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Biomedical subjects

C W Daeschner

Publications and source records attributed to C W Daeschner.

At least 19 recordsLinked to original sources

Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia.

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.

Adolescent↗

Risky behavior in teens with cystic fibrosis or sickle cell disease: a multicenter study.

OBJECTIVE: To determine the prevalence and age of onset of common risky behaviors such as smoking and sexual activity in teens with cystic fibrosis and those with sickle cell disease and to compare their behaviors with those of adolescents in the general population. DESIGN: Survey. SETTING: All five major pediatric tertiary care centers in North Carolina (study participants with sickle cell disease or cystic fibrosis) and North Carolina public schools (comparison population). PARTICIPANTS: Three hundred twenty-one adolescents with cystic fibrosis or sickle cell disease aged 12 to 19 years (mean age, 15.6 years; 49% female). Demographically matched comparison teens for each group were selected from 2760 in-school adolescents (mean age, 16.0 years; 51% female). MAIN OUTCOMES MEASURES: Prevalence of tobacco and marijuana use, alcohol use, sexual intercourse, sexually transmitted diseases, seat belt use, weapon carrying, and age of onset of these behaviors. RESULTS: Chronically ill teens reported significantly less lifetime and current use of tobacco, marijuana, and alcohol; less sexual intercourse; less weapon carrying, less drunk driving, and more seat belt use than their peers. Nonetheless, 21% of the teens with cystic fibrosis and 30% of those with sickle cell disease had smoked; sexual intercourse was reported by 28% and 51%, respectively. Age of onset of these behaviors was frequently older for the chronically ill teens. CONCLUSION: Teens with cystic fibrosis or sickle cell disease took more potentially damaging health risks than might be expected, although the prevalence was lower than reported by their peers. Future longitudinal studies should examine the relationships between chronic illness, physical and psychosocial maturation, and risky behavior. Screening for psychosocial issues, including risky behaviors, should be incorporated into the routine health care of chronically ill teens.

Adolescent↗

Health insurance access to young adult survivors of childhood cancer in North Carolina.

Historically, there has been evidence to support the hypothesis that survivors of childhood cancer have been discriminated against in the private health insurance market in some areas of the United States. Results of previous studies have been inconsistent and have generally focused on a limited number of outcome variables. A retrospective cohort study of young adult survivors of childhood cancer and their siblings was performed to determine the risk of health insurance access problems of childhood cancer survivors in North Carolina. Mailed questionnaires were completed by 182 cancer survivors from three institutions who were diagnosed between 1976 and 1988, and by 101 of their siblings for a response of 62.1%. Using logistic regression in SAS, cancer survivors were found to be more likely to be denied health insurance than their siblings, with an adjusted odds ratio of 15.1. Childhood cancer survivors also had health insurance policies that excluded care for pre-existing medical conditions more often than their siblings (OR = 5.5). In addition, cancer survivors reported problems obtaining health insurance coverage more frequently than their siblings with an adjusted odds ratio of 22.8. In general, survivors of childhood cancer who were diagnosed in North Carolina have had decreased access to health insurance coverage when compared to their siblings of similar age. North Carolina health insurance regulations permit health insurance firms to discriminate against cancer survivors because of their history of illness, often decreasing their access to needed follow-up care.

Adult↗

Benefits of a lower hematocrit during extracorporeal membrane oxygenation?

OBJECTIVE: To determine the possible benefits of maintaining a lower hematocrit than that normally used (0.35 vs 0.45) in neonates treated with extracorporeal membrane oxygenation. DESIGN: Randomized cohort. SETTING: Neonatal and pediatric intensive care units at a university hospital. PARTICIPANTS: Twenty neonates who met criteria for receiving extracorporeal membrane oxygenation from May 1988 to March 1990. INTERVENTIONS: Hematocrits were maintained at 0.35 for neonates in group 1 and 0.45 for neonates in group 2. MEASUREMENTS/MAIN RESULTS: Hematocrits were measured every 4 hours. Visible clots in the major circuit components were recorded. Infants in group 1 received (mean +/- SD) 2.5 +/- 0.6 mL of packed red blood cells per hour of extracorporeal membrane oxygenation while infants in group 2 received 3.8 +/- 0.9 mL of packed red blood cells per hour of extracorporeal membrane oxygenation. In group 1, clots were noted in six of 10 oxygenators and five of 10 bladder reservoirs. In group 2, clots were found in all 10 oxygenators and bladder reservoirs. CONCLUSIONS: Neonates' hematocrits can be maintained safely at 0.35 during extracorporeal membrane oxygenation with significantly less exposure to packed red blood cells and less clotting in the circuit.

