Management of early prostatic cancer in the Nordic countries: variations in clinical policies and physicians' attitudes toward radical treatment options.

To explore the treatment of patients with early localized prostatic carcinoma, we surveyed the departments of urology and general surgery in Denmark, Finland, Norway, and Sweden. Clinical policies and physicians' attitudes toward the radical treatment options varied widely between the countries. A correlation seems to exist between practice patterns and national attitudes toward special technologies.

[Prostate cancer in Scandinavia. Variations in practice and attitude to radical treatment]. / Prostatacancer i Norden. Variasjoner i praksis og holdninger til radikal behandling.

Some controversy persists as to the optimal assessment and treatment of prostate cancer, a lack of consensus reflected in differences in clinical practice. Our survey among departments of urology and general surgery in the Nordic countries showed Danish physicians to be the most conservative, while the most active intervention strategies were found in Finland.

Crucial questions for physiotherapy in Finland.

When planning for health services, questions of production and distribution as well as cost and quality are key issues for health planners and decision makers. The lack of available objective data often makes this work difficult. This paper presents recent efforts in Finland to improve the collection of information needed for planning in the field of physiotherapy.

Medical technology assessment in Finland.

We need five kinds of people to guide us further through the integrated process of medical technology assessment: (a) idea generators; (b) entrepreneurs/product, process and practice "champions"; (c) program managers; (d) gatekeepers/communicators; and (e) sponsors/"coaches." If we focus on idea generators, empirical research quickly points out a significant difference between people who create ideas and those who apply the ideas that others have generated. Entrepreneurs and product "champions" promote change and innovation, take ideas, and attempt to move them forward in organizations to gain their adoption. The third necessary contributor to development in medical technology assessment is referred to as the program manager, the person who handles the supportive functions of planning, scheduling, and finance. Communicators are crucial in getting the results of assessment efforts disseminated. The sponsor or the "coach" is a more senior person who does not carry out the research or directly champion change but who provides the encouragement, support, facilitation, and help in "bootlegging activities" that are necessary to aid junior people in their attempts to move research advances forward in an organization. Whether we find these kinds of people in Finland or not--and how long we take to do so--will determine the path of medical technology assessment in Finland toward the year 2000 and beyond.

Percutaneous absorption of hydrocortisone during and after the acute phase of dermatitis in children.

Percutaneous absorption of hydrocortisone was measured by a four-hour absorption test in 16 children during and after the acute phase of dermatitis. In the acute phase, after the application of 1% hydrocortisone cream the increment in plasma cortisol ranged from 47 to 961 nmol per liter (median 248 nmol/L). After the acute phase the increment was significantly (P less than 0.01) lower: range 18 to 241 nmol per liter (median 95 nmol/L). In addition to local effect, topical hydrocortisone therapy of childhood dermatitis is accompanied by a systemic effect that may be pronounced in the acute phase of disease. Convalescence is connected with a diminished systemic effect due to the restoration of the skin barrier to hydrocortisone.

Effect of percutaneous absorption of hydrocortisone on adrenocortical responsiveness in infants with severe skin disease.

Percutaneous absorption of hydrocortisone was studied in 18 children (aged from 6 weeks to 14 1/2 years) with atopic or seborrhoeic dermatitis, by measuring their serum cortisol before and after application of 1% hydrocortisone cream. Endogenous secretion of cortisol was suppressed with dexamethasone. A 24 h absorption test was performed on nine children. In six, percutaneous absorption was detected. The highest serum cortisol level was reached within the first 6 h. A 4 h absorption test was developed on the basis of the 24 h test. This short absorption test was performed on nine children, and in eight of them absorption of hydrocortisone was detected. The rise of serum cortisol ranged from 98 to 2669 nmol/l. The 2 h ACTH test was performed to evaluate the effect of previous treatment with topical glucocorticoids. Suppressed adrenocortical function was found in five of 13 children, and was associated significantly with high post-application serum cortisol levels. This occurred more often in infants with a severe skin disorder than in older children or in those with mild or moderate skin disease.

