Progestogen-only oral contraceptives and risk of breast cancer in New Zealand

Little is known about the influence of progestogen-only contraceptives on a woman's risk of breast cancer. This issue was examined in a national population-based case-control study in New Zealand. A total of 891 women aged 25 to 54 years with a first diagnosis of breast cancer and 1,864 control subjects, randomly selected from the electoral rolls, were interviewed. Use of progestogen-only pills was reported by 8.7 percent of all control subjects (and by 17.3 percent of those aged 25 to 34 years). The relative risk (RR) of breast cancer in women who had ever used progestogen-only pills was estimated to be 1.1 (95 percent confidence interval [CI]=0.73–1.5). In women aged 25 to 34 years, the RR was 2.3 (CI=1.2–4.3). Women who had started using progestogen-only pills within the last 10 years were at increased risk of breast cancer (RR=1.6, CI=1.0–2.4), whereas those who had first used them earlier were at significantly reduced risk (RR=0.44, CI=0.22–0.90). These findings are similar to results for depot medroxyprogesterone acetate, and a possible analogy with the influence of pregnancy is also suggested.The anthors are with the Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. Address correspondence to: Dr Skegg, Department of Preventive and Social Medicine, University of Otago Medical School, P. O. Box 913, Dunedin, New Zealand. This research was supported by grants from the Medical Research Council of New Zealand and from the Special Program of Research, Development, and Research Training in Human Reproduction, World Health Organization.     

雌激素在MNU诱导大鼠膀胱肿瘤的抑癌作用及治疗膀胱癌的实验研究

 本实验用切除卵巢的WISTAR大鼠。给予N-METHYL-N-NITROSOUREA(MNU)0.5mg进行膀胱内灌注，每周一次，共四周。MNU总量2.0mg，再分别给予戊酸雌二醇和丙酸睾丸素肌肉注射至20周。实验结果表明戊酸雌二醇对MNU诱导的大鼠膀胱肿瘤有抑制作用。另外以苯甲酸雌二醇、戊酸雌二醇，乙烯雌酚，甲地孕酮，黄体酮对小鼠膀胱癌瘤株BST₇₃₉，BTT₇₃₉进行实验治疗研究，果表明对BST₇₃₉、BTT₇₃₉均有治疗作用。     

放射性碘致大鼠甲状腺损伤超微结构的形态计量学研究

本文应用透射电镜观察了在较低剂量１３１Ｉ作用大鼠甲状腺滤泡上皮细胞超微结构的变化特点，分析了线粒体的变异发生率，并应四川大学研制的ＭＩＡＳ－３００图像分析系统和用形态计量学方法，测定了胞质内粗面内质网的二维和三维形态计量学参数。结果表明：所测的各项参数都有随剂量增高而增大的趋势，并呈现较好的效应剂量依赖关系。由此计算的Ｄ２５值和Ｄ５０值，以粗面内质网体积密度的变化最为明显。提示，低剂量１３１Ｉ作用于滤泡上皮细胞，其早期应重视内质网的损伤效应，以及由此导致合成类固醇激素和外源性蛋白质的障碍     

Adrenocortical reserve of neonates born of long-term,steroid-treated mothers

Since corticosteroids have been shown to be transferred across the human placenta, prolonged administration of these drugs during gestation could be expected to suppress the response of the neonatal adrenal gland. Plasma cortisol levels, before and 30 min after the injection of ACTH (36 g/kg), were determined in six neonates who were exposed in utero to prolonged maternal administration of prednisone. The basal plasma cortisol levels of these neonates (6.15±2.57 g%; mean±SEM) were similar to values obtained in eight healthy neonates (5.19±1.36g%). The increment of cortisol levels after ACTH stimulation (16.4±2.07 g%) of the study patients was larger (P<0.01) than the change (10.3±0.82 g%) observed in six older controls. These results indicate a normal neonatal adrenal reserve after prolonged exposure to corticosteroids during fetal life.     

Simultaneous occurrence of papillary intrafollicular and microcarcinomas with bilateral medullary microcarcinoma of the thyroid in a patient with multiple endocrine neoplasia type 2A: report of a case

We report the case of a simultaneous occurrence of papillary intrafollicular and microcarcinomas with bilateral medullary microcarcinoma of the thyroid in a patient with multiple endocrine neoplasia type 2A. The concurrent presence of two thyroid carcinomas is rare. The simultaneous occurrence of two different tumors in the same thyroid each being multifocal and smaller than 1 cm in diameter has not been previously reported in the literature. Furthermore, we define the first case of intrafollicular papillary thyroid carcinoma (carcinoma in situ). Received: June 11, 2001 / Accepted: January 8, 2002     

Effect of clofibrate administration on the esterification and deesterification of steroid hormones by liver and extrahepatic tissues in rats

Treatment of rats with clofibrate markedly stimulated the liver microsomal esterification of estradiol, testosterone, pregnenolone, dehydroepiandrosterone, and corticosterone by acyl-CoA:steroid acyltransferase. This enzyme catalyzes the esterification of estradiol with long-chain fatty acids in both liver and extrahepatic tissues. In untreated control rats, brain had the highest acyltransferase activity per milligram of microsomal protein for estradiol esterification (3- to 4-fold higher than in the liver). Although, treatment of rats with clofibrate stimulated the esterification of estradiol by 9- to 14-fold in the liver, estradiol esterification in kidney, lung, brain, uterus, fat, and mammary glands was not increased, indicating that liver may be uniquely sensitive to induction of acyl-CoA:estradiol acyltransferase by clofibrate. In additional studies, esterase activity for hydrolysis of the oleoyl ester of estradiol was determined in control and clofibrate-treated rats. Clofibrate administration increased esterase activity by an average of 107% in fat and 70% in liver. The results indicate that treatment of rats with clofibrate stimulates the hepatic formation of highly lipophilic fatty acid esters that can be hydrolyzed in the liver and in extrahepatic tissues to the parent steroid hormone by a clofibrate-inducible esterase.     

