Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Induction of class II major histocompatibility antigens on thyroid, adult pancreatic islet, and fetal proislet allografts.

Cultured BALB/c (H-2d) thyroid, adult pancreatic islet and fetal proislet tissues can be accepted permanently in CBA/H (H-2k) recipients until rejection is triggered by the transfer of antidonor strain activated immune T cells. Class II MHC antigens are not expressed on the accepted grafts and are induced following immune cell transfer, but expression is quantitatively and qualitatively different for the different tissues. Thyroid allografts show intense class II MHC antigen expression early after immune cell transfer and before extensive tissue destruction has occurred. In contrast, adult islet and fetal proislet allografts show patchy and cytoplasmic staining usually associated with areas of tissue destruction. Gamma-interferon treatment of tissues in vitro showed that proislet tissue has a greater capacity for class II MHC antigen induction than adult islet tissue. The differences in the capacity for class II MHC induction by fetal and adult islet tissue may be important in relation to the pathogenesis of autoimmune disease.     

A theoretical consideration of some biological parameters involved in cell kinetic investigations of oral leukoplakia and abnormal states in stratified squamous epithelium

The correct interpretation of cell kinetic data for normal epithelia requires a consideration of several interrelating factors. In abnormal states, such as leukoplakia, the lack of appropriate data for these parameters makes such interpretation difficult. Consequently, an altered mitotic index need not indicate an abnormality of cell proliferation.     

The expectations of the dental graduate.

The young dental graduate expects to deliver a certain standard of health care to the community. It is likely that both the standard of care required by the Australian people and the proportion of the population seeking treatment will increase in the coming decades. The dental profession has a responsibility to meet these demands. Although dentists should expect adequate monetary return for their activities, it would be improper to limit entry into the profession solely on the grounds of seeking to maintain some present datum line of "economic viability" of practice.     

Effects of low dose oral contraceptives containing norethindrone and ethinyl estradiol on serum levels of progesterone and pituitary gonadotropins

Serum gonadotropin and progesterone levels were studied in longterm (>18 months) patients receiving oral contraceptives containing either 1.0 mg or 0.5 mg norethindrone in combination with 35 μg of ethinyl estradiol. In ten patients treated with 1.0 mg norethindrone and 35 μg ethinyl estradiol, no mid-cycle surges of LH were noted and LH levels never exceeded 225 ng/ml. FSH levels were generally elevated during the first half of the cycle. Serum progesterone concentrations in these patients and in fourteen additional women whose blood was sampled intermittently were generally less than 1 ng/ml, and no characteristic luteal phase elevation of this hormone was detected. Of six patients treated with 0.5 mg norethindrone and 35 μg ethinyl estradiol, five clearly had no mid-cycle surge of LH, and levels of this hormone never exceeded 250 ng/ml. The concentrations of FSH and progesterone in these patients and serum progesterone levels in two additional women whose blood was sampled intermittently were similar to those found in patients treated with 1 mg norethindrone and 35 μ ethinyl estradiol. In the sixth patient, hormonal levels did not follow the same pattern, but they were not characteristic of ovulation. It is concluded that there is no evidence of cyclic fluctuations in FSH, LH and progesterone characteristic of ovulation in patients treated longer than eighteen months with either 1.0 mg or 0.5 mg norethindrone in combination with 35 μg ethinyl estradiol.