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Biomedical subjects

R D Christensen

Publications and source records attributed to R D Christensen.

At least 127 records · Page 7Linked to original sources
PubMed1989

Immunologic regulation of E. coli K1 by serum from neonatal rats is enhanced following intraperitoneal administration of human IgG.

The effect of 1500 mg/kg intraperitoneal human IgG on the capacity of neonatal rat serum to opsonize and to kill Escherichia coli K1 and to deposit IgG and C3 onto this organism was investigated. Unlike serum from neonatal rats injected with albumin, serum from neonatal rats injected with human IgG opsonized and killed E. coli K1 efficiently. Heat treatment abolished the bactericidal effect of serum from IgG recipients, suggesting a role for complement. A radioimmunobinding assay demonstrated that the capacity of neonatal rat serum to deposit IgG and C3 onto E. coli K1 was impaired. However, intraperitoneal human IgG enabled serum from neonatal rats to deposit human IgG onto the bacteria and enhanced C3 deposition to a level equivalent to that observed with adult rat serum. Therefore, neonatal rats have a functionally competent classic pathway of complement. Human IgG ameliorates the opsonic and bacteriolytic inadequacies of neonatal rat serum that result primarily from a deficiency of antibodies to E. coli.

Animals↗
PubMed1989

Hematopoiesis in the fetus and neonate.

Advances in molecular biology and in hematopoietic progenitor cell culture techniques have produced new tools with which to explore previously enigmatic aspects of developmental hematopoiesis. Studies using these tools are contributing mechanistic understanding to what was previously an entirely descriptive discipline and are generating new insight into the pathophysiology of various cytopenias in fetal and neonatal patients. This review of developmental hematopoiesis will address four related topics: 1) ontogeny of blood cells, 2) ontogeny of hematopoietic progenitors, 3) developmental regulation of hematopoietic growth factors, and 4) developmental aspects of interactions between hematopoietic progenitors and hematopoietic growth factors.

Animals↗
PubMed1989

Neutrophil kinetics in the fetus and neonate.

Delineation of neutrophilic pool sizes and kinetics during the steady state and during various perturbations has improved the clinical approach to adult patients with abnormalities of blood neutrophil concentration. Perhaps a better understanding of neutrophil kinetics in the fetus and neonate might similarly permit a less empiric approach to neutropenia and neutrophilia in newborn infants. The relatively few studies that have been performed suggest that substantial differences in pool sizes and kinetics exist between neonates and adults, with even greater differences between extremely preterm infants and those delivered at term.

Animals↗
PubMed1989

A randomized trial to develop criteria for administering erythrocyte transfusions to anemic preterm infants 1 to 3 months of age.

A randomized trial of erythrocyte transfusion vs no transfusion was performed in 16 preterm infants 1 to 3 months old with hematocrits of less than or equal to 0.29 L/L. To determine which (if any) such patients definitely benefit from transfusion, an analysis of outcome variables was performed. Factors that prospectively identified patients who would benefit from transfusions included a heart rate of greater than 152 beats per minute (P less than .01), apnea/bradycardia (heart rate less than 90/min) requiring intervention to increase the heart rate (P less than .01), and a blood lactate level above the reference range (P less than .02). Additional investigations were performed to determine the cause of the low hematocrits in the study patients. All had diminished, rather than accelerated, erythropoiesis. However, neither the anemia of chronic disorders nor iron deficiency anemia contributed to the diminished erythropoiesis. In all cases, serum erythropoietin levels were below the predicted range (P less than .001). Thus, at least some preterm infants aged 1 to 3 months with hematocrits less than or equal to 0.29 L/L definitely derive benefit from erythrocyte transfusion. The presence of tachycardia, apnea/bradycardia, or an elevated blood lactate may prospectively identify such patients.

Anemia, Neonatal↗
PubMed1989

A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates.

