Proceedings of the physiological society [proceedings].
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Biomedical subjects
Publications and source records attributed to M Fisher.
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Glucagon was infused to maintain plasma concentrations three to six times the basal level (300 to 600 pg per milliliter) into 16 normal and seven non-diabetic obese subjects. Hyperglucagonemia caused only a transient rise of 5 to 10 mg per 100 ml in basal glucose levels and had no effect on oral glucose tolerance or plasma insulin. In three patients with adult and two with juvenile-onset diabetes on maintenance insulin, hyperglucagonemia maintained for two to four days caused no change in plasma glucose of ketone concentration. In contrast, in nine insulin-withdrawn patients the glycemic response to hyperglucagonemia was five to 15 times greater (P less then 0.05) than in normal controls. Hyperglucagonemia does not cause glucose intolerance in normal subjects or bring about deterioration of diabetic control when insulin is available. Glucagon in the insulin-deprived patient can worsen the diabetic state. These findings suggest the primary role of insulin deficiency in the diabetogenic action of glucagon.
Eighteen glaucoma patients each received four pilocarpine regimens in random sequence: 1% and 4% eyedrops and 20mug/hr and 40mug/hr ocular therapeutic systems. Unimportant changes in refraction, near vision, and distance vision occurred during the use of either ocular therapeutic system. Miosis with ocular therapeutic systems was almost always less intense and variable than with eyedrops. Refractive changes occurred in 12 patients following 1% pilocarpine and in 16 patients following 4% pilocarpine drops; decreased distance vision occurred in nine patients after 1% drops and in 12 patients after 4% drops. Fewer patients showed decreases in near vision. In all cases, visual effects peaked one half hour after eyedrop instillations and returned gradually toward normal in the next two to three hours. Intraocular pressure levels were within comparable ranges during all four treatments, but the ocular therapeutic systems maintained pressure at a more constant level.
Serum stimulates the production of prostaglandins by transformed mouse fibroblasts. Hydrocortisone (cortisol) inhibits this stimulation. The half-maximal inhibition occurs at 6x10-9 M. Studies with cells labeled with [3H]arachidonic acid in their lipids show that the stimulation by serum results in the release of arachidonic acid from the cellular lipids, mostly phospholipids. Hydrocortisone inhibits this release but does not inhibit the production of prostaglandins from exogenously supplied arachidonic acid. This inhibition of arachidonic acid release from phospholipids may be the mechanism for the anti-inflammatory action of corticosteroids.
To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range. Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and post-glucose glucagon levels were three- to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two- to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls. Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three- to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glucagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.
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Normal volunteers used 1, 2, and 4% pilocarpine eyedrops, three times daily, or ocular therapeutic systems placed in the conjunctival cul-de-sac to control intraocular pressure. The systems continuously release 20 and 40 mug/hour of pilocarpine for one week. Although the amount of drug delivered to the eye from the ocular therapeutic system was one fifth that obtained from the eyedrops, the decrease of intraocular pressure was comparable. The ocular therapeutic systems produced small, constant effects on visual acuity, refractive error, and miosis that did not cause visual handicaps or require correction. The effects of eyedrops on these visual factors were large and varied and produced marked visual handicaps that were not correctable with spectacles. Despite its comparable hypotensive effect in normal subjects, continuous delivery of pilocarpine by means of an ocular therapeutic system elicits less severe side effects than pilocarpine eyedrops.
The glomerular filtration rate was measured in the sick elderly patients using the single shot 51Cr EDTA method. As would be expected, such patients have worse renal function than the fit elderly. The filtration rate can be usefully predicted from either blood urea or serum creatinine, but a superior prediction is obtained when these factors are combined using a formula derived from multiple regression analysis.
To determine the incidence and the natural history of retroperitoneal masses complicating acute pancreatitis, 104 cases of acute alcoholic pancreatitis were evaluated prospectively for mass formation. Abdominal masses detected by physical examination and serial x-ray films of the upper portion of the gastrointestinal tract were localized to the retroperitoneum by additional contrast studies, including abdominal angiography. Nonoperative management was urged only for patients with an asymptomatic mass. An abdominal mass developed in 19 patients (18%). In eight of these, it disappeared rapidly, but in 11 (11%), it persisted, and was considered to be a pancreatic pseudocyst. Eight of the 11 patients were treated nonoperatively, and the mass resolved without complication three weeks to three months after diagnosis. In three patients, a pseudocyst was confirmed at laparotomy. Exploration was justified by an unstable clinical course in only one instance. A routine surgical approach to an asymptomatic retroperitoneal mass developing after acute alcoholic pancreatitis may not be necessaary in patients who are improving clinically because the mass may resolve without complication.
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