Phenotypic diversity in siblings with partial androgen insensitivity syndrome

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point mutation of the androgen receptor gene affecting two siblings with partial androgen insensitivity syndrome is described. One had cliteromegaly and labial fusion and was raised as a girl, whereas the other sibling had micropenis and penoscrotal hypospadias and was raised as a boy. Both were shown to have the arginine 840 to cysteine mutation. The phenotypic variation in this family is thus dependent on factors other than abnormalities of the androgen receptor gene alone.     

Strontium-90 in newborns and childhood disease

Radioactive strontium-90 concentrations in baby teeth obtained from Suffolk County, New York, rose steadily during the 1980s. Recent levels of strontium-90 are similar to those reported for babies born in the late 1950s-at the height of atmospheric nuclear weapons testing in Nevada. Strontium-90 concentrations increased concomitantly with increases in cancer incidence among Suffolk children under the age of 5 y, a result that mimicked parallel trends observed in the 1950s and early 1960s. Given that effects of strontium-90 on developing cells are most pronounced during the fetal and infant periods, escalating levels should be viewed as a factor in the recent decline in various child health status measures.     

Immunobiology of T helper cells and antigen-presenting cells in autoimmune thrombocytopenic purpura (ITP)

Autoimmune thrombocytopenic purpura (AITP) is a bleeding disease in which autoantibodies are directed against the individual's own platelets, resulting in enhanced Fc-mediated platelet destruction by macrophages in the reticuloendothelial system. Most research in AITP has focused on characterization of the autoantibodies, while little has been devoted to the cellular immune mechanisms leading to autoantibody production. This report summarizes the current state of the literature and argues that enhanced T helper cell/antigen-presenting cell interactions in patients with AITP are the primary stimulus for the development of antiplatelet autoantibody production. Understanding these events is important for eventually identifying disease-initiating platelet autoantigens and ultimately developing specific immunotherapies for AITP.     

Evaluation of an educational module on dengue and Aedes aegypti for schoolchildren in Honduras]

OBJECTIVE: To evaluate the effectiveness of a special course on environmental health and dengue, given to primary school students and intended to promote behavioral changes in the mothers of those students that would lead to the safe handling of water, adequate disposal of trash, and control of household breeding sites of Aedes aegypti, the mosquito vector for dengue. METHODS: In the period from April to November 2002 a community field trial was carried out that included four public schools in the city of Comayaguela, Honduras. Two of the schools formed the intervention group, and the two others made up the comparison or control group. The data collection activities before and after the intervention included knowledge tests for the schoolchildren and the teachers; surveys of the knowledge, attitudes, and practices of the students' mothers; entomological surveys (systematic checking in order to find water containers, to search for mosquito larvae) in the homes of the schoolchildren; in-depth interviews with the students' mothers; observation in the classrooms; and postintervention focus group with the teachers. RESULTS: During the intervention period the largest epidemic of classical dengue ever in the history of Tegucigalpa, the capital of Honduras, occurred. That event prompted the Secretariat of Health to undertake large-scale control activities. In the two intervention schools there was a significant increase in the students' knowledge of the following three variables: dengue caused by a virus, life cycle of the vector, and reduction of breeding sites, which is the most effective measure for controlling the vector (P < 0.0001 for all those increases in knowledge). There were also significant increases in the knowledge of the same variables among the teachers in the intervention schools: dengue caused by a virus (P = 0.03), life cycle of the vector (P = 0.01), and reduction of breeding sites (P = 0.004). Reducing the number of breeding sites as being the best measure for controlling Aedes aegypti was the knowledge variable that showed the greatest change among the mothers in the intervention group (P = 0.02). The values for two of the entomological indices (the House index and the Breteau index) were better in the intervention group than in the control group, but the difference was not statistically significant. However, there was a statistically significant difference in the Breteau index values between the two control group schools and the one intervention school where the education course was implemented more adequately than in the other intervention school. CONCLUSIONS: The application of educational interventions directed to schoolchildren, as a part of a comprehensive plan for controlling Aedes aegypti, is an effective way to raise the awareness of teachers and parents with respect to the problem of dengue, and it also helps in encouraging family members to be involved in reducing breeding sites in the home. In moving to control the dengue vector, this strategy should take into consideration the involvement not only of families but also of civic and public institutions in the community. Given our results, it appears that this approach of using a special course for schoolchildren can constitute a fundamental pillar in the strategy for integrated dengue control.     

Bilateral eventration of the diaphragm with perforated gastric volvulus in an adolescent

Bilateral congenital eventration of the diaphragm almost uniformly presents in infancy with respiratory compromise and is associated with a high mortality rate. Delayed presentation of diaphragmatic eventration in older children and adults may be associated with acute gastric volvulus. Thus, any patient with abdominal pain, vomiting, or nonspecific gastrointestinal symptoms in association with abnormal diaphragmatic findings on chest x-ray should undergo further diagnostic workup with upper gastrointestinal series or computed tomography (CT) scan. Treatment of gastric volvulus requires immediate surgical repair to prevent subsequent necrosis and perforation. The authors describe a case report of bilateral congenital diaphragmatic eventration complicated by a perforated gastric volvulus in a 13-year-old boy. Emergent reduction of the volvulus, closure of the perforated stomach, plication of the diaphragm, and placement of gastrostomy was performed successfully.     