Growth in Cushing syndrome.

Pre- and post-operative growth was analysed in eight children with Cushing syndrome. Six children had Cushing's disease; three of them were treated by bilateral adrenalectomy and three by transphenoidal pituitary adenectomy. One child had an adrenocortical adenoma and another primary adrenocortical nodular dysplasia. The typical cushingoid habitus was not always present during hypercortisolism. In contrast, abnormal deceleration of longitudinal growth and increase in relative weight were constant. The slowing of growth started 0.2-5.1 years before diagnosis. In four children these changes concurred. In three others the excessive weight gain preceded the slowing of growth, by 2.5-7.0 years. In one patient the deceleration appeared first; this was a girl with concomitant coeliac disease. This pattern of growth change occurring before (normal slowing of growth in) late puberty should raise the possibility of hypercortisolism. There was a suggestion of a better growth recovery in Cushing disease after pituitary adenectomy than after bilateral adrenalectomy.

Cortisol augments synthesis of growth hormone, but does not alter synthesis of prolactin and proopiomelanocortin, in the 120- to 125-day fetal ovine pituitary.

In adult animal pituitaries or in cultured pituitary tumor cells, glucocorticoids are regulators of GH, PRL, and proopiomelancortin (POMC) synthesis. However, ovine fetal plasma cortisol concentrations are low until shortly before parturition, suggesting that cortisol may not normally regulate hormone synthesis in the fetal pituitary. To investigate whether cortisol could affect fetal synthesis of GH, PRL, and POMC, we obtained fetal pituitary tissue from normal fetuses and from fetuses which had received cortisol infusion for 48 h. Tissues were labeled in short term organ culture and the newly synthesized proteins were displayed by two-dimensional gel electrophoresis and autoradiography. Results were quantified by computerized integration of the area and density of the autoradiographic spots after high resolution television scanning. Cortisol infusion augmented synthesis of GH in comparison to controls (P = 0.01), but did not alter PRL synthesis. Cortisol also did not inhibit POMC synthesis in either the anterior pituitary or the neurointermediate lobe. These data suggest that the pituitary-adrenocortical slow feedback inhibition of POMC synthesis is not functional in the ovine fetus at 120 to 125-days gestation, but that pituitary somatotropes are responsive to glucocorticoids at this stage of fetal development.

The diagnosis and staging of hypocortisolism in progressing autoimmune adrenalitis.

The course of development of hypocortisolism was studied in 20 patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED) for 1.3-9.3 years during which time the patients underwent at least three 2-h ACTH tests (2hAT). A slow progression of the disease was evident and could be staged. The earliest indicators of incipient failure were subnormality of the 2-h cortisol level alone or with subnormality of the 2-h increment. The increment was then abolished. A normal basal level was maintained longer. Longer forms of the ACTH tests produced normal responses even after the early stages of failure. A constantly elevated ACTH concentration and low cortisol/ACTH ratio in plasma were likewise signs of advanced hypocortisolism. Current criteria of primary hypocortisolism are thus indicators of the late stages of failure only. The presence of circulating adrenocortical antibodies is predictive of hypocortisolism. Some patients had normal 2hAT responses, but antibodies and subnormal cortisol/ACTH ratios. This may represent a state of compensatory activation of the hypothalamic-pituitary-adrenocortical axis.

Risk of relapse in steroid-sensitive nephrotic syndrome: effect of stage of post-prednisone adrenocortical suppression.

Glucocorticoid therapy has been effective in inducing remission in the majority of children with primary nephrotic syndrome. However, glucocorticoid-induced adrenocortical suppression is associated with early relapse, whereas normal adrenocortical function seems to delay the subsequent relapse. We analyzed 201 episodes of prednisone treatment in 47 children with steroid-sensitive nephrotic syndrome by the life-table method. The effect of partial cortisol substitution was studied as well. Adrenocortical function was determined by a two-hour ACTH test. A response of 50% to 100% of the minimum normal response was diagnosed as "moderate" suppression, and a response of less than 50% as "severe." Post-prednisone adrenocortical function was normal in 99 episodes (49%). Adrenocortical suppression occurred in 102 episodes; of these, 68 were considered moderate and 34 severe. Adrenocortical suppression increased both the initial relapse rate and the final risk of a relapse. Severe suppression was always associated with a relapse, the longest remission time being 0.5 year. In moderate suppression, several long, relapse-free intervals were observed, but the risk of relapse was still higher than in episodes with normal adrenocortical function. Cortisol substitution possibly decreased the risk of a relapse after severe adrenocortical suppression, but not after moderate suppression.

Endocrine, histological, and biochemical studies of adrenocorticotropin-producing islet cell carcinoma of the pancreas in childhood with characterization of proopiomelanocortin.

Two 8-yr-old children, a boy and girl, are described with Cushing's syndrome secondary to ectopic ACTH-secreting pancreatic islet cell carcinomas. The girl, seen 28 yr ago, had strong presumptive evidence of ectopic ACTH production and hypercalcemia. The boy, studied recently, had strikingly elevated concentrations of plasma ACTH (1,500 pg/ml) and beta-lipotropin (beta LPH; 2,500 pg/ml) and showed no suppression of urinary 17-hydroxycorticoids or cortisol with low and high dose dexamethasone. He had increased plasma calcitonin (257 pg/ml), glucagon (442 pg/ml), lactate dehydrogenase (497 IU/liter), and alpha-fetoprotein (5,144 pg/ml). He also had hypokalemic alkalosis with elevated plasma deoxycorticosterone (70 ng/ml) and PRA (6.9 ng/ml.h) but normal plasma aldosterone (8.2 ng/dl) and 18-hydroxycorticosterone (7.6 ng/dl). Preoperative localization of the tumor was accomplished by computed tomographic scan of the abdomen with concurrent barium enema. Cell-free translation of the tumor mRNA produced authentic proopiomelanocortin of 35,000 mol wt, indicating that the ACTH and beta LPH were produced by the tumor from a common precursor. After removal of a large amount of metastatic tissue from the boy, clinical progression of the remaining tumor was monitored by measuring plasma ACTH and beta LPH. Episodic secretion of ACTH and beta LPH was demonstrated by taking frequent plasma samples while suppressing pituitary ACTH with oral dexamethasone. Chemotherapy and radiation proved ineffective in controlling the growth of his tumor.

Hormone ontogeny in the ovine fetus. XV. Studies of adenohypophysial hormones after fetal pituitary stalk section: evidence for an extrahypothalamic dopaminergic influence on fetal prolactin secretion.

The administration of a dopamine antagonist, haloperidol, to the ovine fetus in late gestation elevates plasma concentrations of PRL, suggesting tonic dopaminergic inhibition of fetal PRL secretion. The source of this dopaminergic inhibition was investigated in chronically catheterized ovine fetuses (104-135 days of gestation) after hypophysial stalk section (SS; n = 4) and in sham-operated controls (CON; n = 7). Basal PRL levels were similar in the two groups of fetuses. After the administration of TRF (250 micrograms, iv), PRL levels rose comparably in both the SS and CON fetuses. The only difference was a higher mean incremental response (P less than 0.02) in the SS fetuses. The dopamine agonist apomorphine (100 micrograms/kg, iv) induced a similar suppression of fetal PRL concentrations in CON (n = 4) and SS (n = 2) fetuses. After the administration of haloperidol (1 mg, iv) to the CON fetuses (n = 7), the concentration of fetal PRL rose (P less than 0.01). In the SS fetus (n = 4), haloperidol induced a rise in PRL concentrations (P less than 0.01); however, the response to haloperidol was less (P less than 0.01) in SS than in CON fetuses. These data suggest that there is persistent dopaminergic inhibition of PRL secretion in the fetus after complete stalk section, and that the source of this dopamine is extrahypothalamic. The greater incremental PRL response to TRH and the lesser response to haloperidol in the SS fetus than in CON are evidence for a hypothalamic component to the dopaminergic inhibition in the intact fetus. Basal FSH concentrations and the gonadotropin response to LRF were not affected by stalk section in fetuses studied 5-8 days after surgery. Both the PRL and the GH responses to 5-hydroxytryptophan were abolished by stalk section. After stalk section GH levels fell, however, significant concentrations of GH were measurable in fetal plasma in late gestation, which suggests that the fetal pituitary can secrete GH in the absence of hypothalamic stimulation at this stage in gestation.

