Low-Dose Dantrolene Is Effective in Treating Hyperthermia and Hypercapnia, and Seems Not to Affect Recovery of the Allograft After Liver Transplantation: Case Report

Dantrolene is the drug of choice in treatment of malignant hyperthermia. However, dantrolene is hepatotoxic; thus prolonged use is not recommended in patients with active hepatic disease such as acute hepatitis or active cirrhosis because it may result in fatal hepatic failure. Use of dantrolene in a patient with end-stage liver disease undergoing liver transplantation (LTx) in whom suspected malignant hyperthermia developed has been reported rarely. Its effect on the liver allograft, which has sustained cold, warm, and reperfusion injuries, is currently unknown. We report a case in which low-dose dantrolene administered intravenously during LTx was effective in treating hyperthermia, hypercapnia, and hyperkalemia. Furthermore, its reported hepatotoxic effect seemed to not affect recovery of the allograft after LTx.     

Germinal center formation in mice lacking αβ T cells

T cells are essential for inducing clonal B cell expansion in germinal centers during T cell-dependent antibody responses. However, class-switched antibodies are readily detectable in TCRα-deficient mice that congenitally lack αβ T cells, including those such as IgG1 that are considered to be dependent on collaboration between B cells and αβ T cells. This observation suggests that a novel form of B:T collaboration may be evident in TCRα^?/? mice. We report that germinal centers develop spontaneously in mice lacking T cell receptor α genes (TCRα^?/?), despite the absence of αβ T cells. They are not seen in TCRβ^?/? mice kept in similar conditions. Both strains of mice have γδ T cells, but it is a subset of T cells expressing TCRβ and CD4 that is dominant in the germinal centers of TCRα^?/? mice. Exceptionally, germinal centers were associated with CD4⁺ γδ T cells. The expression of CD4 seems to be important, for few extrafollicular T cells have CD4 and CD4 is largely absent from TCRβ^?/? T cells. The CD4⁺ TCRβ cells may help B cells produce autoantibodies that have been identified in TCRα^?/? mice.     

Distribution of, and immune response to, chicken anti-alpha Gal immunoglobulin Y antibodies in wild-type and alpha Gal knockout mice

Chicken antibodies (immunoglobulin Y; IgY) to the alpha Gal epitope (galactose alpha-1,3-galactose) bind to alpha Gal antigens of mouse and porcine tissues and endothelial cells in vitro and block human anti-alpha Gal antibody binding, complement activation and antibody-dependent cell-mediated lysis mechanisms. The activities and toxicity of anti-alpha Gal IgY have not been tested in vivo. In this study, we tested the effects of multiple injections of affinity-purified anti-alpha Gal IgY (AP-IgY) in both wild-type (WT) and alpha-1,3-galactosyltransferase knockout (Gal KO) mice. WT and Gal KO mice were injected once, twice, three, or four times intravenously (i.v.) with AP-IgY and killed at 1 hr or 24 hr. Mice displayed no toxicity to four injections of AP-IgY. Heart, lung, liver, kidney, spleen and pancreatic tissue were evaluated using immunohistochemical techniques for the presence of the alpha Gal epitope using the GSI-B4 lectin, and for bound IgY, as well as mouse IgM and IgG. The binding of AP-IgY antibodies to the endothelium of WT mouse tissues was essentially identical to the pattern of binding of the GSI-B4 lectin after injection of WT mice and death at 1 hr. WT mice killed 24 hr after i.v. injection of AP-IgY showed little remaining bound IgY in their endothelia, indicating that IgY is cleared over that time period. We also evaluated the blood drawn at the time of death for the presence of anti-alpha Gal IgY, anti-IgY IgM and anti-IgY IgG by enzyme-linked immunosorbent assay. Anti-alpha Gal IgY was almost undetectable in WT mouse sera at all injection and killing times. In contrast, Gal KO mouse sera showed increasing anti-alpha Gal IgY levels until 24 hr after the fourth injection, when anti-alpha Gal IgY levels were almost undetectable. Anti-IgY IgM and IgG levels in WT and Gal KO mouse sera showed a typical increase in anti-IgY IgM 24 hr after the second injection (3 days after the first injection) and an increase in anti-IgY IgG 24 hr after the third injection (5 days after the first injection). These results show that IgY binds to alpha Gal epitopes in the WT mice and is cleared sometime over a 24-hr time period and that IgY is an expected immunogen in mice eliciting a rather typical anti-IgY IgM and IgG response.     

