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Biomedical subjects

R D Christensen

Publications and source records attributed to R D Christensen.

At least 163 records · Page 9Linked to original sources
PubMed1982

Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker.

We examined the hypothesis that myeloperoxidase (MPO), a plentiful constituent of neutrophils, might serve as a marker for tissue neutrophil content. To completely extract MPO from either neutrophils or skin, hexadecyltrimethylammonium bromide (HTAB) was used to solubilize the enzyme. With this detergent treatment, 97.8 +/- 0.2% of total recoverable MPO was extracted from neutrophils with a single HTAB treatment; 93.1 +/- 1.0% was solubilized with a single treatment of skin. Neutrophil MPO was directly related to neutrophil number; with the dianisidine-H2O2 assay as few as 10(4) neutrophils could be detected. The background level of MPO within uninflamed tissue was 0.385 +/- 0.018 units per gram of tissue, equivalent to only 7.64 +/- 0.36 X 10(5) neutrophils. In experimental staphylococcal infection, skin specimens contained 34.8 +/- 3.8 units MPO per gram, equivalent to 8.55 +/- 0.93 X 10(7) neutrophils. These studies demonstrate that MPO can be used as a marker for skin neutrophil content: it is recoverable from skin in soluble form, and is directly related to neutrophil number. Further, normal skin possesses a low background of MPO compared to that of inflamed skin.

Animals↗
PubMed1982

Supply and release of storage neutrophils. A developmental study.

Depletion of the mature neutrophil reserve during bacterial sepsis is rare in adults but common in neonates; when it occurs, a fatal outcome is likely. Neutrophil reserve depletion was investigated in groups of premature, 1-day-old and 1-, 2-, and 4-week-old rats by measuring: (1) the size of the neutrophil storage pool, and (2) the proportion of this pool which was released from the storage compartment when a weight-standardized release stimulus was applied. It was found that the premature rat has a small neutrophil storage pool containing 1.29 +/- 0.07 X 10(6) cells/g body weight (mean +/- SE). This pool size increases to contain 4.35 +/- 0.23 X 10(6) cells/g in the 4-week-olds (p less than 0.001). With a standard neutrophil storage pool release stimulus, the premature rats depleted 68 +/- 4% of their neutrophil stores, vs. a depletion o only 13 +/- 6% of the stores in the 4-week-olds (p less than 0.001). The small neutrophil reserve and the exaggerated release of stored neutrophils in neonatal animals are factors which predispose neonates to neutrophil reserve exhaustion during bacterial sepsis.

Aging↗
PubMed1982

Granulocyte transfusion in septic canine neonates.

Newborn dogs were inoculated intratracheally with 0.5-1.0 X 10(8) Staphylococcus aureus/g body weight. Neutropenia (490 +/- 280 neutrophils/mm 3 versus 8,390 +/- 490 control, mean +/- S.E., P less than 0.001), and depletion of the marrow neutrophil storage pool (3 +/- 1% versus 27 +/- 2% storage neutrophils, P less than 0.001) occurred 5-6 h following the inoculation. All animals died at 6-10 h. Additional inoculated pups were selected at random to receive transfusions of either granulocytes, plasma or red blood cells. Granulocyte transfusions (3 X 10(9) neutrophils/kg) improved survival (P less than 0.005), but plasma and red blood cells did not.

Animals↗
PubMed1982

Cellular and extracellular myeloperoxidase in pyogenic inflammation.

We explored the effect of in vitro phagocytosis and in vivo inflammation on the MPO content of functioning neutrophils and on the ability of these cells to export active MPO into the extracellular environment. After ingestion of staphylococci, neutrophils retained 52% of their MPO and released 8% into the medium in active form; the remaining 40% of their MPO could no longer be detected. During bacterial infection induced by intradermally injecting staphylococci, neutrophils harvested from minced infected lesions contained 52% of the MPO of circulating neutrophils that had not reached the lesions. Extracellular fluid from the lesions contained active MPO secreted by the neutrophils, and concentrations of 10-45 U/ml were detected. These data demonstrate that functioning neutrophils can lose approximately half of their MPO. In vitro, 4%-8% of neutrophilic MPO appears in the extracellular space and 40% is inactivated. In vivo, the MPO content of inflammatory neutrophils also decreases, and MPO appears in the extracellular fluid in active form where it is available to participate in a variety of physiologic processes.

