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Often long-term low-dosage glucocorticoid therapy cannot be terminated. This is due to the fact that even low doses which are within the physiological replacement range can cause a detectable, though clinically insignificant suppression of the adrenal gland function, resulting in "corticosteroid withdrawal syndrome". Another reason is the fact that it is necessary to be able to suppress undesirable inflammatory reactions caused by the underlying disease. ACTH testing of the adrenal capacity is widespread, but repeated testing may lead to undesirable side effects, such as allergic reactions. This study investigates the usefulness of testing the function of the pituitary-adrenal axis in predicting withdrawal problems. In 21 patients with chronic inflammatory disease who were treated with glucocorticoid doses of 5 to 10 mg prednisolone equivalent daily for a period of 2 to 131 months, stimulation with 100 microg hCRH (human corticotrophin-releasing hormone) was performed prior to the gradual withdrawal of medication. Blood samples were taken at baseline and after 45 minutes to measure ACTH and cortisol levels. Four weeks after steroid withdrawal the patients were reevaluated for signs of a relapse of the underlying disease in order to establish the necessity of reintroducing steroid therapy. This reevalution comprised clinical criteria, laboratory tests and the patients' own assessment of his/her well-being. In sixteen patients who later successfully withdrew from glucocorticoid therapy, a significant increase in cortisal levels was noticed after stimulation with CRH (p < 0.05). In five patients, with whom steroid withdrawal was not successful, baseline levels of cortisol were significantly lower than in the others (p < 0.05) and no sufficient increase was achieved after stimulation with CRH. These results show that successful withdrawal of a long-term low-dosage glucocorticoid therapy depends on the integrity of the pituitary-adrenal axis. Therefore CRH testing for evaluation of the pituitary-adrenal axis can be helpful in identifying patients in whom glucocorticoid withdrawal would be troublesome.

BACKGROUND: Nitric oxide (NO) is an unstable vasodilator formed by NO synthetase (NOS) from L-arginine (L-Arg) in various cells but its role in the control of pancreatic secretion in humans has not been examined. AIMS: This study was designed to determine the role of endogenous NO in the control of exocrine and endocrine pancreas using NOS inhibitor, NG-monomethyl-L-Arg (L-NMMA). METHODS: Pancreatic secretion was stimulated by intravenous infusion of secretin (80 pmol/kg/h) plus caerulein (50 pmol/kg/h) and duodenal content was aspirated by gastroduodenal tube. Two series of tests with secretagogue infusion were performed, one, with addition of graded doses of L-NMMA and, another, with addition of a constant dose of L-Arg alone followed by L-NMMA alone and finally by a combination of L-Arg and L-NMMA. RESULTS: Addition of L-NMMA in graded doses (2-8 mumol/kg/h) reduced dose dependently the secretin-caerulein stimulated pancreatic enzyme secretion without alterations in the volume flow and bicarbonate outputs. The addition of L-Arg to L-NMMA reversed the inhibitory action of L-NMMA on protein enzyme response to secretin-caerulein in these subjects. Secretin-caerulein infusion caused significant increase in plasma insulin and pancreatic polypeptide levels but without changes in plasma glucagon or somatostatin levels. L-NMMA alone resulted in a significant fall in plasma insulin and pancreatic polypeptide levels, while L-Arg added to pancreatic secretagogue infusion caused a significant increase of plasma insulin and pancreatic polypeptide levels above those attained with secretagogues alone. After the addition of L-Arg to L-NMMA, both plasma insulin and pancreatic polypeptide levels rose significantly above the levels observed with L-NMMA plus secretin-CCK stimulation. CONCLUSION: This study provides evidence that the suppression of NOS reduces pancreatic enzyme secretion and the plasma insulin and pancreatic polypeptide levels suggesting that endogenous NO affects both exocrine and endocrine pancreatic secretion in humans.

