Search PubMedSearch

Biomedical subjects

M E Nesbit

Publications and source records attributed to M E Nesbit.

At least 19 recordsLinked to original sources

Chromosomal abnormalities in skin following total body or total lymphoid irradiation.

Patients undergoing bone marrow transplantation often receive total body or total lymphoid irradiation as part of the conditioning regimen prior to marrow infusion. The cytogenetic effects of this therapy on skin fibroblasts were studied. Fibroblast cultures from eight skin biopsies were harvested in early passages for G-banded chromosome analysis. Four biopsies were from three patients who had high-dose cyclophosphamide and total body radiotherapy; one was from within and one was from outside the radiation field of a patient who had high-dose cyclophosphamide and lymphoid radiotherapy, one was from a patient who had combination chemotherapy alone, and one was from a normal control. No abnormal mitoses were found in the control or the patient who had chemotherapy alone, and only two of 30 mitoses from skin outside the lymphoid radiotherapy field were abnormal. However, most cells (49-88%) from five biopsies within radiotherapy fields were abnormal. Typically, abnormal karyotypes were pseudodiploid and contained multiple balanced rearrangements, of which reciprocal translocations were most common. The data indicate that the radiotherapy used for bone marrow transplantation induces extensive, sustained chromosome abnormalities in vivo in skin fibroblasts.

Adolescent

Expression of myeloid differentiation antigens in acute nonlymphocytic leukemia: increased concentration of CD33 antigen predicts poor outcome--a report from the Childrens Cancer Study Group.

Ninety-eight cryopreserved specimens of acute nonlymphocytic leukemia (ANLL) cells obtained at initial diagnosis of children enrolled on the Childrens Cancer Study Group 251 protocol (CCG 251) were examined by indirect immunofluorescence using four monoclonal antibodies to myeloid differentiation antigens. The relationship between the level of differentiation of ANLL cells as determined by their antigen phenotype and the clinical outcome of treatment, including complete remission (CR) rate, survival, and event-free survival, was evaluated. Most leukemic specimens were determined to express the CD33 antigen (L4F3), a 67-kD protein. Because the level of differentiation of normal myeloid cells is reflected by the concentration of the CD33 antigen expressed, samples were categorized as CD33-bright (immature) versus CD33-dull (mature). Patients with CD33-bright leukemic blasts had a marginally inferior CR rate to those with CD33-dull blasts (P = 0.08). With respect to survival and event-free survival, there was a significantly inferior outcome in the CD33-bright patients (P = 0.04 and P = 0.06, respectively). Reactions of ANLL with anti-CD15 antibody (1G10), anti-CD36 antibody (5F1), or anti-CD17 antibody (T5A7) did not predict clinical outcome. This study indicates that patients whose ANLL blasts displayed the CD33 antigen in an amount associated with immature myeloid cells experienced a worse outcome than patients with ANLL blasts that expressed a phenotype associated with more mature cells.

Antibodies, Monoclonal

Therapy of acute myeloid leukemia in children.

The survival of children with acute myeloid leukemia has improved with the identification of active chemotherapeutic agents and intensification of the post remission therapy using intensive chemotherapy early in the therapy. Other reports in this symposium will report equally good results with intensification early in the treatment using bone marrow transplantation. Additional factors such as long term complications and cost will become important variables to be considered, when considering the appropriate treatment for children with acute myeloid leukemia.

Acute Disease

Neuropsychologic (cognitive) disabilities in long-term survivors of childhood cancer.

Intelligence and academic achievement testing of long-term survivors of childhood cancer reveal a high incidence of memory deficits, visual-spatial skill impairment, and attention deficit disorders. While the results of various studies must be interpreted carefully, the data available identify CNS irradiation and the toxic synergism of CNS irradiation and intrathecal chemotherapy as primary etiologic factors in the neuropsychologic sequelae of curative therapy. Early education intervention is mandatory to identify survivors of childhood cancer who require assistance in overcoming intellectual disabilities.

Attention Deficit Disorder with Hyperactivity

Malignant melanotic neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study.