Animals↗
PubMed1982

Granulocyte transfusions in neonates with bacterial infection, neutropenia, and depletion of mature marrow neutrophils.

During a three-year period, 26 neonates with bacterial infection and neutropenia were studied. In order to assess the marrow neutrophil reserves, bone marrow aspirates were obtained from each of these patients. The neutrophil storage pool (percent polymorphonuclear + band neutrophils + metamyelocytes in 1,000 nucleated marrow cells) was significantly greater in those who survived their infection (mean = 20.1%, range 3.2% to 60.8%) than in those who died (mean = 1.9%, range 0.4% to 5.2%, P less than .002). In an attempt to improve survival in this group, seven neutrophil-depleted patients with sepsis were given granulocyte transfusions and all survived. In contrast only one of nine nontransfused and all survived. In contrast only one of nine nontransfused, neutrophil-depleted infants with sepsis survived (P less than .01). The seven granulocyte recipients were examined for possible adverse effects of the transfusions and none were detected. It is suggested that infected, neutropenic neonates with depletion of mature marrow neutrophils are at high risk for death from sepsis, and that these infants may benefit from granulocyte transfusion therapy.

Agranulocytosis↗
PubMed1981

The leukocyte left shift in clinical and experimental neonatal sepsis.

The leukocyte left shift is commonly used as an adjunct to the early diagnosis of bacterial infection. Many different methods have been employed for its quantification, such as the absolute band count, band/seg ratio, band/total neutrophil ratio, and immature/total neutrophil ratio. We examined blood and bone marrow samples in groups of noninfected and infected neonatal dogs and human beings in order to determine which method most clearly reflects an increased call upon marrow neutrophil reserves and which correlates best with the presence and severity of infection. We found that the neutrophil ratios were more frequently abnormal during neonatal sepsis than was the the absolute band count. All subjects, canine and human, in whom the immature/total neutrophil ratio exceeded 0.800 were found to have depletion of the marrow neutrophil reserves, and those with the most profound depletion died. This study supports the concept that an elevated immature/total neutrophil ratio can aid in the diagnosis of bacterial infection in the newborn infant and suggests that the degree of elevation may serve as a method for detecting subjects at high risk for depletion of the marrow neutrophil reserves and death from sepsis.

Animals↗
PubMed1980

Circulating and storage neutrophil changes in experimental type II group B streptococcal sepsis.

The availibility of neutrophils is an important factor in host resistance to bacterial infection. Therefore, circulating and storage neutrophil quantification was carried out on groups of neonatal rats intranasally inoculated with type II group B streptococci. The dose of type II group B streptococci used produced 56% mortality in 48 neonatal rats with death being due to pneumonia and sepsis. Neutropenia (1300 +/- 150/mm3 versus 2300 +/- 170/mm3; mean +/- S.D.; P < 0.01) and an elevation in band/polymorphonuclear ratio (0.98 +/- 0.04 versus 0.30 +/- 0.04; P < 0.01) were observed in infected neonatal rats 24 hr following inoculation. Femoral marrow as well as splenic and hepatic neutrophil storage compartment quantification revealed dimunition of postmitotic (polymorphonuclear, band, and metamyelocyte) neutrophils in the infected group (P < 0.01) with sparing of the proliferative neutrophils (myeloblasts, promyelocytes, and myelocytes). Repletion of the myeloid but not the splenic or hepatic neutrophil storage compartments with normalization of the neutrophil count and band/polymorphonuclear ratio occurred in animals surviving 72 hr. These studies establish that neutropenia and neutrophil storage pool depletion are prominent features of experimental type II group B streptococci infection in neonates.

