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Biomedical subjects

D A Lipschitz

Publications and source records attributed to D A Lipschitz.

At least 37 records · Page 2Linked to original sources
PubMed1994

Evidence suggesting a negative regulatory role for macrophages in murine erythropoiesis in vivo.

Increasing the rate of erythropoiesis in C57BL/6 mice, either by hypoxia or by the injection of recombinant erythropoietin (Epo), resulted in significant reductions in marrow macrophage number, as assessed by flow cytometry employing the monoclonal antibody against the macrophage antigen Mac-1 and by histologic determination of reductions in the number of marrow esterase-positive cells. This decline was paralleled by decreases in marrow colony-forming unit-macrophage (CFU-M) and colony-forming unit-granulocyte/macrophage (CFU-GM) number. The intramedullary concentration of the cytokines interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha), which are produced by macrophages, was also reduced. Cessation of erythropoiesis was associated with increases in macrophage number, CFU-M and CFU-GM colony number, and IL-1 alpha concentrations. Increased erythropoiesis resulted in reductions in number of burst-forming unit-erythroid (BFU-E) colonies, which were less sensitive to suppression by macrophages as evidence by less increase in colony number when macrophages were removed from the marrow before in vitro BFU-E culture. BFU-E colony number was suppressed less when IL-1 alpha and TNF-alpha were added to cultures obtained from animals with stimulated erythropoiesis. Compared to controls, BFU-E number and suppression by macrophages increased significantly when erythropoiesis was reduced. These observations provide compelling evidence for a regulatory role for macrophages in normal erythropoiesis in vivo, presumably acting as a negative balance to the stimulatory effects of Epo.

Animals↗
PubMed1994

Screening for nutritional status in the elderly.

A comprehensive assessment of nutritional status is a critically important component of any patient evaluation. Based upon clinical information, anthropometric data, and a small number of laboratory investigations, an accurate appraisal of nutritional status should be possible and an appropriate intervention plan can be developed. The actual approach depends on the particular problem discovered. These are discussed in detail elsewhere in this issue.

Aged↗
PubMed1992

The role of macrophages in the regulation of erythroid colony growth in vitro.

Depletion of macrophages from murine marrow by the use of a monoclonal anti-macrophage antibody resulted in a significant increase in the number of erythroid burst forming units (BFU-E). This increase could be neutralized by the addition back to culture of macrophages or macrophage conditioned medium indicating that the suppression was mediated by soluble factors. To further characterize this effect, the addition to culture, either alone or in combination, of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage-containing and macrophage-depleted cultures. The addition of IL-1 alpha to culture stimulated the release of both TNF alpha and GM-CSF and acted synergistically with both cytokines, resulting in a dose-dependent suppression of BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by monoclonal antibodies the addition of IL-1 alpha resulted in a significant increase in BFU-E growth. The addition of GM-CSF to culture caused a dose-dependent suppression of BFU-E that was mediated by TNF alpha, as colony number was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were simultaneously added to culture. TNF alpha-induced suppression of BFU-E only occurred in the presence of macrophages. In macrophage-depleted cultures, a dose-dependent suppression of BFU-E could be induced if subinhibitory concentrations of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly synergistic so that the doses required to induce suppression when added simultaneously was only 10% of that required when either were added to culture alone. Suppression of BFU-E by GM-CSF or the combined addition of GM-CSF and TNF alpha did not require IL-1 alpha because inhibition was not neutralized by the addition of anti-IL-1 alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Anemia in the elderly patient.

Anemia is one of the most common disorders in elderly patients. The pathophysiology of anemia is the same in the young as well as the old. However, the common presence of multiorgan dysfunction or disease in elderly patients can alter the clinical presentation, response to treatment, and prognosis of anemia in this group.

Aging↗
PubMed1992

Analysis of treatment failure in acute nonlymphocytic leukemia patients over fifty years of age. A Southwest Oncology Group study.

