Studies were carried out to further define the sites of interaction of Ca++, cAMP, and somatostatin (SRIF) in the mechanisms governing GH release from acutely dispersed purified somatotrophs obtained from rat adenohypophyses. Both high [K+] and the Ca++ ionophore A23187 stimulated the release of GH. The release induced by high [K+] was accompanied by a small but significant transient increase in intracellular cAMP, while A23187 did not alter basal cAMP levels. The augmented release of GH induced by both secretagogues was blocked by SRIF (1 ng/ml) and by removing Ca++ from the incubation medium (< 85 microM). The transient increase in cAMP induced by high [K+] was not blocked by SRIF or by low Ca++ incubation. These results are consistent with a model whereby an increase in free cytosol Ca++ will result in GH release by exocytosis. This increase in free cytosol Ca++ can come from either intracellular bound Ca++ or from the extracellular compartment. Secretagogues which act via cAMP increase intracellular cAMP levels. The increase in cAMP would then stimulate the translocation of Ca++ from a bound to a free cytosol form. Secretagogues may also stimulate GH release by bypassing cAMP to increase free cytosol Ca++ by directly increasing the influx of Ca++ into the cells or by increasing the intracellular movement of Ca++ to the free cytosol compartment. SRIF would block GH release by acting at the level of the plasma membrane to block Ca++ influx and by inhibiting a step(s) subsequent to the increase in cytosol Ca++.

Studies were carried out to simultaneously measure cAMP and cGMP accumulation and GH release from acutely dispersed purified somatotrophs obtained from rat adenohypophyses. cAMP accumulation was dramatically increased by both prostaglandin E2 (10(-6) M) and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor, 0.5 mM) within 1 min of their addition, while there was a delay of 8--16 min before a significant increase in GH release was seen. SRIF (100, 10, or 1 ng/ml) completely blocked the stimulated release of GH. SRIF also consistently decreased the elevation of cAMP induced by the two secretagogues, but this decrease was small and not always significant. cGMP was unmeasurable (less than 0.02 fmol/1000 cells) in all of our experiments, while basal cAMP levels were about 1 fmol/1000 cells. We conclude that cAMP plays a role in the intracellular mechanisms governing GH release and that SRIF primarily acts subsequent to cAMP elevation, with a possible secondard or minor action on cAMP formation.

cAMP is thought to be an essential intracellular mediator in the release of GH from somatotrophs. Ca++ is required in the incubation medium to elicit GH release in vitro. We have carried out studies using a purified preparation of rat somatotrophs to see whether the Ca++ requirement procedes or follows the accumulation of cAMP induced by prostaglandin E2 (which increases adenylate cyclase activity) and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). Incubation of somatotrophs in low Ca++ medium (less than 85 microM) abolished the release of GH induced by the two secretagogues, while the increase in intracellular cAMP was actually augmented. Thus, Ca++ is required in the incubation medium to express the action of intracellular cAMP.

The case: A 57-year-old man presented to hospital with a 2-week history of progressive malaise, myalgia, fever, nausea, vomiting, diarrhea, polyuria and polydipsia. He had a history of gastresophageal reflux that did not respond to ranitidine. He had started taking oral pantoprazole (40 mg daily) 6 weeks earlier. The patient had a history of coronary artery disease and was taking acetylsalicylic acid (81 mg daily) and atorvastatin (40 mg daily). He reported having taken ibuprofen (400 mg) for myalgia no more than 3 times over the 2-week period before presentation. He had no history of renal disease or drug allergies.On presentation, the patient was afebrile (temperature 36.5°C), with a blood pressure of 127/82 mm Hg, a pulse of 72 beats/min, a respiratory rate of 18 breaths/min and an oxygen saturation of 97% in room air. The jugular venous pressure was measured at the sternal angle. His chest sounds were normal, and there was no pericardial friction rub or peripheral edema. The results of a dermatological examination were unremarkable.The results of laboratory tests are listed in Table 1. Of note, the patient had a serum creatinine level of 300 (normal 53-106) μmol/L. Two years ago, his creatinine level had been 100 μmol/L. He had mild hyperkalemia, but his electrolyte levels were otherwise normal. His leukocyte and eosinophil counts were normal. The ratio of protein to creatinine in his urine was 28 (normal 0-23), and the protein level in a 24-hour urine collection was 410 (normal < 150) mg. Protein electrophoresis showed that the protein in the urine was predominantly albumin. When analyzed by use of Wright stain, the first urine sample was negative for eosinophils, but 1% of the leukocytes in the second sample were eosinophils.Treatment included volume repletion and discontinuation of pantoprazole. Ultrasonography showed that both of the patient's kidneys were of normal size, and that there was normal echogenicity with no hydronephrosis. Over the next 4 days, his creatinine level decreased to 235 μmol/L. A needle core biopsy of 1 of the patient's kidneys was performed on day 6. The biopsy was indicated because the patient had ongoing acute renal failure with major proteinuria for which pre-and post-renal causes had been ruled out (there had been very minor improvement with volume repletion and the results of a renal ultrasound were normal). The biopsy showed moderate-to-severe patchy interstitial infiltrates, predominantly plasma cells with some lymphocytes and occasional eosinophils (Figure 1). Immunoflourescence was negative for IgG, IgA, IgM, C3, C1q and fibrin antibodies. These results supported the diagnosis of acute interstitial nephritis.

successfully treated by prosthetic grafting is reported. This appears to be the forty-third patient to survive surs&al treatment for this condition. HeDatic arterv here has been managed by resection of the aneurysm The third of hepatic artery aneurysm and replacement with a Dacron prosthesis. The from an anomalous Position On the front of the aorta beneath the duodenojejunal aneurysm has a poor prognosis and operative treatment is justified when the diagnosis is made. While ligation will be required in some instances, excision of the aneurysm with restoration of arterial blood-flow to the liver is to be preferred. ANEURYSMS of the hepatic artery are relatively rare. A recent search of the literature reveals only 157 cases CASE REPORT A 67-year-old Italian woman presented to the Royal Prince Alfred Hospital with a 3-week history of upper abdominal pain, nausea, and anorexia. A barium meal was reported as showing a large ulcer on the lesser curvature of the stomach in the region of the antrum. A laparotomy was performed on 3 June, 1970. The stomach and duodenum appeared quite normal, but a pulsatile mass was felt behind the duodenojejunal flexure MESENTERIC ANOMAL HEPATIC ARTERY -1 I ANEURYSM FIG. I.-The position of the aneurysm. ARTERY 4 1 FIG. z-Repair of the hepatic artery with a Dacron prosthesis after excision of the aneurysm. (BristolJ Gonzales> and Chassin> I97O). Of 42 close to the abdominal aorta. Dissection in this area have been successfdlY treated and Only have survived the insertion of a Prosthetic graft. A further case of hepatic artery aneurysm presented revealed a fusiform aneurysm of an anterior branch of the abdominal aorta (Fig. I), measuring 2 cm. in length. After the aneurysm had been dissected further and its neck