Biomedical subjects

S E Wiedmeier

Publications and source records attributed to S E Wiedmeier.

10 recordsLinked to original sources

PubMed2007

Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system.

Various hematological abnormalities have been reported among neonates with Down syndrome. Thrombocytosis, thrombocytopenia, polycythemia, neutrophilia, transient myeloproliferative disorder (TMD), and congenital leukemia have all been reported. The two largest case series previously reported involved 63 and 31 cases. To acquire hematological data from a larger case series, we obtained all CBCs done during the first week after birth on all neonates with Down syndrome cared for in an Intermountain Healthcare (IHC) hospital with a date of birth between January 1, 2001 and December 31, 2005. During this period, 145,522 live births were recorded at 18 hospitals. Down syndrome was recognized in 226 (1 in 644). One hundred fifty-eight (70%) of these had one or more CBCs obtained before the seventh day (144 hr). Neonates who did versus did not have a CBC in the first week had a similar gestational age, birth weight, percentage who were LGA and SGA, and length of stay. Neutrophilia was the most common hematological abnormality detected, with 80% of absolute neutrophil counts above the upper limit of normal for age. Six percent (9/158) had blasts identified on the blood film and three, where this was persistent, were referred to the pediatric hematology service for further evaluation. The next most commonly detected abnormality was thrombocytopenia, with 66% of platelet counts <150,000/microl, and with 6% of counts <50,000/microl. The mean platelet volume did not correlate with the platelet count, but tended to run slightly large (9.2 +/- 1.3 fl), with 24% of values above 10 fl. Only one had a platelet transfusion. Polycythemia was the next most common hematological abnormality detected, with 33% of hematocrit values above 65% or hemoglobin concentrations above 22 g/dl. Six had a reduction transfusion. One patient had significant anemia (hematocrit <15%) and received an erythrocyte transfusion. One had neutropenia associated with an infection after bowel surgery. Neutrophilia, thrombocytopenia, and polycythemia were the most common hematological abnormalities observed among neonates with Down syndrome. Anemia, thrombocytosis, and neutropenia were not more common than among neonates who do not have Down syndrome. Hematological abnormalities were so common in this group that it seems reasonable to recommend that one or more CBCs be obtained on all neonates with Down syndrome.

Blood Cell Count↗

PubMed2006

Low blood neutrophil concentrations among extremely low birth weight neonates: data from a multihospital health-care system.

OBJECTIVE: A blood neutrophil concentration < 1000/microl has been reported to occur in about 8% of neonatal intensive care unit (NICU) patients, at some time during their hospital stay. However, the incidence of this finding among extremely low birth weight (ELBW) neonates (< 1000 g birth weight) is not known. Using data from four NICU's in one health-care system, we sought to estimate the incidence, timing, causes, severity and duration of neutrophil counts < 1000/microl among ELBW neonates. We also tabulated the treatments used for this condition and associations with mortality. METHODS: We performed an historic cohort analysis of all ELBW neonates born during the 36-month period, 1 July 2002 to 30 June 2005, cared for in the four Intermountain Healthcare level III NICU's. RESULTS: Three hundred and thirty-eight ELBW neonates were the subjects of the analysis. Complete blood cell counts (CBCs) were obtained in all (range, 1 to 123 CBCs/patient). Thirty-eight percent (128/338) had one or more neutrophil counts < 1000/microl. In 57% the low neutrophil count persisted for < 24 h; in 43% it persisted for 1 to 7.5 days. Most of the cases (74%) were detected during the first 3 days of life. Twenty-two percent of cases were not detected until after the first week. Low neutrophil counts were more common among the smallest patients, with a 63% incidence in those < or = 500 g, 44% in those 501 to 600 g and 34% in those 801 to 999 g. When low neutrophil counts were recognized during the first 3 days of life, the patients were typically either small for gestational age (SGA; weight < 10th percentile for gestational age) or born after pregnancy-induced hypertension (PIH) (68%), or had early-onset bacterial infection (6%). When recognized after the first 3 days, the patients typically had necrotizing enterocolitis (31%) or a nosocomial bacterial infection (19%). Alloimmune mechanisms were not tested for in any of the cases. No cause for the low counts was identified among 35% of the neutropenic patients. Intravenous immunoglobulins was administered to 28% of cases, and 100% of these were given according to our written guidelines. Recombinant granulocyte-colony stimulating factor was administered to 13% of cases, and 69% of these were given according to guidelines. Neither the presence of low neutrophil counts nor the severity (lowest recorded count) correlated with mortality rate, except in proven early-onset sepsis. CONCLUSIONS: We observed low neutrophil counts among ELBW neonates at a rate five times that reported in the general NICU population. Most cases were present in the first days of life and occurred in SGA neonates or those with PIH. In over 1/3, no cause was discovered. We maintain that more consistency is needed in evaluating and treating neutropenia among ELBW neonates.

