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AIMS: To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non-diabetic controls, and explore potential determinants for this difference. METHODS: Data are from the SEARCH for Diabetes in Youth Case-Control Study. A total of 440 youth with Type 1 diabetes and 191 non-diabetic healthy controls age 10-22 years of non-Hispanic White (NHW), African-American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA(1c)). RESULTS: Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 microg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA(1c) in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity. CONCLUSIONS: Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.

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A novel approach to biotransformation is described using a solid medium matrix and Reemay mesh that gives efficient biotransformation of compounds with minimal matrices in the ensuing gum solids. Using this approach with a newly isolated biotransforming organism, Streptomyces lydicus SX1298, a series of hydroxylations and an O-demethylation is described for selamectin the first endectocide for cats and dogs.

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PURPOSE: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). RESULTS: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. CONCLUSION: Combined hormonal and radiation therapy represents an effective treatment option for patients with adenocarcinoma of the prostate metastatic to pelvic lymph nodes. Combined modality therapy appears to extend the disease-free survival and allow patients to maintain their independent function.

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OBJECTIVES: To evaluate the efficacy of combined radiation and hormonal therapy in patients with prostate cancer metastatic to the pelvic lymph nodes. METHODS: Fifty consecutive patients with node-positive prostate cancer were evaluated by the Departments of Urology and Radiation Oncology at the University of Pennsylvania and offered combined hormonal and radiation therapy. All patients received pelvic radiation to 45 Gy, with a boost dose to the prostate to 65 to 71 gy. Forty-five of the patients were treated with concurrent hormonal therapy consisting of diethylstilbestrol (2 patients), orchiectomy (18 patients), leuprolide (5 patients), or combined androgen blockade (20 patients); the other 5 patients declined hormonal therapy. Patients represented a group with locally advanced disease with a high incidence of T3 tumors (66%), high grade (74%; Gleason score more than 7), high prostate-specific antigen (PSA) (40%; more than 30.0 ng/mL), and a high incidence of gross (36%) or bilateral (30%) adenopathy and a high incidence of multiply involved lymph nodes (62%). RESULTS: Median follow-up of patients is 42 months (range, 10 to 102). All 5 patients declining hormonal therapy relapsed within 18 months and only 1 patient survived longer than 3 years. Among patients treated with combined hormonal and radiation therapy, the 6-year survival rate is 82%, the clinical disease-free survival at 6 years is 71%, and the probability of survival free of recurrence, with a PSA less than 0.2 ng/mL, is 62%. Only two PSA recurrences occurred, both in patients who elected to discontinue hormone therapy. There was no synergistic toxicity observed as a result of combined therapy. CONCLUSIONS: Combined hormonal and radiation therapy offers the potential for extended disease-free survival and may represent an effective treatment option for patients with locally advanced prostate cancer.

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Between 1975 and 1985, 16 adult patients high grade soft tissue sarcomas arising in the head and neck were treated with combined modality therapy at the National Cancer Institute. Fifteen patients underwent an attempt at gross resection, while only a biopsy was performed in 1 patient. All patients received conventionally fractionated, high-dose, post-operative irradiation. Twelve of 16 patients received adjuvant chemotherapy with cyclophosphamide and adriamycin, given concomitantly with radiation therapy. With a median follow-up of 43 months from diagnosis (range 11-116 months), 10 patients (64%) are disease-free. Of these 10 patients, 1 presented with pulmonary metastases and 2 patients later failed in the lung; all pulmonary disease was resected and these patients are disease-free at 80, 115, and 116 months following presentation. Local control was maintained in 12 patients (75%). An analysis of the iso-effect lines for local control shows a slope of 0.32. The median NSD for local control was 1720 ret. We conclude that aggressive local management of high grade sarcomas which combines gross resection and high-dose post-operative irradiation results in excellent local control. The role of adjuvant chemotherapy is less well defined in this small patient series. The acute and late complications of this combined modality approach are manageable.

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The incorporation of 14C-cholesterol into total androgens by testis homogenates and into total androgens and corticosterone by adrenal homogenates was measured in tissues taken from rats deficient in vitamin E, and from rats given vitamin E, from weaning to a maximum of 293 days. The peak of incorporation of 14C into adrenal steroids, androgens and corticosterone, were delayed in the rats deficient in vitamin E, which might suggest a delayed or prolonged period of puberty in vitamin E deficiency. After this period of increased steroidogenesis the deficient rats incorporated consistently less 14C into adrenal steroids and testicular androgens than did the control rats, although the differences were not statistically significant in the experiments described.

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The effect of vitamin E deficiency on three enzyme systems involved in steroidogenesis was investigated. No change was found in vitro activity of cholesterol side-chain cleavage enzyme in adrenal or testicular tissue, or of 11-beta-hydroxylase activity in adrenal tissue. Significantly less 3-beta-hydroxysteroid dehydrogenase activity was found in ovarian tissue from female rats given a diet deficient in vitamin E for 141 days, and in testicular tissue and adrenal glands from male rats given the deficient diet for 280 days. Testicular tissue from male rats given the deficient diet for 91 days showed considerably less 3-beta-hydroxysteroid dehydrogenase activity than did tissue from control rats, but the difference was not statistically significant.

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