The causes of Budd-Chiari syndrome (BCS) comprise several diseases leading to thrombophilia. One of the most common thrombophilic disorders is resistance against activated protein C, caused by a single point mutation of the factor V gene. In December 1993, a 22-year-old patient was given a diagnosis of subacute BCS with occlusion of all major hepatic veins. Placement of a transjugular intrahepatic portosystemic stent shunt led to rapid disappearance of ascites and hepatic encephalopathy. During the following two years, recurrent partial occlusions of the shunt were treated by balloon angioplasty. The cause of the BCS still being unknown, in October 1996 we performed extensive laboratory investigations concerning states of thrombophilia and found moderately elevated IgG anticardiolipin antibodies (19.7 U/ml) and a resistance against activated protein C caused by heterozygosity for a point mutation of the factor V gene (1691G--A; factor V Leiden). As a consequence, oral anticoagulation with coumarin was initiated. In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. Moreover, IgG anticardiolipin antibodies have been negative since then. If BCS is caused by APC resistance, liver transplantation not only treats the chronic liver disease but also cures the state of thrombophilia since factor V is mainly synthesized in the liver.

The gastroprotective and ulcer-healing properties of prostaglandins, especially in gastric ulcers induced by non-steroidal anti-inflammatory drugs, are well established. Ulcer healing is an active process of filling the mucosal defect with migrating and proliferating epithelial cells combined with angiogenesis in granulation tissue at the ulcer bed. Growth factors, especially epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) are crucial in the regulation of the reconstruction of damaged mucosal structures.In this double-blind, randomized, prospective study 40 patients with gastric ulcer were treated with nocloprost, a stable prostaglandin E2 derivative, or with ranitidine. All subjects underwent endoscopy before and after 4 and 8 weeks of anti-ulcer therapy. During endoscopy mucosal biopsies were performed for determination of EGF content in gastric mucosa at the ulcer margin and in the intact mucosa. Additionally, EGF output in saliva and its plasma concentrations were determined in all subjects before and during the treatment.The gastric ulcer healing rate after 4 weeks was significantly higher in patients treated with nocloprost than in those treated with ranitidine (63% versus 39%, respectively). At initial examination the EGF content in the gastric mucosa obtained from the ulcer edge was significantly higher than that in the intact mucosa. There was a significant increase in the EGF content in both the ulcer margin and the intact mucosa in subjects treated with nocloprost but not in patients under treatment with ranitidine. Similarly, patients treated with nocloprost had significantly higher EGF output in saliva and higher EGF concentration in plasma throughout the anti-ulcer therapy.Nocloprost is superior to ranitidine in the treatment of chronic gastric ulcers, and these effects could be due, at least in part, to higher expression and mucosal content of EGF in the ulcer area.

A thirty-year-old male patient suffered subarachnoidal haemorrhage from an angioma positioned in the cranio-cervical transition. After rebleeding twice the patient developed a hydrocephalus internus malresorptivus and excessive natriuresis and polyuria, accompanied by depressed renin activity and extremely low aldosterone plasma levels. Neither fluid restriction and sodium substitution, nor administration of hydro-chlorothiazide/indomethacin affected natriuresis and polyuria. It was only after treatment with fludrocortisone-acetate/hydrocortisone that hyponatraemia and polyuria were resolved. At the same time a ventriculo-peritoneal shunt was applied. Differential diagnosis excluded the syndromes of inadequate antidiuretic hormone secretion, renal and cerebral diabetes insipidus, osmotic receptor hypofunction, chronic renal dysfunction and tubular necrosis. Natriuresis and polyuria developed under dexamethasone therapy. Since patient history, physical examination and laboratory criteria could not explain the electrolyte and fluid imbalance, this might be attributed to the hydrocephalus. Similar disturbances have been reported from other patients with intracranial disorders. Mechanical pressure exercised on the hypothalamus might cause the disturbance of fluid and sodium balance. Assuming a cerebral salt wasting syndrome, a putative natriuretic factor coming from the brain or an imbalance in the cerebral renin-angiotensin-system, as described in rats and dogs, must be discussed.