Animals↗
PubMed1980

Efficiency of neutrophil migration in the neonate.

To assess release of neutrophils from the neutrophil storage pool (NSP) and subsequent neutrophil migration into tissue sites, polyvinyl sponge discs were placed into subcutaneous pockets in either newborn or 4-wk-old rats. After 20 hr, the sponges were removed, and the animals' NSP size and the number of neutrophils which had migrated into the sponges were measured. In response to the sponge stimulus, neonatal rats released 83.6 +/- 1.2% (mean +/- S.E.) of their NSP (106.3 +/- 15.3 X 10(5) neutrophils), whereas the older animals released 28.4 +/- 5.0% (628.5 +/- 124.4 X 10(5) neutrophils) of their NSP (P less than 0.001). Neonatal neutrophils displayed a decreased ability to successfully migrate from the NSP to the sponges. The proportion of released neutrophils accumulating in the sponges was 9.2 +/- 0.6% in the neonates, compared with 58.5 +/- 7,8% (P less than 0.001) in the 4-wk-old rats.

Animals↗
PubMed1979

Pitfalls in the interpretation of leukocyte counts of newborn infants.

Some pitfalls in the interpretation of neonatal leukocyte counts are identified. The well-known variability in neonatal leukocyte counts was investigated by simultaneously sampling arterial, venous and capillary blood, and during periods of rest and mild and violent exercise. Venous blood leukocyte counts were 82% +/- 3.5 (mean +/- SE, P = less than .001) of counts in simultaneously drawn capillary blood from heel punctures; arterial blood counts were 77% +/- 5.3 (P less than .001) of capillary blood values. Following violent crying, capillary blood leukocyte counts increased to 146% +/- 6.1 (P less than .001) of baseline values, and a shift to the left occurred. Milder exercise induced an increase to 113% +/- 5.2 (P less than .05), without a leftward shift. Thus, counts from different vascular sources cannot be considered equivalent. Also, counts from vigorously crying babies may show leukocytosis and a leftward shift, and erroneously suggest bacterial infection. It is recommended that serial counts be obtained from a consistent vascular source in resting babies.

Arteries↗
PubMedDate not supplied

Immunohistochemical localization of erythropoietin and its receptor in the developing human brain.

We have previously shown erythropoietin (Epo) and its receptor (Epo-R) to be present in the fetal human central nervous system (CNS), and Epo to be present in the spinal fluid of normal preterm and term infants. To investigate the cellular specificities and developmental patterns of expression of these polypeptides in the human brain-areas that have not been well researched-we designed the following study. Human brains ranging in maturity from 5 weeks post-conception to adult were preserved at the time of elective abortion, surgical removal (tubal pregnancy, or removal for temporal lobe epilepsy), or autopsy. Immunohistochemistry was used to localize Epo and Epo-R reactivity in brains of different stages of development. Astrocytes, neurons, and microglia were identified in sequential tissue sections by specific antibodies. At 5 to 6 weeks post-conception, both Epo and Epo-R localized to cells in the periventricular germinal zone. At 10 weeks post-conception, Epo immunoreactivity was present throughout the cortical wall, with the most intense immunoreactivity present in the ventricular and subventricular zones. Epo-R, in contrast, was localized primarily to the subventricular zone, with little staining evident in the ventricular zone. In late fetal brains, Epo-R reactivity was most prominent in astrocytic cells, although modest reactivity was observed in certain neuron populations. In contrast, Epo staining localized primarily to neurons in fetal brains, although a subpopulation of astrocytes was also immunoreactive. In postnatal brains, both astrocyte and neuron populations were immunoreactive with antibodies to Epo-R and Epo. From these results it is clear that Epo and its receptor are present in the developing human brain as early as 5 weeks post-conception, and each protein shows a specific distribution that changes with development. We speculate that Epo is important in neurodevelopment, and that it also plays a role in brain homeostasis later in life, functioning in an autocrine or paracrine manner.