Synthesis of growth hormone, prolactin, and proopiomelanocortin by intact adult ovine pituitary tissue in vitro.

Synthesis of GH, PRL, and proopiomelanocortin (POMC) by the adult ovine pituitary was examined by culturing intact tissue explants in vitro and analyzing newly synthesized proteins by two-dimensional gel electrophoresis. Spots on autoradiographs of two-dimensional gels were identified by comigration with known standards, by analysis of tryptic peptides, or both. GH and PRL are the predominant proteins synthesized in the adult ovine pituitary, but their syntheses could not be detected in the neurointermediate lobe of the pituitary, the cerebral cortex, hypothalamus, mammillary body, or placenta. As quantified by cell-free translation in rabbit reticulocyte lysate, 14% of female ovine pituitary mRNA encodes pre-GH and 30% encodes pre-PRL. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ovine pre-GH and pre-PRL have molecular weights of 24,500 and 26,000, respectively, indicating they contain leader peptides of 26-30 amino acids, as found in bovine, rat, and human pre-GH and pre-PRL. POMC, the precursor to corticotropin, endorphin, and other peptides, was synthesized primarily in the neurointermediate lobe of the pituitary, but synthesis was also detected in the anterior lobe. POMC synthesis was not detected in the hypothalamus, cerebral cortex, mammillary body, or placenta.

Blood cell polyamines in children with short stature in reference to growth hormone activity.

The molar ratio or two blood polyamines (spermidine to spermine) was investigated in 54 children with shortness of stature. The long-term reproducibility of this ratio was 9.0%. In children with no endocrine disturbances, the mean ratio was 0.97. In children with isolated growth hormone deficiency, it was 0.61, and in those with growth hormone and ACTH deficiency, it was 0.67, both significantly low values. The ratio showed a significant positive correlation with growth hormone response to insulin hypoglycemia (r = 0.58; P less than 0.001) and with the nitrogen retention response to short-term growth hormone therapy (r = 0.45; P less than 0.001). In contrast, no such correlation was present with cortisol response to hypoglycemia.

Effects of physical training on hormonal responses to exercise in asthmatic children.

A 4-month period of physical training increased the physical working capacity of 16 asthmatic children (aged between 9.3 and 13.6 years) by a mean of 11%. The increase was greater in boys and was negatively correlated with pretraining capacity. Urinary excretion of adrenaline, measured during a submaximal exercise test, decreased during the training period; the decrease was correlated with the increase in working capacity. Be fore the training period, exercise induced an increase in the plasma cortisol level; no increase was evident after training. In contrast, the training did not affect the exercise-induced increase in the plasma growth hormone level.

Growth failure from symptomless celiac disease. A study of 14 patients.

In 14 children and adolescents, abnormally short stature was shown to be due to celiac disease (CD) though the patients had no current gastrointestinal symptoms. Growth failure had appeared in the first years of life, and was associated with a marked lag in bone age. Subnormal growth hormone (GH) responses were demonstrated in 4 patients, and subnormal ACTH responses in 2. In 1 patient permanent isolated GH deficiency coincided with CD. A jejunal biopsy should form part of the routine diagnostic evaluation for abnormally short stature, except in patients who have had normal growth during the first year of life.