Secondary surfactant administration in neonates with respiratory decompensation.

OBJECTIVE: To evaluate blood gases and ventilatory parameters before and after two doses of surfactant in premature infants with respiratory decompensation after recovery from primary respiratory distress syndrome (RDS). STUDY DESIGN: This prospective pilot study enrolled infant's > or =500 g birth weight, from 7 days to 3 months of age, with a secondary respiratory decompensation lasting at least 4 h prior to study entry. Infants received two doses of surfactant, 12 h apart. RESULT: A total of 20 neonates qualified for secondary surfactant administration. PCO2 (P<0.001); pH (P<0.001); mean airway pressure (P<0.05); FiO2 (P<0.05); modified ventilatory indices (P<0.004) and respiratory severity scores (P<0.001) improved significantly at both 12 and 24 h after surfactant administration. CONCLUSION: Secondary surfactant administration may be effective in reducing short-term ventilatory requirements in neonates who have a respiratory decompensation after recovery from initial RDS. Randomized controlled trials are needed to confirm these preliminary findings.     

Factors influencing the relationship between a newborn assessment of gestational maturity and the gestational age interval

This study examines the correlation and agreement between the calculated 'gestational interval' from the date of last menstrual period (LMP) and the Ballard newborn assessment of gestational maturity. It then investigates selected maternal socio-demographic, prenatal, intrapartum and infant factors which may account for differences between these two gestational age determination methods. Single live-born deliveries (n = 10,794) were selected from a 1982-1986 medical university perinatal information data system for analysis. The Ballard assessment overestimates the LMP at earlier gestational ages and underestimates in the post-term range. The discrepancy between LMP and Ballard varies across the range of gestational age values and the extent of variation differs by several maternal and infant risk factors. These findings suggest considerable bias may result from the indiscriminate case mixing of LMP and Ballard values for use in gestational age research or in standardising developmental tests. We highlight the deficiencies in using correlation coefficients or mean differences to assess agreement between these measures.     

Adolescent sexual activity and pregnancy in South Carolina: trends, risks, and practice implications

Using South Carolina vital record data, we examined current trends in teenage pregnancy and the related pregnancy outcome risks for the period 1977 to 1984. A review of the eight-year trends in the pregnancy outcomes of teenaged mothers (less than 18 years old) indicated a significant decline (P less than .05) in the percentage of total South Carolina live infants born to teenaged mothers. While a significant increase in the teenage abortion ratio was detected, the proportion of total South Carolina pregnancies (estimated by the summation of live births, fetal deaths, and induced abortions) among teenagers significantly decreased. Compared to mothers 18 to 34 years old, teenaged mothers were nearly twice as likely to deliver prematurely, while one half as likely to receive adequate prenatal care. Their offspring were at increased risk of low birth weight and had increased fetal and infant death rates. Thirty percent of pregnancies in teenaged mothers were terminated by induced abortion, and 22% of the teenage pregnancies were to mothers aged 15 or younger, emphasizing the importance of not delaying discussions with teens of the issues of adolescent sexuality and contraception.     

Structuring a safer donor-replacement program

BACKGROUND: Replacement donors are more likely than volunteer donors to have positive or abnormal tests for transfusion-transmissible disease. In an effort to increase the donor pool, workers sought to identify a safer replacement-donor subgroup that may be acceptable for routine donations. STUDY DESIGN AND METHODS: In a retrospective review and cohort study, the replacement-donor effect was separated from the new- donor effect. The relative effect the replacement donor has on the risk of transfusion-transmissible diseases, donor retention, and frequency of returning donations was then quantified by comparison against the effect of repeat volunteer donors. RESULTS: The replacement donor had 3.1 times the risk and 0.72 times the donor retention rate and made 0.81 times as many returning donations as the repeat volunteer donor. The figures for the new-donor effect were similar. The two risks were additive, making a new replacement donor particularly hazardous. If replacement donations only from repeat replacement donors were considered, the donor risk and the number of donations per returning donor were made comparable to those for the general (combined) volunteer donor. CONCLUSION: The negative effect of the replacement donor is similar in magnitude to that of the new volunteer donor. A replacement-donation program targeting repeat replacement donors has an acceptable risk profile and may be a valuable adjunct to the collection of blood from general volunteer donors.     

Measurement of glycine in gray and white matter in the human brain in vivo by 1H MRS at 7.0 T

The concentration of glycine (Gly) was measured in gray matter (GM) and white matter (WM) in the human brain using single‐voxel localized ¹H MRS at 7 T. A point‐resolved spectroscopy sequence with echo time = 150 ms was used for measuring Gly levels in various regions of the frontal and occipital lobes in 11 healthy volunteers and one subject with a glioblastoma. The point‐resolved spectroscopy spectra were analyzed with LCModel using basis functions generated from density matrix simulations that included the effects of volume localized radio‐frequency and gradient pulses. The fraction of GM and white matter within the voxels was obtained from T₁‐weighted image segmentation. The metabolite concentrations within the voxels, estimated with respect to the GM + WM water concentrations, were fitted to a linear function of fractional GM content. The Gly concentrations in pure GM and white matter were estimated to be 1.1 and 0.1 mM, with 95% confidence intervals 1.0–1.2 and 0.0–0.2, respectively. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU- E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti- HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.     

Differential effect of Serratia protease on platelet surface glycoproteins Ib and V

The effect of a zinc metalloprotease from Serratia marcescens on platelet surface glycoproteins (GP) Ib and V was analyzed. Increasing protease treatments caused progressive loss of GP Ib with appearance of the major fragment, glycocalicin, in the supernatant solution. No GP V was detected in the supernatant solution, and protease-pretreated platelets had the same capacity as control platelets to release fragment 1 of GP V in response to thrombin. The Serratia protease- pretreated platelets did show the lag before thrombin-induced dense granule secretion, characteristic of platelets modified by pretreatment with other nonstimulating proteases. Treatment with Serratia protease gives the only demonstrated selective loss of GP Ib without apparent effect on GP V. It suggests that GP V (1) does not depend on GP Ib for its association with platelets and (2) is not the substrate for protease modification of platelet function.     

Purification and properties of heparin-releasable lipoprotein- associated coagulation inhibitor

The lipoprotein-associated coagulation inhibitor (LACI) is present in vivo in at least three different pools: sequestered in platelets, associated with plasma lipoproteins, and released into plasma by intravenous heparin, possibly from vascular endothelium. In this study we have purified the heparin-relesable form of LACI from post-heparin plasma and show that it is structurally different from lipoprotein LACI. The purification scheme uses heparin-agarose chromatography, immunoaffinity chromatography, and size-exclusion chromatography and results in a 185,000-fold purification with a 33% yield. Heparin- releasable LACI (HRL), as analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis, under reducing conditions, appears as a major band at 40 Kd and a minor band at 36 Kd. Immunoblot analysis suggests that the 36-Kd band arises from carboxyl-terminus proteolysis that occurs during the purification. HRL has a specific activity similar to that of HepG2 or lipoprotein LACI. HRL and lipoprotein LACI combine with lipoproteins in vitro while purified HepG2 LACI does not. I125-labeled HRL, injected into a rabbit, is cleared more slowly than I125-labeled HepG2 LACI, which may be due to attachment to lipoproteins in vivo. Preliminary evidence suggests that HRL is associated with vascular endothelium, possibly by attachment to glycosaminoglycans.