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Biomedical subjects

D Warren

Publications and source records attributed to D Warren.

At least 55 records · Page 3Linked to original sources

High levels of granulocyte and granulocyte-macrophage colony-stimulating factors in cord blood of normal full-term neonates.

Because several human hematopoietic growth factors have been identified and shown to be effective for treatment of congenital or iatrogenic neutropenias, and cord blood contains stimulatory activities for blood-forming cells, we postulated that identification of these factors and analysis of their regulatory role in normal neonates would provide a rationale for their use in treating neonatal infections associated with neutropenia. We studied the plasma levels of granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF, respectively) and the frequency of granulomonopoietic colony-forming cells (CFU-GM) in the umbilical cord blood of normal term neonates. Plasma growth factor levels were measured by a biologic assay. Circulating hematopoietic progenitors were assayed for colony formation with different recombinant growth factors used as exogenous growth stimulators. The cell cycle status of these progenitors was analyzed by the thymidine suicide technique. At birth the leukocyte count (mean +/- SD) was 11.0 +/- 3.9 x 10(9)L and the neutrophil count was 5.6 +/- 2.6 x 10(9)/L. The incidence of CFU-GM was significantly higher in umbilical cord blood than in normal adult peripheral blood (p less than 0.005) with up to 40% of the cells in S phase (less than 10% in normal adults). Plasma levels of G-CSF and GM-CSF at birth were 40.8 +/- 2.8 U/ml and 19.9 +/- 5.2 U/ml, respectively (normal adult plasma levels 2.5 +/- 1.5 U/ml for G-CSF and undetectable for GM-CSF). These high levels of G-CSF and GM-CSF in umbilical cord blood of normal neonates might play a role in maintaining adequate neutrophil production.

Adult↗

A large outbreak of epidemic keratoconjunctivitis: problems in controlling nosocomial spread.

Between July 1985 and January 1986, 401 patients with adenovirus epidemic keratoconjunctivitis (EKC) were seen at the Illinois Eye and Ear Infirmary. Of the cases, 110 (27%) were nosocomial; the other 291 patients had community acquired infection. The highest attack rates of EKC occurred in patients attending specialty clinics; the overall attack rate among clinic patients was 4.7/1,000 clinic visits. All nosocomial cases were caused by adenovirus type 8; community acquired cases were a mixture of adenovirus types 8 and 37. Adenoviruses were isolated from conjunctival cultures up to 14 d after the onset of clinical illness. Initial efforts to prevent nosocomial transmission were unsuccessful. However, when a plan to triage all patients on entry to the infirmary and to sort patients and personnel caring for infected patients into cohorts was implemented, nosocomial transmission of EKC was promptly and effectively halted, despite the continuation of the community epidemic for another 4 mo. This outbreak clearly demonstrates the efficacy of rigorous infection control in preventing nosocomial transmission of adenovirus EKC.

Adenoviridae Infections↗

Usefulness of head injury instruction forms in home observation of mild head injuries.

We prospectively studied a group of patients with mild head injury discharged for home observation to determine whether written instructions assisted in recall of signs and symptoms, increased patient satisfaction, or resulted in any additional benefit over verbal explanations alone. We also evaluated the level of comprehension required to understand the written instructions in their present form. Over a three-month period, 72 patients (43 male, 29 female) with a mean age of 4.4 (SD +/- 3.9) years were studied. In addition to verbal explanations for all parents, 38 parents received written instructions. Each group remembered 4/7 (57%) of signs and symptoms and was equally satisfied with verbal explanations. The majority (84%) of parents who received instruction sheets intended to keep these for further reference. Low recall of two instructions may be due to poor comprehension of the language used. We conclude that written instructions (1) did not add significantly to recall, (2) may provide reassurance to parents, and (3) need to be written in simple lay terms in order to be understood by the parents/patients served.

Child↗

Lymphoma models for B cell activation and tolerance. VI. Reversal of anti-Ig-mediated negative signaling by T cell-derived lymphokines.

