Respiratory syncytial virus infection in children with bronchopulmonary dysplasia

Little is known about the risk of severe illness from respiratory syncytial virus infection in children with bronchopulmonary dysplasia. A prospective study was done of the natural history of respiratory syncytial virus infection in 30 children less than 2 years of age with bronchopulmonary dysplasia who were in a home oxygen program. Surveillance to identify children with acute respiratory symptoms was done by weekly telephone interview. Symptomatic children were examined, oxygen saturation was determined by oximetry, and nasopharyngeal lavage fluid was collected for virus cultures and rapid respiratory syncytial virus antigen tests. During the 4-month study period (December to April), 27 children had one or more acute respiratory illnesses, and respiratory syncytial virus developed in 16/27 (59%). Passive smoking and greater than or equal to four members in the home increased the risk of symptomatic respiratory syncytial virus (P less than .01 and P less than .03, respectively). Of 16 children, 11 (69%) required hospitalization. Of the 11 hospitalized children with respiratory syncytial virus, nine were either still receiving oxygen at home or required oxygen therapy within the previous 3 months v none of five nonhospitalized children (P less than .005). Five of the hospitalized children were greater than 12 months of age and five had respiratory syncytial virus infection previously that had been confirmed by culture results. Hospitalizations were prolonged and complicated. Seven of 11 children were hospitalized for greater than 1 week; four were admitted to the intensive care unit; four were treated with ribavirin aerosol, and two needed mechanical ventilation. There were no deaths.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased frequency of dentate granule cells with basal dendrites in the hippocampal formation of schizophrenics

In the hippocampal formation of schizophrenics, the detailed morphology of Golgi-impregnated granule cells was examined. These granule cells of the dentate gyrus are interposed between the rostral entorhinal cortex and the hippocampus proper. In these limbic regions significant cytoarchitectural alterations in schizophrenics are reported, giving rise to the concept of a prenatal limbic maldevelopment in schizophrenia. Compared to controls, the frequency of dentate granule cells with basal dendrites was significantly increased in schizophrenics [43% (+/-3)] vs. [22% (+/-2) in the control group]. In epilepsy, dentate granule cells of epileptic patients also develop basal dendrites, which is explained as an adaptive process of plasticity. Similarly, the hippocampal alterations described in schizophrenics could be the sequela of primary entorhinal cytoarchitectural alterations. Since the increase in basal dendrites seems to reflect a process of continuous plasticity, suggesting an increased rate of postnatal granule cell generation, the synthesis of a prenatal limbic maldevelopment with an ongoing process of plasticity might, therefore, supersede the hypothesis of a neurodegeneration in schizophrenia.     

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.     

A prototype transduction tag system (delta LNGFR/NGF) for noninvasive clinical gene therapy monitoring

The dramatic expansion of clinical gene therapy trials requires the development of noninvasive clinical monitoring procedures, which provide information about expression levels, expression kinetics, and spatial distribution of transduced therapeutic genes. With the development of such procedures, invasive sampling of tissue probes from patients potentially could be reduced significantly. In this study, an experimental platform for the rational design and in vitro testing of suitable receptor-ligand couples as components of future transduction tag systems for noninvasive gene therapy monitoring applications was developed. Initially, the feasibility of the delta LNGFR/nerve growth factor (NGF) transduction tag system was investigated; this system employs a mutated version of the low-affinity nerve growth factor receptor (p75mut or delta LNGFR) lacking the entire cytoplasmic domain. Specific binding of 125I-radiolabeled NGF was demonstrated for two stable delta LNGFR-transduced cell lines, but not for delta LNGFR-negative parental control cell lines. An additional binding analysis performed in a MicroImager directly confirmed binding of radiolabeled ligands (125I-NGF, 125I-anti-p75 monoclonal antibody) to the p75mut expressed on intact target cells, but not on control cells. Subsequent binding studies employing NGF radiolabeled with the positron-emitting isotope 124I demonstrated a specific binding for LNGFR+ PC12 cells. Consequently, the first in vitro proof of a transduction tag approach based on the specificity of the 124I-NGF/LNGFR interaction was provided, which opens up the possibility for future noninvasive positron emission tomography monitoring in clinical gene therapy trials.     

Orbital trauma.

In this review, a number of current issues on the management of orbital trauma are discussed including the indications for orbital exploration in zygomatic complex fractures, the utility of transantral endoscopy in orbital trauma surgery, and preferred implant materials in orbital reconstruction. We emphasize the need for a classification system to define some of the clinical terms used in describing orbital trauma, to improve communication between clinical services, and to standardize the clinical literature on orbital trauma.