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.     

Conformational changes and development of proteinase K resistance in surface-immobilized PrP

The prion protein, and an increasing number of other cellular proteins, can undergo conformational transitions leading to soluble oligomers and insoluble aggregates. We have previously shown that the transition of the prion protein from its native form to its infectious (PrP^Sc) conformation can be monitored with epitope specific antibodies while the protein is immobilized on the surface of a Biacore surface plasmon resonance sensor chip. (Leclerc et al EMBO J 20:1547–1554 2001). The folding pathways leading to insoluble aggregates (amyloids) and soluble oligomers are believed to be distinct. We report here the use of epitope-specific antibody Fab fragments and surface plasmon resonance measurements on immobilized PrP to investigate the conditions leading to either folding pathway. We found that full-length SHaPrP(29-231) and truncated SHaPrP(90-231) prion protein can be induced to undergo the transition to proteinase K-resistant PrP^Sc aggregates on a sensor chip. This transition is temperature and buffer dependent and can be blocked by the presence of antibody Fab fragments binding to epitopes important for the conformational change. We demonstrate that the use of monoclonal antibodies combined with surface plasmon resonance technology is suitable to monitor the environmental conditions leading to conformational changes in the prion protein. The methodology is applicable to other amyloid- and oligomer-forming proteins and should be useful for the evaluation of antibodies or small molecules preventing protein misfolding.     

Caesarean section at term: the relationship between neonatal respiratory morbidity and microviscosity in amniotic fluid

Objectives

The incidence of neonatal respiratory morbidity following an elective caesarean section is 2–3 times higher than after a vaginal delivery. The microviscosity of surfactant phospholipids, as measured with fluorescence polarisation, is linked with the functional characteristics of fetal surfactant and thus fetal lung maturity, but so far this point has received little attention in new-borns at term. The aim of the study is to evaluate the correlation between neonatal respiratory morbidity and amniotic microviscosity (Fluorescence Polarisation Index) in women undergoing caesarean section after 37 weeks’ gestation.

Study design

The files of 136 women who had undergone amniotic microviscosity studies during elective caesarean deliveries at term were anonymised. Amniotic fluid immaturity (AFI) was defined as a Fluorescence Polarisation Index higher than 0.335.

Results

Respiratory morbidity was observed in 10 babies (7.3%) and was independently associated with AFI (OR: 6.11 [95% CI, 1.20–31.1] with p = 0.029) and maternal body mass index (OR: 1.12 [95% CI, 1.02–1.22] with p = 0.019). Gestational age at the time of caesarean delivery was inversely associated with AFI (odds ratio, 0.46 [95% confidence interval, 0.29–0.71], p < 0.001), especially before 39 weeks, and female gender was associated with an increased risk (odds ratio, 3.29 [95% confidence interval, 1.48–7.31], p = 0.004).

Conclusions

AFI assessed by amniotic microviscosity was significantly associated with respiratory morbidity and independently correlated with shorter gestational age especially before 39 weeks. This finding provides a physiological rationale for recommending delaying elective caesarean section delivery until 39 weeks of gestation to decrease the risk for respiratory morbidity.     

Comparative Analysis of Bupivacaine and Ropivacaine for Infiltration Analgesia for Bilateral Breast Surgery

Local anesthesia infiltration has been established as a preferred method of perioperative analgesia in many cosmetic operations. In an attempt to maximize the risk-benefit ratio of local anesthesia, a study was conducted to compare efficacy of two local anaesthetic agents. Bupivacaine was compared to ropivacaine in a bilaterally symmetrical breast surgery model. A local anaesthetic solution containing either bupivacaine or ropivacaine was infiltrated into each of the breasts of 15 patients undergoing either breast augmentation or breast reduction. Both surgeon and patient were blinded to the nature of local anaesthetic agent injected. Patients were requested to score their pain at 1, 2, 6, and 10 hours after surgery on a visual analog scale. The results were analyzed statistically using a cross-sectional time-series regression model employing the random effects option of the xtreg command from Strata Release 6 statistical software. We found that overall analgesia achieved with bupivacaine and ropivacaine infiltrations was not statistically different. The use of a higher dose of ropivacaine is likely to have removed the clinical advantage noted for the bupivacaine group. There was, however, a statistical and clinical difference in the efficacy of local anaesthetic infiltration of both agents in breast augmentation patients as compared to breast reduction patients, local anaesthetic being less effective in patients who had submuscular breast augmentation than in patients who had breast reduction. In view of these findings, it appears reasonable to recommend the use of ropivacaine in high-dose infiltration breast analgesia, as it is reported to be less cardiotoxic than bupivacaine. Serious attention needs also to be given to the adequacy of field infiltration of local anesthesia in submuscular breast augmentation.     

Pregnancy impact on uterosacral ligament and pelvic muscles using a 3D numerical and finite element model: preliminary results

Introduction and hypothesis

We studied the geometry of and changes in structures that play an important role in stabilizing the pelvic system during pregnancy using a numerical system at different gestational ages and postpartum.