Fourteen participating centers registered 33 patients on a Southwest Oncology Group Study of adults with acute non-lymphocytic leukemia (ANLL). Induction consisted of cytosine arabinoside 70 mg/m2 days 1-7 by continuous intravenous (i.v.) infusion, VP-16 50 mg/m2 i.v. over 1 hour days 1-3, and daunomycin 30 mg/m2 i.v. bolus days 1-3. Twenty-five patients (median age 69 years) were evaluable for response. Eleven (44%) achieved a remission marrow but only 8 fulfilled both blood and marrow criteria for complete remission. Of the 11 patients with a remission marrow, there were no patients over 70 years of age. Major coexisting disease data were evaluated. Only 5 patients had no major coexisting disease and 4 of those 5 achieved a remission marrow. The study illustrates and underscores the following problems of remission induction in the elderly: (a) increased susceptibility to the stress of the induction period, with 6 patients (24%) dying before treatment day sixteen; (b) disease resistance to antileukemic therapy with persistent ANLL in 6 patients (24%), despite two induction courses; and (c) hematopoietic stem cell sensitivity in the elderly with marrow regeneration failure documented in 2 patients (8%) following induction. Acute nonlymphocytic leukemia in the elderly has a poor prognosis, and novel therapeutic approaches are warranted.

Aged↗
PubMed1992

An approach to nutrition screening for older Americans.

The Nutrition Screening Initiative suggests an adaptable, tiered approach to screening for poor nutritional status in older Americans. The first level of screening is a checklist to be completed by elderly individuals or their caregivers. This checklist, which will be widely disseminated, describes the warning signs of poor nutritional status. It is anticipated that individuals will approach their physicians on the basis of scores on this checklist. Also included are two screening tests designed to help clinicians more easily detect poor nutritional status, or risk factors for poor nutrition, in their patients. The level I screen is to be completed by a social service or health care professional, or by other trained personnel. The level II screen focuses on additional information to be obtained following referral to a physician or other qualified health care professional.

Aged↗
PubMed1991

Effect of age on second messenger generation in neutrophils.

Neutrophils from healthy elderly donors generate significantly less diacylglycerol (DAG) and inositol triphosphate (IP3) than neutrophils from young donors, following stimulation by the chemotactic peptide, formyl-methionyl-leucylphenylalanine (FMLP). The defect in signal transduction occurred at a point proximal to the generation of IP3 and DAG, since the reduction in FMLP-induced superoxide generation was corrected if the intervening signal transduction steps were bypassed, either by priming with a substimulatory dose (1.62 nmol/L) of phorbol myristate acetate (PMA), by ionophore elevation of cytosolic calcium, or by using a stimulatory dose of PMA (1.62 mumol/L). FMLP receptor number and affinity were unaffected by aging. On FMLP activation, neutrophils from old, as compared with young, volunteers showed significantly greater and more long-lasting decreases in the concentrations of phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP2). This indicates a reduction with age in the metabolically active precursor pools responsible for the generation of IP3 and DAG. In contrast, aging had little effect on the production of phosphatidic acid (PA), which has recently been suggested to serve as a major activator of the NADPH oxidase. This may explain why the decrease in IP3 and DAG production was not accompanied by a comparable decrement in superoxide generation, which was only 17% lower in the old than in young donor neutrophils. Thus, aging is associated with reductions in the concentration of critically important phosphoinositides, resulting in diminution in the ability to produce key second messengers. Although the aged neutrophil is largely able to compensate for the decrements in signal transduction, its reserve capacity is compromised, making it particularly vulnerable to external insults that also impair function.

Adolescent↗
PubMed1991

Protein-energy undernutrition and the risk of mortality within 1 y of hospital discharge in a select population of geriatric rehabilitation patients.

