Safety of levocetirizine treatment in young atopic children: An 18-month study

There are more than 40 H(1)-antihistamines available worldwide. Most of these medications have never been optimally studied in prospective, randomized, double-masked, placebo-controlled trials in children. The aim was to perform a long-term study of levocetirizine safety in young atopic children. In the randomized, double-masked Early Prevention of Asthma in Atopic Children Study, 510 atopic children who were age 12-24 months at entry received either levocetirizine 0.125 mg/kg or placebo twice daily for 18 months. Safety was assessed by: reporting of adverse events, numbers of children discontinuing the study because of adverse events, height and body mass measurements, assessment of developmental milestones, and hematology and biochemistry tests. The population evaluated for safety consisted of 255 children given levocetirizine and 255 children given placebo. The treatment groups were similar demographically, and with regard to number of children with: one or more adverse events (levocetirizine, 96.9%; placebo, 95.7%); serious adverse events (levocetirizine, 12.2%; placebo, 14.5%); medication-attributed adverse events (levocetirizine, 5.1%; placebo, 6.3%); and adverse events that led to permanent discontinuation of study medication (levocetirizine, 2.0%; placebo, 1.2%). The most frequent adverse events related to: upper respiratory tract infections, transient gastroenteritis symptoms, or exacerbations of allergic diseases. There were no significant differences between the treatment groups in height, mass, attainment of developmental milestones, and hematology and biochemistry tests. The long-term safety of levocetirizine has been confirmed in young atopic children.     

The rate of heat storage mediates an anticipatory reduction in exercise intensity during cycling at a fixed rating of perceived exertion

The aim of the present study was to examine the regulation of exercise intensity in hot environments when exercise is performed at a predetermined, fixed subjective rating of perceived exertion (RPE). Eight cyclists performed cycling trials at 15°C (COOL), 25°C (NORM) and 35°C (HOT) (65% humidity throughout), during which they were instructed to cycle at a Borg rating of perceived exertion (RPE) of 16, increasing or decreasing their power output in order to maintain this RPE. Power output declined linearly in all three trials and the rate of decline was significantly higher in HOT than in NORM and COOL (2.35 ± 0.73 W min⁻¹, 1.63 ± 0.70 and 1.61 ± 0.80 W min⁻¹, respectively, P < 0.05). The rate of heat storage was significantly higher in HOT for the first 4 min of the trials only, as a result of increasing skin temperatures. Thereafter, no differences in heat storage were found between conditions. We conclude that the regulation of exercise intensity is controlled by an initial afferent feedback regarding the rate of heat storage, which is used to regulate exercise intensity and hence the rate of heat storage for the remainder of the anticipated exercise bout. This regulation maintains thermal homeostasis by reducing the exercise work rate and utilizing the subjective RPE specifically to ensure that excessive heat accumulation does not occur and cellular catastrophe is avoided.     

Site selection for fat autotransplantation: Some observations

The use of autologous fat for implantation has recently received renewed attention in the plastic surgery literature. Autologous fat reportedly has been used for the treatment of wrinkles and Romberg's disease, and for buttock and breast augmentation. While some measure of success has been achieved, many surgeons report that substantial resorption of fat tissue occurs at the site of implantation. There is lack of unanimity regarding the ideal site for extraction or injection in order to minimize fat resorption. Adipose tissue samples were taken from women undergoing surgical procedures on the abdomen, gluteal-femoral region, and breast. Facial adipose tissue samples from men and women were also analyzed. Adipocytes were isolated chemically and sized microscopically. Activity of the lipogenic enzyme adipose tissue lipoprotein lipase (ATLPL) was measured in frozen samples. Results suggest that femoral site samples are somewhat larger (NS) and have greater lipogenic activity (p<0.03) than other sites. In our study, small facial samples had very low or unmeasurable levels of ATLPL activity. Perhaps cell size and lipogenic activity should be considered when selecting tissues for autotransplantation.     