Intravenous immune globulin (750 mg/kg), or an equivalent volume of a placebo, was administered during the first week of life, in a randomized trial, to 20 preterm neonates weighing 710 to 1800 g. A variety of laboratory and clinical values were measured serially and analyzed for possible untoward effects. Serum IgG levels were also determined serially. No differences in heart rate, respiratory rate, urine output, blood glucose, serum osmolality, BUN, SGPT, pH, blood gasses, serum electrolytes, total or direct bilirubin, blood leukocyte concentration, absolute neutrophil count, or blood platelet concentration were observed between the intravenous immune globulin (IVIG) and placebo recipients before or following IVIG administration. The red blood cell concentration of IVIG recipients diminished transiently and only slightly (P less than .05). Serum IgG levels increased from 503 +/- 162 mg/dL (X +/- SD) to 1492 +/- 201 mg/dL 15 minutes after the IVIG administration (P less than .001). After 8 days, serum IgG levels were still elevated, at 675 +/- 297 mg/dL. All patients randomized to receive the placebo experienced a diminution in serum IgG over this 8-day period (P less than .01). All 20 patients survived and none in either group had a documented nosocomial infection. This study suggests that IVIG can safely be administered to preterm neonates, resulting in serum IgG levels comparable to those of term infants.

Blood Chemical Analysis↗
PubMed1988

Haematopoietic progenitor cells in an infant who developed pancytopenia following an extensive burn.

We observed a 24-month-old infant who developed anaemia, thrombocytopenia and neutropenia while recuperating from an extensive burn. In order to determine the mechanism(s) responsible for the pancytopenia, we quantified marrow-derived haematopoietic progenitor cells, assessed the relative proliferative rate of haematopoietic progenitor cells, and sought the presence of progenitor cell inhibitors. The concentration and relative proliferative rate of pluripotent progenitors (CFU-GEMM) were elevated. No inhibitors of progenitor cells were observed; in fact, the patient's serum contained very high levels of stimulatory activity for CFU-GEMM as well as for granulocyte-macrophage progenitors (CFU-GM). However, the marrow concentration of erythroid progenitors (BFU-E and CFU-E) was diminished. We conclude that the anaemia in this patient was the result of either hypoproduction of differentiated erythroid progenitors or intramyeloid destruction of early erythroid cells. In contrast, the neutropenia was likely to be due to accelerated neutrophil consumption at a rate that exceeded the capacity for increasing neutrophil production.

Anemia↗
PubMed1988

Developmental changes in pluripotent hematopoietic progenitors.

In rats of various prenatal and postnatal ages, the number of pluripotent hematopoietic progenitor cells (CFU-GEMM) in the blood, liver, spleen and bone marrow was determined, and their cell-cycle characteristics compared. Similar to human neonates, fetal and neonatal rats had a much higher concentration of CFU-GEMM in the blood than did mature animals (2060-8320 CFU-GEMM/ml blood at 15 days gestation vs. 20-120/ml at six weeks of age, P less than 0.001). However, the total body pool of CFU-GEMM/g body weight was significantly less in fetal animals than in adults (2010 CFU-GEMM/g, range 850-2650/g at 20 days gestation vs. 10 550/g, range 7900-14,900/g at 6 weeks, P less than 0.001). The proportion of CFU-GEMM killed by tritiated thymidine was 2% (0-12%) in adults rats, whereas younger animals had progressively higher rates, reaching over 90% (68-100) in fetal animals (P less than 0.001). Following incubation with Interleukin 3 (IL-3), the thymidine suicide rate of CFU-GEMM from mature rates increased significantly (from 4 +/- 3% to 53 +/- 4%, P less than 0.01), but no increase was detected in CFU-GEMM from fetal rats. These features might contribute to the limited capacity of neonatal subjects to significantly increase production of the progeny of CFU-GEMM.

Age Factors↗
PubMed1988

Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with the "anemia of prematurity".

