Mathematically directed single-cut osteotomy for correction of tibial malunion

In 1986 and 1987, four patients with tibial malunion involving both angular and torsional misalignment underwent surgical correction by a single-cut technique based on a mathematical model of long bone deformity. The technique involved a single surgical cut, followed by rotation of the two fragments along the osteotomy plane. The orientation of the osteotomy is based on a computer-assisted design. The deformity is measured on radiographs, computed tomography, and clinical exam and is then plotted on graphs to find the osteotomy orientation. The deformity involved varus and extension in four cases, internal rotation in 2, and external rotation in two. The deformities ranged from 9 to 26 degrees. The cutting angle of the osteotomy ranged from 50 to 66 degrees as measured from the transverse plane. Actual lengthening of 1 cm and functional lengthening over 1.5 cm was obtained without the use of bone graft. As no wedge of bone was removed, all corrected bones were easily suited to rigid internal fixation across the cut surface. In all cases, the desired correction was obtained within measurable error, and union was obtained with minimal immobilization. There were no soft tissue or joint contractures, and no neurovascular complications. In one patient, who had had four prior surgical procedures on the involved limb, an infection developed 6 weeks postoperatively that required debridement and delayed primary closure. As the technique involves only one cut, no wedge of bone is removed, no shortening occurs, and the osteotomy is highly suitable for rigid internal fixation. The described technique is the first to integrate in a precise way the correction of torsion with the correction of angular deformity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Cryopreservation of human oocytes: a review of current problems and perspectives

It is well recognized that the ability to cryopreserve unfertilizedhuman oocytes would make a significant contribution to infertilitytreatment. However, despite considerable interest, very fewsuccessful pregnancies have arisen from cryopreserved oocytesafter thawing, insemination and transfer of the subsequent embryo.The reasons for this lack of progress may well result from adearth of information on how the various biophysical changesduring a cryopreservation regimen affect human oocyte function.Recently, fundamental studies on the effects of cooling, membranepermeability, cryoprotectant addition and ice formation havebeen performed on human oocytes by a number of groups, and theseform the basis of the current review. It is likely that successfulhuman oocyte cryopreservation will only follow once these factorsare fully understood, but the existing base of knowledge shouldprovide a platform for further improvements in the techniquescurrently employed.