Nocturnal Dexamethasone versus Hydrocortisone for the Treatment of Children with Congenital Adrenal Hyperplasia

Classic congenital adrenal hyperplasia affects approximately 1 in 15,000 children. Current treatment strategies using multiple daily doses of hydrocortisone lead to suboptimal outcomes. We tested the hypothesis that nocturnal administration of dexamethasone will suppress the hypothalamic-pituitary-adrenal axis more effectively than standard hydrocortisone treatment by blocking the inherent diurnal secretion of ACTH. We performed a pilot study of five prepubertal patients comparing CAH control during two 24-hour hospitalizations, one on hydrocortisone and the other on dexamethasone. The patterns of adrenal suppression differed markedly between hydrocortisone and nocturnal dexamethasone, with significant suppression of the morning rise in ACTH, 17-hydroxyprogesterone, and androstenedione while on dexamethasone. On hydrocortisone therapy, there is a marked variation in ACTH and adrenal hormones depending on time of day and timing of hydrocortisone administration. Longer-term studies are needed to investigate the lowest effective dose and potential toxicity of nocturnal dexamethasone to determine its utility as a therapy for CAH

Susceptibility to intestinal infection and diarrhoea in Zambian adults in relation to HIV status and CD4 count.

BACKGROUND: The HIV epidemic in sub-Saharan Africa has had a major impact on infectious disease, and there is currently great interest in the impact of HIV on intestinal barrier function. A three year longitudinal cohort study in a shanty compound in Lusaka, Zambia, carried out before anti-retroviral therapy was widely available, was used to assess the impact of HIV on susceptibility to intestinal infectious disease. We measured the incidence and seasonality of intestinal infection and diarrhoea, aggregation of disease in susceptible individuals, clustering by co-habitation and genetic relatedness, and the disease-to-infection ratio. METHODS: Adults living in a small section of Misisi, Lusaka, were interviewed every two weeks to ascertain the incidence of diarrhoea. Monthly stool samples were analysed for selected pathogens. HIV status and CD4 count were determined annually. RESULTS: HIV seroprevalence was 31% and the prevalence of immunosuppression (CD4 count 200 cells/microL or less) was 10%. Diarrhoea incidence was 1.1 episodes per year and the Incidence Rate Ratio for HIV infection was 2.4 (95%CI 1.7-3.3; p < 0.001). The disease-to-infection ratio was increased at all stages of HIV infection. Aggregation of diarrhoea in susceptible individuals was observed irrespective of immunosuppression, but there was little evidence of clustering by co-habitation or genetic relatedness. There was no evidence of aggregation of asymptomatic infections. CONCLUSION: HIV has an impact on intestinal infection at all stages, with an increased disease-to-infection ratio. The aggregation of disease in susceptible individuals irrespective of CD4 count suggests that this phenomenon is not a function of cell mediated immunity

Performance of a Nonelectric Infant Warmer in Rwandan Health Centers.

Background. Neonatal hypothermia remains a challenge in resource-limited settings. Methods. We conducted a prospective mixed-methods cohort study in rural Rwandan health centers to assess the performance of an infant warmer we designed for low-resource settings. All hypothermic infants were eligible for enrollment. Outcomes. Safety: incidence of adverse reactions. Effectiveness: attainment of euthermia, rate of temperature rise. Feasibility: correct use of warmer, signs of wear. Interviews of caregivers and nurses. Findings. Of 102 encounters, there were no adverse reactions. Of 80 encounters for hypothermia when infants on warmer for ≥1 hour, 79 achieved euthermia; 73 in ≤2 hours. Of the 80 encounters, 64 had temperature rise ≥0.5°C/h. Of the 102 encounters, there were no instances of the warmer being prepared, used, or cleaned incorrectly. Five out of the 12 warmers exhibited wear. Interview participants were predominantly positive; some found time for readiness of warmer challenging. Interpretation. The warmer performed well. It is appropriate to study in larger scale

HUT observations of carbon monoxide in the coma of Comet Levy (1990c)

