The effect of glucose on the growth hormone response to glucagon and propranolol-glucagon in normal subjects.

The mean (+/- SE) peak level of serum growth hormone (GH) after intramuscular injection of glucagon in ten normal adult men was 15.1 +/- 2.1 ng/ml; glucose infusion suppressed the mean peak GH to 9.6 +/- 3.7 ug/ml (p less than 0.05). Pretreatment of eight of these subjects with propranolol caused a modest increase in the mean peak GH after glucagon (19.4 +/- 2.8 ng/ml) but did not improve the mean peak GH after glucagon when glucose was infused (8.7 +/- 2.8 ng/ml). Individual analysis of the peak GH showed that glucose infusion did not uniformly suppress the peak GH after glucagon; in seven subjects the peak GH was suppressed but in three it was not. Conclusions: (1) The GH response after glucagon is usually due to a fall in serum glucose after the initial rise in serum glucose induced by glucagon. (2) Nevertheless, since glucose does not consistently inhibit the GH response after glucagon, a second mechanism probably exists by which glucagon stimulates GH secretion. (3) Glucose completely suppresses the propranolol-induced increase in the GH response to glucagon; an adrenergic mechanism may be involved in the control of GH secretion by glucose.     

Current status of anticoagulant therapy

Anticoagulant therapy has stood the test of time. Full-dose heparin and warfarin prevent recurring pulmonary embolism and deep venous thrombosis. Their use is indicated in patients who have experienced venous thromboembolism unless contraindications are compelling. Low-dose heparin is successful in preventing the initial episode of venous thrombosis in most patients at high risk for the development of thrombophlebitis. Warfarin reduces the incidence of systemic embolization in patients with heart disease and atrial fibrillation and in patients with artificial heart valves. Evidence is accumulating to suggest that warfarin may still retain an important role in the management of patients with myocardial infarction. However, bleeding remains an inevitable risk in patients receiving anticoagulant therapy. The risk, however, can be diminished when both the physician and patient understand the mechanism of action of the drugs and the factors that predispose to bleeding.     

Pathophysiologic observations on premature opening of the aortic valve utilizing a technique for multiplane echocardiographic analysis.

The use of a simple technique for multiplane echocardiographic analysis and study of the effect of arrhythmia enabled us to investigate the mechanism of premature opening of the aortic valve in two patients with subacute aortic insufficiency. In one patient, premature opening evolved with the development of left ventricular dilatation and failure. In this case the prematurity of opening in each beat was related to diastolic filling time and was accompanied by septal recoil and by premature closure of the mitral valve. We classified this as the diastolic duration-dependent subgroup. In the second patient, who had a hypertrophied, non-dilated left ventricle, premature opening depended on atrial contraction and was independent of diastolic filling time. This case defined an atrial contraction-dependent subgroup. In the light of these findings we analyzed previously reported cases in patients with acute severe aortic insufficiency. These patients appear to fall into the diastolic duration-dependent subgroup.     

Blood pressure elevation in pregnancy

The hypertensive disorders of pregnancy remain major health problems. Blood pressure elevation in pregnancy may be associated with a number of disorders, the most common being preeclampsia-eclampsia, essential hypertension, and chronic parenchymal renal disease. The etiology of preeclampsia-eclampsia continues to be a subject of argument and research. This condition is characterized clinically by hypertension, proteinurea, and edema occurring after the 24th wk of pregnancy and is characterized pathophysiologically by salt and water retention, increased vascular reactivity, and possibly by slow intravascular coagulation. Clinical management continues to be based on rest, sedation, mild salt restriction, osmotic diuresis, and anticonvulsants. Magnesium sulfate or combinations of hydralazine and veratrum alkaloids are used for acute control of blood pressure.Pregnancy is usually well tolerated by patients with mild essential hypertension but can be associated with superimposed preeclampsia-eclampsia, abruptio placentae, and increased fetal mortality in patients with severe hypertension. Standard antihypertensive agents are used to manage blood pressure in such patients with the exceptions of reserpine, which causes increased fetal respiratory tract secretions, and guanethidine, which causes marked postural hypotension in the pregnant subject.A subgroup of patients have been identified who develop blood pressure elevation in late pregnancy that remits within 10 days after delivery. Persistence of hypertension beyond this period calls for evaluation of secondary causes of hypertension and appropriate therapy.     

