Actions of growth hormone-releasing factor and somatostatin on adenylate cyclase and growth hormone release in rat anterior pituitary

The interaction of growth hormone-releasing factor (GRF) and somatostatin (SRIF) on adenylate cyclase activity and growth hormone release was investigated in pituitary homogenates and 2-day cultured rat anterior pituitary cells. GRF stimulated growth hormone release by about 3-fold (ED50 1.6 X 10(-12) M) and caused a rapid 15-fold increase in cyclic AMP production (ED50 6.0 X 10(-12) M). The increase in cyclic AMP was due to direct stimulation of adenylate cyclase by GRF, which caused a 4-fold increase in the activity of the enzyme measured in anterior pituitary homogenates. GRF-induced cyclic AMP formation and GRF-stimulated adenylate cyclase activity were maximally inhibited to the extent of about 50% by 10(-8) M somatostatin. In contrast, GRF-stimulated growth hormone release was completely inhibited by somatostatin (ID50 3.2 X 10(-11) M), suggesting a second site of action of somatostatin. These studies demonstrate that GRF stimulates growth hormone release via activation of adenylate cyclase and a rise in intracellular cyclic AMP. In addition, these findings indicate that the inhibitory action of somatostatin on growth hormone release is exerted at two levels, one at the level of adenylate cyclase affecting the production of cyclic AMP, and the other beyond the formation of the nucleotide, at a site which modulates the release of growth hormone from the cell.     

Versorgungsqualit?t im medikament?sen und pr?ventiven Bereich bei Patienten mit und ohne koronare Herzkrankheit

Zusammenfassung. Hintergrund und Ziel:   Die ambulante Versorgung von Patienten mit einer koronaren Herzkrankheit (KHK) sollte neben der Diagnostik vor allem die medikamentöse Therapie und Prävention gewährleisten. Ziel dieser Studie war die Erhebung der Versorgungsqualität im medikamentösen und präventiven Bereich bei Patienten mit einer KHK. Patienten und Methodik:   Die prospektive Untersuchung wurde von März 1999 bis Februar 2002 am Universitätsklinikum Bergmannsheil, Bochum, durchgeführt. Eingeschlossen wurden 300 konsekutive Patienten mit der Einweisungsdiagnose KHK ohne Herzinfarkt und Koronarangiographie in der Vergangenheit. Diagnostik und Therapie richteten sich nach den aktuellen Leitlinien. 248 Patienten (82,7%), 116 davon mit einer angiographisch nachgewiesenen KHK, wurden nach 1 Jahr erneut untersucht. Ergebnisse:   Bei der Abschlussuntersuchung erhielten nur noch 70,9% der Patienten mit einer KHK einen -Blocker und 83,6% einen Thrombozytenaggregationshemmer. Der Bodymass-Index, der Anteil übergewichtiger Patienten und der HbA_1c bei Diabetikern änderten sich im Verlauf der Untersuchung nicht. Nach 1 Jahr hatten 48,0% der Patienten einen systolischen Blutdruck > 139 mmHg, 22,6% einen diastolischen Wert > 89 mmHg. Bei der Nachkontrolle lag der LDL-Wert in 57,0% der Fälle oberhalb der empfohlenen Zielbereiche. Der hohe Anteil inadäquat therapierter Patienten war sowohl in der Gruppe der Patienten mit wie ohne KHK nachweisbar. Schlussfolgerung:   Die medikamentöse Therapie und die primär- wie sekundärpräventiven Maßnahmen der beobachteten Patienten waren mangelhaft. Es zeigten sich deutliche Defizite in der Versorgungsqualität dieser Patienten. Offensichtlich mangelt es nicht an der Verfügbarkeit evaluierter, effektiver und effizienter Maßnahmen, sondern an deren Umsetzung in die Praxis. Ärztlicherseits sollten Bemühungen zur Implementierung der vorhandenen evidenzbasierten Leitlinien verstärkt werden.     

Cutaneous necrosis from calcific uremic arteriolopathy

Calcific uremic arteriolopathy (calciphylaxis) is an uncommon complication of chronic renal failure that is associated with high morbidity and mortality. We report 16 patients (13 female) who presented between 1985 and 1996. All patients developed painful livido reticularis that progressed to cutaneous necrosis and ulceration (11 cases on the proximal extremities and five cases on the distal extremities). Two patients with predominately distal leg disease survived; the cause of death in the other 14 patients was sepsis (six patients), withdrawal from dialysis (three), cardiac arrest (three), and gastrointestinal hemorrhage (two). Mesenteric ischemia from intestinal vascular calcification occurred in two cases. Clinical factors identified included the use of warfarin therapy in seven cases and significant weight loss (>10% body weight) in seven cases in the 6 months preceding the development of calcific uremic arteriolopathy. Skin pathology was studied in 12 cases, with all showing calcific panniculitis and small vessel calcification. Electron microscopic spectral analysis of the mineral content of the calcific lesions in the subcutaneous tissue showed only calcium and phosphorous. In two cases, substitution of low molecular weight heparin for warfarin therapy resulted in clinical improvement. Current theories of pathogenesis and treatment are reviewed. This study confirms the high morbidity and mortality of calcific uremic arteriolopathy producing ischemic tissue necrosis while drawing attention to significant weight loss and warfarin therapy as risk factors for the development of ischemic tissue necrosis. Hyperbaric oxygen therapy warrants further study.     

Neurogenic tumours: clinical and therapeutic aspects (author's transl)

Tumours of the nervous system are rare. Clinical and therapeutic aspects are discussed with relation to 54 cases. The benign tumours of the peripheric nerves such as neurinomas and neurofibromas, show a high rate of malignant degeneration. For this reason, every tumour of the soft tissues has to be removed and should be examined by the pathologist. In cases of retroperitoneal and intestinal localisation an early diagnosis is frequently impossible. For differential diagnosis laparotomy or thoracotomy are always indicated. X-ray examinations of the kidneys, the thorax as well as the intestines and mesenteric vessels show satisfactory results. The neurogenic sarcomas and neuroblastomas are discovered late because of their hidden localisation and poor symptoms. The poor prognosis has not been improved by cytostatsis and radiation.