Biomedical subjects
Publications and source records attributed to P Lanzkowsky.
This report describes a case of HLADR+, CD34- acute undifferentiated leukemia (AUL) diagnosed in an 18-year-old male. A definition of AUL and a system for its classification are proposed on the basis of the current state of knowledge about phenotypic features of AUL cells and their clonal counterparts that exist during early stages of normal hematopoiesis.
Outpatient adherence to oral medication regimens was evaluated in 50 adolescents and young adults with cancer: 21 patients with acute lymphoblastic leukemia or Hodgkin disease who were to take prednisone as a component of their chemotherapy regimen, and 29 patients with Hodgkin disease whose chemotherapy had been discontinued and who were to take penicillin for postsplenectomy prophylaxis. Of the 21 adolescent patients with acute lymphoblastic leukemia or Hodgkin disease who were to take prednisone as outpatients, 11 patients were found to be nonadherent to treatment (52%). Among the 29 adolescents for whom penicillin was prescribed for postsplenectomy prophylaxis, nonadherence was detected in 14 patients (48%). If a method is available, laboratory assessment to determine adherence should be performed in adolescents and young adults receiving long-term therapy, particularly if one wishes to draw valid conclusions regarding efficacy of various treatment protocols.
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Six children with juvenile chronic myelocytic leukemia (JCML) with adverse prognostic features were treated with intensive combination chemotherapy similar to that utilized in patients with acute nonlymphocytic leukemia (ANLL). Despite obtaining hematologic remissions after induction therapy, clinical findings of extramedullary disease persisted. The use of intensive post-induction chemotherapy did not erradicate persistent extramedullary disease, and all patients developed hematologic relapse and progressive disease at a median of 8 months. The median survival of the treated patients was 15 months. The use of intensive ANLL therapy in poor prognosis JCML does not improve the survival rates reported with less intensive regimens but does have value in producing hematologic remissions that may be useful in preparing patients for bone marrow transplant.
A patient with severe chronic Epstein-Barr virus (EBV) infection (CEBVI) of 6 years duration developed an EBV+ T-cell lymphoma. To determine whether the development of the T-cell tumor was linked to EBV, we studied this patient's EBV-specific immune response and her T-cell tumor tissue for evidence of EBV infection. Peripheral blood lymphocytes from this patient were systematically studied for immune function and response to EBV. Tumor tissue was examined for EBV genome and for evidence of EBV replication. This patient failed to develop anti-EBV nuclear antigen (EBNA) antibodies and had decreased mitogen responsiveness. Her T-cells showed a broad suppression of both autologous and allogeneic B-cells, which was coincident with clinical hypoimmunoglobulinemia. A selective cytotoxic T-cell defect toward autologous EBV-infected B lymphoblasts, which could not be corrected by the addition of lymphokine-mediated T-cell help, was also documented. A lymph node biopsy taken 5 years after her clinical presentation revealed lymph node architecture completely effaced by a diffuse CD3+, CD4+, Ia+, CR2+ T-cell lymphoma containing EBNA and linear, replicating EBV DNA. Select CEBVI patients with humoral and combined cellular aberrations in the immune response to EBV may be predisposed to the development of EBV+ T-cell tumors.
Since thrombotic phenomena have important roles in the vasoocclusive manifestations in sickle cell disease (SCD), protein C (PC) was determined in 32 children with SCD during steady state and vasoocclusive crisis (VOC) and in controls. Children with SCD during steady state had significantly lower PC levels as compared to controls. During VOC there was marked decrease in PC as compared to levels during steady state, and these levels increased to initial levels or higher with clinical improvement. It is postulated that the decreased levels of PC in SCD are probably secondary to increased consumption as well as decreased production because of altered liver function. This data suggests that decreased levels of PC may increase the risk of thrombosis in these patients.
Tumor specimens from 33 patients with neuroblastoma were assayed for amplification of the N-myc oncogene and RNA expression to determine whether N-myc RNA expression levels correlated with N-myc gene amplification and clinical outcome. N-myc gene amplification was detected in one stage II tumor, one stage IV-S tumor, and seven stage III or IV tumors. In each case, N-myc RNA expression roughly paralleled N-myc gene amplification. However, enhanced N-myc RNA expression was not confined to tumors with N-myc gene amplification: all of the early (stage I and II) tumors, five stage IV-S tumors, and 12 advanced (stage III and IV) tumors had levels of N-myc RNA that were elevated up to 50-fold. While N-myc gene amplification correlated with prognosis, there was no such correlation with levels of N-myc RNA expression. The precise role of the N-myc gene in the pathogenesis of neuroblastoma remains unclear.
