Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis.

BACKGROUND. The antibody Ki-67 binds to nuclei in all cell cycle phases except GO and can be used to measure growth fraction. Because proliferative activity has been linked to prognosis in neoplasia, the authors analyzed 100 cases of colorectal carcinoma, each with 3 or more years of follow-up, using Ki-67 immunostaining. METHODS. The Ki-67-positive nuclear area and total nuclear area of carcinoma cells in 20 microscopic fields were measured by computed morphometry. A Ki-67 score (percent positive nuclear area x 100) was calculated. The following characteristics also were recorded for each case: patient age and sex, tumor site and size, modified Dukes' stage, spread beyond bowel wall, lymph node status, tumor grade, histologic type, extramural venous spread, tumor growth pattern, fibrosis, lymphocytic infiltration, and mitotic rate. RESULTS. Ki-67 scores ranged from 1 to 90 (mean, 34.6). Ki-67 scores were higher in Stage A disease (versus Stage B, C, and D disease) but were not associated with survival. Survival curves differed by stage, lymph node metastases, infiltrative growth pattern, lymphocytic infiltration, fibrosis, extramural venous spread, and tumor grade in a univariate analysis. The infiltrative growth pattern (P = 0.04) and lymphocytic infiltration (P = 0.003) were features associated independently with survival after adjusting for modified Dukes' stage. Furthermore, the lack of a significant lymphocytic infiltrate was associated with a death rate 3.4 times greater than that occurring in patients with Stage B disease with a significant infiltrate. CONCLUSIONS. The authors conclude that proliferative activity in colorectal carcinoma as measured by Ki-67 immunostaining was not associated with prognosis.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

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.