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.      

Bile duct stones: percutaneous transhepatic removal

Percutaneous transhepatic intervention for transduodenal removal of biliary stones was performed 38 times in 34 patients with obstructive jaundice, biliary colic, and cholangitis. The technique entailed the percutaneous transhepatic placement of a modified Dormia basket in the common duct with the flexible tip in the duodenum. The stones were passed into the duodenum and were crushed, or were crushed in the common duct and passed as fragments into the duodenum. In addition to the snare procedure, monooctanoin was used 18 times to dissolve remaining fragments of stone and sludge that could not be snared and passed into the duodenum. The average time for completion of the procedure was 10 days. There were no deaths from the procedure. The complication rate was 21%--probably no greater than would occur with surgery in a similar patient population. The procedure can be performed when endoscopic retrograde cholangiopancreatography and sphincterotomy with stone removal is technically impossible or refused, and in patients who have previously undergone choledochojejunostomy.     

Growth in children with steroid sensitive nephrotic syndrome

Background: Nephrotic syndrome in children usually has an onset between 2–8 years of age and steroids form the mainstay of management. Therapy may affect growth in children with relapsing nephrotic syndrome. This study was carried out to correlate growth with the cumulative dose of steroids in children with steroid sensitive nephrotic syndrome (SSNS).     

Fluid collections in the intraperitoneal and extraperitoneal spaces: comparison of MR and CT

Fourteen patients with abnormal subdiaphragmatic fluid collections (eight intraperitoneal, two extraperitoneal, and four intra- and extraperitoneal) were examined with computed tomography (CT) and magnetic resonance (MR) imaging. MR and CT provided equivalent information concerning the presence and extent of fluid collections in 13 of the 14 cases. Image acquisitions with two different repetition times (TRs) and two echo times (TEs) were necessary, in most cases, to detect and discriminate between different types of pathologic fluids. Transudative ascites demonstrated long T1 and T2 relaxation times, whereas abscesses, phlegmon, pancreatic pseudocyst, exudative pancreatitis, and chronic hematoma demonstrated an intermediate or short T1 and a long T2.     

Evaluating community health worker performance in India

In 1977 the Government of India launched a health care experimentin which volunteers were used to provide a basic health careservice. Community health workers have also been used in manysmall, non-governmental programmes. Although much has been saidabout the selection and training of such workers, there havebeen very few attempts to evaluate their actual work performance.This paper makes the plea for more, regular evaluations of theiractivities by those involved in the programmes: communities,supervisors and health workers themselves. Such evaluationsare useful even if they are only done on a small scale. Whatis described here is a small study of the performance of part-timecommunity health workers (PTCHWs) in a programmme initiatedin 1977 by the Community Health Department of the ChristianMedical College in Vellore, South India. It concludes that thePTCHWs with the highest performance scores have, on the whole,less education, more experience, less population to cover andmore intense supervision.