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T Darville

Publications and source records attributed to T Darville.

25 records · Page 2Linked to original sources
PubMed1994

Intravenous immunoglobulin modulates human mononuclear phagocyte tumor necrosis factor-alpha production in vitro.

Mononuclear phagocytes (MO) secrete tumor necrosis factor-alpha (TNF) in response to inflammatory stimuli, most notably the bacterial product lipopolysaccharide (LPS). Cross-linking of MO Fc receptors also induces TNF release. Immunoglobulin for i.v. use is currently being investigated for the treatment and prophylaxis of neonatal sepsis and for the treatment of various syndromes of autoimmune dysfunction in children and adults. We examined the in vitro effect of immunoglobulin-gamma (IgG) on neonatal (cord blood) monocyte and adult MO TNF production. Kinetic studies were performed on MO incubated with IgG alone and on MO preincubated with IgG and stimulated with interferon-gamma/LPS. Incubation of MO in IgG (1-25 g/L) for 2, 6, and 24 h did not stimulate TNF secretion or production. However, enhanced TNF secretion was detected in MO preincubated in IgG and subsequently stimulated with interferon-gamma/LPS. TNF secretion by cord blood monocytes was increasingly enhanced by preincubation for 6 h with 1, 10, and 25 g/L IgG (2413.1 +/- 1389.4, p < 0.05; 4070.4 +/- 3069.2, p < 0.005; and 6383.7 +/- 2982.2, p < 0.005 versus 1215 +/- 575.9 ng/L, respectively, in cells preincubated in medium alone). Significant enhancement was also detected in cord blood monocytes preincubated in IgG for 2 h. TNF secretion by adult MO was similarly enhanced (6082.0 +/- 1732.8, p < 0.05; 7158.8 +/- 3938.2, p < 0.05; and 7302.7 +/- 3451.4, p < 0.05 versus 3353.2 +/- 2946.7 ng/L for 1, 10, and 25 g/L IgG, respectively, versus preincubation in medium alone). In additional experiments performed with Fc, Fab, and F(ab')2 fragments, only F(ab')2 fragments yielded positive results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Safety profile and efficacy of cefotaxime for the treatment of hospitalized children.

Cefotaxime has been used to treat serious bacterial infections in children since 1982. With the predominant use of cephalosporins in pediatrics, reports of adverse effects of certain compounds have increased. A retrospective review is presented of 2,243 cases of children receiving therapy with cefotaxime in order to evaluate the safety profile and efficacy of cefotaxime in the treatment of serious infections in hospitalized children. Overall, 57 (2.5%) children experienced adverse reactions. These included local reactions in 6 (0.3%), rash in 28 (1.2%), diarrhea in 15 (0.97%), vomiting in 10 (0.7%), abdominal pain in 1 (0.1%), headache in 3 (0.4%), and drug fever in 1 (0.1%). No cases of hemolytic anemia, bleeding, or hyperbilirubinemia were found. Efficacy of treatment for different disease categories ranged from 90.5% to 100%. The percentage of children in any treatment group with a particular laboratory abnormality following initiation of cefotaxime therapy ranged from 0% to 2.6%, and rates of superinfection with bacteria or Candida were 0.4% to 1.7%. Cefotaxime has the distinct advantage of high rates of efficacy and low rates of complications and superinfection among children hospitalized for serious infections.

Adolescent↗
PubMed1992

Surface matrix binding alters murine peritoneal mononuclear phagocyte TNF-alpha and IL-6 induction.

Interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) are important promotors of mononuclear phagocyte (MO) activation. Signals derived from binding to a surface matrix also participate in promoting the activation process of MO. In this study, we examined the relative contribution of adherence in augmenting murine MO activation for cytokine production. Kinetic studies compared the production and secretion of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) by MO cultured as adherent monolayers to those of MO cultured as suspended cells in teflon vessels. All cells were maximally stimulated in vitro with IFN-gamma and LPS prior to analysis. Immunoprecipitation analysis of protein and RNA slot blots showed that both secreted protein and mRNA representing TNF and IL-6 are delayed two to six hours in nonadherent MO cultures compared to adherent MO cultures. Moreover, data from bioassays confirmed that these cytokines were completely functional in both systems examined. Although IFN-gamma/LPS were able to stimulate production and secretion of TNF and IL-6 in the nonadherent cells, without cell-matrix interaction, the process was significantly delayed. These data support the hypothesis that the physical event of adherence significantly facilitates the production of specific cytokines by activated MO.

Animals↗
PubMedDate not supplied

The systemic inflammatory response syndrome (SIRS): immunology and potential immunotherapy.

Despite widespread advances in intensive care practices, and more potent and effective antimicrobials, septic shock continues to have a mortality rate of greater than 40%. Although antimicrobials can treat the etiologic organism, they do not alter the host response. It is becoming clear that invading organisms and other insults induce the release of cytokines and secondary mediators by the host. These mediators produce alterations in cellular, metabolic and physiologic functions producing the clinical picture of septic shock. Recent advances in cellular and molecular biology have permitted the identification of some of the mediators involved in this inflammatory cascade. Potential therapies are being developed which block or interrupt their activity. Treatment populations must be meticulously defined if we are to extract useful information concerning the efficacy of these new treatment modalities. In the following, proposed definitions for clinical patterns seen in patients with sepsis, and their inherent problems when applied to pediatrics are discussed. The pathophysiology of sepsis is discussed, and specific therapies designed to interrupt the inflammatory cascade are examined.

Bacterial Infections↗