The melanotic neuroectodermal tumor of infancy is an uncommon neoplasm typically of early childhood which has a predilection for the head and neck region, particularly the maxilla. Except for one previous example in the literature, this tumor has consistently behaved in a benign fashion. This study documents the clinical course and pathologic findings of a tumor which began in the maxilla of a 4-month-old boy, followed by a local recurrence, metastasis to a cervical lymph node and finally, widespread dissemination and death at 18 months, 24 months and 38 months, respectively. The tumor was initially composed of nests consisting of melanin-containing cells and small dark cells. An elevated vanillylmandelic acid level was recorded during the course of the disease. At autopsy, the tumor in lymph nodes, liver, bone and soft tissues had a monotonous pattern of small dark cells similar to a conventional neuroblastoma. Previous ultrastructural studies indicate that the melanotic neuroectodermal tumor of infancy is composed of melanocytes and neuroblast-like cells. Our case provided the unique opportunity to examine in sequence the ultrastructural and in vitro characteristics of a recurring and eventually metastasizing melanotic neuroectodermal tumor. Although the neuroblast-like cells were initially difficult to identify by electron microscopy, a melanin-producing cell line and a separate nonpigmented cell line were successfully isolated from various tumor explants. Various stages of melanosome development were identified in the pigmented cells from the local recurrences and in vitro. Dibutyryl cAMP accentuated the formation of pigment and dendritic development in the melanocytes and dendrites only in the small nonpigmented cells. Electron dense granules were observed in the cultured smaller cells and also in the lymph node and soft tissue metastases. Tyrosine hydroxylase activity was demonstrated in the neuroblast-like cells. In the final biopsy and autopsy material, only the neuroblast-like cells remained and the tumor resembled a conventional neuroblastoma.

Culture Techniques

Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis.

Nineteen patients whose bone marrow smears showed histiocytic hyperplasia with prominent hemophagocytosis were found to have a clinicopathologic syndrome associated with active viral infection. High fever, constitutional symptoms, liver function, and coagulation abnormalities and peripheral blood cytopenias were characteristic findings. Hepatosplenomegaly, lymphadenopathy, bilateral pulmonary infiltrates, and skin rash were often present. Fourteen of the patients were immunosuppressed. Active infection by herpes group viruses was documented in 14 patients and by adenovirus in 1. The bone marrow of most patients also showed decreased granulopoiesis and erythropoiesis with normal to increased numbers of megakaryocytes. Treatment generally consisted of supportive therapy and withdrawal of immunosuppressive drugs. Thirteen patients recovered. Lymph node biopsy and autopsy material showed generalized histiocytic hyperplasia with hemophagocytosis. The relationship of this disorder to familial hemophagocytic reticulosis, familial erythrophagocytic lymphohistiocytosis, histiocytic medullary reticulosis, and malignant histiocytosis is discussed. Immunosuppressive and cytotoxic therapy may be contraindicated in the treatment of this virus-associated syndrome.

Adolescent

Localized bone marrow relapse in acute lymphoblastic leukemia.

Localized bone marrow relapse is rare in acute lymphoblastic leukemia. Discordant bone marrow specimens were found in an 11-year-old asymptomatic girl who had been in remission for six years and off chemotherapy for 2 1/2 years. One bone marrow sample showed marked leukemic infiltration, whereas marrow from another site was normal. Three months later, with normal peripheral blood counts, she developed severe back pain and x-ray evidence of vertebral collapse and periosteal changes in the pubic bone. At that time three of the four areas of bone marrow sampled showed leukemic involvement. Reinduction therapy was begun, and she is now in remission on maintenance chemotherapy. At this time, it is unclear whether routine performance of marrow aspirations and biopsies from multiple sites, in periodic follow-up examinations of patients with acute leukemia would allow earlier detection of relapse frequently enough to justify the procedure. The issue of localized bone marrow involvement, if more common than previously reported, should be addressed at the time a decision is being made to discontinue therapy.

Bone Marrow

Histoplasmosis simulating lymphoma in children.

The experience of two Mineapolis hospitals with histoplasmosis over a 10-yr period was reviewed. Six of eleven pediatric patients with histoplasmosis presented with systemic symptoms, a mediastinal mass, and no pulmonary infiltrates. A clinical diagnosis of lymphoma was made in each case. Immediate radiation therapy for respiratory compromise was considered in one patient before pathologic diagnosis revealed primary histoplasmosis of the mediastinum. Although immediate therapy with steroids or irradiation is often considered in patients who have acute respiratory embarrassment caused by a mass, histologic confirmation of the diagnosis is always indicated before such therapy is instituted. Primary histoplasmosis of the mediastinum may be more common than previously thought.

Adolescent

A follow-up report of long-term survivors of childhood acute lymphoblastic or undifferentiated leukemia. A report for Childrens Cancer Study Group.

