Mapping of an autosomal dominant gene for Dupuytren's contracture to chromosome 16q in a Swedish family.

Mapping of an autosomal dominant gene for Dupuytren's contracture to chromosome 16q in a Swedish family.Dupuytren's contracture (DC) (OMIM 126900) is the most common connective tissue disease of mankind and has both heritable and sporadic forms. The inherited form is most frequently observed among the xanthochroi peoples of Northern Europe where its most common manifestations are thickening of the palmar fascia and contracture of the fingers. We ascertained a five-generation Swedish family in which DC is inherited in an autosomal dominant manner with high, but incomplete, penetrance by the end of the fifth decade. Blood was collected from all affected and informative unaffected family members for the performance of a genome-wide scan at a resolution of approximately 8 cM for all autosomes. Linkage was established to a single 6 cM region between markers D16S419 and D16S3032 on chromosome 16. A maximal two-point logarithm of odds (LOD) score of 3.18 was achieved at microsatellite marker D16S415 with four other markers in the region producing LODs of >1.5.

Physician-partnering models offer legal alternatives to traditional gain-sharing.

The HHS Office of Inspector General has condemned gain-sharing arrangements between hospitals and physician groups as being in violation of the civil monetary penalty section of the Social Security Act. Several physician-hospital partnering models, however, are not restricted by the OIG, though arrangements based on these models must be structured carefully so as not to run afoul of other Federal regulations. These models include consultation, program reinvestment, payer contracting, equity/joint ventures, and quality incentive programs.

DNA ploidy of ovarian dysgerminomas: correlation with clinical outcome.

Abnormal nuclear DNA content, as determined by flow cytometry, when combined with conventional prognostic variables such as tumor grade or stage at diagnosis, appears to identify patients who are at increased risk for recurrence of disease. The DNA content of ovarian dysgerminoma, a tumor that is homologous to testicular seminoma and is found in young women of childbearing age, was studied to determine if there is a correlation between DNA content and outcome. Such information would be useful in selecting treatment regimens and making possible the preservation of childbearing potential in women who are likely to have a good outcome. The specimens from 23 cases of ovarian dysgerminoma seen at our institution between 1950 and 1985 were analyzed by DNA flow cytometry. Five of the tumors were diploid (21%) and nineteen were nondiploid (79%). Patient outcome was not predicted any better by nuclear DNA content than by conventional prognostic variables.

Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects.

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.

Analysis of the risk reduction of prophylactic partial mastectomy in Sprague-Dawley rats with 7,12-dimethylbenzanthracene-induced breast cancer.

The effectiveness of prophylactic mastectomy in preventing breast cancer was studied in female albino Sprague-Dawley rats. Group A served as untreated controls. Groups B, C, and D underwent 50%, 75%, and total mastectomies 2 weeks after the administration of 7,12-dimethylbenzanthracene (DMBA). Group E was initially subjected to total mastectomy. Two weeks after surgery, group E received 5 mg of DMBA intravenously. Group F underwent sham procedures. All animals were sacrificed at age 8 months. The mean number of tumors per animal developing in groups A through E was 5.00, 5.17, 4.67, 5.46, and 5.20, respectively. There was 0.21 tumor per animal in group F. The mean time to tumor development in groups A through E was 11.33, 10.05, 9.88, 19.25, and 19.38 weeks, respectively. All results were subjected to an analysis of variance. There was no statistically significant difference in the number of DMBA-induced tumors in groups A through E. Groups D and E had a significant prolonged time to tumor development. The overall risk of the development of breast tumors was not significantly reduced by prophylactic mastectomy. Residual breast tissue after prophylactic mastectomy is at increased risk for the development of breast tumors. The risk of developing breast tumors in this model is not reduced in proportion to the amount of breast tissue removed. (This study suggests that subcutaneous mastectomy in high-risk individuals may not have appropriate prophylaxis against the development of carcinoma of the breast.)

The effectiveness of prophylactic subcutaneous mastectomy in Sprague-Dawley rats induced with 7,12-dimethylbenzanthracene.

Fifty-day-old female, albino Sprague-Dawley rats were induced with DMBA, a potent carcinogen that reliably causes multiple breast tumors. Prophylactic subcutaneous mastectomy was performed 2 weeks after injection. Control animals had no breast tissue removed and developed 5.14 tumors per animal, or 1.3 tumors per quadrant. Animals subjected to 50 percent (unilateral) mastectomy developed 5.4 tumors per animal, with 0.72 tumors per surgical quadrant. Animals that underwent 75 percent (three quadrant) mastectomy developed 4.33 tumors per animal, or 0.48 tumors per surgical quadrant. The incidence of tumors was significantly reduced in the surgical areas. However, the risk of any animal developing a breast neoplasm was not reduced in direct proportion to the percentage of breast tissue removed. We believe that this model may prove valuable in evaluating prophylactic subcutaneous mastectomy.