Adult height in patients with childhood onset atopic dermatitis

Cross sectional studies have reported impaired growth in children with atopic dermatitis. If this growth impairment is irreversible, it would be expected to adversely influence final height attainment. The standing heights and other anthropometric parameters were assessed in 35 adults with onset of atopic dermatitis before 5 years of age and a control group of 35 adults with adult onset contact dermatitis or psoriasis. There was no significant difference in the standing height SD score, mid-parental height SD score, sitting height SD score, subischial leg length SD score, nor body mass index between the atopic dermatitis and control groups. The standing height SD score was not significantly different among: (a) patients with atopic dermatitis affecting less than 50% of their body surface area and those with greater than 50% affected; (b) patients using the four different potency topical corticosteroids; and (c) patients with atopic dermatitis without asthma and those with coexisting asthma. It is concluded that short stature is not a feature of our group of adult patients with onset of atopic dermatitis before 5 years of age, continuing into adulthood, and severe enough to require specialist care. This suggests that if growth impairment occurs in childhood, it is likely to be temporary and reversible.     

Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Brigadier General Theodore C Lyster [correction of Lister], MD: father of American aviation medicine

Aviation medicine came into existence as a recognized entity when certain standards were established during and shortly after World War I. During this time, accident rates were high. In fact, a larger number of pilots were dying in accidents than in combat. Figures from Great Britain's casualty list at the close of the first year of World War I indicated that for every 100 aviators killed, 60 died as a result of some individual physical defect, 30 from some form of recklessness or careless behavior, 8 as a result of some mechanical defect in the airplane, and only 2 at the hands of the enemy. Aviators were found to be in poor physical condition. Because there were no established regulations with regard to workloads, aviators were frequently found to have been flying to a point beyond exhaustion. Because of workload, chronic fatigue, and emotional stress, aviators were constantly called upon to perform superhuman feats when not in peak physical condition. Errors in judgement were common. The majority of pilots lost weight as a somatic sign of stress. This was recognized by Theodore Lyster [corrected] who had recently been appointed as the Chief Surgeon, Aviation Section of the U.S. Army. Such problems were not diagnosed by medical officers because they were not trained to recognize them. Theodore Charles Lyster [corrected] was the son of Captain William J. and Martha Doughty Lyster [corrected]. He was an Army "brat" who entered the world on July 10, 1875. His childhood was spent in various posts around the country. At the age of 7, Lyster [corrected] contracted yellow fever while living in Fort Brown, TX. The boy was treated by William Gorgas, a young post surgeon. Gorgas was credited with the young boy's recovery. Later, Gorgas was to marry Lyster's [corrected] aunt making Lyster [corrected] his nephew by marriage. Having survived the yellow fever infection, young Lyster [corrected] had a lifelong immunity to the disease.     

Epidemiologic aspects of pediatric multiple trauma in a Spanish urban population

BACKGROUND/PURPOSE: Trauma is still the most frequent cause of mortality and disability in childhood and adolescence. An epidemiologic prospective study on children under 16 years of age with multiple trauma (MT) was conducted in a large Spanish urban university hospital over a 6-year period. METHODS: Of 1,937 children admitted at the pediatric trauma unit for musculoskeletal injuries from March 1988 until March 1994, 56 patients including 37 boys and 19 girls had MT. MT was considered when at least 2 long bones were fractured or there was a fracture of 1 long bone combined with an injury of 4 other major anatomic regions (face and neck, thorax, abdomen, or neural system). The severity of injuries was evaluated according to the modified injury severity score (MISS). RESULTS: Injury to pedestrians was the most frequent cause of MT (54%). The overall mortality rate of the series, including those children dying during transport to the hospital was 11.5%. The average MISS for the whole group was 15 (range, 5 to 59). Head trauma was the most frequent associated injury (52%), two thirds of which were considered minor injuries (Glasgow Coma Scale >15). Seventy-seven fractures were registered, 10% of which were open fractures. External fixation was the most common surgical technique among operated fractures. The average hospitalization period was 16 (median, 13; range, 1 to 150) days. Children with a MISS above 18 points showed a significant longer hospitalization period (mean, 31 +/- 45 days) as compared with those with MISS below 18 points (mean, 10 +/- 7 days; P < .05). There was a strong correlation between the MISS and both the period of hospitalization at the pediatric intensive care unit and the total length of hospital stay. CONCLUSIONS: Pedestrian accidents caused by motor vehicles in children playing at the street contributed most significantly to MT in the urban pediatric population. Special care for prevention must be taken in the age group of 6 to 10 years. Head injury was the main cause of death in children with multiple trauma. MISS was found to be a good predictor of survival and duration of hospital stay in pediatric MT.     

Modeling the Impact of PrEP Programs for Adolescent Sexual Minority Males Based on Empirical Estimates for the PrEP Continuum of Care

PurposePre-exposure prophylaxis (PrEP)—an effective and safe intervention to prevent HIV transmission—was recently approved by the Food and Drug Administration for use by adolescents. Informed by studies of sexual behavior and PrEP adherence, retention, and promotion, we model the potential impact of PrEP use among at-risk adolescent sexual minority males.MethodsWe simulate an HIV epidemic among men who have sex with men (MSM) aged 13–39. We assume adult MSM ages 19–39 have had PrEP available for 3 years with 20% coverage among eligible MSM based on the Centers for Disease Control and Prevention guidelines. PrEP interventions for ages 16–18 are then simulated using adherence and retention profiles drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies across a range of uptake parameters (10%–100%). Partnerships across age groups were modeled using parameterizations from the RADAR study. We compare the percent of incident infections averted (impact), person-years on PrEP per infection averted (efficiency), and changes in prevalence over 10 years.ResultsAs compared to no PrEP use, baseline PrEP adherence and retention among adolescent sexual minority males drawn from the ATN113 and Enhancing Preexposure Prophylaxis in Community studies averted from 2.8% to 41.0% of HIV infections depending on the fraction of eligible adolescent sexual minority males that initiated PrEP at their annual health-care visit. Improved adherence and retention achieved with an array of focused interventions from real-world settings increased the percent of infections averted by as much as 26%–70%.ConclusionsEmpirically demonstrated improvements in the PrEP continuum of care in response to existing interventions can substantially reduce incident HIV infections among adolescent sexual minority males.