Methods

We developed a parturient numerical model to assess pelvic structures at different gestational stages (16, 32, and 38 weeks) and postpartum (2 months and 1 year) using magnetic resonance imaging (MRI). Organs, muscles, and ligaments were segmented to generate a 3D model of the pelvis. We studied changes in the length of uterosacral ligaments (USL) and thickness of the puborectal portion of the levator ani muscle (LAM) during and after pregnancy. We used this model to perform finite element (FE) simulation and analyze deformations of these structures under stress from the increase in uterine weight.

Results

Analysis reveals an increase in the length of US ligaments at 16, 32, and 38 weeks. Two months after delivery, it decreases without returning to the length at 16 weeks of pregnancy. Similar changes were observed for the puborectal portion of the LAM. Variations observed in these structures are not equivalent to other anatomical structures of pelvic suspension. FE simulation with increased uterus weight does not lead to those findings.

Conclusion

This analysis brings new elements and a new focus for discussion relating to changes in pelvic balance of parturient women that are not simply linked to the increase in uterine volume.

     

Predictors of positive sentinel lymph node in thin melanoma

Background

The treatment of thin melanoma (Breslow thickness <1.0 mm) may include sentinel lymph node (SLN) biopsy (SLNB). The validity of SLNB for thin melanoma remains widely debated. The purpose of this study was to elucidate pathologic factors that are predictive of SLN positivity.

Methods

A retrospective analysis of a prospective database revealed 1,199 patients diagnosed with primary cutaneous melanoma. Multiple logistic regression was used to determine an association between pathologic factors and SLN positivity.

Results

Thin melanomas were identified in 469 patients (39%). Of these, 147 patients (31%) underwent SLNB. Positive SLNs were found in 16 patients (11%). Multiple logistic regression demonstrated that both ulceration (odds ratio, 5.27; P = .047) and thickness (odds ratio, 46.69; P = .022) were associated with SLN positivity.

Conclusions

Patients with thin melanomas >.75 mm and/or ulceration should be considered for SLNB.     

The combination of topiramate and diazepam is partially neuroprotective in the hippocampus but not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy

Lithium-pilocarpine induces status epilepticus (SE), leading to extensive damage and spontaneous recurrent seizures (SRS). Neuroprotective and antiepileptogenic effects of topiramate (TPM) associated with diazepam (DZP) were investigated in this model. SE was induced by LiCl and pilocarpine. TPM (10, 30 or 60 mg/kg) was injected at the onset of SE and 10h later and DZP (2.5 and 1.25mg/kg) at 2 and 10h after SE. TPM treatment was continued twice daily for 6 days. Other rats received two injections of DZP on the day of SE. Cell counting was performed on thionine-stained sections 14 days after SE and after 2 months of epilepsy. Occurrence and frequency of SRS were video-recorded. The MRI T2-weighted signal was quantified in hippocampus and ventral cortices. DZP-TPM treatment induced partial neuroprotection in CA1 and hilus, and tended to increase the percentage of rats with protected neurons in layer III/IV of the ventral entorhinal cortex. The latency to and frequency of SRS were not modified by DZP-TPM. T2-weighted signal was decreased in hippocampus 3 days after SE at all TPM doses and in ventral hippocampus after epilepsy onset. In conclusion, although DZP-TPM treatment was able to partially protect two areas critical for epileptogenesis, the hippocampus and ventral entorhinal cortex, it was not sufficient to prevent epileptogenesis.     

Correction to: Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents with Autism Spectrum Disorder: Design of Two Phase III Studies (SIGN Trials)

Journal of Autism and Developmental Disorders - The author of the article would like to add a video abstract as a supplementary material for a published article. The supplementary file is published...     

Metabolic activity in the brain of juvenile and adult rats with a neonatal ventral hippocampal lesion

Longitudinal studies on patients for schizophrenia suggest that functional brain perturbations precede the onset of symptoms. Rats with a neonatal ventral hippocampal lesion (NVHL) are considered as a heuristic neurodevelopmental model of schizophrenia. We characterized basal metabolic changes observed in NVHL rats before and after the age when known behavioral alterations have been reported. Male pups were lesioned with ibotenic acid at postnatal day 7 (PD7). We measured local cerebral metabolic rates for glucose (LCMRglc) by the quantitative autoradiographic [¹⁴C]2‐deoxyglucose technique at pre‐ (PD21) and postpubertal (PD42) ages when NVHL rats do not express abnormal dopamine related behaviors, and at adulthood (PD70). We observed a widespread increase in LCMRglcs in PD21 NVHL indicative of an ongoing intense reorganization of the brain while at PD42, increases were less extended. At PD70, changes in glucose metabolism were restricted to specific systems, such as the auditory system, the cerebellum, the serotonergic median raphe, and median septum. These data show in a heuristic animal model of schizophrenia that functional metabolic changes within the brain could precede the onset of dopamine‐related behavioral alterations and lead to a distinct ensemble of functional changes in adulthood in systems that may be relevant to schizophrenia. © 2009 Wiley‐Liss, Inc.