A cohort study of pregnancy outcome after amniocentesis in twin pregnancy

We conducted a retrospective cohort study to assess the risk of amniocentesis in twin pregnancy for adverse outcomes. The study base consisted of women who had an amniocentesis performed during twin pregnancy and a comparison representative sample of women who carried a twin pregnancy, but did not have invasive prenatal diagnosis. The 227 women in each of the exposed and non-exposed groups were residents of the state of New South Wales, Australia, over the period 1980-92, and were matched on maternal age and period of the infant's birth. Nearly 10% of twin pregnancies among the women having an amniocentesis were affected by a stillbirth, and the stillbirth rate among exposed fetuses (5.3%) was nearly twice as high as among non-exposed fetuses (3.1%). After adjustment for confounding and excluding abnormalities, there was a non-significant elevated relative risk of stillbirth after exposure to amniocentesis. The analysis by type of amniocentesis (with and without methylene blue dye) was limited by small numbers, but the burden of risk was primarily among women who had dye exposure during amniocentesis (relative risk = 3.64, 95% confidence interval = 1.15, 11.48). This increase remained after adjusting for confounding, although the confidence interval was wide. In conclusion, we were unable to establish with certainty whether an increased risk of stillbirth could be ruled out among women who had any type of amniocentesis in twin pregnancy.     

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.     

Association of a group I intron with its splice junction in 50S ribosomes: implications for intron toxicity

The effect of genetic context on splicing of group I introns is not well understood at present. The influence of ribosomal RNA conformation on splicing of rDNA introns in vivo was investigated using a heterologous system in which the Tetrahymena group I intron is inserted into the homologous position of the Escherichia coli 23S rRNA. Mutations that block splicing in E. coli result in accumulation of unspliced 23S rRNA that is assembled into 50S complexes, but not 70S ribosomes. The data indicate that accommodation of the intron structure on the surface of the 50S subunit inhibits interactions with the small ribosomal subunit. Spliced intron RNA also remains noncovalently bound to 50S subunits on sucrose gradients. This interaction appears to be mediated by base pairing between the intron guide sequence and the 23S rRNA, because the fraction of bound intron RNA is reduced by point mutations in the IGS or deletion of the P1 helix. Association of the intron with 50S subunits correlates with slow cell growth. The results suggest that group I introns have the potential to inhibit protein synthesis in prokaryotes by direct interactions with ribosomes.     

An analysis of simultaneous variation in protein structures

The simultaneous substitution of pairs of buried amino acid side chains during divergent evolution has been examined in a set of protein families with known crystal structures. A weak signal is found that shows that amino acid pairs near in space in the folded structure preferentially undergo substitution in a compensatory way. Three different physicochemical types of covariation 'signals' were then examined separately, with consideration given to the evolutionary distance at which different types of compensation occur. Where the compensatory covariation tends towards retaining the combined residue volumes, the signal is significant only at very low evolutionary distances. Where the covariation compensates for changes in the hydrogen bonding, the signal is strongest at intermediate evolutionary distances. Covariations that compensate for charge variations appeared with equal strength at all the evolutionary distances examined. A recipe is suggested for using the weak covariation signal to assemble the predicted secondary structural elements, where the evolutionary distance, covariation type and weighting are considered together with the tertiary structural context (interior or surface) of the residues being examined.      

A meta-analysis of non-Hodgkin's lymphoma among farmers in the central United States

A meta-analysis of studies examining the association between non-Hodgkin's lymphoma (NHL) and employment as a farmer in the central United States was performed to verify the observation by Blair et al. [1993] that this group is at excess risk of NHL. Six studies were selected for the meta-analysis, and the estimator of relative risk calculated was 1.34 (95% confidence interval (CI) = 1.17, 1.55). Exposures associated with NHL and associated with agricultural commodities frequently produced in the central United States are infectious microorganisms and pesticides. Examination of the production patterns of the farms in this region did not reveal a single specific risk factor consistently found on all farms; however, past production patterns suggest that exposure to either infectious microorganisms or pesticides might be a risk factor for NHL in this group of farmers.     

A major gene affecting age-related hearing loss in C57BL/6J mice

A major gene responsible for age-related hearing loss (AHL) in C57BL/6J mice was mapped by analyses of a (C57BL/6J x CAST/Ei) x C57BL/6J backcross. AHL, as measured by elevated auditory-evoked brainstem response (ABR) thresholds, segregated among backcross mice as expected for a recessive, primarily single-gene trait. Both qualitative and quantitative linkage analyses gave the same genetic map position for the AHL gene (Ahl on chromosome 10, near D10Mit5. Marker assisted selection was then used to produce congenic lines of C57BL/6J that contain different CAST-derived segments of chromosome 10. ABR test results and cochlear histopathology of aged progenitors of these congenic lines are presented. Ahl is the first gene causing late-onset, non-syndromic hearing loss that has been reported in the mouse.