Autologous bone marrow transplantation in acute myelogenous leukemia: in vitro treatment with myeloid cell-specific monoclonal antibodies

Second or third chemotherapy-induced remissions in acute myelogenous leukemia (AML) are limited by early relapse of the leukemia. We developed monoclonal antibodies (MoAbs) that are cytotoxic to myeloid leukemia cells to treat bone marrow from these patients ex vivo for autologous transplantation. In this pilot study, bone marrow was harvested from ten patients with AML in remission, treated with one or two complement-fixing MoAbs, PM-81 and AML-2-23, which react with myeloid differentiation antigens, incubated with rabbit complement, and cryopreserved. These MoAbs were chosen because they have broad reactivity with AML cells but not with pluripotent progenitor cells. At the time of transplant, 6 patients were in second complete remission, 1 each was in third complete or partial remission, and 2 were in early first relapse. The patients were treated with cyclophosphamide (60 mg/kg a day for 2 days) and total body irradiation (200 cGy twice a day for 3 days) and given infusions of MoAb-treated bone marrow. Full bone marrow reconstitution was observed in eight patients; two patients did not recover platelets. Seven of the ten patients are surviving and disease-free at 21.0, 15.0, 13.0, 10.0, 6.0, 3.0, and 2.0 months posttransplant. Treating bone marrow with MoAbs to myeloid differentiation antigens does not interfere with pluripotential stem cell engraftment. Longer follow-up and a controlled study are necessary to prove that the apparent efficacy of this therapeutic approach in some patients is attributable to MoAb-mediated killing of leukemia cells.     

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 prepubertal children with Noonan syndrome, aged between 5. 4 and 14. 3 y, and all with a height < 1. 4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0. 15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean ± SD height velocity increased by 4. 0 ± 1. 6 cm/y in the Noonan syndrome group and by 3. 6 ± 1. 3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0. 53 ± 0. 46 ( p < 0. 001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight ( r = 0. 48, p < 0. 05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.     

Glucocorticoid receptors in cord blood lymphocytes of healthy neonates and of preterms suffering from respiratory distress syndrome

We measured the number of glucocorticoid receptors (GR) in cord blood lymphocytes and the binding affinity (K_d) in 15 term and in 20 preterm babies. Thirteen preterms of the latter group received prenatal steroid treatment. Seven preterms developed neonatal respiratory distress syndrome (NRDS). The number of GR and the K_d were similar in the term and preterm (with and without NRDS) babies. The maximum thymidine incorporation into DNA of cord blood lymphocytes from all preterms, with or without NRDS was suppressed when compared to that from term babies or adults. This could partly be explained by the antenatal steroid treatment. Sensitivity (ID₅₀) of the lymphocytes for the inhibitory effect of dexamefhasone was the same in all groups. In this study on the number and function of GR in lymphocytes, we were unable to find a relation between the functionality of the GR and the development of NRDS.     

A possible autocrine role for interleukin-6 in two lymphoma cell lines

Interleukin-6 (IL-6) is a growth factor with diverse biologic activity. Originally described as a T-cell product that enhances immunoglobulin (Ig) secretion in antigen-stimulated B cells, it also affects the growth of T cells, plasmacytomas, hybridomas, and hematopoietic stem cells. We report the expression and secretion of IL-6 by two lymphoma cell lines, OCI-LY3 and OCI-LY12. Addition of recombinant IL-6 stimulated their growth, whereas addition of polyclonal anti- recombinant IL-6 (anti-rIL-6) had a marked inhibitory effect on proliferation. These results suggest an autocrine role for IL-6 in the growth of these lymphoma cells in culture.     

Mild cognitive impairment and 10-year trajectories of disability in the Iowa Established Populations for Epidemiologic Studies of the Elderly cohort