Blood Coagulation↗

Fine needle aspiration biopsy cytology as an adjunct in the diagnosis of childhood sarcoidosis.

Fine needle aspiration biopsy cytology performed in three children with sarcoidosis expedited clinical investigation and diagnosis of their disease. Each patient had a different clinical presentation; in two of them lymphoma was part of the initial differential diagnosis. Aspiration cytology in all cases revealed collections of epithelioid histiocytes, and multinucleate foreign body-type giant cells, without accompanying necrosis or acute inflammation. A diagnosis of non-caseating granulomas consistent with sarcoidosis was made in all aspirates. Special stains for identification of organisms performed on the smears of one case, and culture of aspirate material from one case were negative. Subsequent serum angiotensin converting enzyme levels in all patients were elevated. Chest x-ray films in all patients showed mediastinal and hilar lymphadenopathy. One patient had an interstitial pulmonary infiltrate. All patients responded to steroid therapy. Fine needle aspiration biopsy can be a useful diagnostic tool in the evaluation of children with suspected sarcoidosis.

Adolescent↗

Suppression of graft-versus-host reaction in severe combined immunodeficiency with maternal-fetal T cell engraftment.

Simultaneous engraftment of maternal T cells and T cells from unrelated transfusion donor in an infant with severe combined immunodeficiency disease (SCID) was identified by HLA typing blood lymphocytes of the patient, her triplet siblings, parents, and the platelet donor from whom the patient received nonirradiated platelet transfusion. T cell grafts from both the mother and platelet donor were stable for several months, but the graft-versus-host reactions (GvHR) remained mild and immune function was deficient. We hypothesize that immunosuppressive effects of a maternal-fetal GvHR may have modified the expected lethal GvHR from platelet donor's T cells.

Agammaglobulinemia↗

Decreasing blood donor exposure in neonates on extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) has been successful treatment (80% survival) in over 2,000 neonates with severe respiratory failure (80% predicted mortality without ECMO). Neonates on ECMO require frequent blood product replacement, which increases donor exposure (DE) and the risk of transfusion related complications. Successful, widespread usage of ECMO in neonatal respiratory failure is placing increased numbers of surviving infants at risk for acute and long-term transfusion related problems. We assessed DE rates in 21 consecutive neonatal ECMO survivors. In the first 12 patients packed red blood cell (PRBC) transfusions were administered as 10 mL/kg body weight for hematocrit less than 45%. PRBC exchange transfusions were used in patients with hematocrit less than 45% and hypervolemia. Fresh frozen plasma (FFP) and cryoprecipitate (CRYO) infusions were used empirically for evidence of hemorrhage. DE rates (donors per ECMO day, mean +/- SD) were: PRBC (2.8 +/- 0.6), FFP/CRYO (0.5 +/- 0.7), and platelet (2.0 +/- 1.0), with a total donor exposure rate of 5.3 +/- 2.0 donors per ECMO day. Mean duration of ECMO was 4.6 +/- 2.0 days and total DE per infant was 22.8 +/- 9.5 donors per ECMO run. In a protocol (n = 9) to minimize DE risks, exchange transfusions were eliminated and PRBC transfusion volumes were increased to 15 mL/kg. Empiric use of FFP and CRYO was discontinued. The blood bank divided standard units of PRBCs into four aliquots and dispensed each aliquot sequentially before dispensing blood from another unit.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Donors↗

Effects of iron, copper, zinc, calcium, and magnesium on human lymphocytes in culture.

The effects of simultaneous changes of calcium, magnesium, iron, copper, and zinc concentrations were evaluated in normal human T and B lymphocytes, cultured in cation-depleted media. Optimal concentrations for thymidine incorporation (TI) in both cell populations were Fe and Zn 15 microM and Cu 5 microM; for T cells Ca 2 mM and Mg 4 mM; for B cells Ca 4 mM and Mg 6 mM. TI decreased with increasing molarity of cations and the decrease was particularly apparent with Cu. Minimal amounts of Ca and Mg (0.5 mM) were necessary for growth, even in presence of optimal concentrations of Fe, Cu, and Zn. Fe and Cu showed synergistic stimulatory effects at low concentrations and synergistic inhibitory effects at high concentrations. Antagonism between Fe and Zn, Cu and Zn, and Ca and Zn was also demonstrated. CD4/CD8 increased with PHA stimulation in presence of Zn, and decreased with ConA stimulation in presence of Zn or Fe. The results demonstrate: (1) the relationship and interdependence of Fe, Cu, and Zn concentrations in modulating the growth of normal lymphocytes; (2) the stimulatory effects of Fe on B cells and Zn on CD8 positive cells; (3) the inhibitory effect of Cu at concentrations lower than those of Fe and Zn; (4) the requirement of Ca and Mg in certain concentration and ratio for the action of the other cations; and (5) the Ca and Mg requirement for the growth of B cells higher than T cells.

