Growth of native Hawaiian school children: I. Research design,stature, and weight measurements

A semilongitudinal survey of the growth of native Hawaiian school children, focused on the development of fatness, has been carried out on the Island of Hawaii. Four cohorts of children, first studied in grades one, four, seven, and ten, were measured annually for four years. Several factors, including percentage of Polynesian ancestry, identification with Hawaiian culture, socioeconomic status, dietary intake, and physical fitness, have been considered for their potential relationship to the development of fatness Data presented here indicate that native Hawaiian boys tend to be taller for their age than NHANES-II medians until age 14 years, but are not significantly taller than their non-Hawaiian classmates. Native Hawaiian boys and girls are heavier for their age than NHANES-II medians at most ages and are significantly heavier than non-Hawaiian classmates. Percentage of Polynesian ancestry is a significant predictor variable of both stature-for-age and weight-for-age among native Hawaiian children in the first and fourth grade cohorts. Study of fatness in a genetically heterogeneous Polynesian population that is relatively homogeneous in regard to modernization may yield insights into genetic contributions to the problem of obesity among Pacific Islanders.     

Natural killer cell activity in the rat. Analysis of effector cell morphology and effects of interferon on natural killer cell function in the athymic (nude) rat

Athymic (nude) rats were found to have increased levels of natural killer (NK) activity, 3? to 5?fold higher than in euthymic rats. Studies were performed to determine the nature of the NK cells in these animals and the basis for their increased cytotoxic reactivity. Large granular lymphocytes (LGL), which were previously shown to be the NK cells in euthymic rats, were increased 2- to 7-fold in the peripheral blood and spleen of nude rats. The LGL, enriched by centrifugation on discontinous Percoll density gradients, were shown to have augmented NK activity similar to that seen with LGL-enriched fractions from euthymic rats. These results indicate that the NK cells in euthymic and athymic rats are morphologically and functionally similar, and that the higher NK activity in nude rats appears to be mainly attributable to an increased proportion of effector cells. In a single-cell cytotoxicity assay, interferon pretreatment of LGL was shown to increase: (a) the percentage of LGL which form conjugates with target cells; (b) the percentage of conjugate-forming cells which kill; and (c) the kinetics of lysis. Different effects were seen depending on the target cell tested.     

Pharmacokinetic and experimental data on beta-lactam antibiotics in the treatment of patients

The in vitro and animal model studies on optimal dosage of the newer beta-lactams are summarized and put into historical perspective. They provide a rationale for dosage schedules that continuously maintain inhibitory serum and tissue concentrations throughout the dosage interval. In vitro studies on the post-antibiotic effect (PAE) with beta-lactams revealed only short time periods of post-antibiotic growth suppression with gram-positive cocci and no post-antibiotic effect with gram-negative bacilli. A smilar lack of persistent growth suppression was observed with beta-lactams in a neutropenic mouse thigh infection model for both gram-positive and gram-negative bacteria. In the same animal model, dosing regimens of beta-lactams which continuously provided serum concentrations above the MIC were more efficacious than those that did not. The newer third-generation cephalosporins have prolonged half-lives and can maintain serum levels above the MIC for most pathogens, even when dosed at widely spaced intervals.     

Intermale aggression and infanticide in aged C57BL/6J male mice: Behavioral deficits are not related to serum testosterone (T) levels and are not recovered by supplemental T

