Variant angina pectoris: Investigation of indexes of sympathetic nervous system function

One thousand forty-five spontaneous episodes of S-T segment elevation were observed in three patients over a total of 72 days of continuous electrocardiographic monitoring. Eighty-nine percent of episodes were asymptomatic; chest pain tended to occur with episodes longer than 3 minutes, and ventricular ectopy occurred almost exclusively with symptomatic episodes. Nitroglycerin regularly relieved angina or S-T elevation, or both.

Plasma and urinary catecholamines and their metabolites were normal. Episodes of variant angina were not associated with a generalized increase in sympathetic outflow because serum catecholamine levels at the onset and termination of the S-T abnormalities were not elevated. Controlled trials of propranolol showed no significant beneficial effect. Propranolol significantly increased the length of episodes of S-T elevation in one patient, increasing ventricular irritability. The overall course of variant angina was quite variable, with spontaneous and long-lasting remissions, necessitating cautious interpretation of clinical trials.     

Effects of pharmacologic hyperglucagonemia on plasma amino acid concentrations in normal and diabetic man

Four normal and five insulin dependent diabetic men received a 2 h pharmacologic glucagon infusion (50 ng/kg/min) resulting in plasma glucagon levels (4400 pg/ml) similar to those seen in glucagonoma patients. In normal subjects in whom plasma insulin concentrations rose significantly (239 uU/ml) and the blood level of 15 of the 18 amino acids measured fell significantly. In contrast, in the diabetic men who secreted no insulin in response to glucagon (no rise in C-peptide levels), only 10 of 18 amino acid levels fell significantly. The branched chain amino acids valine, leucine and isoleucine, as well as tyrosine and phenylalanine were among the 8 amino acids which showed no change in response to glucagon in the diabetics. Thus, glucagon appears to have no acute affect on branched chain amino acid levels in man.     

The disposal of an intravenously administered amino acid load across the human forearm

This study was designed to examine the role of the skeletal muscle in man in the disposal of an intravenously administered L-amino acid solution. Arterio-deep venous differences of amino acids, glucose and lactate, and blood flow across the human forearm were measured in 9 healthy normal male volunteers (age = 27 ± 2 yr, weight = 79 ± 4 kg and height = 180 ± 2 cms) after an overnight fast (12 hr). Glucose and alanine turnover rates were estimated using a continuous infusion of 3-³H-glucose and U-¹⁴C-alanine isotopes. All measurements were obtained during steady state conditions, basally and two hours after the start of an L-amino acid infusion (8.5% solution). During the control period there was a significant release of total alpha amino nitrogen (AAN) equal to $\text{300 ± 97 nmole}\text{100 g}$ forearm muscle/min with alanine and glutamine accounting for over 80% of that amount ($\text{260 ± 24 nmole}\text{100 g}\text{forearm muscle/min}$). The release of the branched chain amino acids (BCAA) was only significant for valine, while the release of each of the keto acids of leucine and valine, α-ketoisocaproate and α-ketoisovalerate ($\text{37 ± 12 and 36 ± 7 nmole}\text{100 ml}\text{forearm muscle/min respectively}$) was significant from zero and exceeded the release of the corresponding amino acids ($\text{13 ± 17 and 24 ± 7 nmole}\text{100 g}\text{forearm muscle/min for leucine and valine respectively}$). The infusion of the L-amino acid solution resulted in a reversal of amino acid balance across the forearm. There was a net uptake of AAN of $\text{1195 ± 209 nmole}\text{100 g}$ forearm muscle/min with the BCAA accounting for $\text{513 ± 75 nmole}\text{100 g}$ forearm muscle/min or 49 ± 6% of the uptake. The net uptake of BCAA by skeletal muscle did not exceed 35% of the amount infused. The release of α-ketoisocaproate and α-ketoisovalerate showed no significant change from basal levels. The output of alanine and glutamine persisted in response to the infusion; while alanine output dropped by 40%, glutamine output increased by 50% ($\text{68 ± 23 and 218 ± 42 nmole}\text{100 g}\text{forearm muscle/min respectively}$), yet the combined release of alanine and glutamine did not change significantly from basal levels. Amino acid infusion resulted in a twofold increase in insulin and glucagon. Plasma glucose fell from 5.3 ± 0.05 mM basally to 5.04 ± 0.06 mM (p < 0.05), while blood lactate increased from 0.587 ± 0.03 mM to 0.639 ± 0.025 mM (p < 0.05); similarly there was a time dependent increase in glucose uptake by muscle ($\text{from}\text{0.857 ± 0.08}\text{to}\text{1.27 ± 0.07 μ}\text{mole}\text{100 g}\text{forearm muscle/min}$, p < 0.05) and lactate release ($\text{0.226 ± 0.03}\text{to}\text{0.297 ± 0.045 μ}\text{mole}\text{100 g}\text{forearm muscle/min}\text{, p < 0.05}$). These results indicate that a significant amount of the amino acids infused, and specifically the BCAA are extracted by human skeletal muscle, and mostly retained as such for later use. The data obtained under the conditions of the present study also indicate that tissues other than skeletal muscle are as important in the overall handling of these amino acids. However, it remains to be seen whether these findings can be extrapolated to other physiological conditions.     

