A prospective randomized,double-blinded,placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy

BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical abortion. This randomized, double-blinded, placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 250 women with gestations < or = 56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol. Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 114 out of 119 subjects (95.7%) after mifepristone followed by vaginal misoprostol. In all, 110 out of 125 subjects (88.0%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (P < 0.05). CONCLUSIONS: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone. The 88% efficacy obtained with vaginal misoprostol alone may be clinically acceptable when mifepristone is not available.     

Limitations of a convolution method for modeling geometric uncertainties in radiation therapy: the radiobiological dose-per-fraction effect

The convolution method can be used to model the effect of random geometric uncertainties into planned dose distributions used in radiation treatment planning. This is effectively done by linearly adding infinitesimally small doses, each with a particular geometric offset, over an assumed infinite number of fractions. However, this process inherently ignores the radiobiological dose-per-fraction effect since only the summed physical dose distribution is generated. The resultant potential error on predicted radiobiological outcome [quantified in this work with tumor control probability (TCP), equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and generalized equivalent uniform dose (gEUD)] has yet to be thoroughly quantified. In this work, the results of a Monte Carlo simulation of geometric displacements are compared to those of the convolution method for random geometric uncertainties of 0, 1, 2, 3, 4, and 5 mm (standard deviation). The alpha/betaCTV ratios of 0.8, 1.5, 3, 5, and 10 Gy are used to represent the range of radiation responses for different tumors, whereas a single alpha/betaOAR ratio of 3 Gy is used to represent all the organs at risk (OAR). The analysis is performed on a four-field prostate treatment plan of 18 MV x rays. The fraction numbers are varied from 1-50, with isoeffective adjustments of the corresponding dose-per-fractions to maintain a constant tumor control, using the linear-quadratic cell survival model. The average differences in TCP and EUD of the target, and in NTCP and gEUD of the OAR calculated from the convolution and Monte Carlo methods reduced asymptotically as the total fraction number increased, with the differences reaching negligible levels beyond the treatment fraction number of > or =20. The convolution method generally overestimates the radiobiological indices, as compared to the Monte Carlo method, for the target volume, and underestimates those for the OAR. These effects are interconnected and attributed to assuming an infinite number of fractions inherent in the implementation of the convolution technique, irrespective of the uniqueness of each treatment schedule. Based on the fraction numbers analyzed (1-50), and the range of fraction numbers normally used clinically (> or =20), the convolution method can be used safely to estimate the effects of random geometric uncertainties on prostate treatment radiobiological outcomes, for both the target and the OAR. Although the results of this study is likely to apply to other clinical sites and treatment techniques other than the four-field, further validation similar to those done in this study may be necessary prior to clinical implementation.     

Age independent and position-dependent alterations in motor unit activity of the biceps brachii

In the biceps brachii, age-related differences in synaptic excitability and muscle architecture may affect motor unit (MU) activity differently depending on the position of the forearm. It was hypothesised that as a result of these age-related differences, greater changes in MU activity would accompany a change in forearm position in old when compared with young men. Six young (22 ± 3 years) and six old (84 ± 3 years) men maintained isometric elbow flexion at 10% of maximal voluntary contraction (MVC) during changes in forearm position. Forty-nine MUs in the short (SBB) and long (LBB) heads of the biceps brachii were followed. Motor unit recruitment and de-recruitment thresholds, motor unit discharge rates (MUDRs), and MU discharge variability were measured. Although an age-related decrease in MU recruitment thresholds, and increase in MU discharge variability was evident, changes in forearm position influenced MUDRs similarly in young and old men (P = 0.27). Motor unit recruitment thresholds of the SBB were highest in the pronated position (8.2 ± 2.9 %MVC), whereas in the LBB they were highest in the supinated position (8.6 ± 2.0 %MVC). Motor unit discharge rates of the LBB did not change with forearm position. In the SBB, MUDRs were highest when the forearm was supinated, and also greater when compared with the LBB in this position. No position-dependent changes were observed for MU discharge variability in the LBB, but the SBB exhibited greatest MU discharge variability in the pronated position. The results suggest that MU activity is modulated following a change in forearm position, but the response is similar in young and old adults.     