Physiologic implications of helium as a carrier gas for inhaled nitric oxide in a neonatal model of Bethanecol-induced bronchoconstriction.

OBJECTIVE: To compare heliox to nitrogen-oxygen (nitrox) as a carrier gas for inducible nitric oxide (iNO) in the presence of pharmacologically inhaled bronchoconstriction. We hypothesized that respiratory resistance and gas exchange would improve when iNO is delivered with heliox. DESIGN: Interventional laboratory study. SETTING: An academic medical research facility in the northeastern United States. SUBJECTS: Sedated, ventilated newborn piglets. INTERVENTIONS: Newborn piglets (n = 16; 2.3 +/- 0.1 kg) were placed on a flow-controlled ventilator and given intravenous Bethanecol (2 x 1 mg/kg followed by 1 mg/kg/hr) to induce bronchoconstriction. Piglets were randomized to heliox or nitrox (Fio2 = 0.3) and given 80 ppm iNO. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, blood chemistry, and pulmonary mechanics were recorded at 30-min intervals for 2 hrs. Bethanecol dosing increased inspiratory respiratory resistance (cm H2O/L/min; p < .01) and decreased respiratory compliance (mL/cm H2O/kg; p < .01). Following carrier gas assignment, hemodynamics and respiratory compliance were similar between groups and respiratory resistance decreased (p < .01) in the heliox group. Over 2 hrs with iNO therapy, Paco2 increased (p < .01) whereas blood pH decreased (p < .01) in the heliox group. Respiratory resistance trended downward, oxygenation index improved (p < .01), and blood methemoglobin levels trended higher for nitrox compared with heliox. CONCLUSIONS: The INOvent was effective for controlling heliox delivery of iNO. Despite marked reduction in respiratory resistance with heliox gas ventilation in a neonatal model of pharmacologic bronchoconstriction, nitrox might perform better as a delivery vehicle for iNO.     

A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes

OBJECTIVE: To determine whether use of a primary pull-through would result in equivalent perioperative and long-term complications compared with the two-stage approach. SUMMARY BACKGROUND DATA: During the past decade, the authors have advanced the use of a primary pull-through for Hirschsprung disease in the newborn, and preliminary results have suggested excellent outcomes. METHODS: From May 1989 through September 1999, 78 infants underwent a primary endorectal pull-through (ERPT) procedure at four pediatric surgical sites. Data were collected from medical records and a parental telephone interview (if the child was older than 3 years) to assess stooling patterns. A similar group of patients treated in a two-stage fashion served as a historical control. RESULTS: Mean age at the time of ERPT was 17.8 days of life. Comparing primary ERPT with a two-stage approach showed a trend toward a higher incidence of enterocolitis in the primary ERPT group compared with those with a two-stage approach (42.0% vs. 22.0%). Other complications were either lower in the primary ERPT group or similar, including rate of soiling and development of a bowel obstruction. Median number of stools per day was two at a mean follow-up of 4.1 +/- 2.5 years, with 83% having three or fewer stools per day. CONCLUSIONS: Performance of a primary ERPT for Hirschsprung disease in the newborn is an excellent option. Results were comparable to those of the two-stage procedure. The greater incidence of enterocolitis appears to be due to a lower threshold in diagnosing enterocolitis in more recent years.     

Increased Ifng and Il10 Expression Correlate with Disease in Rodent Models Experimentally Infected with Modoc Virus

Flaviviruses present an ongoing threat to global public health, although the factors that contribute to the disease remain incompletely understood. We examined an acute Modoc virus (MODV) infection of two rodent models. Viral RNA was detected in the kidneys, spleen, liver, brain, urine, and sera of experimentally infected deer mice, a reservoir host of MODV, and Syrian hamsters, a known disease model. As expected, clinical outcomes differed between species, and the levels of viral RNA recovered from various tissues demonstrated signs of differential replication and tissue tropism. Multivariate analysis indicated significance in the profile of expressed genes between species when analyzed across tissues and over time (p = 0.02). Between-subject effects with corrected models revealed a significance specific to the expression of Ifng (p = 0.01). the expression of Ifng was elevated in hamsters as compared to deer mice in brain tissues at all timepoints. As the over-expression of Ifng has been shown to correlate with decreased vascular integrity, the findings presented here offer a potential mechanism for viral dissemination into the CNS. The expression of IL10 also differed significantly between species at certain timepoints in brain tissues; however, it is uncertain how increased expression of this cytokine may influence the outcome of MODV-induced pathology.