Association between Latex Sensitization and Repeated Latex Exposure in Children

Background: Children with spina bifida are at greater risk for latex and ethylene oxide sensitization. The authors' aim in this study was to evaluate the role of previous surgical procedures in the development of sensitization to latex and ethylene oxide.

Methods: The authors investigated 80 children 1-16 yr old, separated into 3 groups. Two groups had a history of 3 or more general anesthetics: 29 children had spina bifida (spina bifida group) and 31 had undergone multiple surgeries for another disease (multiple surgeries group). A control group of 20 children had undergone less than 1 anesthetic. Clinical manifestations with latex, perioperative anaphylactic reactions, and number of previous anesthetics were recorded. Skin prick tests with a commercial extract of latex, four common inhalant allergens, and radioallergosorbent test to latex and ethylene oxide were performed.

Results: The three groups did not differ significantly with respect to age, sex, and atopic status. Mean number of anesthetics was comparable in the spina bifida and the multiple surgeries group. Latex sensitization was common in the spina bifida group (59%) and in the multiple surgeries group (55%) but not in the control group (0%, P < 0.05). Ethylene oxide sensitization was significantly more frequent in the spina bifida group than in the multiple surgeries group (44% vs. 19%; P = 0.052) and strongly associated with latex sensitization. Mean number of previous anesthetics was greater in children sensitized to latex (8.4 vs. 3.9; P < 0.05).     

Polymerization of 1,3-dienes with methylaluminoxanetriacetylacetonatovanadium

Various 1,3-dienes (1,3-butadiene, isoprene, 2-ethyl-1,3-butadiene, (E)- and (Z)-1,3-pentadiene, (E)-2-methyl-1,3-pentadiene) were polymerized with the soluble catalyst system methylaluminoxane/V (acac)₃ (acac: acetylacetonato). Butadiene and (Z)-1,3-pentadiene gave trans-1,4 polymers, at low and room temperature. Isoprene, 2-ethyl-1,3-butadiene and (E)-2-methyl-1,3-pentadiene gave trans-1,4-polymers at low temperature (< ?20°C), but polymers of mixed cis/trans structure at room temperature. (E)-1,3-pentadiene gave polymers of mixed 1,2/trans-1,4 structure either at low or room temperature. An interpretation of the results is reported.     

Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models

The optimization of the dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-one R(2) and R(12) positions led to the identification of the first MLK1 and MLK3 subtype-selective inhibitors within the MLK family. Compounds 14 (CEP-5104) and 16 (CEP-6331) displayed good potency for MLK1 and MLK3 inhibition with a greater than 30- to 100-fold selectivity for related family members MLK2 and DLK. Compounds 14 and 16 were orally active in vivo in a mouse MPTP biochemical efficacy model that was comparable to the first-generation pan-MLK inhibitor 1 (CEP-1347). The MLK1 structure-activity relationships were supported by the first-reported X-ray crystal structure of MLK1 bound with 16.     

Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase

Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib. Through a series of targeted modifications on an ALK inhibitor diaminopyrimidine scaffold, our research group has driven improvements in ALK potency, kinase selectivity, and overall pharmaceutical properties. Optimization of this scaffold has led to the identification of a potent and efficacious inhibitor of ALK, 25b. A striking feature of 25b over previously described ALK inhibitors is its >600-fold selectivity over insulin receptor (IR), a closely related kinase family member. Most importantly, 25b exhibited dose proportional escalation in rat compared to compound 3 which suffered dose limiting absorption preventing further advancement. Compound 25b exhibited significant in vivo antitumor efficacy when dosed orally in an ALK-positive ALCL tumor xenograft model in SCID mice, warranting further assessment in advanced preclinical models.     

Modeling new neuron function: a history of using computational neuroscience to study adult neurogenesis

Adult neurogenesis is a sophisticated biological process whose function has remained a mystery to neuroscience researchers. To address this question, a number of unique modeling studies have explored the computational implications of adding new neurons to the adult dentate gyrus. Models of neurogenesis fall into two broad categories: abstract models that explore the function of new neurons in simple networks, and biologically based models that investigate the role of new neurons in networks based on the anatomy of the hippocampus. In this review, we summarize the strategies and results of these different modeling approaches, and we discuss their conclusions and limitations in the face of new biological findings.     

Refinement in the technique of perihepatic packing: a safe and effective surgical hemostasis and multidisciplinary approach can improve the outcome in severe liver trauma

Background

Since 2005, we refined the technique of perihepatic packing including complete mobilization of the right lobe and packing around the posterior paracaval surface, lateral right side, and anterior and posteroinferior surfaces.

Methods

Two groups of patients with grade IV/V liver trauma underwent perihepatic packing before and after 2005. The study group included 12 patients treated with the new technique. The control group included 23 patients treated with the old technique.

Results

All 13 patients except one who died within 24 hours were treated with the old technique. The overall survival rate was 75% in the patients treated with the new technique (vs 30.4%, P < .02); the liver-related mortality was 8.3% versus 34.8% (P = not significant). The mean survival time in the intensive care unit was longer in the latest group (39.4 vs 22.3 days, P = not significant). The incidence of rebleeding requiring repacking was 16.7% in the patients who underwent new packing versus 45.5% in the patient who were treated with the old technique (P = not significant). The overall (81.8% vs 100%, P = not significant) and liver-related morbidity rate (18.2% vs 41.7%, P = not significant) and the incidence of abdominal sepsis (9.1% vs 41.7%, P = not significant) decreased.

Conclusions

Our refined technique of perihepatic packing seems to be safe and effective.     

Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation

Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1beta and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.