Healthy aged adul (24–26 months of age) and young adult (2–4 months of age) C57BL/6J male mice were assessed for intermale aggression, pup-killing behavior (infanticide), and circulating levels of testosterone (T). When compared to young adult male mice, aged adult males were highly variable in the exhibition of both androgen-dependent behaviors. Significant numbers of aged males exhibited deficits in aggression and pup-killing while other animals were as behaviorally active as their young male counterparts. Assessment of serum T showed that aging did not produce a reduction in levels of the steroid and individual variability in androgen-dependent behavior of aged males was not related to plasma levels of the hormone. When aged non-aggressive and non-killer males were exposed to supplemental T by way of subcutaneously implanted silastic capsules, circulating levels of the steroid were elevated but T-dependent behavior was not recovered. These findings, in combination with those previously reported for copulatory behavior, indicate that the deficits observed in the androgen-dependent behavior of aged male mice cannot be attributed to a breakdown in the production of testicular androgens. While neural refractoriness to T may account in part for deficits in androgen-dependent behavior of aged males, the variability that is observed in the reproductive behaviors of aged male rodents ultimately may be related to other sources of variation such as perinatal environment.     

Central command and the cutaneous vascular response to isometric exercise in heated humans

Cutaneous vascular conductance (CVC) decreases during isometric handgrip exercise in heat stressed individuals, and we hypothesized that central command is involved in this response. Seven subjects performed 2 min of isometric handgrip exercise (35% of maximal voluntary contraction) followed by postexercise ischaemia in normothermia and during heat stress (increase in internal temperature ∼1°C). To augment the contribution of central command independent of force generation, on a separate day the protocol was repeated following partial neuromuscular blockade (PNB; i.v. cisatracurium). Forearm skin blood flow was measured by laser-Doppler flowmetry, and CVC was the ratio of skin blood flow to mean arterial pressure. The PNB attenuated force production despite encouragement to attain the same workload. During the heat stress trials, isometric exercise decreased CVC by ∼12% for both conditions, but did not change CVC in either of the normothermic trials. During isometric exercise in the heat, the increase in mean arterial pressure (MAP) was greater during the control trial relative to the PNB trial (31.0 ± 9.8 versus 18.6 ± 6.4 mmHg, P < 0.01), while the elevation of heart rate tended to be lower (19.4 ± 10.4 versus 27.4 ± 8.1 b.p.m., P = 0.15). During postexercise ischaemia, CVC and MAP returned to pre-exercise levels in the PNB trial but remained reduced in the control trial. These findings suggest that central command, as well as muscle metabo-sensitive afferent stimulation, contributes to forearm cutaneous vascular responses in heat stressed humans.     

Neural responses to free field and virtual acoustic stimulation in the inferior colliculus of the guinea pig

Virtual auditory space (VAS) stimuli based on outer ear transfer functions became increasingly important in spatial hearing research. However, few studies have investigated the match between responses of auditory neurons to VAS and free-field (FF) stimulation. This study validates acoustic spatial receptive fields (SRFs) of 183 individual midbrain units using both VAS and FF stimuli. The first-spike latency, which varied systematically across SRFs, was 14.9 +/- 8.3 (SD) ms in FF, and 15.1 +/- 8.3 ms in VAS. Spike-count-based SRFs measured 0-20 dB above the neural threshold covered on average 44.5 +/- 18.0% of the recorded sphere in FF and 45.5 +/- 18.7% in VAS. The average deviation of the centroid position of SRFs using FF and VAS stimuli was 7.4 degrees azimuth and 3.3 degrees elevation. The average spike rate remained unchanged. The SRF overlap recorded using FF and VAS stimuli (mean: 71.3 +/- 12.6%) or repeated FF stimuli (70.2 +/- 14.2%) was high and strongly correlated (r = 0.96; P < 0.05). The SRF match observed with FF and VAS stimuli was not significantly altered over a range of stimulus levels (paired t-test P = 0.51; n = 6). Randomized VAS barely affected SRF sizes, centroids, or maximum spike count but decreased the average minimum response to 59% compared with sequential stimulation (paired t-test; P = 0.05; n = 26). SRF recordings in VAS excluding the acoustic distortions of the recording equipment differed from those in VAS incorporating the equipment (paired t-test P = 0.01; n = 5). In conclusion, neurophysiological recordings demonstrate that individualized VAS stimuli provided a good simulation of a FF environment.     