Effects of insulin at two dose levels on gluconeogenesis from alanine in fasting man

We have determined the effect of insulin infused at 1 and 5 mU/kg/min on gluconeogenesis from alanine in 48-hr fasted men. The conversion of alanine to glucose was measured by the arterial-hepatic venous catheterization technique combined with the infusion of ¹⁴C-alanine. During insulin infusion, euglycemia was maintained by variable glucose infusion. When insulin was infused at 1 mU/kg/min the net splanchnic production of ¹⁴C-glucose was suppressed by 80% but glucagon infused at the end of the study resulted in substantial release of ¹⁴C-glucose from the liver suggesting marked accumulation of labeled glucose in glycogen. When insulin was infused at 5 mU/kg/min the splanchnic release of ¹⁴C-glucose was also markedly suppressed but in contrast to the lower insulin dose very little labeled glucose accumulated in glycogen. Neither the high nor the low dose insulin infusion had any effect on net splanchnic alanine uptake and plasma glucagon levels fell by 35% in both protocols. These data demonstrate that in 48-hr fasted man, (1) a small increment in insulin concentration will suppress glucose production but mostly by diverting the newly formed glucose into glycogen; (2) at higher concentrations, insulin will inhibit glucose production mainly by suppressing gluconeogenesis; and (3) this insulin-induced suppression of gluconeogenesis is due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine.     

Use of droperidol-fentanyl sedation for cardiac catheterization in children

Droperidol-fentanyl sedation for cardiac catheterization was evaluated in 106 consecutive children ≥ two years of age. The dose of 0.025 c.c. per kilogram of body weight (maximum 1 c.c.) produced adequate sedation in all but two patients without producing significant hypoventilation or heart rate changes. In patients without left heart volume overload or myocardial disease, left ventricular volume studies and pressurevelocity indices of contractile state were normal. Side effects were rarely encountered and easily controlled or reversed with diphenhydramine. Although we recommend this combination for cardiac catheterization sedation, we would not recommend exceeding our dosage schedule.     

Unstable Coronary Artery Disease: Comparison of Medical and Surgical Treatment

In eighty-eight patients with arteriographic findings of obstructive coronary artery disease and the clinical picture of unstable angina pectoris, a decision on operative or nonoperative management was made by the attending physician. Fifty-three of them subsequently underwent aortocoronary saphenous vein bypass grafting and 35 were continued on a program of medical therapy. A marked difference in the course after the first 30 days was noted, with most of the surgically managed patients being either asymptomatic or greatly improved following coronary artery bypass. Two-thirds of the medically treated patients had persistent severe angina pectoris and none was asymptomatic in a follow-up period averaging 20 months. There were 2 late deaths in the medical group and none in the surgical group.These findings indicate that coronary artery bypass operations can be performed with low risk during the unstable phase of coronary artery disease and that relief of angina can be anticipated. In contrast, nonoperative management of unstable coronary artery disease carries an appreciable risk of death or myocardial infarction, and the majority of patients treated nonoperatively continue to experience angina.     

Management of genital herpes simplex virus infection occurring during pregnancy

Genital herpes simplex virus (HSV) infection during pregnancy has caused considerable concern among lay and professional personnel in the past 10 years. Knowledge concerning the potential hazards of HSV to the newborn infant has increased the use of cesarean section for women who have or are suspected of having genital HSV infection near or at the time of labor. Because of this, a 57-month prospective study was begun at Vanderbilt University Hospital and its affiliate, Nashville General Hospital, January 1, 1976, and involved HSV culturing of all suspected genital herpes lesions during pregnancy. Those patients with positive HSV cultures prior to labor and without a subsequent negative culture underwent cesarean section. Those patients whose cultures reverted to negative were considered candidates for vaginal delivery. During the study period, there were 16,381 deliveries at the two institutions. One hundred twenty pregnant women were cultured, with 80 being HSV culture negative and 40 culture positive. The outcome of these pregnancies as well as a review of the experience with neonatal HSV infection in Middle Tennessee is presented. It is concluded that by utilizing HSV cultures of genital lesions as a guide to determining the route of delivery, the incidence of cesarean sections and neonatal HSV infection can be kept to a minimum.