Adult↗
PubMedDate not supplied

Granulocyte-macrophage colony-stimulating factor and interleukin-5 concentrations in premature neonates with eosinophilia.

OBJECTIVE: Eosinophilia is common among premature neonates, but little is known about the cytokines responsible for influencing its onset in neonates. In adults and transgenic mice, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-5 (IL-5) influence the development of eosinophilia. We sought to prospectively determine whether these cytokines correlated with the development of eosinophilia in premature infants. STUDY DESIGN: We measured the absolute eosinophil count (AEC) and serial serum concentrations of GM-CSF and IL-5 in premature neonates with eosinophilia. RESULTS: Among 201 premature neonates, 21 had an eosinophil count of > 700/microliter (occurrence, 10.5%). Of these 21 neonates, 4 had mild (700/microliter to 999/microliter), 13 had moderate (1000/microliter to 2999/microliter), and 4 had severe (> 3000/microliter) eosinophilia. No differences in gestational age or age at onset of eosinophilia were observed between the groups, but the duration of eosinophilia was less with mild than with moderate or severe eosinophilia. A total of 20 of the 21 patients had an infection or necrotizing enterocolitis diagnosed within 48 hours of the onset of eosinophilia. In patients with mild and moderate eosinophilia, serial GM-CSF and IL-5 concentrations were below the lowest enzyme-linked immunosorbent assay standard. There was no correlation between AEC and GM-CSF or IL-5 concentration in these infants. However, in one patient with severe eosinophilia, two distinct elevations in IL-5 were noted (34.6 and 46.0 pg/ml); each peak occurred 7 to 8 days before a peak in eosinophil count. CONCLUSION: Eosinophilia is relatively common, and in those neonates with the highest AECs, the duration of eosinophilia can last for > 6 weeks. The majority of cases of eosinophilia occurred in temporal proximity to an infectious illness or necrotizing enterocolitis. Serum concentrations of IL-5 were elevated in only one of our patients with severe eosinophilia.

Biomarkers↗
PubMedDate not supplied

Epidemiologic and outcome studies of patients who received platelet transfusions in the neonatal intensive care unit.

STUDY DESIGN: We conducted a historic cohort study of neonates who received platelet transfusions at the National Institute of Perinatology, Mexico City, from January 1997 to May 2000. We obtained descriptive and outcome data, and assessed demographic and laboratory means of predicting "good candidates" for a future recombinant thrombopoietin (rTpo) trial. RESULTS: A minority of the transfused patients (11.4%) received only one transfusion; the majority (88.6%) received multiple transfusions. Neonates who received one or more platelet transfusions were more likely to die (24.5% mortality) than neonates who received no platelet transfusions (3.7% mortality). Regression analyses indicated that the presence of liver disease was the best predictor of a "good candidate" for rTpo administration. CONCLUSION: The majority of neonates in our institution who receive platelet transfusions receive multiple, not single, transfusions. Receiving any platelet transfusion is a marker for high risk of death. Neonates with liver disease who receive platelet transfusions might be a reasonable group for a phase I rTpo trial.

Cohort Studies↗
PubMedDate not supplied

Neutrophil transfusion on septic neutropenic neonates.

Depletion of the mature marrow neutrophil stores occurs commonly in neonates with bacterial sepsis and correlates with a fatal outcome. This report discusses the feasibility and efficacy of neutrophil transfusions in such patients and describes two who received neutrophil transfusions and survived without adverse sequelae.

Adolescent↗
PubMedDate not supplied

Use of whole blood exchange transfusion to supply neutrophils to septic, neutropenic neonates.

When neutropenia due to exhaustion of the marrow neutrophil reserve, develops in a neonate with bacterial sepsis the likelihood of survival is very small. We report such a case who was treated with a double-volume exchange transfusion using fresh unstored whole blood. We were able to determine a net gain of 5 x 10(8) neutrophils per kg. Then, in neutropenic neonatal animals, neutrophil transfusion by double-volume exchange transfusion with unstored blood was investigated.

Agranulocytosis↗