[Diabetes mellitus and breast cancer. A retrospective follow-up study]. / Diabetes mellitus und Mammakarzinom. Eine retrospektive Verlaufsstudie.

The influence of diabetes mellitus on the course of breast cancer was investigated retrospectively in 752 patients. Possible unfavourable prognostic factors like overweight, lipid disorders, age and menopausal status were considered as confounders in a Cochran-Mantel-Haensel analysis. There was no difference in primary tumor status and lymph node involvement between patients with diabetes mellitus and nondiabetic patients. Diabetic patients had more often overweight, lipid disorders and were older than nondiabetic patients. Metastatic disease was highly significant correlated with primary tumor status (p less than 10(-6)) lymph node involvement (p less than 10(-10)) and diabetes mellitus (p less than 10(-5)). Overweight, lipid disorders, age and menopausal status were not correlated with metastatic disease. A possible explanation of the correlation between diabetes mellitus and metastatic disease could be hyperinsulinism in type IIB diabetes. A type IIB diabetes in most of the patients included in this study is very plausible because of the correlation between overweight, lipid disorders, old age and diabetes mellitus. This type of diabetes is characterised by a relative resistence to insulin in the target tissues and a prolonged and exceeding insulin secretion. Experimental data demonstrate that insulin stimulates the growth of breast cancer cell in vivo and in vitro.

Plasma exchange and concomitant therapy in TTP.

Since plasma exchange was introduced in the management of thrombotic thrombocytopenic purpura (TTP) in 1977, patient survival rate has increased from 10 to 80%. However, approximately 50 subsequent case reports in the literature provide no consensus as to the optimal therapy. We review here 4 episodes of TTP in 3 patients. In all cases, treatment was started with intensive FFP plasma exchange combined with administration of antiplatelet agents and corticosteroids. Remission was achieved in 3 out of 4 episodes although all required individualization of the medication regimen. In the remaining patient, cytotoxic therapy (vincristine) and ultimately splenectomy were required to achieve stable remission. The variable clinical response to these therapeutic protocols indicates that TTP may not represent a single homogeneous disease entity but rather may involve various underlying pathologies. We conclude that the most effective present therapy for the management of TTP is daily plasma exchange with fresh frozen plasma infusions combined with antiplatelet agents and steroids. Vincristine and splenectomy should only be employed if this protocol proves ineffective.

Combined hMG/hCG treatment in subfertile men with idiopathic normogonadotrophic oligozoospermia.

Forty-eight patients with idiopathic normogonadotrophic oligozoospermia were treated with hMG plus hCG over a period of 3 months. Total sperm output increased by an average of 15.3 million spermatozoa per ejaculate and a similar significant increase was seen in the percentage of motile spermatozoa. Sixteen of the 48 men increased their sperm output by 25 million or more. Follow-up information was available in 33 patients. Ten pregnancies were reported within one year after initiation of treatment. Six of 12 responders impregnated their wives, whereas only 4 pregnancies were reported in a group of 21 non-responders. Endocrinological investigations showed no differences in mean basal levels of LH and FSH, or in the gonadotrophin response to a 100 micrograms GnRH stimulation between responders and non-responders. However, mean basal plasma testosterone concentration was significantly lower in the responder group than in the non-responders. Responsiveness to gonadotrophin treatment tended to be better in patients with basal plasma testosterone concentration lower than 4.5 ng/ml. Combined hMG/hCG treatment in subfertile men with idiopathic oligozoospermia seems to be efficient in only a small proportion of cases.

17-ketosteroid reductase deficiency -- plasma steroids and incubation studies with testicular tissue.

The patient, diagnosed as a case of testicular feminisation in infancy, was examined at the age of 15 years because of severe symptoms of virilising puberty with poor breast development. Plasma steroid analyses revealed a 10-fold elevated androstenedione concentration (A: 1562 ng/100 ml). Testosterone (T: 266 ng/100 ml) was in the male pubertal range. Thus the A/T-ratio was far above normal. The oestrone/oestradiol ratio was also elevated (Oe1/Oe2: 10.2/2.2 ng/100 ml). A, T, Oe1 and Oe2 could not be suppressed by dexamethasone, but reacted promptly to fluoxymesterone (A: 781 ng/100 ml). hCG caused a further increase of the A/T-radio (2220/246 ng/100 ml); ACTH did not alter the A-concentration. These findings together with simular investigations after gonadectomy suggest that the failure to convert A to T and Oe1 to Oe2 is essentially located in the testes. In vitro incubations of testicular tissue showed reduced 17-ketosteroid reductase activity in tissue slices and in the subcellular fractions microsomes and cytosole. This form of male pseudohermaphroditism can easily be detected already in infancy, if steroid analyses and stimulation tests are performed. In case of female sex assignment patients should be submitted to early orchidectomy in order to avoid virilisation in puberty.