Hysterectomy,decidualization, LH concentrations and corpus luteum function in the rat

In 1923 Loeb described that the uterus plays an important role in the control of corpus luteum function in the guinea pig: removal of the uterus resulted in a prolongation of the luteal phase. Similar findings have been reported for several other mammalian species (Anderson, 1972). In the rat, hysterectomy does not alter the duration of the estrous cycle (Perry and Rowlands, 1961), but the duration of pseudopregnancy (the equivalent of the luteal phase in the reproductive cycle of other mammalian species) is extended after hysterectomy.The fact that hysterectomy leads to a prolonged luteal phase in certain mammalian species, pointed to the existence of a uterine luteolytic factor (Schomberg, 1969). Some evidence for the existence of a uterine luteolytic substance is available for the rat. It was shown that after removal of the endometrium the duration of pseudopregnancy was extended to almost that observed in hysterectomized rats (Waynforth, 1965). Hechter, Fraenkel, Lev and Soskin (1940) could reduce in the rat the duration of pseudopregnancy with uterine transplants. Furthermore, the duration of pseudopregnancy was shortened after injections of endometrial suspensions (Bradbury, Brown and Gray, 1950) or aqueous endometrial extracts (Dobrowolski, Snochowski and Stupnicki (1974). These observations suggest that the endometrium is the source of the luteolytic factor, and recently evidence was provided that a prostaglandin could be the uterine luteolytic factor (Pharriss, Tillson and Brickson, 1972; Labhsetwar, 1974). Studies in sheep (McCracken, Carlson, Glew, Goding, Baird, Green and Samuelsson, 1972) and in the guinea pig (Blatchley, Donovan, Horton and Poyser, 1972) have provided some evidence for this concept. Also in the rat a prostaglandin may be the uterine luteolytic factor: treatment with prostaglandin F_2α terminates pseudopregnancy in the rat by reducing ovarian and peripheral progesterone concentrations (Pharriss and Wyngarden, 1969; Behrman, Yoshinaga and Greep, 1971). The fact, however, that only a slight increase in F prostaglandins around day 7 of pseudopregnancy and no increase in E prostaglandins was observed (Saksena, Watson, Lau and Shaikh, 1974) throws some doubt upon the idea that a prostaglandin is the luteolytic factor in the rat. On the other hand, the finding that in a bioassay the dose-response curve of endometrial extract from pseudopregnant rats runs parallel with that of prostaglandin F_2α; (Dobrowolski et al., 1974) could be considered as evidence that a prostaglandin is the uterine luteolytic factor in the rat.In the present paper the effects of hysterectomy and decidualization on certain aspects of pseudopregnancy in the rat are discussed.     

Differentiated thyroid carcinoma in the elderly

The overall prognosis of patients with differentiated thyroid cancer is excellent, but the prognosis is rapidly worsening, when the disease is diagnosed in elderly patients. Old patients more often present with poor prognostic features, such as large tumors, follicular or Hürthle cell subtypes, extrathyroidal growth and distant metastases. Therefore, an optimal therapeutic approach is recommended. Current therapy includes a total thyroidectomy, if necessary combined with a lymph node dissection and followed by high dose radioiodine ablation. Radioiodine therapy in elderly patients meets specific problems, concerning thyroid hormone withdrawal, side effects of 131I and nursing problems. Additional treatment of residual, recurrent or metastatic disease must be tailored, according to the stage of the disease, and should not be denied on the basis of chronological age. Lifelong treatment with suppressive thyroid hormone therapy does not lead to important long-term side effects at old age.     

One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults

OBJECTIVE: Increased colonic epithelial cell proliferation has been found in various conditions associated with increased risk of colorectal cancer including acromegaly. In a placebo-controlled study we determined the effect of growth hormone (GH) replacement therapy in GH deficient adults on the colonic epithelial proliferation rate. PATIENTS AND DESIGN: Sixteen GH deficient adults were randomised to low dose GH therapy (1 U (0.5 mg) subcutaneously per day, n = 5), high dose GH therapy (2 U daily, n = 5) or placebo (n = 6) during 6 months. Thereafter, all patients were treated with 2 U of GH daily during a 6-months open extension period. MEASUREMENTS: Plasma Insulin-like growth hormone I (IGF-I) and IGF binding protein 3 (IGF BP3) concentrations were measured using commercial RIA kits. The colonic epithelial proliferation rate, expressed as overall crypt labelling index (LI) using 5-bromo-2'-deoxyuridine (BrdU) immunostaining, was determined at baseline, after 6 months treatment and at the end of the 6 months open extension period. RESULTS: IGF-I rose from 8.9 +/- 6.7 to 34.6 +/- 20.0 nmol/l after 6 months in 8 GH treated patients (P < 0.01 from baseline; P < 0.01 from change with placebo). In the extension study, plasma IGF-I was also increased in the patients who previously received placebo (P < 0.02, n = 5). LI was evaluable in 14 biopsies at baseline, in 16 after 6 months and in 14 after 12 months. Overall crypt LI did not change in 8 GH treated patients after 6 months (P > 0.40 from baseline; P > 0.80 from change with placebo). In the extension study, overall crypt LI was also unchanged in those patients who received GH after placebo (n = 5, P > 0.40) and in those who continued GH replacement (n = 9, P > 0.60; P > 0.80 from change in initially placebo treated patients). Separate evaluation of the LI at the basal, mid and luminal portions of the colonic crypts also did not reveal any effect of GH treatment on BrdU labelling. CONCLUSIONS: Six to 12 months of GH replacement therapy, aimed to increase plasma IGF-I into the (high) physiological range, does not adversely affect colonic epithelial cell proliferation as a biomarker for the risk of development of colorectal cancer.     

Lack of relationship between 11beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients

OBJECTIVES: To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11beta-hydroxysteroid dehydrogenase (11betaHSD) mediated cortisol to cortisone interconversion towards cortisol, and to evaluate whether changes in insulin sensitivity induced by antecedent hyperinsulinaemia are related to changes in the 11betaHSD setpoint. PATIENTS AND MEASUREMENTS: The urinary ratio of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone ((THF + allo-THF)/THE) and of free cortisol/free cortisone (UFF/UFE), as well as the plasma cortisol/cortisone ratio were measured in 8 male type 2 diabetic patients and 8 healthy male subjects without and after 24 h of insulin infusion. Insulin was infused at a rate of 30 mU/kg/h with blood glucose being clamped at euglycaemic levels in healthy subjects and at isoglycaemic levels in diabetic patients. Insulin sensitivity was assessed by measurement of whole body glucose uptake (M-value) during a 3-4 h euglycaemic clamp, directly after the 24 h insulin infusion and compared to the M-value on a control day, at least 1 week apart from the 24 h insulin infusion. RESULTS: Despite impaired insulin sensitivity (M-value, 11.6 +/- 7.7 vs. 28.5 +/- 11.6 micromol/kg/minutes, in type 2 diabetic and healthy subjects, respectively, P < 0.05), urinary (THF + allo-THF)/THE ratio and baseline plasma cortisol/cortisone ratio at 0800 h were similar in type 2 diabetic patients (0.82 +/- 0.07 and 3. 77 +/- 0.70, respectively) and healthy subjects (0.76 +/- 0.14 and 3. 81 +/- 0.88, respectively, ns). Insulin sensitivity was not correlated with urinary (THF + allo-THF)/THE ratio nor with baseline plasma cortisol/ cortisone. In type 2 diabetic patients, insulin sensitivity was further impaired by antecedent hyperinsulinaemia (P < 0.05), but the urinary (THF + allo-THF)/THE ratio (0.80 +/- 0.14, ns) and the plasma cortisol/cortisone at 0800 h (3.66 +/- 0.72, ns) did not change. In healthy subjects, insulin sensitivity did not change significantly (M-value, 22.5 +/- 9.7 micromol/kg/minutes, ns), although the urinary (THF + allo-THF)/THE ratio (0.92 +/- 0.25, P < 0.05) and the plasma cortisol/cortisone (4.59 +/- 0.63, P < 0.05) increased. Insulin did not affect the UFF/UFE ratio in either group. CONCLUSION: The present study does not support the hypothesis that insulin resistance in type 2 diabetes mellitus is associated with an overall change in the 11betaHSD set point towards cortisol. In view of the stimulatory effects of insulin and cortisol on adipogenesis, long-term stimulation of 11betaHSD reductase activity by insulin could aggravate visceral obesity.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.