Surgical treatment of aneurysms of the abdominal and thoracic aorta

The danger of an arteriosclerotic abdominal aortic aneurysm is clearly related to the size of the aneurysm. From available clinical data it seems logical to recommend elective surgical excision and graft replacement of abdominal aneurysms 6 cm or greater in diameter because of the considerable danger of rupture of untreated aneurysms of this size. Although small aortic aneurysms do rupture, most patients with small abdominal aneurysms may be safely followed with examination at regular intervals. Surgery is reserved for those who demonstrate evidence of aneurysm expansion. The operative mortality rate for elective surgical excision of abdominal aortic aneurysms is by no means negligible but has probably diminished recently to levels of approximately 5% in the hands of experienced surgeons. Achievement of an operative mortality rate in this range requires sensible case selection, expeditious operative management and skillful postoperative care with particular attention to problems of hypoxemia in the early postoperative period.Patients with ruptured abdominal aortic aneurysms require immediate aneurysm resection for survival. Of those patients with ruptured abdominal aneurysms who reach the hospital alive, approximately 60% should be salvaged at present by emergency surgery.The prognosis of the patient with a thoracic aortic aneurysm depends upon the etiology of the aneurysm. Syphilitic aneurysms of the thoracic aorta are now fortunately rare but appear to have a high incidence of rupture. The prognosis of patients with arteriosclerotic aneurysms, which characteristically involve the descending thoracic aorta, appears to be considerably better than that of patients with aneurysms of the abdominal aorta for unknown reasons. Since the removal of thoracic aneurysms ordinarily requires extracorporeal bypass and is associated with an operative mortality rate in the range of 20%, considerable judgment must be exercised in case selection for elective resection of such aneurysms.The surgery of dissecting aneurysms of the thoracic aorta has recently been modified by the widespread acceptance of antihypertensive drug therapy for acute dissection. Surgery may be reserved, hopefully on an elective basis, for those patients with significant aortic valvular insufficiency, significant aneurysmal dilatation of the dissected aorta, or symptomatic involvement of a major aortic branch in the dissection.     

Progressive systemic sclerosis with eosinophilia and a fulminating course

A case of progressive systemic sclerosis, with blood and pleural fluid eosinophilia and a fulminating course, is presented. Wide-mouth colonic diverticula developed within 10 weeks. Death from renal failure occurred five and a half months after the onset of symptoms. The possibility of eosinophilia as a marker of severe disease in progressive systemic sclerosis is raised.     

Myocardial scintigraphy by infarct-avid radiotracers

Specific radioindicators are sequestered by acute myocardial infarctions, and their uptake is detectable by external detection systems, such as the Anger scintillation camera. The resultant scintigraphic image may be used to estimate infarct size, although inferior and subendocardial infarcts may pose difficulties. Infarct localization as to anatomic area of the heart is also reasonably accurate.The majority of the clinical experience has been with technetium chelates, particularly ^99mTc-tetracycline and ^99mTc-pyrophosphate. Optimal imaging with ^99mTc-tetracycline is within the first 3 days after infarction, with gradual return to normal of the scintigraphic appearance after this time. While larger infarcts remain positive for longer periods of time, significant uptake or reappearance of uptake after the initial period may be helpful in the identification of reinfarction or extension after an initial infarct. Tetracycline appears to be sequestered only by acutely infarcted myocardium, and therefore is a sensitive agent for distinguishing normal, previously infarcted, and ischemic myocardium from acutely infarcted myocardium.The major clinical experience has been with ^99mTc-pyrophosphate, a bone-seeking radionuclide. The major advantage of ^99mTc-pyrophosphate over ^99mTc-tetracycline is the earlier imaging interval. Optimal scans are obtained at 1–2 days after infarction and only 90 min after the administration of ^99mTc-pyrophosphate (as opposed to 24 hr with ^99mTc-tetracycline). While ^99mTc-pyrophosphate is a quite sensitive indicator of infarction, there is suggestive evidence that ischemic as well as infarcted myocardium sequesters the agent. In addition, various other conditions, including cardioversion, rib fractures, left ventricular aneurysms, and breast tumors may cause uptake of ^99mTc-pyrophosphate and lead to false positive myocardial infarct scintigrams. Thus, while only a few patients with negative scans who have been imaged at the appropriate time will turn out to have clinically detectable infarcts, a somewhat larger number without infarction will have positive scans, particularly those patients with unstable angina pectoris but without clinical infarction.While the final role of acute myocardial scintigraphy remains to be determined, its contribution to the further understanding of the pathogenesis of ischemia and infarction, as well as its clinical utility, has been significant.     

Renal artery dysplasia in a patient with membranoproliferative glomerulonephritis.

A 27 year old man with nephrotic syndrome due to membranoproliferative glomerulonephritis had multifocal stenoses of the renal and intestinal arteries. The arterial lesions demonstrated by angiograhy closely resembled those of medial fibromuscular dysplasia. The dysplasia progressed over a five year period to involve both renal arteries from their extrarenal segments through their interlobar branches. Low serum levels of complement components C3 and C4, focal reduplication of the glomerular basement membrane on light microscopy, and the patterns of glomerular localization of IgG and C3 by immunofluorescence were characteristic of type I membranoproliferative glomerulonephritis. The development of the arterial dysplasia in a patient with chronic glomerulonephritis suggests a common immunologic pathogenesis of both disorders.     