OBJECTIVES: To apply diagnostic criteria for mild cognitive impairment (MCI) to a geographically representative sample, to estimate the prevalence of MCI, and to estimate 10-year trajectories of incident disability for cognitively intact participants and subgroups with MCI. DESIGN: Prospective cohort; 10 years of follow-up. SETTING: Community-based survey of noninstitutionalized population aged 65 and or older in two rural Iowa counties (Washington and Iowa). PARTICIPANTS: Iowa Established Populations for Epidemiologic Studies of the Elderly (aged > or = 65; N = 3,673; 61.3% female; 99.9% white). MEASUREMENTS: Age, sex, education, Short Portable Mental Status Questionnaire (SPMSQ), 20-item word recall, activities of daily living (ADLs), instrumental activities of daily living (IADLs), chronic medical conditions. RESULTS: MCI was prevalent in 24.7% of participants at baseline. Most participants in the overall cohort remained stable or changed slowly (< or = 1 new limitations) over 10 years (63.1% for SPMSQ, 89.3% for word recall, and 61.7% for ADL disability). For MCI/no prevalent IADL disability (Stage 1 MCI), disability progression was similar to that in the cognitively intact subgroup (median = 0.08 vs 0.05 disabilities per year). For MCI plus prevalent IADL disability (Stage 2 MCI), the median rate of change was equivalent to that of the severely impaired (0.23 disabilities per year; interquartile range = 0.12-0.36). CONCLUSION: Unlike participants with MCI who reported no IADL limitations, those with such limitations were more likely to develop ADL disability--a prerequisite for a diagnosis of dementia.     

Demonstration of burst-promoting activity of recombinant human GM-CSF on circulating erythroid progenitors using an assay involving the delayed addition of erythropoietin

We demonstrate through the use of an in vitro assay involving the delayed addition of erythropoietin that human recombinant GM-CSF, cloned from a mature T cell line, Mo, clearly has burst-promoting activity (BPA) on peripheral blood erythroid progenitors at picomolar concentrations. Delay for up to 72 hours of the addition of erythropoietin to semi-solid methylcellulose cultures of concentrated peripheral blood progenitors minimizes or eliminates BPA-independent erythroid colony formation with little loss of BPA-dependent erythroid colony formation. This assay will prove useful in accurately detecting sources of BPA.     

Depression morbidity in later life: prevalence and correlates in a developing country.

OBJECTIVE: To investigate the one-month prevalence of depression morbidity and its association with sociodemographic characteristics, health and functional status, and use of health services in community residents aged 60 years and over in Brazil. METHODS: This study used a cross-sectional design of face-to-face interviews (N = 7,040) in Rio Grande do Sul State, Brazil. Participants were household residents aged 60 years and older. Measurements included the Short Psychiatric Evaluation Schedule (six-item version) and questionnaire that assessed sociodemographic characteristics, self-reported health status, systemic illnesses, activities of daily living (ADL), use of medical services, and social support. RESULTS: The overall prevalence of depression morbidity was 22% (men: 18%, women: 25.2%). In controlled analyses, younger age, low income, rural origin, never or no longer married, poor self-rated health, presence of systemic illnesses, visual, hearing, or ADL impairments, hospitalization in the past 12 months, and lack of exercise or employment were significantly associated with depression morbidity, whereas living alone was nearly so associated. Gender, education, minority race, or outpatient visits in the previous six months were not associated with depression morbidity. CONCLUSION: The overall prevalence of depression morbidity was among the highest previously reported for older persons. In controlled analyses, prevalence declined as age increased, and rates were higher for those with lower income and poorer social, health, and functional status, but did not differ significantly by gender, education, or race/ethnicity. Increased attention should be paid to identifying depression morbidity in those with adverse circumstances and to identifying ameliorating interventions.     

Anomalous ABO inheritance explained by ovum transplantation

BACKGROUND: Modern fertilization techniques can lead to unexpected ABO phenotypes in newborn infants and can raise questions as to maternity, paternity, and infant misidentification. Ovum transplantation can result in an infant with an ABO phenotype that is unexpected, given the birth mother's ABO type. STUDY DESIGN AND METHODS: A group AB, Rh- positive female infant was born to a group O, Rh-positive woman as a result of ovum transplantation. The case report is provided. RESULTS: The birth mother typed group O, Rh-positive both before and after delivery. The infant typed group AB, Rh-positive on cord blood and heelstick specimens. CONCLUSION: Ovum transplantation can result in newborns whose ABO phenotypes are unexpected, in relation to the birth mother's ABO type. To ensure patient privacy, such fertilization techniques may not be clearly documented in the delivery room chart. A complete obstetric history helps prevent repeat phlebotomies, expensive and unnecessary typing studies, and concern of the clinical staff with possible sample or infant misidentification.     

Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN- gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL- 3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.