Cohort Studies↗

PubMed2006

Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system.

OBJECTIVES: Thrombocytopenia is common in neonatal intensive care units (NICU), with 18 to 35% of patients developing this problem before hospital discharge. It might be even more common among extremely low birth weight neonates (ELBW, < or = 1000 g birth weight). However, little is known about thrombocytopenia in the ELBW population. We sought to determine the incidence, timing, causes, platelet transfusions given, and outcomes of thrombocytopenia among ELBW neonates. STUDY DESIGN: We performed a cohort analysis of all 284 ELBW neonates born during 2003 and 2004 cared for in any of the Intermountain Healthcare level III NICUs. RESULTS: Multiple platelet counts were obtained in all 284 (range, 4 to 441 platelet counts/patient). Of the 284, 208 (73%) had one or more platelet counts < or =150 000/microl. Most were detected during the first days of life; 80% were detected during the first week and only 20% were detected thereafter. Thrombcytopenia was more common among the smallest patients; 85% incidence among those < or =800 g, 60% among those 801 to 900 g, and 53% among those 901 to 1000 g. Platelet transfusions were given to 129 of the 208 thrombocytopenic neonates. More than 90% were given prophylactically (the patient was not bleeding). The mortality rate among those that received platelet transfusions was twice that of those that received no platelet transfusions (P < 0.01). In 48% of cases, the cause of the thrombocytopenia went undiagnosed. The most common explanations were being small for gestational age or delivered to a hypertensive mother, DIC, bacterial infection, fungal infection, and necrotizing enterocolitis, respectively. CONCLUSIONS: We observed thrombocytopenia among ELBW neonates at a rate more than twice that reported among the general NICU population. Much remains to be discovered about the etiology and best treatments of thrombocytopenia among ELBW neonates.

Cohort Studies↗

PubMed1994

Age- and microenvironment-associated influences by platelet-derived growth factor on T cell function.

Platelet-derived growth factor (PDGF) is produced by numerous cell types in response to a variety of activation signals. Although the role of PDGF in cellular proliferation is well established, the immunomodulatory effects of this peptide growth factor are only now being delineated. We previously established that PDGF alters the profile of lymphokines produced by activated T cells obtained from the peripheral lymph nodes of adult mice. We now report that T cells residing in lymphoid organs that receive their major afferent lymphatic drainage from gut mucosa are relatively resistant to the effects of this growth factor. As the vast majority of peripheral T cells are in the recirculating T cell pool, these findings suggest that tissue-specific microenvironmental factors function to regulate the sensitivity of T cells to PDGF-mediated influences. Additional studies have determined that the normal process of aging is accompanied by a systemic loss in T cell responsiveness to PDGF. Although the T cells of immature (2-wk-old) and young adult mice are responsive to the immunomodulatory influences of PDGF, T cells of aged animals (> 100 wk) are relatively resistant to its effects. Some of the immune abnormalities noted to occur during the aging process appear to represent a consequence of the dysregulated production of IL-6. We therefore evaluated whether IL-6 was responsible for modifying the sensitivity of T cells to PDGF. Data presented herein demonstrate that IL-6 abrogates the ability of PDGF to modify lymphokine production by T cells after activation. Therapeutic measures capable of reducing spontaneous IL-6 production in aged mice restored the ability of their T cells to respond to PDGF, suggesting that the dysregulated production of IL-6 within the aged host interferes with the ability of PDGF to convey important microenvironmental information to T cells residing in peripheral lymphoid organs.

Aging↗

PubMed1991

Thymic modulation of IL-2 and IL-4 synthesis by peripheral T cells.