From an original group of 229 patients with acute lymphoblastic leukemia or acute undifferentiated leukemia diagnosed in 1963 and 1964, 15 patients who achieved greater than 2 1/2 years continued complete remission were assigned either to continue with maintenance therapy or to discontinue therapy. Five of the 15 patients have died after surviving from six to ten years from the time of diagnosis. Of the remaining ten patients, all are alive and free of disease for more than 14 years from diagnosis. No relapses or deaths have occurred in patients off therapy for greater than five years. In this small series of patients, there was no difference in survival in the continued or discontinued therapy groups. No overt adverse effects of therapy have been seen in the ten surviving patients. These encouraging data need to be extended and confirmed, utilizing patients treated with the more sophisticated therapeutic approaches employed in modern protocols for ALL/AUL. Identification of adverse effects of therapy will require appropriate and careful surveillance of large groups of successfully treated patients.

Acute Disease

Cycochemical profiles in acute lymphoblastic leukemia.

Lymphoblasts from 61 untreated patients with acute lymphoblastic leukemia (ALL), classified according to the French-American-British (FAB) morphologic classification, were studied for cytochemical characteristics and membrane surface markers. Seventy-three % (eight of 11) of patients with E-rosette positive lymphoblasts (T ALL) had strong focal paranuclear acid phosphatase (AcP) activity in more than 75% of their lymphoblasts; lymphoblasts from only 6% (three of 48) (p = 0.005) of patients with E-rosette negative, surface immunoglobulin negative lymphoblasts (non-T, non-B ALL) exhibited this characteristic AcP activity. The non-T, non-B ALL cases that manifested focal paranuclear AcP activity had clinical features more characteristic of the T ALL cases. The distribution of beta-glucuronidase activity in the lymphoblast cytoplasm was similar to that of AcP for T ALL and non-T, non-B ALL but the stain was generally more difficult to interpret THan the AcP and was a less reliable indicator of immunologic type of ALL. The periodic acid-Schiff (PAS) and nonspecific esterase stains were not useful in distinguishing between T ALL and non-T, non-B ALL but PAS negativity was associated with certain clinical features within the non-T, non-B ALL group. Cytochemical evaluation of the lymphoblasts at diagnosis in patients with ALL may be useful in identifying subsets of ALL that have distinct immunologic and clinical characteristics and important therapeutic and prognostic implications.

Acid Phosphatase

Childhood leukemia-lymphoma. Heterogeneity of phenotypes and prognoses.

Results are reported on 724 children and adolescents with acute leukemia-lymphoma. One hundred patients had immunologic marker analysis that defined the major phenotypic groups, i.e., T-cell, B-cell (Burkitt), myeloid, and the most frequent form, non-T, non-T "common" or "undifferentiated" acute leukemia. Pre-T, pre-B, and "null" leukemias are included in the latter group. Response to therapy and survival was best in non-T, non-B acute lymphocytic leukemia, intermediate in T-cell disease, and worst in B-cell (Burkitt) disease. Additional factors resulting in decreased survival include elevated peripheral leukocyte count, presence of enlarged nodes, less depression of hemoglobin and platelets, and age greater than 7 years (all associated with 'lymphomatous" disease). Other factors resulting in decreased survival include age under 3 years and depression of serum immunoglobulins. Definition of the heterogeneity of childhood leukemia-lymphoma dictates differing forms of therapy for the various types of these diseases.

Adolescent

Effective dose of L-asparaginase for induction of remission in previously treated children with acute lymphocytic leukemia: a report from Childrens Cancer Study Group.

L-Asparaginase, in the dose of greater than or equal to 6000 IU/sq m three times weekly, was demonstrated to be an effective agent in reinduction of remissions in childhood leukemia. Four hundred thirteen children with acute lymphocytic leukemia were treated with L-asparaginase. Doses i.m. ranged from 300 to 12,000 IU/sq m. None of the patients had received prior asparaginase therapy. 6-Mercaptopurine was given p.o. concurrently. All of the patients had experienced several previous relapses, and their disease was not responsive to 6-mercaptopurine. L-Asparaginase was found to be effective in reinducing remissions at the following rates: 9.5% for 300 IU/sq m; 35.1% for 3,000 IU/sq m; 53.5% for 6,000 IU/sq m; and 62.5% for 12,000 IU/sq m. The drug was given three times weekly for four weeks. Hypersensitivity reactions occurred in 6.5% of patients.

Asparaginase