Triiodothyronine and thyroxine content of desiccated thyroid tablets

Triiodothyronine (T₃) and thyroxine (T₄) were measured by radioimmunoassay in Pronase hydrolysates of four lots each of 1- and 2-grain tablets of desiccated thyroid (Thyroid, Armour) and thyroglobulin (Proloid, Warner-Chilcott). The methodology used was verified by studies of tablets containing known quantities of T₄ and T₃. One grain of desiccated thyroid contained 12 ± 1 and 64 ± 3 μg (mean ± SD) of T₃ and T₄ per tablet, respectively ($\text{T}{}_4\text{T}{}_3$ molar ratio, 4.3). A 1-grain tablet of thyroglobulin contained 16 ± 2 and 55 ± 5 μg of T₃ and T₄, respectively with a $\text{T}{}_4\text{T}{}_3$ ratio of 2.9. Two-grain tablets generally contained twice the quantity of T₃ and T₄ in the 1-grain preparations. The variation in T₃ and T₄ content between the four lots of each tablet strength for each product was 10% or less. These estimates of T₃ and T₄ content are 1.5- to 2-fold greater than those previously published. This difference probably results from the more sophisticated methodology now available which does not require chromatographic separation of T₃ and T₄ or iodometry. Using calculations based on published estimates of T₄ and T₃ absorption and of the $\text{T}{}_3\text{T}{}_4$ potency ratio, it would appear that the T₃ content of desiccated thyroid and thyroglobulin provide approximately 39% and 51%, respectively, of the thyromimetic activity of these two medications.     

A survey of growth hormone secretion and action

The many stimuli of HGH secretion have been considered, and the major aspects of HGH's actions briefly reviewed. We have advanced our reasons for believing that some actions attributed to HGH are basically pharmacologic. This applies, in particular, to the so-called “insulinlike” effects. A detailed examination of specific effects of HGH has been made in the light of this assumption. We have indicated that SF may mediate many of GH's effects, in particular, the effects of HGH on protein, collagen, and polysaccharide synthesis in cartilage, and possibly, HGH's anabolic effects in skeletal muscle.Clearly, one of the major problems confronting investigators is to delineate clearly which effects of HGH are direct, and which are mediated by a second factor. An allied and no less important problem is to determine which of these effects are physiologic and where in the human these effects occur. A basic understanding of the complex secretory mechanism for HGH seems much more advanced than progress in solving the latter problems.     

Quantitative aspects of the metabolic response to pancreatic islet transplantation in rats with severe ketotic diabetes.

Injection of 100-140 mg/Kg of streptozotocin produced severe, ketotic diabetes in 12 pairs of adult rats. Transplantation of intact islets of Langerhans from syngeneic adult donors into a muscle pocket or a pouch created from pancreatic tissue of one animal from each pair eliminated ketonemia in the immediate postoperative period, while ketonemia persisted in the sham-operated controls. Mean survival of transplanted animals was 145 days, versus 70 days for controls. Mean body weight increased and blood sugar decreased in transplanted animals compared with controls; the differences were greatest in those animals which received the largest number of islets per unit body weight. In one animal, all metabolic indices returned to normal for a period of 8 wk following transplantation of 650 islets. After gaining to 300% of initial body weight, diabetes reappeared in this transplanted animal and was again reversed by a second transplantation. The metabolic data indicate that: (1) islet tissue from adult donors survives and functions in severely diabetic, ketotic hosts; and (2) metabolic response to transplantation is a function of the ratio of islet tissue to body mass, a minimum ratio of about 2-3 islets/gm body weight being required to maintain normal homeostasis.     

Improvement of growth hormone response to stimulation in primary aldosteronism with correction of potassium deficiency

Potassium depletion frequently occurs in primary aldosteronism and has been implicated as the cause of the impaired carbohydrate tolerance frequently associated with this syndrome. Glucose, insulin, and growth hormone regulation were studied in a 42-yr-old, male patient with an aldosterone-secreting adenoma when the patient was potassium-depleted and again after potassium repletion. Potassium repletion was documented by serial body potassium measurements, with an increase in body potassium from 2400 mEq to 2850 mEq after 400 mg spironolactone and 80 mEq supplemental potassium chloride were administered daily for 7 days. Potassium repletion resulted in improvement of the patient's glucose tolerance test, with a decrease in the peak glucose level from 184 mg/100ml to 130 mg/100ml and an increase in the peak insulin level from 46 μU/ml to 85 μU/ml. Intravenous administration of arginine resulted in a subnormal insulin response to 28 μU/ml in the base-line test and an increase to 59 μU/ml after potassium stores were repleted. Growth hormone response to arginine infusion was also initially minimal at 12.5 ng/ml, increasing markedly to 26 ng/ml after potassium replenishment. Insulin-induced hypoglycemia resulted in a depressed growth hormone response of 8 ng/ml when the patient was potassium-deficient, but a normal response of 30 ng/ml after potassium repletion.These observations demonstrate that impairment of both insulin and growth hormone responses to stimulation occur in primary aldosteronism with potassium depletion. These abnormalities may be reversed by potassium repletion.