Malformations in infants of very low birth weight

The incidence of lethal, serious and trivial malformations was determined in a consecutive series of 675 infants who weightd 1500 g or less (very low birth weight infants). All patients were born in one maternity hospital. Most of the 169 survivors were followed until at least five years of age. Of these children, 15 had a trivial malformation that either disappeared spontaneously or was corrected surgically. A further five children have a significant or serious residual defect. There were 506 perinatal and infant deaths and 51 of the babies who died had malformations confirmed at necropsy. In 30 of these, death was inevitable. There were 10 seriously malformed infants for whom survival was possible, but in six cases, the diagnosis was obvious at birth. The patients were treated between 1966 and 1970 when techniques of intensive care were evolving. Consequently, some of the infants who died would have survived with the treatment now available. Amongst the perinatal deaths in this report, only 2.0% had a serious malformation compatible with survival.     

A system of alias assignment for unidentified patients requiring emergency hospital admission

Many patients are admitted to emergency facilities without positive identification. In the past, these patients were usually assigned a temporary alias name (i.e., John Doe, Jane Doe) which was then changed after positive identification. We have discerned several problems with this procedure and have subsequently developed a coordinated system of alias identification in our hospital. This system allows for: a large pool of distinct alias identities, pre-assignment of hospital numbers to unidentified patients before arrival, and a smooth administrative transition as records are changed from the alias to the true identity.     

Idiopathic bilateral optic atrophy in the rhesus macaque

PURPOSE: To document the existence of idiopathic bilateral optic atrophy (BOA) in rhesus macaque monkeys and to characterize the structural and functional consequences of this condition. METHODS: In vivo assessment of retinal and optic nerve structure included fundus biomicroscopy and stereophotography. Functional analyses included transient pattern-reversal electroretinography (PERG) and full-field flash ERG, with both white flashes while dark adapted and red flashes on a blue background used to assess the photopic negative response (PhNR). Also measured were visual evoked cortical potentials (VEPs) and multifocal (mf)ERGs, with both a standard fast and slowed (7F) stimulation sequence. Post mortem histologic evaluation was performed on a subset of five animals with BOA and compared with data from 22 healthy normal animals. Blood tests, including vitamin E, B(12), folate, lead, and complete blood cell count with differential were obtained on the four animals that remained alive. RESULTS: Animals with BOA showed temporal pallor of the optic nerve head and thinning of the retinal nerve fiber layer (RNFL) between the temporal vascular arcades (i.e., of the papillomacular bundle). Severity of optic atrophy and RNFL loss varied between animals from mild to severe, but was similar in the two eyes of each animal. Functional changes included greater loss of the PERG N95, compared with the P50 component and substantial reduction of mfERG high-frequency components. The mfERG low-frequency components were slightly larger than normal. None of the full-field flash ERG amplitudes (a-wave, b-wave, oscillatory potentials, or PhNR) was significantly different from normal. There were no consistent abnormalities found in the results of any blood test. Histologic findings included axonal loss and gliosis limited to the temporal optic nerve, reduction of nuclei within the retinal ganglion cell layer, and thinning of the temporal retinal RNFL. CONCLUSIONS: The existence of BOA in nonhuman primates warrants caution on the part of investigators who use these animals in experimental models of ophthalmic disease.     

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine

The utility of plasmid DNA as an immunogen has been limited by its weak immunogenicity. In the present study, we evaluated the ability of a family of linear polyethylenimine (PEI) polymers, complexed to plasmid DNA, to augment DNA expression in vivo and to enhance antigen‐specific adaptive immune responses. We showed that four of five structurally different PEIs that we evaluated increased in vivo DNA expression 20‐ to 400‐fold, and enhanced DNA‐induced epitope‐specific CD8+ T‐cell responses 10‐ to 25‐fold in BALB/c and C57BL/6J mice respectively, when delivered intravenously. Functional studies of the PEI‐DNA‐induced CD8+ T‐cell responses demonstrated that formulation of DNA with PEI was associated with increased numbers of cells secreting type I cytokines. In addition, PEI‐DNA complexes improved antigen‐specific T_H1‐helper cell and humoral responses. Most importantly, the PEI‐DNA complexes elicited memory cellular responses, capable of rapid expansion and accelerated clearance of a lethal dose of recombinant Listeria monocytogenes. Lastly, we identified physical properties of PEI‐DNA complexes that are associated with enhanced DNA‐elicited immunogenicity. These findings demonstrate that PEI polymers can play an important role in the development of DNA‐based vaccines in the setting of infectious disease prevention and cancer therapy.