Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma is the most common fetal neoplasm, with an incidence of 1 in 40,000 births. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality. We identified nine fetuses with sacrococcygeal teratomas that were diagnosed antenatally and managed at the University of North Carolina Hospitals over a 7-year period. We retrospectively reviewed the charts of mothers and infants and recorded data concerning perinatal and surgical management. Six infants survived the neonatal period. All infants diagnosed after 20 weeks' gestation survived. Fetal hydrops developed in three fetuses, all of whom died. Inadequate ventilation secondary to prematurity was a contributing factor in each lethal case. Diagnosis at an early gestational age, development of fetal hydrops, and premature delivery predicted a poor prognosis. When possible, we recommend that delivery be delayed to allow for fetal development. Stabilization of the infant should be attempted before resection of the teratoma.     

Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma is the most common fetal neoplasm, with an incidence of 1 in 40,000 births. Fetuses with this malformation are at risk for significant perinatal morbidity and mortality. We identified nine fetuses with sacrococcygeal teratomas that were diagnosed antenatally and managed at the University of North Carolina Hospitals over a 7-year period. We retrospectively reviewed the charts of mothers and infants and recorded data concerning perinatal and surgical management. Six infants survived the neonatal period. All infants diagnosed after 20 weeks' gestation survived. Fetal hydrops developed in three fetuses, all of whom died. Inadequate ventilation secondary to prematurity was a contributing factor in each lethal case. Diagnosis at an early gestational age, development of fetal hydrops, and premature delivery predicted a poor prognosis. When possible, we recommend that delivery be delayed to allow for fetal development. Stabilization of the infant should be attempted before resection of the teratoma.     

Inhibition of angiogenesis by blocking activation of the vascular endothelial growth factor receptor 2 leads to decreased growth of neurogenic sarcomas.

Neurogenic sarcomas are incurable, common malignant human peripheral nerve tumors subject to local recurrence and systemic metastasis. In this study, the vascularity, vascular endothelial growth factor (VEGF) expression, and effects of inhibiting VEGF receptor on growth of neurogenic sarcomas were examined. Vascularization and VEGF expression were 6.4- and 15-fold higher in tumors than in normal nerves. The small molecule inhibitor (SU5416) of VEGF receptor 2 had no effect on neurogenic sarcoma cell lines in vitro, but the growth of a human tumor explant xenograft model was reduced by 54.8% compared to vehicle. Reduction in tumor growth was due to decreased tumor angiogenesis, leading to reduction of tumor cell proliferation and increased apoptosis. Inhibiting VEGF function may therefore be a useful adjuvant therapy for neurogenic sarcomas.     

Horizontal cell glutamate receptor modulation by NO: mechanisms and functional implications for the first visual synapse.

Neurons of the horizontal cell retinal neural network are subject to modulation by the neurotransmitter nitric oxide (NO). We have examined the effects of NO on glutamate receptor function in isolated horizontal cells from the perch (Perca fluviatilis) using the concentration ramp technique to simultaneously record receptor current and agonist concentration. Dose-response curves for glutamate (0-1 mM) and kainate (0-200 microM) were measured in the presence and absence of 1-2 mM sodium nitroprusside (SNP), 1 mM 8-Br-cGMP, 100 microM cyclothiazide or 200 microM dopamine as modulators. SNP increased the EC50 (i.e. decreased affinity) for glutamate and increased Imax (i.e. increased efficacy), whereas 8-Br-cGMP increased EC50, but not Imax. In the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor desensitization blocker cyclothiazide, the SNP-induced increase in EC50 persisted, but the increase in Imax was blocked. The increase in EC50, but not the increase in Imax was also observed when the non-desensitizing agonist kainate (100-200 microM) was applied in the presence of SNP. When 2 mM SNP and 200 microM dopamine were applied together, they increased Imax (740 vs. 2455 pA) and EC50 (422 vs. 682 microM). Our findings indicate that NO modulates horizontal cell glutamate responses by reducing the affinity of receptors for glutamate while simultaneously increasing the maximal current. The shift in affinity is cGMP-mediated and independent of desensitization. The action of NO on horizontal cell glutamate receptors is distinct from, but synergistic with. that of dopamine. Glutamate receptor modulation by NO qualitatively predicts the action of NO on horizontal cell light responses in situ and may alter transmission at visual synapses according to adaptational conditions.     