Noxious stimuli excite neurons in nucleus submedius of the normal and arthritic rat

Anatomical studies have revealed the existence of an ascending pathway originating in the spinal cord and medullary dorsal horn, relaying in nucleus submedius (Sm) in medial thalamus and terminating in ventrolateral orbital cortex. It has been suggested that this pathway may be involved in the transmission of nociceptive information. In the present study extracellular recordings were obtained from neurons in Sm of anesthetized arthritic and normal rats. Mechanical and thermal stimuli were delivered to various regions of the body to determine the types of somatic stimuli which could activate Sm neurons. Over 40% of the 146 neurons studied responded to somatic stimuli. In the normal rats only high intensity mechanical and thermal stimuli were effective in inducing responses. In the arthritic rats lower intensity mechanical stimuli, joint movements and high intensity thermal stimuli were effective. Such stimuli produce nociceptive reactions in the freely moving arthritic rat. Almost all the responses were excitatory and generally lasted the entire duration of the 15-s stimuli employed. In some cases after-discharges were present. The receptive fields of the neurons were in almost all cases large and bilateral. These findings support the hypothesis that Sm may be involved in mediating the affective-motivational aspects of pain.     

A recycling framework for the construction of Bonferroni‐based multiple tests

In this paper we describe Bonferroni‐based multiple testing procedures (MTPs) as strategies to split and recycle test mass. Here, ‘test mass’ refers to (parts of) the nominal level α at which the family‐wise error rate is controlled. Briefly, test mass is split between different null hypotheses, and whenever a null hypothesis is rejected, the part of α allocated to it may be recycled to the testing of other hypotheses. These recycling MTPs are closed testing procedures based on raw p‐values associated with testing the individual null hypotheses, and the class of such MTPs includes, for example, serial and parallel gatekeeping, fallback and Holm procedures. Graphical displays and a concise algebraic notation are provided for such MTPs. This recycling approach has pedagogical advantages and may facilitate the tailoring of MTPs for different purposes. Copyright © 2009 John Wiley & Sons, Ltd.     

Comparison of versions 1.0 AND 1.5 of the UltraSensitive AMPLICOR HIV-1 MONITOR test for subjects with low viral load

We compared the performance of two UltraSensitive AMPLICOR HIV-1 MONITOR kits (version 1.5 [v1.5] versus v1.0) by retesting 404 plasma samples with low viral loads (<3,000 copies/ml) with both kits. With 292 samples that initially had <50 copies/ml by the v1.0 kit, the v1.5 assay was more sensitive than the v1.0 assay for samples with human immunodeficiency virus type 1 RNA near the 50-copy/ml cutoff (P = 0.0146). Median numbers of copies per milliliter were similar for 112 samples with 50 to 3,000 copies/ml with no difference in sensitivity with a 200-copy/ml cutoff.     

Safety of cetirizine in infants 6 to 11 months of age: a randomized,double-blind,placebo-controlled study

BACKGROUND: H(1)-antihistamines are widely used for symptom relief in allergic disorders in infants and children; however, there are few prospective, randomized, double-blind, controlled studies of these medications in young children, and to date, no such studies have been conducted in infants. OBJECTIVE: This prospective, randomized, parallel-group, double-blind, placebo-controlled study was designed to evaluate the safety of the H(1)-antihistamine cetirizine, particularly with regard to central nervous system and cardiac effects, in infants age 6 to 11 months, inclusive. METHODS: Infants who met the entry criteria for age and had a history of treatment with an H(1)-antihistamine for an allergic or other disorder were randomized to receive 0.25 mg/kg cetirizine orally or matching placebo twice daily orally for 1 week. RESULTS: The mean daily dose in cetirizine-treated infants was 4.5 +/- 0.7 mg (SD). No differences in all-cause or treatment-related adverse events were observed between the cetirizine- and placebo-treated groups. A trend was observed toward fewer adverse events and sleep-related disturbances in the cetirizine group compared with the placebo group. No prolongation in the linear corrected QT interval was observed in cetirizine-treated infants compared with either baseline values or with values in placebo-treated infants. CONCLUSIONS: We have documented the safety of cetirizine in this short-term investigation, the first randomized, double-blind, placebo-controlled study of any H(1)-antihistamine in infants. Additional prospective, randomized, double-blind, placebo-controlled, long-term studies of cetirizine and other H(1)-antihistamines are needed in this population.