We have recently described three "immature" B cell lymphomas which are exquisitely sensitive to growth inhibition by anti-Ig reagents and may serve as models for tolerance induction in normal B cells. These cells are inhibited from cell cycle progression into S after receiving a negative signal in early G1. In this paper, we demonstrate that the growth inhibition by anti-Ig can be prevented and reversed by the addition of supernatants from T cell lines. One such line, called Tova, produces factors which restore normal levels of DNA synthesis in the presence of concentrations of anti-Fab or anti-kappa immunoglobulins which cause up to a 90% inhibition of thymidine incorporation in a 2- to 3-day culture period. This factor is at least partially effective when added up to 24 hr after anti-Ig to unsynchronized lymphoma cells and it does not alter the growth of control cultures. Studies using synchronized lymphoma cells indicated that the T cell factor permitted cycle progression into S when added during the early G1 exposure to anti-kappa and was less effective when added late in G1. Preliminary characterization suggests that both B cell growth factor II (interleukin 5) and B cell stimulatory factor 1 (interleukin 4) have additive activity in this system, although another unidentified lymphokine may also be involved. The relevance of T cell reversal of Ig receptor-mediated negative signaling to neonatal B cell tolerance is emphasized.

Animals↗

T-cell hybridomas specific for self and foreign thyroglobulins.

We have used somatic cell fusion techniques to produce and characterize murine T-cell hybridomas with specificity for self and foreign thyroglobulin (Tg). Two interleukin-2 (IL-2)-releasing I-Ak-restricted hybrid clones with specificity for self determinants on syngeneic Tg were derived from Tg-specific T-cell lines. These two autoreactive hybridomas were independently derived and were clonotypically distinct as determined by restriction fragment length polymorphism of the Ti beta-chain gene, but showed a similar pattern of cross-reactivity against rat and human (but not porcine) Tg. A third T-cell hybridoma showed a previously unknown specificity for the immunizing (non-inbred) Tg, but not for syngeneic Tg, indicating responsiveness to an allelic determinant. Although T-cell hybridization techniques have previously had only minimal application in experimental autoimmunity, this represents an approach to the study of Tg-specific T-cell responses at the molecular level.

Animals↗

Transmission of neonatal listeriosis in a delivery room.

Two cases of neonatal listeriosis occurred in a hospital within a two-week period. Both infants were infected with the same organism, Listeria monocytogenes, type 1a, bacteriophage type 6 (lysotype 1652). Both infants were born in the same delivery room, 17 hours apart. The index patient became septic shortly after birth and died after 48 hours despite antibiotic therapy. The mother of the index patient was febrile and had chorioamnionitis. The second infant became ill with meningitis at 13 days of age. Neither infants nor mothers were attended by the same medical or nursing staff nor were they in the same labor or postpartum areas or nurseries. However, both infants were resuscitated in the same delivery room after birth by means of laryngoscope, suction catheter, and emergency resuscitation (Ambu) bag. Although it was hospital policy to clean and sterilize resuscitation equipment after use, the equipment had only been wiped with alcohol between patients in this instance, since sterile replacement equipment was not available during the early-morning hours when the index birth occurred. Therefore, we believe the contaminated resuscitation equipment was the source of infection in the second infant. This episode emphasizes the importance of appropriate disinfection of respiratory resuscitation equipment to prevent nosocomial infection due to L monocytogenes, an unusual but important pathogen in neonates.

Cross Infection↗

Deferoxamine injection does not affect bleomycin-induced lung fibrosis in rats.

Bleomycin is an antineoplastic agent that causes a dose-related lung fibrosis that limits its therapeutic effectiveness. It has been proposed that the cellular toxicity and antitumor effects of bleomycin occur by formation of O2-Fe(II)-bleomycin complexes that degrade DNA and release O2- and OH radicals that attack other cellular components. Twice daily injections of the iron chelator deferoxamine were utilized in an attempt to ameliorate bleomycin-induced lung fibrosis. They failed to diminish bleomycin-induced lung inflammation and fibrosis in rats.

Animals↗

Liver function studies on rhesus monkeys (Macaca mulatta) following the administration of hydrazine sulfate.

Hydrazine sulfate (Hs), a known occupational toxin and putative cancer therapeutic agent, was administered iv at various doses to rhesus monkeys in an effort to measure its effects upon the liver. Function tests included indocyanine clearance (ICG Vmax and Km), serum bile acid levels and serum enzyme activities, including alanine aminotransferase, gamma glutamyl transferase, and a panel of 19 other blood chemical constituents. Hepatic function and other biochemical tests were generally within the normal range following single-dose Hs administration (10-40 mg/kg) and did not suggest the presence of significant liver injury. Two monkeys receiving 80 mg/kg Hs exhibited extensive hepatic lipidosis without biochemical or histologic signs of necrosis. Hs, administered iv, appears to produce little or no hepatic toxicity.

Alanine Transaminase↗

The short-term dynamics of social organization in preschool triads.

Sequential dependencies in solitary and interactive states of social organization were examined as a function of age, sex, and type of toy in 12 triads of 3 1/2- and 5-year-old children. Each triad was observed during 2 30-min sessions, one in which objects with highly specific functions (e.g., dolls, trucks) were available, and one in which objects with relatively ambiguous functions (e.g., pipe cleaners, cardboard cylinders) were present. The results indicated that, while old and young triads did not differ in the tendency to initiate triadic interaction when the preceding state was solitary, old triads were more likely than young triads to maintain the triadic state and to shift to that state from the dyadic state. Boy triads were more likely than girl triads to remain in a solitary state and less likely to shift to and remain in a dyadic state, though no sex difference was found in the transition probabilities when the preceding state was triadic. Triads were more likely to remain in a solitary state in the presence of high-specificity toys than in the presence of low-specificity toys. Verbal metacommunication was more frequent among old triads than young triads, and it facilitated maintenance, but not initiation, of interactive states. The distinction between initiation and maintenance tendencies was formalized in a Markov model of the dynamics of social organization, and the parameter estimates yielded by the model were used to provide a simplified description of the "main" effects of age, sex, and type of toy. It is argued that models such as this one are useful in circumventing certain restrictions on the possible interpretations of raw sequential statistics.

Child Development↗

Induction of cholinergic expression in developing spinal cord cultures.

The induction of choline acetyltransferase (ChAT) by cAMP derivatives was studied in dissociated spinal cord cultures. Dibutyryl cAMP (dbcAMP) and 8-bromo cAMP (1 mM) produced a 2-3-fold stimulation of ChAT activity in developing cultures whereas 8-bromo cGMP had no effect. A phosphodiesterase inhibitor, 3-isobutyl-l-methylxanthine, also increased (2-fold) ChAT activity in immature cultures. Significant elevations in ChAT were detected after 2 h incubation with dbcAMP. Maximum enzyme induction was observed 24 h after dbcAMP supplementation to the culture medium. Developmental studies revealed that ChAT could be induced on days 2-16 in culture. The largest induction of ChAT activity was observed on day 7 in culture. After day 19, when control enzyme activity attained levels of mature cultures, cAMP-mediated ChAT induction was no longer observed. Cycloheximide and actinomycin D blocked ChAT induction whereas basal enzyme activity remained unaffected. Culture protein content was not changed after 1-day exposure to dbcAMP. 125I-Tetanus toxin fixation after dbcAMP treatment revealed a 20% decrease from control in neuronal surface during days 7-9 in culture. These data indicated that cAMP derivatives produced a rapid increase in cholinergic expression during a specific period of development in spinal cord cultures. There appears to be specificity to this effect, as total neuronal surface does not respond in the same manner as ChAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

An outbreak of congenital rubella in Chicago.

After an outbreak of rubella in Chicago in 1978, an intensive survey of local health care personnel and hospital records identified 31 infants with congenital rubella syndrome (CRS). Rubella virus was isolated from 11 infants; rubella-IgM antibodies were demonstrated in seven infants; ten babies had persistent high rubella hemagglutination-inhibition (HI) titers. The incidence of CRS in Chicago between July 1978 and June 1979 was 48.9 per 100,000 live births. Mothers of babies with CRS frequently remembered a crash-illness during pregnancy (56%), were unmarried (74%), and were primigravidas (64%). No mother had received rubella vaccine. Review of prenatal rubella HI testing and follow-up immunization in one hospital showed that only eight (10.8%) of 74 seronegative women received rubella vaccine physicians need to place increased emphasis on detection and vaccination of susceptible adult women.

Adolescent↗

External monitoring of kidney transplant function using Tc-99m(Sn)DTPA.

The purpose of this study was to evaluate the use of an external counting technique to provide daily monitoring of kidney transplant function by measuring the renal clearance of Tc-99m(Sn)DTPA. During the first few weeks following transplant, 15 patients had their renal clearance of Tc-99m DTPA measured daily over periods of 5-24 hr. Clearance rates were compared with daily plasma creatinine levels, and the effects of diurnal variation, drug treatment, and physical activity noted. The results show that any significant fall in clearance rate of chelate, indicating a rejection episode, preceded a rise in plasma creatinine levels by at least 24 hr. One episode of transplant failure presented as a sudden deterioration in clearance rate of chelate; in the others the change was more gradual but was still apparent within hours. It is considered that this noninvasive, low-dose, easy-to-perform technique is of considerable value in extended daily monitoring of renal function and is superior to standard daily or twice-weekly renography for the early detection of transplant rejection.

Creatinine↗