In this paper we provide several lines of evidence to support the hypothesis that the thymus can exert regulatory influences on the functional capabilities of mature recirculating T cells. Our studies demonstrate that while the IL-2-producing potential of T cells that repopulate the secondary lymphoid organs of lethally irradiated and stem cell-reconstituted mice is significantly reduced compared to that of T cells harvested from normal mice, the amount of IL-4 produced by the T cells of these experimental animals is equivalent to, or greater than, the amount produced by T cells from control animals. In addition, we determined that the amount of biologically active IL-2 and IL-4 secreted by T cells harvested from lethally irradiated animals who reconstitute their hematopoietic and immune systems under the influence of nonirradiated thymic epithelial grafts is essentially identical to the amount produced by T cells harvested from nonirradiated control animals. Collectively, these findings suggest that: (1) the alterations observed in the lymphokine-producing potential of T cells harvested from lethally irradiated and stem cell-reconstituted mice is not due to a direct effect of ionizing radiation on the T lymphocytes themselves, and (2) the exposure of the epithelial cells of the thymus to ionizing radiation during marrow-ablative regimens abrogates or modifies a component of thymic function which can influence the lymphokine-secreting potential of recirculating T cells. Further evidence for thymic involvement in the regulation of lymphokine production by peripheral T cells comes from our finding of a post-thymectomy time-dependent reduction in the capacity of T cells from animals to produce IL-2. Coincident with this reduction, T cells harvested from peripheral lymphoid organs of thymectomized animals demonstrated an augmentation in their IL-4-producing capabilities. The finding that treatment of thymectomized animals with the androgen steroid hormone dehydroepiandrosterone reestablished a normal IL-2-producing potential by their T cells makes it unlikely that the reduced capacity to produce IL-2 was secondary to a loss in fresh thymic emigrants.

Animals↗

PubMed1989

Dual effects of pertussis toxin on murine neutrophils in vivo. I. Pertussis toxin inhibits extravasation potential of mature neutrophils while simultaneously stimulating granulopoiesis.

Pertussis toxin (Ptx) has been employed as an adjuvant by many investigators to augment various types of cell-mediated and humoral immune responses. Recent work from our laboratory indicates that the exacerbation of delayed-type hypersensitivity (DTH) and contact hypersensitivity (CH) responses observed in Ptx-treated mice may be mediated by an absolute increase in the number of circulating neutrophils capable of migrating into tissue sites of antigen challenge. The purpose of the present study was to analyze the effects of Ptx on neutrophils and neutrophil function in vivo. Evidence is presented here suggesting that Ptx has both direct and indirect effects on neutrophils following its in vivo administration to normal mice. Mature neutrophils that are directly exposed to the actions of Ptx in vivo exhibit a marked reduction in their ability to extravasate into tissue sites of inflammation. These findings are consistent with those that have been reported following the exposure of isolated neutrophils to the effects of Ptx in vitro (i.e., that Ptx has an inhibitory effect on many of the functional capabilities of isolated neutrophils). Moreover, we have also determined that Ptx can affect the kinetics of neutrophil production indirectly through its ability to stimulate granulopoiesis. Ptx-exposed mice develop a protracted peripheral blood neutrophilia following toxin administration. Although the mechanism(s) involved in stimulating increased neutrophil production is presently unclear, both dexamethasone and indomethacin (cyclooxygenase pathway inhibitors) are able to function synergistically with Ptx to produce a markedly enhanced neutrophilia in exposed mice. We propose that the capacity of Ptx to augment CH and DTH responses and act as a potent adjuvant may relate, in part, to its ability to alter the rate of neutrophil production in vivo.

Animals↗

PubMed1988

Effect of ionizing radiation on thymic epithelial cell function. I. Radiation-spared thymic epithelial grafts expedite the recovery of T cell function in lethally irradiated and fetal liver reconstituted mice.

