Adrenarche and the evolution of human life history.

Adrenarche, the prepubertal onset of adrenal production of dehydroepiandrosterone sulfate (DHEAS), is a distinctive aspect of the human life course. Yet its evolutionary origins remain unexplained. Production of DHEAS is associated with the development of the zona reticularis, a novel histological layer within the adrenal gland, derived from the fetal adrenal gland, and associated with primates more generally. Evidence that DHEAS is a neurosteroid, together with the fact that increases in DHEAS parallel patterns of cortical maturation from approximately age 6 years to the mid-20s, suggests that DHEAS may play an important role in extended brain maturation among humans. DHEAS has demonstrated effects on mood in humans, and acts at neuron receptor sites. I suggest three ways in which DHEAS may play a role in human brain maturation: 1) increasing activity of the amgydala; 2) increasing activity of the hippocampus; and 3) promoting synaptogenesis within the cortex. I propose that associated changes in fearfulness and anxiety, and memory, could act to increase social interaction with nonfamiliar individuals and shape cognitive development. Comparison with the African apes suggests that the timing of adrenarche in chimpanzees may be similar to that in humans, though the full course of age-related changes in DHEAS and their relationship to reproductive and brain maturation are not clear. The role of DHEAS as a physiological mechanism supporting increased brain development, extended life span, and decreased sexual dimorphism is most compatible with Kaplan et al.'s (2000) theory of the evolution of human life history and intergenerational transfers.     

Pycnogenol® as an Adjunct in the Management of Childhood Asthma

A randomized, placebo-controlled, double-blind study involving 60 subjects, aged 6-18 years old, was conducted over a period of 3 months to determine the effect of Pycnogenol® (a proprietary mixture of water-soluble bioflavonoids extracted from French maritime pine) on mild-to-moderate asthma. After baseline evaluation, subjects were randomized into two groups to receive either Pycnogenol® or placebo. Subjects were instructed to record their peak expiratory flow with an Assess® Peak Flow Meter each evening. At the same time, symptoms, daily use of rescue inhalers (albuterol), and any changes in oral medications were also recorded. Urine samples were obtained from the subjects at the end of the run-in period, and at 1-, 2-, and 3-month visits. Urinary leukotriene C₄/D₄/E₄ was measured by an enzyme immunoassay. Compared with subjects taking placebo, the group who took Pycnogenol® had significantly more improvement in pulmonary functions and asthma symptoms. The Pycnogenol® group was able to reduce or discontinue their use of rescue inhalers more often than the placebo group. There was also a significant reduction of urinary leukotrienes in the Pycnogenol® group. The results of this study demonstrate the efficacy of Pycnogenol® as an adjunct in the management of mild-to-moderate childhood asthma.     

Compulsive respiratory stereotypies in children with autistic features: Polygraphic recording and treatment with fenfluramine

Syncopes due to compulsive respiratory stereotypies were studied in eight patients with autistic features. Most had been referred for episodes thought to be intractable epileptic seizures. Polygraphic recording showed two types of syncope, one induced by prolonged apnea and the other by a prolonged Valsalva maneuver. Fenfluramine, 1.5–3 mg/kg per day, was given in an open trial. In four of five cases with frequent Valsalva maneuvers, respiratory stereotypies and syncopes were suppressed for 2–18 months. Patients with periodic apneas were more severely retarded and had less clear benefit. Side effects consisted of dose-dependent sedation and mild weight loss which stabilized without interrupting treatment. We suggest that these syncopes are volitional and may be associated with pleasant sensations. A double-blind placebo-controlled trial of fenfluramine seems warranted in such patients.     

Detection of wheat gliadin contamination of gluten-free foods by a monoclonal antibody dot immunobinding assay

Unfractionated wheat gliadin was used to produce murine monoclonal antibodies to gliadin. A dot immunobinding assay, using these antibodies, was developed to detect possible gliadin contamination of nominally gluten-free flour, using dilute ethanol extracts spotted onto nitrocellulose membranes. The sensitivity of the assay was less than 10 micrograms/ml of unfractionated gliadin which permitted the detection of trace amounts of gliadin present in certain wheat starch based 'gluten-free' products. The assay detected not only wheat gliadin, but also prolamine extracts of rye, barley and oats; maize, soya and potato extracts as well as the control proteins casein and ovalbumin, gave negative results. The assay is of value as a simple and rapid method of screening foods for their suitability for consumption by patients with coeliac disease.     

Herpes zoster ophthalmicus with delayed cerebral infarction and meningoencephalitis

Herpes zoster ophthalmicus can be complicated by a delayed ipsilateral cerebral angiitis which may cause infarction and a smoldering meningoencephalitis. We describe such a case treated successfully with steroids and acyclovir. It is important to consider the diagnosis of this disorder early since therapeutic intervention may prevent an otherwise high morbidity and mortality. Steroids may have to be continued for some time after clinical resolution, using the ESR as a guideline for decreasing dosages.     

Quinine potently blocks single K+ channels activated by dopamine D-2 receptors in rat corpus striatum neurons

In single channel recordings from acutely dissociated neurons of the rat corpus striatum, a membrane K+ channel which is activated by dopamine D-2 receptors was blocked by nanomolar concentrations of quinine. An intermittent partial blockade was observed at 4-10 nM quinine, with a voltage dependence consistent with quinine binding to the channel near the extracellular surface of the membrane. A nearly complete blockade of channel current was observed at 100 nM quinine and above. Such concentrations are known to be too low to block various other ion channels, and may be attained in human brain at antimalarial dosages of quinine. Blockade of this channel by quinine may provide a useful experimental probe of dopaminergic function, as an alternative to D-2 receptor binding site blockade by neuroleptics.