To assess possible side effects of transcranial magnetic stimulation on the release of anterior pituitary gland hormones three different examinations on 10 males were performed following a standardized protocol. Plasma levels of prolactin, FSH, LH, hGH and cortisol were determined before and after stimulation. Cortical stimulation had no specific influence on the plasma levels of the hormones examined.

Subcutaneous injection of synthetic protamin-zink-somatostatin completely prevents endotoxin-induced leucocytosis in normal rats. Piromen-induced elevated stab neutrophil, neutrophil and monocyte counts remain within the normal range during somatostatin administration. There is an inhibiting effect of synthetic protamin-zink-somatostatin on the wet weights of granulation tissue of cotton pellet granulomata, too. Incorporation of 35S-sulfate in sulfated mucopolysaccharides of granulation tissue in cotton pellet granulomata is not inhibited. Intravenous administration of synthetic linear somatostatin decreases stab neutrophil and neutrophil blood count in patients with acute bacterial leucocytosis. After the termination of somatostatin infusion a rebound phenomenon occurs. In healthy subjects lymphocyte count increases during somatostatin infusion. This effect can not be demonstrated in patients with bacterial leucocytosis.

The clinical course of systemic lupus erythematosus (SLE) is characterized by general symptoms such as fatigue, loss of weight, and fever, by cutaneous lesions such as facial erythema, by hematologic abnormalities such as leuko- and thrombocytopenia, and by organ involvement, e.g. of kidney and heart. Values of circulating immune complexes (CIC), complement consumption, and anti-ds-DNA antibody titer are generally used for monitoring disease activity (1-5). One single serological test by which disease activity can be reliable monitored is not yet available.

In normals and patients with acute bakterial leukocytosis synthetic somatostatin decreases cell count of stab neutrophils, neutrophils and eosinophils. After termination of somatostatin infusion a rebound phenomenon occurred. In healthy normals lymphocyte count increases during somatostatin infusion. This effect outlasts the end of infusion for more than 24 h. No significant effect could be demonstrated in patients with a bacterial leukocytosis.

Prolactin concentration was measured 20 minutes after each seizure in 8 patients with grand mal, 2 patients with complex partial seizures and 5 patients with petit mal seizures. In the group of grand mal and complex partial seizures serum prolactin showed markedly increased levels. After petit mal seizures there was no change in serum prolactin concentration. The possible causes for changes in serum prolactin after a seizure in children are discussed.

Oral carbohydrate tolerance tests with xylose, galactose and lactose were performed. After an interval of at least 24 h the same tests were repeated following an i.v. bolus and during infusion of somatostatin. Somatostatin does not influence xylose absorption. However, absorption of galactose and lactose is significantly reduced (p less than 0.01/0.008) during somatostatin infusion. On the other hand, serum levels of galactose remain unchanged despite administration of somatostatin, when galactose is given parenterally. The results support the assumption that the absorption process in small intestine is affected by somatostatin. Possible effects of somatostatin on hormones regulating the intestinal absorption and on energy-depending carrier mechanisms are discussed.

It is generally accepted that protein kinase C-α (PKC-α) is an important enzyme in the cellular regulation of growth and differentiation by phosphorylating proteins. Recent studies have described a point mutation of PKC-α (position 908 of the genetic sequence, codon GAC becoming GGC) in invasive human pituitary tumours which leads to an exchange of amino acids in the protein. We investigated 11 human pituitary tumours to evaluate the data obtained previously. cDNA was subcloned and up to ten individual clones were sequenced from each tumour, resulting in 85 clones analyzed in total. All of the pituitary adenomas showed a normal wild-type sequence of PKC-α DNA. Even if the tumour was 'invasive' (infiltration of the dura mater) no mutation at position 908 of the sequence was found. Moreover, using Western blot analyses we did not observe any differences in PKC-α protein expression in invasive as compared with non-invasive pituitary adenomas. Until now we have been unable to confirm the data of other investigators, suggesting that mutated PKC-α is an inconsistent feature of invasive pituitary tumours. Journal of Endocrinology (1997) 153, 131–137