B-Lymphocytes↗

Observations on the use of a cation exchange resin for the preparation of metal-depleted media for lymphocyte culture.

A chelating resin specific for divalent cations (Chelex) was used to prepare metal-depleted media for lymphocyte culture. A batch procedure (resin in pH 7.4 phosphate buffer/specimen, 1:1) removed 70-80% of iron, 77-87% of copper and 88-98% of zinc, calcium and magnesium. At variance with other reports, when a resin/specimen ratio of 1:4 was used, iron chelation decreased to 40%, whereas other cation chelation remained unchanged. Best chelation for iron and calcium was obtained at pH 5-6.4; for copper, zinc and magnesium, at pH 7.4-8.0. During the procedure protein content decreased by 8-10%; arginine and lysine by 80%; asparagine, cystine, tyrosine and phenylalanine by 60%, other amino acids by 35%. These new data suggest that cation-depleted media prepared with Chelex may be used to study the effects of cations on lymphocytes in culture, provided that the most appropriate pH and resin/specimen ratio are selected and adequate amino acid replacement is performed. Results on normal human lymphocytes are reported.

Cation Exchange Resins↗

Copper, zinc, and iron in normal and leukemic lymphocytes from children.

Copper, zinc, and iron were quantitated in the serum and lymphoid cells of the peripheral blood of healthy children and children with acute lymphocytic leukemia. Copper and iron concentrations in serum and cells were significantly higher and zinc concentration in the cells significantly lower in leukemic patients than in healthy donors, whereas the increase of zinc in the serum was not significant. The concentration of all minerals was higher in T-cell enriched preparations. There was a significant correlation between copper and iron and between copper and zinc, but not between iron and zinc in normal and leukemic lymphocytes. No correlation was demonstrated among the three minerals in the serum. There were no significant differences associated with ethnicity, age, sex, type of leukemia, or number of leukemic cells. However, a group of five children with non-B-, non-T-cell acute lymphocytic leukemia, nonreactive skin tests, and low serum immunoglobulins had high concentrations of copper and iron and low concentration of zinc in their leukemic cells. Since copper, zinc, and iron are associated with lymphocyte maturation and regulation of immune function, these new data will provide a tool for the study of the relationship between changes in concentrations of these metals and the modification of the immune response often present in hematologic cancers.

Child↗

Zinc deficiency and blood lymphocyte function with sickle cell disease.

A relationship between zinc deficiency and lymphocyte function in children with sickle cell disease (SCD) has been suggested. Number and function of B and T lymphocytes were assessed in 3 matched groups of children: normal subjects with Hb A and normal zinc; patients with SCD; and normal zinc (SCD-N); and patients with SCD and decreased zinc (SCD-D). Percentages of B and T cells, response to cutaneous antigens and increases in tetanus antibody titres were similar among all groups. Absolute numbers of WBC, lymphocytes and B and T cells were markedly increased in SCD-N (p less than 0.001) and to a lesser degree in SCD-D (p less than 0.01). Controls and SCD-N had a normal response to all mitogens, which was not inhibited by SCD-D sera. SCD-D had a depressed response to PHA (p less than 0.001), which was not corrected by zinc addition in vitro. These findings indicate that B cell function and T cell-dependent delayed hypersensitivity are normal in children with SCD and are independent of body zinc status. They also suggest some abnormality of T helper cells in the presence of zinc deficiency, and in the absence of a demonstrable serum inhibitor.

Adolescent↗

Glucose-6-phosphate dehydrogenase Beaumont: a new variant with severe enzyme deficiency and chronic nonspherocytic hemolytic anemia.

Studies were carried out on erythrocytes and fibroblasts from a 3-year-old white male with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency and chronic non-spherocytic hemolytic anemia. Red blood cell G6PD activity was less than 0.02% of normal values. Since the child's fibroblasts had 2-4% of normal enzymic activity, they were utilized as a source of enzyme for kinetic studies. The G6PD demonstrated marked heat lability, a normal Km value for glucose-6-phosphate (56 mumol/l), a nearly normal pH-activity curve, and increased utilization of 2-deoxyglucose-6-phosphate (76% of the rate with glucose-6-phosphate). These studies clearly indicate that this is a new molecular variant (G6PD Beaumont).

Adult↗