. Receptors for the Fc fragment of IgG have been demonstrated on the basis of a few cases. The drug VP 16-213 has been shown to be very effective in treatment of untreated and previously treated patients.
A 70-year-old woman developed acute leukemia and a serum IgM spike. She entered complete remission with an adriamycin, vincristine, cytosine arabinoside, and prednisone combination. Bone marrow remission was maintained with intermittent cytosine arabinoside; however, she developed large skin nodules which partly remitted following adriamycin, vincristine, cyclophosphamide, and prednisone combination. They very rapidly recurred, and she died soon after. Autopsy revealed extensive tumor in the abdomen, pelvis, and thoracic cavity, but no bone marrow involvement. Histology revealed a "starry sky" appearance. Cytology showed undifferentiated cells with vacuolated cytoplasm resembling Burkitt lymphoma cells. Peroxidase and esterase stains were negative. There was strong pyroninophilia and the periodic acid-Schiff reaction showed granular activity in the cytoplasm. Electron microscopic appearances also resembled Burkitt lymphoma. Cytogenetic studies were normal, with no Ph1 chromosome. Immunofluorescence demonstrated surface IgM and a little IgA. 3H-thymidine incorporation was high, indicating rapid growth. Dibutyral cyclic adenosine monophosphate (cAMP) stimulated growth, which was further evidence of the lymphoid origin of the tumor. The close resemblance of this tumor to Burkitt lymphoma emphasizes the difficulties in systematically classifying the lymphomas.
Moderately high levels of activity of the enzyme terminal deoxyribonucleotidyl transferase (TdT) were found in the leukemic cells of a patient with acute lymphyocytic leukemia. The proliferating cells were B lymphocytes bearing IgG antibody, and the disease was associated with an IgG monoclonal spike and a mediastinal mass. The observations in this case suggest that TdT is related more to the immaturity and proliferation of certain lymphoid stem cells than to their progress toward B- or T-cell differentiation.
Fifty pre-school children thought to have ingested potentially poisonous substances were studied, together with 50 controls. An interview of each child and mother was undertaken in the home situation. Seven at-risk factors make a child more likely to ingest a toxic substance. These are: greater accommodation changes by the family, father having had a large number of jobs, paternal past history of accidents, child's exploring ability, child's past history of poisonings, an abnormal appetite in children older than two years old and lower stimulation indices in 2-5 year-olds. Attention is drawn to the similarity between many of these factors and childhood abuse and neglect.
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Conflicting evidence has been published as to the prognostic significance of the periodic acid-Schiff (PAS) reaction and cell size in acute lymphocytic leukemia (ALL). Therefore, a large collaborative study was undertaken to evaluate the prognostic significance of the PAS reaction and cell size of bone marrow lymphoblasts obtained at the time of diagnosis in children with ALL. Known prognostic factors (age and white blood cell [WBC] counts) were also evaluated. Data from 80 newly diagnosed cases of ALL were analyzed. These patients were treated with similar therapy by members of the Pediatric Division of the Southwest Oncology Group. The PAS reaction was scored. Microlymphoblasts were defined as having a diameter of less than or equal to 12 micron; macrolymphoblasts, greater than 12 micron. Patients 10 years and older at the time of diagnosis had a significantly shorter duration of first remission and survival than those younger than 10 years. Those with pretreatment peripheral WBCs of less than or equal to 25,000/microliter had significantly longer duration of first remission and survival than those with a peripheral WBC greater than 25,000/microliter. There was no significant difference in duration of first remission or survival in patients having predominantly macrolymphoblastic or microlymphoblastic marrows. PAS reaction was of no value in predicting the duration of first remission or survival.
Eighteen (72%) of 25 evaluable and previously untreated patients with adult acute lymphoblastic leukemia entered complete remission (CR) following induction therapy with adriamycin, vincristine, and prednisone in a Southwest Oncology Group study. Remission maintenance therapy with methotrexate and 6-mercaptopurine resulted in a median duration of CR of 10.2 months. The addition of Adriamycin to prednisone and vincristine may be beneficial in slow responders or nonresponders to these two drugs and in patients with initially high peripheral blood blast counts.
