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Notes: Objective To investigate the use of low dose aspirin in the reduction of perinatal morbidity and mortality in women with unexplained raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns.Design Prospective randomised controlled trial.Setting A tertiary referral obstetric service.Subjects One hundred and sixty-four women referred to our unit with raised maternal serum alpha-fetoprotein and a structurally normal fetus had abnormal uteroplacental Doppler waveform patterns at 24 weeks of gestation.Intervention Women were randomly allocated to two groups, receiving either low dose aspirin 75 mg (n= 76) or placebo (n= 88) daily until delivery.Main outcome measures Preterm labour, low birthweight, the occurrence of placental abruptions and perinatal mortality.Results The frequency of severely small for gestational age infants (birthweight 〈 5th centile) was reduced in the aspirin treated group to 16% compared with 25% in the placebo group (95% CI –21% to 13%). The frequency of delivery before 34 weeks of gestation was 26% in the aspirin group and 42% in the placebo group (95% CI–30% to 1%). The perinatal mortality was 240/1000 in the aspirin group and 320/1000 in the placebo group (95% CI–22% to 6%). None of these reductions was statistically significant. Although the frequency of placental abruptions was similar in the two groups, significantly more babies died from abruption in the aspirin treated group (91%versus 30%, 95% CI 28% to 94%). Low dose aspirin did cause a significant reduction (P= 0.008) in deaths from causes other than placental abruption.Conclusion This trial revealed a benefit of low dose aspirin therapy in women with raised maternal serum alpha-fetoprotein and abnormal uteroplacental Doppler waveform patterns, but the effect was smaller than expected. Although a reduction in deaths from small preterm babies was observed, there was an increase in the number of deaths following placental abruption without a significant increase in the number of abruptions. We recommend that this should be considered before giving aspirin to these high risk women and that other investigators should specifically look for this effect.

Notes: Objective To determine whether Doppler waveforms from the uteroplacental circulation could improve the prediction of pregnancy outcome in women with raised maternal serum alpha-fetoprotein and a structurally normal fetus. The study further attempts to determine whether the presence of an early diastolic notch would constitute a better screening test than waveform patterns.Design An observational study.Setting A tertiary referral obstetric service.Subjects All women referred to St George's Hospital with a raised maternal serum alpha-fetoprotein had waveform measurements from the uteroplacental circulation after exclusion of fetal abnormalities. Pregnancy outcome was determined by questionnaire sent to the referring clinicians.Main outcome measures Adverse perinatal outcome in the form of preterm labour, low birthweight and perinatal mortality.Results Data from 332 cases were available for analysis. Women with a normal pattern of uteroplacental waveforms had a perinatal mortality of 9.6/1000. Women with a uniform high resistance pattern had a perinatal mortality of 846/1000, and those with a mixed resistance pattern had a perinatal mortality of 268/1000. Overall there were 27 cases of placental abruption which accounted for eight of the 50 perinatal deaths. The remainder were due to prematurity or low birthweight or both. The presence of the early diastolic notch did not improve on the waveform patterns in the prediction of perinatal death.Conclusion Women with raised maternal serum alpha-fetoprotein and normal Doppler waveform patterns from the uteroplacental circulation can be reassured, but mixed or uniform high resistance patterns should encourage increased surveillance and a search for intervention therapies.

Notes: The large, growth-induced magnetic anisotropy in amorphous rare earth-transition metal alloys such as Tb-Fe are shown to depend strongly on the deposition temperature and only weakly on deposition rate or deposition technique (e.g., sputtering versus electron beam co-evaporation). These dependencies can be well fit with a thermally activated form involving minimization of surface energy during the growth by a re-orienting of adatom configurations over potential energy barriers. In this model, the growing film lowers its surface energy by a partial alignment of local clusters, presumably such as to maximize the number of in-plane bonds, although chemical effects undoubtedly also play an important role. These effects are somewhat analogous to a surface reconstruction which becomes trapped into the growing film by low bulk diffusion rates. In particular, a two-level model with a flat distribution of energy barriers is here shown to provide an excellent fit to the observations. Such a model leads to a ln(t) dependence on deposition rate and an exponential dependence on deposition temperature. We have also studied the subsequent irreversible relaxation of the anisotropy upon annealing. This relaxation is strongly influenced by the original growth temperature. In particular, the higher the original growth temperature, the more resistant the film is to subsequent relaxation. This result has important technological implications. As is commonly observed, the relaxation is well fit by a two-level model, again with a flat distribution of energy barriers over a range of energies, producing a ln(t) dependence on annealing time and a thermally activated dependence on annealing temperature. In annealing, of course, the lower energy state is isotropic, unlike the surface-induced anisotropic state produced during growth. The influence of the growth temperature on this relaxation implies that the actual process of creating the anisotropic state during the growth has the consequence of eliminating free volume in the sample, thereby raising the energy barriers to subsequent relaxation.

Notes: Transforming growth factor-β2 promotes healing in a variety of animal models and exhibits clinical effects thought to be mediated by connective tissue formation. Two clinical trials were conducted to evaluate the safety and effect of transforming growth factor-β2 purified from bovine bone and delivered topically to venous stasis ulcers three times per week for up to 6 weeks by means of a lyophilized collagen vehicle. The first was an open-label trial comparing transforming growth factor-β2 purified from bovine bone (0.5 µg/cm2) with a placebo consisting of lyophilized collagen vehicle-without active drug. After no safety issues arose in that trial, a prospectively randomized, closed-label, observer-blinded, three-armed trial was conducted to compare bovine transforming growth factor-β2 (2.5 µg/cm2) with the collagen matrix placebo vehicle and with a standard dressing. Standardized elastic compression was applied to all test extremities. The rate of reduction of ulcer area as measured by planimetry was the primary measure of effect. No serious safety-related events occurred in either trial. Clinical evaluation suggested that improvement in the quality and quantity of granulation tissue appeared to precede epithelialization of ulcers treated with bovine transforming growth factor-β2. In both studies, treatment with bovine transforming growth factor-β2 appeared to have a positive effect on the rate of ulcer closure, whereas ulcers in the control groups continued to exhibit impaired healing. In the open-label study, the mean rate of closure of ulcers treated with bovine transforming growth factor-β2 was significantly greater than that of ulcers treated with placebo. There was likewise enhanced reduction in ulcer area in the ulcers treated with bovine transforming growth factor-β2 in the second trial. However, because of a higher variability in patient response and a greater placebo effect, the difference was not significant. The placebo was not worse than the standard care arm, thereby showing that the vehicle is not injurious to healing. The combined results of the two trials suggest that, at doses of 0.5 to 2.5 µg/cm2, bovine transforming growth factor-β2 is safe as a topically applied agent in a collagen matrix vehicle and can have a positive effect on closure of venous stasis ulcers. Large multicenter trials appear to be indicated to evaluate fully the potential utility of transforming growth factor-β2 in accelerating closure of chronic dermal ulcers.