We used cells from marrow aspirations that had been performed on 10 infants with the "anemia of prematurity" and tested the responsiveness of their erythroid colony-forming units (CFU-E) to recombinant human erythropoietin. For comparison, we also tested marrow-derived CFU-E from five healthy adults, and circulating CFU-E from cord blood of five healthy neonates. CFU-E from the anemic infants had a 50% maximal response at 0.073 +/- 0.024 U erythropoietin per milliliter (mean +/- SD). They were therefore at least as responsive as were CFU-E from adults, which displayed a 50% maximal response at 0.118 +/- 0.076 U/ml, and as were circulating CFU-E of cord blood origin, which had a 50% maximal response at 0.109 +/- 0.047 U/ml. Because CFU-E from infants with the "anemia of prematurity" appeared highly sensitive to erythropoietin in vitro, we propose that its administration to these patients would likely result in a significant increase in erythrocyte production in vivo.

Anemia, Neonatal↗
PubMed1988

Circulating and storage neutrophils in septic neonatal rats treated with immune globulin.

Marked neutropenia, complete depletion of the neutrophil storage pool, and death within 48 h were observed in newborn rats intrapulmonically inoculated with 10(5) type III group B streptococci (GBS). Intraperitoneal administration of 225 mg of intravenous human immune globulin (IVIG) immediately after intrapulmonic inoculation of GBS significantly lessened the degree of neutropenia and prevented depletion of the neutrophil storage pool and death. No effect of IVIG on neutrophil production was observed in vitro, in cultures of granulocytic progenitor cells, or in vivo, as assessed by quantifying circulating and storage pools in normal neonatal rats injected with IVIG. IVIG, however, markedly hastened release of neutrophils from the reserves into the blood and hastened the arrival of neutrophils at the site of the bacterial injection (the right lung). Specific antibody to GBS, as opposed to a nonspecific IgG effect, appeared to be responsible for the improvements in neutrophils kinetics and for survival of the animals.

Animals↗
PubMed1988

Neutrophil-mediated killing, opsonization, and serum-mediated killing of Escherichia coli K1 by neonatal rats.

Neonates are particularly susceptible to infection with Escherichia coli K1. To investigate the mechanisms which lead to this susceptibility, we examined: (a) the bactericidal activity of neutrophils; (b) opsonization, and (c) the bactericidal activity of serum in developing rats. Neutrophils from adult rats killed E. coli K1 more efficiently than did neutrophils from young animals. Opsonization of E. coli by serum of prematurely delivered rats was poor. Serum from prematurely delivered and term rats promoted growth of E. coli K1, while serum from adult rats killed greater than 95% of the organisms within 90 min. However, the mixture of heat-inactivated serum from adult rats plus serum from prematurely delivered rats killed E. coli K1.

Animals↗
PubMed1988

Erythroid colonies derived from fetal blood display different growth patterns from those derived from adult marrow.

Fetal blood may be useful for the study of hematopoietic development in humans. However, the methods used to study blood cell colonies in adults may not be optimal for the study of colonies derived from fetal blood. Using cord blood from six healthy term pregnancies and marrow from six healthy adult volunteers, we compared the chronology of emergence, morphology, and differentiation of progenitor cell colonies from the two sources. In cultures of adult marrow, erythroid colony-forming unit colonies reached maximal concentrations after 8.5 +/- 0.3 days of culture (mean +/- SEM), but erythroid colony-forming unit colonies derived from fetal blood reached maximal concentrations sooner, after 6.5 +/- 0.2 days (p less than 0.01). Single-centered-erythroid burst-forming unit colonies from adult marrow (45 +/- 5/10(5) light-density, "accessory-cell"-depleted cells) reached a peak at 14 days, but from cord blood they were significantly greater at 9 days (200 +/- 15/10(5) cells) than at 14 days. When studying fetal blood erythroid colony-forming unit and "mature-erythroid burst-forming unit," colonies should be enumerated earlier than when studying adult marrow-derived progenitors. Otherwise, the concentrations of these progenitors will be significantly underestimated.

Adult↗