Prenatal transmission of hepatitis B virus to neonates born to serum hepatitis B virus DNA-positive mothers.

Hepatitis B virus (HBV) DNA was detected by in vitro enzymatic DNA amplification techniques in 66.7% (six of nine) of hepatitis B virus surface antigen (HBsAg)-positive and in 21.1% (7 of 33) of HBsAg-negative pregnant women. Five of the HBV DNA and HBsAg-positive women and one HBV DNA-positive but HBsAg-negative woman gave birth to infants positive for serum HBV DNA at time of birth. These results suggest that HBsAg-negative pregnant women are potentially capable of transmitting HBV DNA to their infants.     

The use of a bioactive skin substitute decreases length of stay for pediatric burn patients

BACKGROUND: To optimize burn care for children, the authors introduced a protocol incorporating the use of a bioactive skin substitute, TransCyte (Advanced Tissue Sciences, La Jolla, CA). This study was designed to determine whether this management plan was safe, efficacious, and decreased hospital inpatient length of stay (LOS) compared with conventional burn management in children. METHODS: All pediatric burns greater than 7% total body surface area (TBSA) that occurred after October 1999 underwent wound closure with TransCyte (n = 20). These cases were compared with the previous 20 consecutive burn cases greater than 7% TBSA that received standard therapy. Standard therapy consisted of application of antimicrobial ointments and hydrodebridement. The following information was obtained: burn mechanism, age, size of burn, requirement of autograft, and LOS. Data were analyzed using the student's t test. RESULTS: Data for age, percent TBSA burn and LOS are reported as means +/- SEM. The children who received standard therapy were 2.99 +/- 0.7 years compared with those receiving TransCyte were 3.1 +/- 0.8 years. There was no difference between the treatment groups with regard to percent TBSA burn: standard therapy, 14.3 +/- 1.4% TBSA versus TransCyte, 12.7 +/- 1.3% TBSA. There was no difference in the type of burns in each group, the majority were liquid scald type, 70% in the standard therapy group versus 90% in the TransCyte group. Only 1 child in the TransCyte group required autografting (5%) compared with 7 children in the standard therapy group (35%). Children treated with TransCyte had a statistically 6 significant decreaed LOS compared with those receiving standard therapy, 5.9 +/- 0.9 days versus 13.8 +/- 2.2 days, respectively (P =.002). CONCLUSIONS: This is the first study using TransCyte in children. The authors found that this protocol of burn care was safe, effective, and significantly reduced the LOS. This new approach to pediatric burn care is effective and improves the quality of care for children with burns.     

Children and adolescents living with HIV and AIDS: a review

Worldwide, more than one million children are infected with human immunodeficiency virus (HIV) and in the United States it has become the sixth leading cause of death among 15-24-year-olds. Despite the trend of increasing rates of infection, advances in therapies have led to survival past 5 years of age for more than 65% of infected children. This global health threat will therefore continue to have a significant impact on child and adolescent psychiatry and psychology. This paper reviews current studies and reports on the consequences of the acquired immunodeficiency syndrome (AIDS) epidemic in the psychiatric care and development of children and adolescents infected by HIV. From a search of all the English-language-based literature on pediatric AIDS, 140 studies are reviewed which address HIV infection and its psychological and social implications. Several topics of mental health significance are examined: (1) the epidemiology of HIV, (2) neurocognitive development among those infected, (3) psychological impact of infection, and (4) the family and social context of HIV. The transition of HIV from an acute, lethal disease to a subacute, chronic disease has enormous implications for the neurocognitive and psychosocial development of children and families. As children and adolescents infected with HIV continue to live longer, normal developmental milestones and educational needs will take on new significance. Many children will continue to be adversely impacted by non-HIV factors such as poverty, inadequate medical services, and a lack of social support. This review outlines recent developments that hold promise to effectively reduce the treatment burden on the infected, their families, and health care providers and to decrease the incidence of transmission to the uninfected.     

Efectividad de ivacaftor en vida real en niños con fibrosis quística y mutación G551D

Introduction

Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has been shown to improve the nutritional status and lung function of cystic fibrosis patients with the G551D mutation in clinical trials. The objective of this study was to describe the real-world progress of children receiving ivacaftor.