Asthma and the diver

Self-contained underwater breathing apparatus (scuba) diving has grown in popularity, with nearly 9 million sport divers in the United States alone. Approximately 7% of the population has been diagnosed with asthma, which is similar to the percentage of divers admitting they have asthma. Numerous concerns exist regarding subjects with asthma who choose to participate in recreational diving. Among these concerns are pulmonary barotrauma, pneumomediastinum, pneumothorax, arterial gas embolism, ear barotrauma, sinus barotrauma, and dental barotrauma. Despite these concerns, a paucity of information exists linking asthma to increased risk of diving complications. However, it has long been the norm to discourage individuals with asthma from participating in recreational scuba diving. This article examines the currently available literature to allow for a more informed decision regarding the possible risks associated with diving and asthma. It examines the underlying physiological principles associated with diving, including Henry’s law and Boyle’s law, to provide a more intimate understanding on physiological changes occurring in the respiratory system under compressive stress. Finally, this article offers a framework for guiding the patient with asthma who is interested in scuba diving. Under the right circumstances, the patient with asthma can safely participate in recreational diving without apparent increased risk of an asthma-related event.     

The serotonin transporter gene as a QTL for ADHD.

Molecular studies of attention deficit hyperactivity disorder (ADHD) have identified susceptibility genes for the categorically diagnosed disorder using operational diagnostic criteria. Here, we take a QTL approach to mapping genes for ADHD using a composite continuous index of ADHD behavior in a large epidemiological sample. Previous studies of clinical ADHD suggest that two functional polymorphisms in the serotonin transporter gene (SLC6A4), one in the 5'-regulatory region of the gene (5-HTTLPR) and the other a VNTR (5-HTTVNTR) in the second intron, as well as a single nucleotide polymorphism in the 3'-untranslated region (3'-UTR SNP), may be associated with the disorder. Here, we investigate these polymorphisms as well as an additional ten SNPs spread across the gene. We found significant association with the long (L) allele of the 5-HTTLPR; P = 0.019, but neither the 5-HTTVNTR nor the 3'-UTR SNP were significantly associated. Significant associations (P < 0.05) were found for a further 5 the 10 other markers tested. We found evidence for two haplotype blocks spanning the region. We found strong evidence for association with the first haplotype block (comprised of four markers), with the significance of a combined primary and secondary test of association reaching an empirical P value = 0.0054 for the global test and an empirical P value = 0.00081 for the largest local test. Thus, we show here that SLC6A4, which has a major influence on brain serotonin availability, may be a QTL for ADHD.     

How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?

Therapy for rhinitis improves sleep quality and symptoms of daytime sleepiness. This improvement with therapy may be secondary to anti-inflammatory effects, leading to a reduction of inflammatory mediators, or to a mechanical reduction of congestion directly leading to improvement in sleep disturbance. We combined our data from 3 placebo-controlled studies of intranasal corticosteroids in patients with perennial rhinitis to determine whether a correlation between the reduction of congestion and improved sleep and daytime somnolence existed. The pooled data of budesonide, flunisolide, and fluticasone demonstrated significantly decreased nasal congestion, sleep problems, and sleepiness in treated patients. The data demonstrated a correlation between a reduction in nasal congestion and an improvement of sleep (P < .01) and daytime somnolence (P = .01). Thus, topical intranasal corticosteroids should be used to decrease nasal congestion and to improve sleep and daytime somnolence in patients manifesting these symptoms.     

Excitatory effects of serotonin on rat striatal cholinergic interneurones

We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 μ m ) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 ± 193% of control. Selective agonists of 5-HT_1A, 5-HT₃, 5-HT₄ and 5-HT₇ receptors did not affect cholinergic interneurone firing, while the 5-HT₂ receptor agonist α-methyl-5-HT (30 μ m ) mimicked the excitatory effects of serotonin. Consistently, the 5-HT₂ receptor antagonist ketanserin (10 μ m ) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT₂ receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents.