Albert J. Wasserman

Tissue lipoprotein lipase in normal individuals and in individuals with exogenous hypertriglyceridemia and the relationship of this enzyme to assimilation of fat.

Lipoprotein lipase activity (LLA) was measured in the adipose tissue of six healthy subjects and five members of a family in whom the trait for familial exogenous hypertriglyceridemia was segregating. The lipase activity measured was characteristic of lipoprotein lipase: increased by feeding, dependent on the presence of serum, and inhibited by sodium chloride and protamine sulfate. When compared with lipase activity in healthy individuals, LLA was grossly deficient in two siblings with postabsorptive chylomicronemia and was intermediate in both parents and one sibling, who had normal postabsorptive triglycerides. These findings are compatible with autosomal recessive inheritance. The hormone-sensitive lipolytic enzyme responsible for mobilization of free fatty acids from adipose storage was normal in the hyperlipemic subjects. After a 104-g fat meal, the serum triglyceride increased more in subjects heterozygotic for LLA deficiency than in the healthy subjects, and there was a relatively greater increase in chylomicrons and very low density lipoproteins in the affected individuals. These observations demonstrate the physiologic importance of lipoprotein lipase in removal of these lipoprotein groups and further clarify the differences between endogenous and exogenous hypertriglyceridemia.

Effect of Reserpine in Raynaud's Phenomenon

The responses of the blood vessels of the hand to intra-arterial infusion of tyramine and to application of ice to the forehead were examined in patients with Raynauds phenomenon and in normal subjects. The vasoconstrictor responses to tyramine and to ice were not significantly different in the patients and control subjects. Following intra-arterial administration of reserpine the vasoconstrictor response to tyramine was unaffected, while that in response to ice was significantly reduced to a comparable extent in both the patients and the control subjects. Catecholamine concentrations in brachial arterial and hand venous plasma were not significantly different in the patients and in the control subjects. Following oral administration of reserpine (1 mg/day) the vasoconstrictor responses to intra-arterial tyramine and to the application of ice were markedly reduced in patients with Raynauds phenomenon. In response to this form of treatment eight of the nine patients followed for 1 to 3 years showed improvement characterized by decreased frequency and severity of vasospastic attacks and by healing of ulcerations. In two patients the improvement was temporary despite continued reserpine therapy.

Cerebrovascular response to acute hypocapnic and eucapnic hypoxia in normal man

Alterations in human cerebral blood flow and related blood constituents were studied during exposure to acute hypoxia. Observations were made during serial inhalation of decreasing O(2) concentrations with and without maintenance of normocarbia, during 8 min inhalation of 10% O(2), and after hyperventilation at an arterial P(O2) of about 40 mm Hg. In the range of hypoxemia studied, from normal down to arterial P(O2) of about 40 mm Hg, the magnitude of the cerebral vasodilator response to hypoxia appeared to be largely dependent upon the coexisting arterial CO(2) tension. The mean slope of the increase in cerebral blood flow with decreasing arterial O(2) tension rose more quickly (P < 0.05) when eucapnia was maintained when compared with the slope derived under similar hypoxic conditions without maintenance of eucapnia. When 12 subjects inhaled 10% oxygen, cerebral blood flow rose to more than 135% of control in four whose mean decrease in arterial CO(2) tension was - 2.0 mm Hg. The remaining eight had flows ranging from 97 to 120% of control, and their mean decrease in CO(2) tension was - 5.1 mm Hg. When mean arterial P(O2) was 37 mm Hg, hyperventilation was carried out in 10 subjects. Arterial P(O2) increased insignificantly, arterial P(CO2) declined from 34 to 27 mm Hg (P < 0.05), and cerebral blood flow which had been 143% of control decreased to 109%, a figure not significantly different from control.These data demonstrate the powerful counterbalancing constrictor effects of modest reductions in CO(2) tension on the vasodilator influence of hypoxia represented by arterial P(O2) reductions to about 40 mm Hg. Indeed, mild hyperventilation completely overcame the vasodilator effect provided by an arterial O(2) tension as low as 40 mm Hg. The effects of hypoxia on the control of the cerebral circulation must be analyzed in terms of the effects of any associated changes in CO(2) tension.

Anticoagulants in acute myocardial infarction. The failure of anticoagulants to alter mortality in a randomized series.

Abstract 1. 1. The effect of anticoagulation therapy on mortality and morbidity in 147 consecutive male patients with acute myocardial infarction was evaluated. 2. 2. The patients were divided into three groups: those adequately anticoagulated, those inadequately anticoagulated, and those not anticoagulated. The patients were randomly assigned, and the groups were shown to be comparable, except for an increased incidence of a history of previous heart failure in the untreated group. 3. 3. There was no significant reduction in mortality in the anticoagulated groups when compared to the control group. 4. 4. The incidence of thromboemboli was too low to be of significance in assessing the effects of anticoagulants as antithrombotic agents. 5. 5. We conclude from this study that routine anticoagulation therapy is not indicated in acute myocardial infarction, and that factors other than those affected by anticoagulants determine the prognosis in this disease.

Mechanism and pattern of human cerebrovascular regulation after rapid changes in blood CO2 tension.

Mechanism and pattern of human cerebrovascular regulation after rapid changes in blood carbon dioxide tension

An Apomorphine‐Induced Vomiting Model for Antiemetic Studies in Man

Apomorphine-induced vomiting is often used for preclinical efficacy testing of putative antiemetics in normal volunteers. The usual technique of individual intravenous titration for finding the threshold emitic dose of apomorphine in each subject is slow and tedious. We used a uniform dose of 0.05 mg/kg apomorphine given subcutaneously to test the antiemetic action of metoclopramide and votracon in ten healthy, young male volunteers. All ten subjects vomited in response to this dose of apomorphine when pretreated with placebo. Pretreatment with metoclopramide prevented vomiting in all subjects, and votracon prevented vomiting in two. Apomorphine, 0.05 mg/kg, subcutaneously appears to be an appropriate challenge dose for testing compounds for antiemetic activity in normal human volunteers.

Clinical communicationAnticoagulants in acute myocardial infarction: The failure of anticoagulants to alter mortality in a randomized series☆

Abstract 1. 1. The effect of anticoagulation therapy on mortality and morbidity in 147 consecutive male patients with acute myocardial infarction was evaluated. 2. 2. The patients were divided into three groups: those adequately anticoagulated, those inadequately anticoagulated, and those not anticoagulated. The patients were randomly assigned, and the groups were shown to be comparable, except for an increased incidence of a history of previous heart failure in the untreated group. 3. 3. There was no significant reduction in mortality in the anticoagulated groups when compared to the control group. 4. 4. The incidence of thromboemboli was too low to be of significance in assessing the effects of anticoagulants as antithrombotic agents. 5. 5. We conclude from this study that routine anticoagulation therapy is not indicated in acute myocardial infarction, and that factors other than those affected by anticoagulants determine the prognosis in this disease.

Human Cerebrovascular Response to Combined Hypoxia and Hypercapnia

The N2O technique was used in 6 human subjects to measure cerebral blood flow and metabolism during hypoxia and hypercapnia induced by the inhalation of 10% O2-5% CO2. Ventilation increased from 7.7 to 46.3 liters/min; Pao2 decreased from 88 to 62 mm Hg; Paco2 increased from 38 to 45 mm Hg (for each P <.01). Mean cerebral blood flow increased from 56 to 97 ml/100 g/min (P <.01). Because cerebral O2 consumption was unchanged, the technique of estimating changes in cerebral flow from arterial-jugular venous O2 differences was used to follow changes during the first 10 min of inhalation of 10% O2-5% CO2 in 6 additional subjects. The rapidity of cerebral vasodilatation was increased by this combination of stimuli. The enhanced respiratory response produced by breathing 10% O2-5% CO2 appeared responsible for the more rapid cerebrovascular response and may offer some protective benefits. Comparisons of the present data with previous studies lead to the conclusion that simultaneous hypoxia and hypercapnia have additive dilator effects on the cerebral vasculature. Thus, the observed increases in cerebral flow were the sum of their individual effects.

Effects of α- and β-adrenergic blocking agents on serum prolactin levels in women with hyperprolactinemia and galactorrhea

Abstract The effects of α- and β-adrenergic blocking agents on the serum prolactin levels of six women with hyperprolactinemia and galactorrhea were investigated. There was no indication that pituitary adenomas were etiologic agents for the hyperprolactinemia. Serum prolactin could be lowered with oral l -dopa. When intravenous phentolamine (an α-adrenergic blocking agent) or intravenous propranolol (a β-adrenergic blocking agent) were administered for 1 hour, there was no significant change in serum prolactin levels.

Tolerance to pirprofen and preliminary efficacy trial in rheumatoid arthritis.

Pirprofen is an anti‐inflammatory drug derived from propionic acid. The compound inhibits the inflammatory response in the paw edema test, the cotton pellet granuloma test, and the adiuvant arthritis model in rats. Animal studies indicated a propensity to cause gastrointestinal ulcerations. Normal human subiects tolerated doses up to 600 mg per day. Occult fecal blood loss was rare. A preliminary efficacy study in 3 patients with definite, active rheumatoid arthritis showed apparent therapeutic benefit in doses of 200 to 400 mg daily. Pirprofen 400 mg per day was therapeutically eqUivalent to indomethacin 100 mg per day in 18 patients with definite, active rheumatoid arthritis in a double‐blind comparison. Adverse effects appeared to be more frequently abdominal in origin during pirprafen and more often central nervous system related during indomethacin. No serious manifestations of toxicity were noted in these studies.