A case of solitary cecal plasmacytoma is described with strong evidence of IgGk paraprotein production demonstrated by immunofluorescence and electromicroscopy. This is the ninth case of colonic plasmacytoma reported in the English literature and the first to show positive immunofluorescence.
A combination of cytomorphological features and cytochemical staining reactions in the diagnoses of the different types of acute leukemia removes much of the subjective difficulty of diagnosis. The number of cytochemical stains used may be limited, and in our experience the PAS, combined NCE and ANE reactions, and either SB or Px staining will yield as much diagnostic information as needed in most cases. With regard to the prognostic implications, it would appear at the present time that the amount of ANE staining in the cytoplasm of blasts is inversely proportional to the chances of remission induction and length of survival in cases of acute leukemia. However, further studies must be carried out to verify this finding before using the information to compliment other prognostic variables, such as age of patient, previous therapy, cytokinetics, etc.
Possible predictive criteria of the refractoriness to therapy of the blastic phase of Ph-1-positive chronic granulocytic leukemia (CGL) have been sought. Eight cases in the blastic phase were studied. The blasts were noted to be of two types: some displayed a high nuclear:cytoplasmic ratio with deep blue cytoplasm, while others had a comparatively low nuclear:cytoplasmic ratio and bluish gray cytoplasm containing a few small granules. Electron microscopic studies showed a variety of features, including defective organelles and giant mitochondria. Cytochemical staining revealed the majority of blast cells to be peroxidase- and Sudan black-negative; granular PAS positivity was the rule. Serial cytogenetic studies demonstrated increasing aneuploidy. Bone marrow biopsy showed myelofibrotic changes in two cases. Two patients entered complete remission with prednisone and vincristine and with Ara-C and thioguanine, respectively. It is concluded that the blastic phase of CGL may manifest heterogeneity.
In a series of 130 cases of acute leukemia studied by cytochemical staining techniques, 10 cases cytochemically diagnosed as "pure" monocytic leukemia were seen. Cytochemical staining of bone marrow aspirates from these patients revealed all leukemic cells to be Sudan black negative. No positive reactions were observed for peroxidase or naphthol AS-D chloroacetate esterase. All cases demonstrated strong alpha-naphthyl acetate esterase positivity; and fluoride-inhibited naphthol AS-D acetate esterase positivity was observed in 8 of 9 cases tested. The P.A.S. reaction showed diffuse fine to coarse granules. Oil red O stain was positive in 8 of 9 cases, and the beta-glucuronidase activity was strong in 5 of 9 cases. Light microscopy revealed cells with monocytic or histiocytic morphology. Electron microscopic studies in 2 cases demonstrated features consistent with leukemic monocytic or histiocytic morphology; none was suggestive of granulocytic or lymphocytic leukemia. Five of 6 patients treated with drug regimens including prednisone and vincristine entered a complete remission; the other obtained a partial remission. Two patients achieved complete remission after treatment with Adriamycin, 1 following a relapse. Three patients who received cytosine arabinoside as their only therapy died soon after treatment was commenced. It is suggested that the cytochemical similarity but morphological differences in those patients may be objectively used to group them as cases of histiomonocytic leukemia.
In a series of 78 cases of acute lymphocytic leukemia, seven were found to demonstrate blast cells staining strongly for both the periodic acid-Schiff reaction and alpha-naphthyl acetate esterase. It is suggested that these features may represent a subclassification of acute lymphocytic leukemia or may be a marker for the leukemic phase of lymphoma.
A patient with an autoimmune thrombocytopenic syndrome was treated unsuccessfully with splenectomy. Treatment with corticosteroids and 6-mercaptopurine was partially successful, but the patient developed peripheral neuropathy and over signs of Hodgkin's disease. The latter reponded completely to radiation therapy, but the thrombocytopenia was not reversed until combination chemotherapy was given. The association of thrombocytopenia with Hodgkin's disease is reviewed.
Peripheral blood samples were drawn from 50 patients (25 males and 25 females) with no apparent haematologic disorders. Smears were stained for Periodic Acid-Schiff and beta-glucuronidase reactions. Diffuse to moderate activity was observed in leucocytes for both stains. There was a significant difference in males and females in positive reactions in monocytes stained for beta-glucuronidase and in lymphocytes and granulocytes stained for PAS.