A murine model system was developed to determine whether ionizing radiation has a detrimental influence on thymic epithelium, cell function. Normal mice were lethally irradiated, grafted intracamerally with normal fetal thymic epithelium, and then reconstituted with fetal liver cells. These animals were compared with a group of animals who received their thymic grafts before the irradiation protocol. Analysis of the reconstitution of T cell function in peripheral lymph nodes and spleens at various times post transplantation demonstrated that animals with radiation-spared thymic grafts had superior proliferative responses to T cell mitogens and alloantigens. It was also determined that the capacity of these animals to elicit contact hypersensitivity responses was significantly greater when compared with animals whose thymic grafts had been radiated. The observed difference in T cell function could not be ascribed to a difference in the rate of export of mature T cells from the thymic grafts since the absolute number of Thy-1+, L3T4+, or Lyt-2+ lymphocytes present in the peripheral lymphoid compartment of our two groups of animals was equivalent. Immunohistologic analysis of the thymic grafts demonstrated a marked reduction in the medullary compartment of the repopulated grafts that had been exposed to ionizing radiation. The results of this study suggest: 1) that irradiation of the thymic microenvironment during marrow ablative preparative regimens may be in part responsible for some of the immune alterations observed in marrow transplant recipients, and 2) that our model system may provide a valuable tool for delineating the roles played by medullary and cortical epithelial cells of the thymus on the T cell maturation and education processes.

Animals↗

PubMed1987

Resurgence of acute rheumatic fever in the intermountain area of the United States.

We describe an outbreak of acute rheumatic fever that occurred in the intermountain area centered in Salt Lake City, Utah. Seventy-four children meeting the modified Jones criteria for the diagnosis of acute rheumatic fever were evaluated by the staff at Primary Children's Medical Center, Salt Lake City, from January 1985 through June 1986. This represents an eightfold increase over the average annual incidence at this hospital during the past decade. Carditis, a dominant feature of the outbreak, was confirmed by auscultation in 53 of the patients (72 percent). An additional 14 patients were found to have mitral regurgitation by Doppler ultrasound examination, raising the total incidence of carditis to 91 percent. The children were predominantly from white (96 percent) middle-class families with above-average incomes and with ready access to medical care. There was no apparent increase in the incidence of streptococcal disease or other explanation for the marked increase in acute rheumatic fever. However, mucoid M type 18 and M type 3 group A streptococcal strains were isolated from several siblings of the patients and from schoolchildren (chosen at random) in the area. We conclude that acute rheumatic fever remains an important health problem in the United States.

Acute Disease↗

PubMed1987

Murine responses to immunization with pertussis toxin and bovine serum albumin: I. Mortality observed after bovine albumin challenge is due to an anaphylactic reaction.

It has been suggested that pertussis toxin (Ptx) is involved in the pathogenesis of the adverse neurologic reactions that can occur in infants and children after pertussis immunization. One group of investigators has recently reported that a clinical syndrome with pathological features very similar to post-pertussis vaccination encephalopathy can be induced in specific strains of mice after their immunization with bovine serum albumin (BSA) and Ptx. The aim of this investigation was to further characterize the immunologic mechanisms operative in this murine model. Studies were undertaken to determine whether the role played by Ptx in this condition required the A-protomer of the toxin to enter a cell and ADP-ribosylate a nucleotide binding protein (a Class I activity) or was dependent upon the binding of the B-oligomer of the toxin to the surface of target cells (a Class II activity). The results of our experiments have established that the disease induced by coimmunizing mice with Ptx and BSA is due to an immediate type hypersensitivity reaction rather than an encephalopathy and that the mechanism of action of Ptx in this system seems to be dependent upon a Class II activity of the toxin and independent of its ADP-ribosyl transferase activity.

Adenosine Diphosphate Ribose↗

PubMed1987

Implantation of thymic epithelial grafts into the anterior chamber of the murine eye: an experimental model for analyzing T-cell ontogeny.

The object of this investigation was to establish whether the intracameral implantation of thymic epithelial grafts could be utilized as a valid in vivo experimental model for probing the possible mechanisms whereby the sympathetic innervation of the thymus influences thymocyte dynamics. Our findings suggest that deoxyguanosine-treated thymic epithelial grafts, implanted into the anterior chamber of the eye, were receptive to host lymphoid progenitor cells, capable of supporting T-lymphocyte maturational processes, and were able to export mature T cells to the secondary lymphoid organs of a previously T-cell deficient host. In addition, we verified that the number of lymphoid cells recovered from a thymic epithelial graft which had been implanted into an anterior chamber devoid of sympathetic nerve input was generally greater than the number of lymphoid cells recovered from a matched graft which had been implanted into an anterior chamber which had an intact sympathetic nerve supply. Based on the results of these studies, investigative efforts can now be directed at studying a number of important aspects associated with the relationship between T lymphocyte ontogeny and the sympathetic nervous system.

Animals↗