Surface components of Onchocerca volvulus

A technique employing Sephadex G25 gel filtration has been developed for the rapid isolation and purification of live microfilariae of Onchocerca volvulus from subcutaneous nodules and skin samples. Microfilariae, adult worms and L3 larvae have been surface radiolabelled using the Iodogen technique. Two proteins have been characterised on the surface of uterine microfilariae: these have apparent molecular weights of 14,800 and 15,000. A MW 15,000 protein was the only molecule labelled on the surface of skin microfilariae. Ten proteins were labelled on adult male worms: these have molecular weights of 15,000, 17,500, 20,000, 22,000, 24,000, 29,000, 32,000, 37,000, 42,000, and 50,000. Some, if not all, of these proteins were also identified on female worms. Seven proteins were labelled on the surface of L3 larvae: these have molecular weights of 17,500, 48,000, 50,000, 52,000, 54,000, 57,000, and 105,000. Three of the adult surface proteins were precipitated by selected human infection serum: these are the MW 17,500, 32,000 and 42,000 molecules. The microfilarial surface proteins were not precipitated by human infection serum. The antiserum used in these experiments was shown by Western blot analysis to contain high levels of antibody with specificity for microfilarial and adult antigens. Indirect immunofluorescent assays showed these sera to contain antibody which bound to the surface of adult worms and eggs but not microfilariae. The possibility that skin microfilariae absorb host serum albumin was investigated: Western blot analysis and surface immunofluorescence assays using a specific anti-human albumin serum gave negative results. Fluorescent lectin binding studies revealed the presence of stage-specific carbohydrate moieties exposed on the surface of adult worms and eggs. Microfilariae do not have surface carbohydrate determinants.     

Viral antigen expression in the pancreas of DHBV-infected embryos and young ducks

The time course of appearance of viral antigen-positive pancreatic cells was examined in both congenitally duck hepatitis B virus (DHBV)-infected duck embryos and experimentally DHBV-infected posthatch ducks. In the embryos, the earliest detectable viral antigen-positive pancreatic cells were localized to islets and identifiable as endocrine on the basis of hormone expression. Non-islet-associated, viral antigen-positive cells appeared at a late stage of embryogenesis, following the onset of chymotrypsinogen production by exocrine tissue; a number of these viral antigen-positive cells were directly identifiable as exocrine on the basis of chymotrypsinogen expression. By contrast, in the pancreas of experimentally infected posthatch ducks, the appearance of viral antigen-positive exocrine cells (chymotrypsinogen-positive) predated the appearance of antigen-positive islet cells. These results are consistent with the possibility that viral antigen expression in exocrine tissue is dependent on the state of cell maturation.     

Pattern of collagen fiber orientation in the ovine calcaneal shaft and its relation to locomotor-induced strain

Background: Gebhardt (1905. Arch. Entwickl. Org., 20:187–322) originated the hypothesis that the direction of collagen fibers in bone is a structural response to the type of mechanical load to which the bone is subjected. He proposed that collagen fibers aligned parallel to the loading axis are best suited to withstand tensile strain, whereas fibers oriented perpendicular to the loading axis are best able to resist compressive strain. Research comparing load patterns with fiber alignment in bone have tended to support Gebhardt's hypothesis. The aim of the present study is to further test this hypothesis by assessing the correspondence between the distribution of strain and the distribution of collagen fiber orientation in a bone that is subjected to compound loading (i.e., both tension and compression at different phases during the loading cycle). The ovine calcaneum was selected to meet this criterion. Methods: Calcaneum surface strain distributions were obtained from experimental results reported by Lanyon (1973. J. Biomech. 6:41–49). Histological sections of the calcaneal shaft were prepared and observed using circularly polorized light (CPL) microscopy to determine the distribution of collagen fiber alignment. The observed alignment pattern was then compared with the predicted pattern based on Gebhardt's hypothesis. Results: Contrary to previous studies, our findings show no clear correspondence between the strain type of greatest magnitude and the direction of collagen fibers. Areas of bone characterized by high compression and low tension showed predominantly longitudinal collagen alignment (contra to Gebhardt). Conclusions: It is argued that even small magnitudes of tension operating on local areas of bone may be sufficient to induced collagen alignment favorable to this type of strain, even when greater magnitudes of compressive strain are acting on the same bone volume. © 1995 Wiley-Liss, Inc.     

Sublingual captopril — a pharmacokinetic and pharmacodynamic evaluation

Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril.Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: C_max, 234 ng·ml^–1; t_max, 45 min; AUC (0–3 h), 15.1 g·ml^–1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: C_max, 228 ng·ml^–1; t_max, 75 min; AUC (0–3 h), 17.0 g·ml^–1. min. t_max was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent.The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. t_max for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.