Renal tumors of childhood occasionally exhibit histopathologic and clinical features that preclude accurate diagnosis. Molecular and cell culture techniques may be helpful in better characterizing these cases. This approach was used to examine unusual bilateral renal tumors from a young boy. The left kidney tumor was an undifferentiated neoplasm with light microscopic features suggestive of both Wilms' tumor and neuroblastoma, and the right kidney tumor was identified as multilocular cystic nephroma (MLCN). In vitro tissue culture of tumor cells and hybridization experiments with an N-myc oncogene DNA probe contributed to a revised diagnosis of intrarenal neuroblastoma of the left kidney. A cell line established from the left tumor exhibited neurite outgrowth and was positive for neuron-specific enolase and synaptophysin. N-myc was greater than ten-fold amplified in chromosomal DNA from the left kidney tumor. Measurement of N-myc RNA expression enabled distinction between benign and malignant tumor tissue. The detection of N-myc gene amplification predicted a poor prognosis which was confirmed by the patient's subsequent clinical course.
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An 11 year old girl developed progressive upper gastrointestinal ulceration and recurrent episodes of intravenous catheter associated polymicrobial septicaemia. Evaluation failed to establish a cause. After exclusion of the parents and careful surveillance of the patient she improved, supporting the diagnosis of suspected child abuse (a form of Meadow's syndrome).
A 12-year-old girl with acute lymphoblastic leukemia (ALL) had two types of acquired cytogenetic abnormalities in her pretreatment peripheral blood and bone marrow: hyperdiploidy due to tetrasomy 8, 10, and 21; and, in the hyperdiploid cells, a shift from heterozygosity to homozygosity for a polymorphic variant on chromosome 15. Both abnormalities disappeared after chemotherapy, when the patient entered clinical remission. It has recently been found that shifts to homozygosity occur in retinoblastoma and Wilms' tumor. Our observation extends this finding to leukemia and indicates that such shifts may have general importance in tumorigenesis.
Two cases of benign isolated cutaneous histiocytosis X in newborn infants are reported. Clinically, the lesions mimicked chicken pox, and the histologic findings in skin biopsies were indistinguishable from those described in infantile Letterer-Siwe disease. Electron microscopy showed Langerhans' cells with the classical trilaminar, racket-shaped granules. Our cases a well as 10 of the 21 previously reported cases showed spontaneous resolution of the skin lesions. Since this is a benign spontaneous resolving histiocytosis, we recommend that no therapy be given provided that no other signs of systemic involvement are found.
Iron deficiency is the most common nutritional deficiency in children and is widespread in childhood populations throughout the world. Although many sophisticated tests have been devised for the diagnosis of iron deficiency the most reliable criterion of iron deficiency anemia is the hemoglobin response to an adequate therapeutic trial of iron. Following the reticulocytosis peak hemoglobin rises at an average of 0.25 to 0.4 g/dl/day and hematocrit at a rate of 1% per day. If the response to iron falls short of this response other causes of the anemia should be sought by detailed hematologic investigation. In addition to making a diagnosis of iron deficiency anemia it is incumbent on the physician to demonstrate its cause.
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Newborn rats born to iron deficient mothers (IDM) were found to have significantly lower hemoglobin, sucrase, lactase and maltase levels compared to control newborn rats. Rats born to IDM and nursed by IDM, when sacrificed at 21 days of age, had statistically significantly lower hemoglobin, serum iron, sucrase, lactase and maltase levels compared to control rats. Rats born to IDM, but nursed by iron sufficient mothers (ISM) and sacrificed at 21 days of age, had hemoglobin, serum iron and sucrase levels compared to control rats whereas lactase and maltase were not corrected by 21 days of nursing by ISM. Rats burn to IDM and nursed by either IDM or ISM for 21 days were given intramuscular iron dextran and placed on iron sufficient diet (ISD) for 7 days. These animals experienced correction of the hemoglobin, serum iron, sucrase and maltase levels compared to control rats, whereas intestinal lactase was not corrected by 7 days of ISD and intramuscular iron. Rats born to ISM, nursed by IDM and sacrificed on day 21 had significantly lower hemoglobin, serum iron and intestinal lactase levels compared to control rats. Rats both to ISM and nursed by IDM were given intramuscular iron dextran on day 21 and placed on an ISD from day 21-28. These animals had a return in hemoglobin, serum iron, sucrase and maltase levels comparable to control rats. Rats born to and nursed by ISM and maintained on an iron deficient diet from day 21-84 had significantly lower hemoglobin, serum iron, sucrase, lactase and maltase levels compared to control rats. Rats born to and nursed by ISM, maintained on iron deficient diet from day 21-84, and then given intramuscular iron dextran on day 84 and maintained on an ISD until day 92, experienced correction of the hemoglobin, serum iron and lactase levels compared to control rats. Intramuscular iron and 7 days of ISD did not correct the sucrase and maltase levels in these rats. Lactose tolerance tests in iron deficient rats showed flat curves compared to controls. After iron treatment, lactose tolerance curves returned to control values. Iron deficiency in rats in utero, during the nursing and postweaning period causes, in addition to anemia, a reduction in jejunal disaccharidase activity because of an alteration in the enzymes of the brush border membrane. Varying degrees of reduction and response of certain disaccharidases to iron treatment are dependent on the time of iron deprivation in relationship to the intra-uterine and postnatal development of the digestive and absorptive functions in the small intestine. Alterations in the levels of disaccharidases demonstrated in this paper represents another aspect of the spectrum of biochemical effects of iron deficiency.
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