Observations of comet Levy (1990c) were made with the Hopkins Ultraviolet Telescope during the Astro-1 Space Shuttle mission on 10 Dec. 1990. The spectrum, covering the wavelength range 415 to 1850 A at a spectral emission of 3 A (in first order), shows the presence of carbon monoxide and atomic hydrogen, carbon, and sulfur in the coma. Aside from H I Lyman-beta, no cometary features are detected below 1200 A, although cometary O I and O II would be masked by the same emissions present in the day airglow spectrum. The 9.4 x 116 arcsec aperture corresponds to 12,000 x 148,000 km at the comet. The derived production rate of CO relative to water, 0.13 + or - 0.02, compared with the same ratio derived from IUE observations (made in Sep. 1990) which sample a much smaller region of the coma, 0.04 + or - 0.01, suggests the presence of an extended source of CO, as was found in comet Halley. Upper limits on Ne and Ar abundance are within an order of magnitude or solar abundances

α4* Nicotinic Receptors in preBotzinger Complex Mediate Cholinergic/Nicotinic Modulation of Respiratory Rhythm

Acetylcholine and nicotine can modulate respiratory patterns by acting on nicotinic acetylcholine receptors (nAChRs) in the preBötzinger complex (preBötC). To further explore the molecular composition of these nAChRs, we studied a knock-in mouse strain with a leucine-to-alanine mutation in the M2 pore-lining region (L9′A) of the nAChR α4 subunit; this mutation renders α4-containing receptors hypersensitive to agonists. We recorded respiratory-related rhythmic motor activity from hypoglossal nerve (XIIn) and patch-clamped preBötC inspiratory neurons in an in vitro medullary slice preparation from neonatal mice. Nicotine affected respiratory rhythm at concentrations ∼100-fold lower in the homozygous L9′A knock-in mice compared with wild-type mice. Bath application of 5 nm nicotine increased the excitability of preBötC inspiratory neurons, increased respiratory frequency, and induced tonic/seizure-like activities in XIIn in L9′A mice, effects similar to those induced by 1 μm nicotine in wild-type mice. In L9′A mice, microinjection of low nanomolar concentrations of nicotine into the preBötC increased respiratory frequency, whereas injection into the ipsilateral hypoglossal (XII) nucleus induced tonic/seizure-like activity. The α4*-selective nAChR antagonist dihydro-β-erythroidine produced opposite effects and blocked the nicotinic responses. These data, showing that nAChRs in the preBötC and XII nucleus in L9'A mice are hypersensitive to nicotine and endogenous ACh, suggest that functional α4* nAChRs are present in the preBötC. They mediate cholinergic/nicotinic modulation of the excitability of preBötC inspiratory neurons and of respiratory rhythm. Furthermore, functional α4* nAChRs are present in XII nucleus and mediate cholinergic/nicotinic modulation of tonic activity in XIIn

Signal Processing

Contains research objectives, summary of research and reports on two research projects.Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300U. S. Coast Guard (Contract DOT-CG-13446-A

Rosetta-Alice Observations of Exospheric Hydrogen and Oxygen on Mars

The European Space Agency's Rosetta spacecraft, en route to a 2014 encounter with comet 67P/Churyumov-Gerasimenko, made a gravity assist swing-by of Mars on 25 February 2007, closest approach being at 01:54UT. The Alice instrument on board Rosetta, a lightweight far-ultraviolet imaging spectrograph optimized for in situ cometary spectroscopy in the 750-2000 A spectral band, was used to study the daytime Mars upper atmosphere including emissions from exospheric hydrogen and oxygen. Offset pointing, obtained five hours before closest approach, enabled us to detect and map the HI Lyman-alpha and Lyman-beta emissions from exospheric hydrogen out beyond 30,000 km from the planet's center. These data are fit with a Chamberlain exospheric model from which we derive the hydrogen density at the 200 km exobase and the H escape flux. The results are comparable to those found from the the Ultraviolet Spectrometer experiment on the Mariner 6 and 7 fly-bys of Mars in 1969. Atomic oxygen emission at 1304 A is detected at altitudes of 400 to 1000 km above the limb during limb scans shortly after closest approach. However, the derived oxygen scale height is not consistent with recent models of oxygen escape based on the production of suprathermal oxygen atoms by the dissociative recombination of O2+.Comment: 17 pages, 8 figures, accepted for publication in Icaru