To determine whether undernourished elderly patients are at increased risk for mortality, independent of nonnutritional factors affecting outcomes, 109 patients were evaluated at admission to a geriatric rehabilitation unit (GRU) and then followed prospectively for 1 y after hospital discharge. During the interval of observation, 33 (30%) patients died, 11 before hospital discharge and 22 within the year subsequent to discharge. Of the 81 nutritional and nonnutritional variables analyzed, the best predictor of mortality, as determined by stepwise-discriminant-function analysis, within 1 y of hospital discharge was the percent of usual body weight lost in the year previous to admission, followed by the subscapular skinfold thickness and the discharge Katz Index of Activities of Daily Living (ADL) score. Percent of weight lost was also the strongest predictor of 1-y post-GRU-admission mortality. These results provide compelling evidence for the importance of nutritional status in predicting both in-hospital and postdischarge mortality in a population of frail, male GRU patients.

Activities of Daily Living↗
PubMed1991

Malnutrition in the elderly.

Malnutrition is known to be very common in hospitalized and institutionalized elderly. Various studies report an incidence ranging from 33% to 67% of all patients. Recent evidence also suggests that the presence of nutritional deficiencies is associated with increased morbidity, mortality, and greater use of health care resources. The problem is compounded by the lack of resources in most acute care hospitals and nursing homes to obtain an adequate nutritional assessment or to monitor nutritional status over time. This report will present an overview of nutritional problems in the elderly, and provide an approach aimed at identifying patients at high risk of being malnourished in order to develop rational strategies for management. The role of nutritional factors in the development of pressure sores will also be discussed.

Aged↗
PubMed1991

Consensus of the Nutrition Screening Initiative: risk factors and indicators of poor nutritional status in older Americans.

Dietetics professionals must become even more proactive in taking the lead in the nutritional screening and assessment of older Americans. They can do so by encouraging all health care providers to become familiar with each older American's circumstances and needs. In addition, as individuals and as a professional health care association, we should urge our colleagues and institutions to establish regular longitudinal surveillance and continuity of care in nutrition services delivery. The timely, appropriate, and cost-effective delivery of nutritional screening, assessment, and care will improve the health and well-being of this valued segment of the US population. Dietetics professionals are a vital part of this process.

Activities of Daily Living↗
PubMed1990

Impact of nutrition status on morbidity and mortality in a select population of geriatric rehabilitation patients.

To determine whether the level of protein-calorie undernutrition at presentation correlated with the subsequent risk of developing in-hospital complications independently of nonnutrition factors influencing outcomes, a prospective study was conducted of 110 consecutive admissions to a Geriatric Rehabilitation Unit (GRU) of a Veteran's Administration hospital. In total, 54 variables were evaluated as possible predictors of outcomes. The risk of developing at least one complication while on the GRU was studied by using multivariate techniques (discriminant function analysis) and was found to correlate with, in order of significance, functional status as admission, serum albumin concentration at admission, amount of weight lost in the year before admission, and the presence or absence of a renal or pulmonary disease. Nutrition variables also independently correlated with the risk of developing an infectious complication or a major life-threatening complication and dying within the hospital. These data indicate the importance of nutrition status in geriatric rehabilitation patients.

Aged↗
PubMed1990

Effect of age on phorbol-ester stimulation of human neutrophils.

When stimulated by phorbol 12-myristate 13-acetate (PMA), superoxide generation in neutrophils from old volunteers was modestly lower than neutrophils from young subjects. PMA receptor number and affinity were normal. Protein kinase C (PKC) translocation to the membrane was normal but its activation was reduced. PMA-induced total endogenous phosphorylation and phosphorylation of individual proteins showed no age-related differences as determined by SDS-PAGE analysis. These minimal alterations in neutrophil function contrast with the much more significant decrements in superoxide generation and calcium homeostasis noted when neutrophils from old volunteers are stimulated by chemotactic peptide formyl-methionyl-leucine-phenylalanine (FMLP) (Lipschitz et al., 1988). It is well recognized that phorbol activates the cell through a mechanism that bypasses the membrane-receptor. Taken together with our observations with FMLP, these results point to a membrane-associated deficiency in the signal transduction pathway, most likely through receptor coupling or alterations in membrane lipids. They also demonstrate that there is not an overall reduction of metabolic responses in neutrophils from the elderly.

Adult↗