An example of some of the practical problems associated with the interim monitoring of accumulating time to event data is illustrated through an EORTC clinical trial in locally advanced breast cancer which studied the effects of both hormonal therapy and chemotherapy using a 2 x 2 factorial design. The data monitoring process is described and summaries of the interim statistical analyses and the analysis for publication of the clinical results are provided. The results 2.5 years after closing the trial to patient entry differed quite markedly from those observed during the period of patient accrual, thus showing the potential dangers of drawing conclusions based on only short term follow-up data.

Adult↗

PubMedDate not supplied

Progesterone-transforming enzyme activity in the hypothalamus of the male rat.

The aim of the present study was to assess the activities of the progesterone (Pr) transforming enzyme systems 3alpha-oxidoreductase (3alpha-OR), 5alpha-reductase (5alpha-R) and 20alpha-oxidoreductase (20alpha-OR) in the hypothalamus of the male rat, at different stages of sexual maturation and following castration and adrenalectomy. Special attention was paid to transformation to 3alpha-reduced compounds previously shown to inhibit FSH synthesis and secretion. Homogenates of hypothalamic tissue were incubated with 14C-progesterone. Pr-metabolites were isolated, identified by gas chromatography/mass-spectrometry (GC/MS) and measured by liquid scintillation counting (LSC). In adult rats a ratio of 6:2.5:1 for 5alpha-R:3alpha-OR:20alpha-OR enzyme- activities was found. The hypothalamic 5alpha-R and particularly 3alpha-OR activities were considerably higher before puberty (10-20 day old rats) than in adulthood. Adrenalectomy in adult rats resulted in an increased activity of the three enzyme systems. No significant changes were seen following castration. Among the isolated metabolites, 3alpha-hydroxy-pregn-4-en-20-one (3alpha-Pr) and 3alpha-hydroxy-5alpha-pregnane-20-one (5alpha,3alpha-Pr) were identified. Conversion to both these neurosteroids was considerably higher during prepuberty than in adulthood. The finding that before puberty the hypothalamus has a markedly increased capacity to convert Pr to 3alpha-reduced compounds, such as 3alpha-Pr, known to effectively inhibit FSH release, warrants further research into the mechanisms regulating the hypothalamic formation of biologically active Pr derivatives and their role in the regulation of gonadotropin secretion.

Adrenalectomy↗

PubMedDate not supplied

Voice problems in female-to-male transsexuals.

Voice therapy with the aim of raising a client's fundamental frequency is a common practice in the reassignment of male-to-female transsexuals. In female-to-male transsexuals on the other hand voice therapy is usually not considered since the administration of androgens is assumed automatically to change the voice in the direction of the desired sex. The present study examined whether the voice change in female-to-male transsexuals is indeed as straightforward as it is assumed. Results from a sample survey involving 16 female-to-male transsexuals and longitudinal data from two clients suggest that the voice change in female-to-male transsexuals is not always totally unproblematic. A voice assessment and some counselling before the hormone therapy are recommended.

Adult↗

PubMedDate not supplied

Recombinant humane thyrotropin (rhtSH) a new aid in the diagnosis and treatment of thyroid carcinoma with radio-iodine.

By example of two cases a newly available tool, the recombinant humane thyroid stimulating hormone (rhTSH) is discussed in its use as an adjunct in diagnosing and treating differentiated thyroid carcinoma with radio-iodine. This product is an easier and safe alternative to the necessary rise of TSH induced by thyroid hormone withdrawal and concurrent hypothyroidism. Although discrepancies in favour of the classical approach have been demonstrated in some patients, the clinical relevancy of these must be weighted against the advantage of avoiding undesirable symptoms and possible tumour growth by the use of rhTSH. The role of rhTSH in the follow-up diagnosis and radioiodine treatment of thyroid carcinoma will undoubtedly increase in importance.

Aged↗

PubMedDate not supplied

Surgical therapy in transsexual patients: a multi-disciplinary approach.

A transsexual patient has the constant and persistent conviction that he or she belongs to the opposite sex, thus creating a deeply seated gender identity conflict. With psychotherapy being unsuccessful, it has been proven that in carefully selected patients, gender reassignment or adjusting the body to the mind (both with hormones and surgery) is the best way to normalize their lives. Optimal treatment of these patients requires the multidisciplinary approach of a gender team with the input of several specialties. Such a team consists of a nucleus of physicians who sees the patient more frequently: the psychiatrist, the endocrinologist, the plastic surgeon, the gynecologist and the urologist and a more peripheral group that sees the patients more incidentally: the psychologist, the otorhinolaryngologist, the dermatologist, the speech therapist, the lawyer, the nurse and the social worker. Between 1987 and 1999, a total of 71 male-to-female (MTF) and 54 female-to-male transsexuals have undergone gender confirming surgery in our hospital. This article gives a review and an update on the different surgical procedures as well as on the outcome in our patient population. The results in this series of patients clearly demonstrate that a close cooperation of the different surgical specialties, within our multidisciplinary gender team, is the key to success in treating transsexual patients.

Female↗