Thyroid hormones in the pathogenesis and treatment of obesity

Thyroid hormones (TH) are potent modulators of adaptive thermogenesis and can potentially contribute to development of obesity. The decrease of T₃ in association with reduction of calorie intake is centrally regulated via decreases in leptin and melanocortin concentrations and peripherally via a decrease in deiodinase activity, all aimed at protein and energy sparing. The use of TH in the treatment of obesity is hardly justified except in cases of elevated thyrotropin (TSH) with low/normal T₃ and T₄ and/or a low T₃ or T′₃/T₄ or a high TSH/T₃ ratio. TH treatment with small doses of T₃ can also be exceptionally applied in obese patients resistant to dietary therapy who are taking β-adrenergic blockers or with obesity developed after cessation of cigarette smoking and with hyperlipidemia and a concomitant high thryrotropin/T₃ ratio. Supplementation with Se²⁺ and Zn²⁺ may be tried along with more severe calorie restriction to prevent decline of T₃.     

Multiple sclerosis,interferon beta and clinical thyroid dysfunction

The objective of this study was to investigate frequency and presentation of clinical thyroid dysfunction in patients treated with interferon beta (IFN-beta). We have collected the cases of clinical thyroid dysfunction in 700 consecutive patients receiving IFN-beta for multiple sclerosis (MS). Five patients (four women, one man) treated with IFN-beta1b developed hyperthyroidism. Three of them have secondary progressive MS, and two have relapsing-remitting MS. It was necessary to stop IFN-beta in three cases; these patients still require carbimazole after several months. In the two other cases, hyperthyroidism disappeared spontaneously. Two patients (one man and one woman) treated with IFN-beta1a developed hypothyroidism. One of them required l-thyroxine. Lastly, an increased thyroid volume without modification of thyroid hormones plasma levels was discovered in a patient receiving IFN-beta1a. Among patients treated with IFN-beta, clinical thyroid dysfunction is much rarer than laboratory thyroid dysfunction. However, this side-effect is sometimes severe.     

Modulation by thyroid hormones of rat parotid amylase secretion stimulated by 5-hydroxytryptamine

The effects of 5-hydroxytryptamine (5-HT) upon amylase secretion by rat parotid glands were studied in three groups of animals: (a) intact control rats (euthyroid rats); (b) hypothyroid rats obtained by surgical thyroidectomy 2 wk before the experiments; and (c) hyperthyroid rats obtained by the administration of sodium l-triiodothyronine for 2 wk before the experiments. Hyperthyroid rats showed significantly higher baseline amylase release than control rats. When the glands were stimulated with 5-HT (30 micro m), amylase release was significantly lower in the hypothyroid group and higher in the hyperthyroid rats than in control group. Addition of cholinergic, adrenergic or substance P antagonists did not modify 5-HT-stimulated amylase activity. The effects of 5-HT were partly but significantly blocked by the addition of 10 micro m methysergide (HT1/2/7 receptor blocker) in the three groups of rats. In contrast, 10 micro m ketanserine (HT2A receptor blocker) partly blocked the response to 5-HT only in the hyperthyroid animals. It was concluded that 5-HT induces amylase secretion by rat parotid glands through specific serotoninergic receptors, and that thyroid status modulates the 5-HT effect.     

Functional capacity of the thyroid autograft: an experimental study

BACKGROUND: The aim of this study was to investigate the functional capacity of thyroid autografts after total thyroidectomy in a rabbit model. MATERIAL AND METHODS: Thirty-eight rabbits underwent total thyroidetomy. One of the two thyroid lobes was cut into 1-mm pieces and was introduced intramuscularly into the right quadriceps muscle (group A, n = 10), the right rectus abdominalis muscle (group B, n = 10), and the right sacrodorsalis muscle (group C, n = 10). Another group of 8 rabbits underwent total thyroidectomy without autologous implantation and served as the control group (group D). The animals were observed for 8 weeks with weekly measurements of thyroid hormones. At the end of the 8th week, a scintigram was performed. The autografts were removed 2 days later. RESULTS: The thyroid hormone levels showed a gradual decrease until the 2nd-5th week after implantation, followed by a gradual increase and establishment of euthyroid levels between the 5th and 8th weeks. Respectively, an increase of thyreotropin hormone was noted with maximal values in the 4th week, followed by a gradual decrease until the end of the 8th week. The scintigram at the end of the 8th week revealed the presence of functional thyroid tissue in all cases. Functional thyroid follicles were found in all animals who survived. In 35.7% of the autografts, we noted the development of fibrous tissue and gigantocytic granulomas in the periphery, which could be interpretated as a "foreign body" reaction. CONCLUSION: Thyroid autografts can completely substitute thyroid function after total thyroidectomy.