Characterization of chlorhexidine-releasing, fast-setting, brushite bone cements

The effect of antibacterial chlorhexidine diacetate powder (CHX) on the setting kinetics of a brushite-forming beta-tricalcium phosphate/monocalcium phosphate monohydrate (beta-TCP/MCPM) cement was monitored using attenuated total reflection Fourier transform infrared spectroscopy. The final composition of the set cement with up to 12 wt.% CHX content before and after submersion in water for 24h, the kinetics of chlorhexidine release and the total sample mass change in water over four weeks was monitored using Raman mapping, UV spectroscopy and gravimetry, respectively. Below 9 wt.%, CHX content had no significant effect on brushite formation rate at 37 degrees C, but at 12 wt.% the half-life of the reaction decreased by one-third. Raman mapping confirmed that brushite was the main inorganic component of the set cements irrespective of CHX content, both before and after submersion in water. The CHX could be detected largely as discrete solid particles but could also be observed partially dispersed throughout the pores of the set cement. The percentage of CHX release was found to follow Fick's law of diffusion, being independent of its initial concentration, proportional to the square root of time and, with 1mm thick specimens, 60% was released at 24h. Total set cement mass loss rate was not significantly affected by CHX content. On average, cements exhibited a loss of 7 wt.% assigned largely to surface phosphate particle loss within the initial 8h followed by 0.36 wt.% per day.     

Brushite-collagen composites for bone regeneration

Brushite-based biomaterials are of special interest in bone regeneration due to their biocompatibility and biodegradability; on the other hand, collagen is a well-known osteoconductive biomaterial. In the present study a new brushite-collagen composite biomaterial is reported. This new biomaterial was prepared by combining citric acid/collagen type I solutions with a brushite cement powder. The obtained biomaterial was a cement paste, with improved handling properties. The effect of collagen on the setting reaction of brushite cement was studied, and was found to speed up the cement setting reaction. The cement paste set into a hard ceramic material within 18.5+/-2.1min and had compressive strength similar to that of spongeous bone (48.9+/-5.9MPa in dry conditions and 12.7+/-1.5MPa in humid conditions). The combination of collagen with citric acid revealed an interesting synergistic effect on the compressive strength of the composite material. Moreover, this new biomaterial had excellent cohesion properties (ninefold better than brushite cement), and high cellular adhesion capacity (threefold higher than brushite cement). The composite biomaterial described in this study combines good handling properties, compressive strength, cohesion and cell adhesion capacity, along with the osteoconductive and biodegradable properties inherent in brushite and in collagen-based biomaterials.     

Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients.

Oligonucleotide fingerprinting of genomic DNA from oral isolates of four different Candida species other than C. albicans and atypical chlamydospore-positive isolates from human immunodeficiency virus (HIV)-positive individuals and AIDS patients was investigated as a means for differentiating between isolates within individual species. Oligonucleotides composed of simple repetitive sequence motifs, including (GACA)4, (GATA)4, (GGAT)4, (GTG)5, and (GT)8, all yielded fingerprints suitable for strain segregation of 8 C. tropicalis isolates, 12 Torulopsis (Candida) glabrata isolates, 8 atypical Candida isolates, and, except for (GATA)4, 2 C. krusei probe in turn and so generate several distinct DNA fingerprints of the same DNA sample. However, none of the probes yielded fingerprints suitable for strain segregation with three C. parapsilosis isolates. The (GATA)4 probe was also used to detect restriction fragment length polymorphisms among a genetically closely related group of atypical Candida isolates on primary isolation from an additional HIV-infected patient. These chlamydospore-positive atypical Candida isolates were sucrose positive, were of C. albicans serotype A, hybridized weakly with the C. albicans-specific mid-repeat sequence probe 27A, and yielded fingerprint profiles by random polymorphic DNA analysis that were distinct from those derived from C. albicans isolates. The C. stellatoidea ex-type strain NCPF 3108 was indistinguishable from the atypical Candida isolates in all these tests and also yielded an identical carbohydrate and nitrogen source assimilation profile by using the ID 32C yeast identification system.     

Isolation and expression of the gene for a major surface protein of Giardia lamblia.

To study the interactions between the parasitic protozoan Giardia lamblia and its environment, we have cloned the gene that encodes the two major surface-labeled trophozoite protein species. Sequence analysis of this gene reveals a single open reading frame specifying a hydrophilic, cysteine-rich (11.8%) protein of 72.5-kDa molecular mass with an amino-terminal signal peptide and a postulated hydrophobic membrane-spanning anchor region near the carboxyl terminus. Most of the cysteine residues (58 of 84) are in the motif Cys-Xaa-Xaa-Cys, which is dispersed 29 times throughout the sequence. Antibodies against the recombinant protein react with the entire surface of live trophozoites, including flagella and adhesive disc. These antibodies inhibit trophozoite attachment, prevent growth, and immunoprecipitate the major approximately 66- and 85-kDa proteins from surface-labeled live trophozoites. The recombinant Escherichia coli also expresses polypeptides of approximately 66- and 85-kDa molecular mass, which are not fusion proteins. This suggests that the processing and/or conformational changes that lead to production of these two peptide species in E. coli reflect those that occur in Giardia. The abundance of cysteine residues suggests that the native proteins on the parasite surface may contain numerous disulfide bonds, which would promote resistance to intestinal fluid proteases and to the detergent activity of bile salts and would help to explain the survival of Giardia in the human small intestine.