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.     

Antimicrobial use and outcomes in patients with multidrug-resistant and pansusceptible Salmonella Newport infections, 2002-2003

Multidrug-resistant Salmonella Newport with decreased susceptibility to ceftriaxone (MDR-AmpC) is becoming increasingly common in its food animal reservoirs and in humans. Few data exist on rates of antimicrobial use or differences in clinical outcomes in persons infected with MDR-AmpC or other Salmonella strains. We conducted a case-comparison analysis of data from a multistate population-based case-control study to identify antimicrobial treatment choices and differences in clinical outcomes in those infected with MDRAmpC compared to pansusceptible S. Newport. Of isolates from 215 laboratory-confirmed S. Newport cases, 54 (25%) were MDR-AmpC, 146 (68%) were pansusceptible, and 15 (7%) had other resistance patterns; 146 (68%) patients with S. Newport were treated with antimicrobial agents and 66 (33%) were hospitalized. Over two-thirds of cases at low-risk for serious complications received antimicrobial therapy, most commonly with fluoroquinolones, to which this strain was susceptible. There were no significant differences in symptoms, hospitalization, duration of illness, or other outcomes between the persons infected with MDR-AmpC and pansusceptible S. Newport. Although currently prevalent MDR-AmpC S. Newport strains remains susceptible to the antimicrobial most commonly prescribed for it, continued efforts to reduce unnecessary use of antimicrobial agents in food animals and humans are critical to prevent further development of resistance to quinolones and cephalosporins, which is likely to lead to substantial adverse outcomes.     

Calcium taste preference and sensitivity in humans. I. Gender comparisons

Calcium is an essential nutrient, particularly during growth and during reproduction, and the latter is probably why the avidity for calcium may be greater in females of some species. However, in humans, despite widespread belief in calcium appetite, it has not been studied experimentally. Here we compared the hedonic responses of 17 men and 24 women to test whether women show a greater avidity for calcium in line with its greater biological significance for them. We find no gender difference in the hedonic response to calcium, and no change with the menstrual cycle.     

The effect of automated landmark identification on morphometric analyses

Morphometric analysis of anatomical landmarks allows researchers to identify specific morphological differences between natural populations or experimental groups, but manually identifying landmarks is time‐consuming. We compare manually and automatically generated adult mouse skull landmarks and subsequent morphometric analyses to elucidate how switching from manual to automated landmarking will impact morphometric analysis results for large mouse (Mus musculus) samples (n = 1205) that represent a wide range of ‘normal’ phenotypic variation (62 genotypes). Other studies have suggested that the use of automated landmarking methods is feasible, but this study is the first to compare the utility of current automated approaches to manual landmarking for a large dataset that allows the quantification of intra‐ and inter‐strain variation. With this unique sample, we investigated how switching to a non‐linear image registration‐based automated landmarking method impacts estimated differences in genotype mean shape and shape variance‐covariance structure. In addition, we tested whether an initial registration of specimen images to genotype‐specific averages improves automatic landmark identification accuracy. Our results indicated that automated landmark placement was significantly different than manual landmark placement but that estimated skull shape covariation was correlated across methods. The addition of a preliminary genotype‐specific registration step as part of a two‐level procedure did not substantially improve on the accuracy of one‐level automatic landmark placement. The landmarks with the lowest automatic landmark accuracy are found in locations with poor image registration alignment. The most serious outliers within morphometric analysis of automated landmarks displayed instances of stochastic image registration error that are likely representative of errors common when applying image registration methods to micro‐computed tomography datasets that were initially collected with manual landmarking in mind. Additional efforts during specimen preparation and image acquisition can help reduce the number of registration errors and improve registration results. A reduction in skull shape variance estimates were noted for automated landmarking methods compared with manual landmarking. This partially reflects an underestimation of more extreme genotype shapes and loss of biological signal, but largely represents the fact that automated methods do not suffer from intra‐observer landmarking error. For appropriate samples and research questions, our image registration‐based automated landmarking method can eliminate the time required for manual landmarking and have a similar power to identify shape differences between inbred mouse genotypes.     

Sensorimotor integration in the primate superior colliculus. II. Coordinates of auditory signals

Based on the findings of the preceding paper, it is known that auditory and visual signals have been translated into common coordinates at the level of the superior colliculus (SC) and share a motor circuit involved in the generation of saccadic eye movements. It is not known, however, whether the translation of sensory signals into motor coordinates occurs prior to or within the SC. Nor is it known in what coordinates auditory signals observed in the SC are encoded. The present experiment tested two alternative hypotheses concerning the frame of reference of auditory signals found in the deeper layers of the SC. The hypothesis that auditory signals are encoded in head coordinates predicts that, with the head stationary, the response of auditory neurons will not be affected by variations in eye position but will be determined by the location of the sound source. The hypothesis that auditory responses encode the trajectory of the eye movement required to look to the target (motor error) predicts that the response of auditory cells will depend on both the position of the sound source and the position of the eyes in the orbit. Extracellular single-unit recordings were obtained from neurons in the SC while monkeys made delayed saccades to auditory or visual targets in a darkened room. The coordinates of auditory signals were studied by plotting auditory receptive fields while the animal fixated one of three targets placed 24 degrees apart along the horizontal plane. For 99 of 121 SC cells, the spatial location of the auditory receptive field was significantly altered by the position of the eyes in the orbit. In contrast, the responses of five sound-sensitive cells isolated in the inferior colliculus were not affected by variations in eye position. The possibility that systematic variations in the position of the pinnae associated with different fixation positions could account for these findings was controlled for by plotting auditory receptive fields while the pinnae were mechanically restrained. Under these conditions, the position of the eyes in the orbit still had a significant effect on the responsiveness of collicular neurons to auditory stimuli. The average magnitude of the shift of the auditory receptive field with changes in eye position (12.9 degrees) did not correspond to the magnitude of the shift in eye position (24 degrees). Alternative explanations for this finding were considered. One possibility is that, within the SC, there is a gradual transition from auditory signals in head coordinates to signals in motor error coordinates.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cardiac applications of EPR imaging

This review summarizes the development and application of a variety of EPR imaging modalities including spatial, spectral-spatial (spectroscopic), gated-imaging and oxygen mapping to cardiovascular studies. It has been hypothesized that free radical metabolism, oxygenation and nitric oxide generation in biological organs such as the heart may vary over the spatially defined tissue structure. We have developed instrumentation optimized for 3D spatial and 3D or 4D spectral-spatial imaging of free radicals at 1.2 GHz. Using this instrumentation high quality 3D spectral-spatial imaging of nitroxyl (nitroxide) metabolism was performed, as well as spatially localized measurements of oxygen concentrations, based on the oxygen-dependent line-broadening of the EPR spectrum. Both exogenously infused probes and endogenous radicals were used to obtain the images. It is demonstrated that the EPR imaging is a powerful tool which can provide unique information regarding the spatial localization of free radicals, oxygen and nitric oxide in biological organs and tissues.