Benjamin H. Barbour

Alpha-Methyl Dopa for the Treatment of Hypertension Clinical and Pharmacodynamic Studies

AN AGENT inhibiting chemical formation of vasopressor substances gives promise of a superior approach to the treatment of arterial hypertension. Alpha-methyl-3,4-dihydroxyl-1-phenylalanine (alpha-methyl DOPA*), a decarboxylase inhibitor, acts at least partly in this manner.1-3 In contrast to other medications in wide use for the treatment of hypertensive vascular disease, this drug does not block transmission of autonomic impulses but lowers the concentration of norepinephrine and serotonin in the tissues.4-6 In drugs exerting more generalized interference with autonomic functions, the side effects of constipation, nasal stuffiness, dry mouth, visual disturbances, and impotence have not yet been eliminated. The preliminary clinical observations of Oates, Gillespie, Udenfriend, and Sjoerdsma7 established the potential value of alpha-methyl DOPA as an antihypertensive drug. Side effects commonly noted during treatment with rauwolfia alkaloids, the ganglionic blocking drugs, and the postsympathetic blocking agents, did not usually accompany the use of the new drug. More extensive clinical experience reported from various centers, including our own, confirms these findings.8 14 In assessing the place of alpha-methyl DOPA as an addition to the al-

Nontraumatic hemopericardium: An analysis of 105 cases

Abstract One hundred five cases of nontraumatic hemopericardium were encountered among 21,000 consecutive autopsies at the Los Angeles County Hospital. The causes in order of frequency were acute myocardial infarction, sixty-three and ruptured aneurysm, thirty-five, of which thirty were of the dissecting type. There were four syphilitic aneurysms and one mycotic aneurysm of a coronary artery. Hemopericardium was the result of metastatic carcinoma in four and a blood dyscrasia in three cases.

CLINICAL EVALUATION OF GUANETHIDINE IN HYPERTENSION

The amidoxime, (2-[octohydro-l-azocinyl]-ethyl)-guanidine sulfate, was developed as an antihypertensive agent and given the generic name guanethidine.’ ,2 This followed the preliminary work with other amidoximes by Mull and his associates.s The main chemotherapeutic action of these substances is due to the blockade of the sympathetic nervous system, apparently at the site of their peripheral terminals? I t should be noted that they enhance the pressor response of the pyrocatechol derivates, which contain the structure

Theoretical Evaluation of a Patient-Artificial Kidney System Using the Kiil Dialyzer.

Abstract A mathematical model of the patient-artificial kidney system has been developed that can accurately predict body chemical distribution changes during hemodialysis—over a wide range of system parameters—for urea and creatinine. This article validates the model by using considerable amounts of clinical data from two selected patients and data from only a single dialysis from ten randomly chosen patients. The validated model was used to predict the fraction removed during dialysis of the total amount of urea and creatinine in the body. These data were plotted as a function of: (1) blood-flow rate; (2) length of dialysis; (3) initial blood concentrations; and (4) patient weights. In the vast majority of patients undergoing hemodialysis today with the Kiil Dialyzer, end-dialysis blood concentrations, as well as the amounts of material removed during dialysis, may be accurately predicted. Only the weight of the patient and his blood-flow rate into the dialyzer must be known to accomplish this prediction, since the current treatment result is dialyzer limited (dependent only on the dialyzer parameters).

Peripheral arterial and renal venous angiotensin concentration.

Summary Nephrectomized dog blood contains pressor material in very low concentrations (62 ± 28 mμg%). Recovery of synthetic angiotensin II was variable (30–70%). Peripheral arterial angiotensin concentration was elevated by an infusion of angiotensin, but patients with essential hypertension had angiotensin concentrations lower than during the infusion and their angiotensin concentration was the same as in normotensives. Sodium intake did not influence angiotensin concentration in renal venous blood. The presence of renal artery stenosis did not elevate renal venous angiotensin concentration on the affected side.

The Hippuran renogram.

tively concentrated by renal tissue. During the test, the radioactivity from each kidney area is detected by separate externally placed scintillation counters and a simultaneous recording from each counter is graphically inscribed. Thus, recordings of radioactivity externally over the left and the right kidneys give an immediate record of each kidney’s function so that a ready comparison can be easily made. The use of radioactive material in measuring renal function was first employed by Oeser and Billion2 in Germany when they measured the urinary output of a radioactive iodinated dye after an intravenous injection. Taplin and coworkers4 established the basis for external count-

The use of carbethoxysyringoyl methylreserpate in hypertension

Abstract 1. (1) Single intravenous doses of carbethoxysyringoyl methylreserpate given to 2 patients with moderately severe hypertension produced a marked hypotensive effect. 2. (2) Four individuals with severe hypertension in the accelerated phase showed encouraging responses to prolonged intramuscular administration of this new drug. 3. (3) In the oral form, carbethoxysyringoyl methylreserpate can be given in relatively large doses without serious side effects. This should be of value in those patients unable to tolerate reserpine.

Fixed-Bed Charcoal Hemoperfusion in the Treatment of Drug Overdose and Chronic Renal Failure

The fixed bed charcoal hemoperfusion system has now been applied extensively in animals and humans for evaluation of safety and efficacy in a variety of disorders.1,2 It is clearly appropriate that all of the methods which have been applied to treating intoxication by hemoperfusion be considered together although it is doubtful that an agreement will be reached on the superiority of one technique over any other at this time. The classic loose-bed arrangement of clean charcoal packed loosely in a column with blood perculating through its matrix was initially evaluated by Yatzidis and it was found to have some intolerable side effects, particularly on formed blood elements.3 Furthermore, charcoal particulate emboli was a definite threat to the safty of such a device. Chang in his pioneering studies of the artifical cell attempted to overcome both problems of emboli as well as the platelet depression by placing a thin coat over the charcoal.4 A still unsettled issue using Chang’s approach is the probability that the coat will decrease charcoal’s absorability and therefore its efficiency, partially offseting the advantage of charcoal as a therapeutic agent to remove noxious substances.

Past, Present, and Future of Artificial Kidney Treatment

Abstract The past has seen the evolution of hemodialysis from a very complex operation to a systematized approach which allows the procedure to be instituted by minimally trained individuals. The first big advance in the application of hemodialysis to the problem of chronic renal insufficiency came in 1960 when a permanently implanted arteriovenous plastic fistulae was established. Improvements in dialyzer design and the logistics of hemodialysis since then have resulted in expansion of hemodialysis facilities. There is still a deficit between facilities available and suitable patients in need of therapy. Closure of this gap will depend upon a cheap, small, disposable dialyzer which most patients can operate themselves. In addition, an improvement in kidney transplantation results will remove many patients from the pool of those needing hemodialysis. It is likely that other medical applications of hemodialysis will be discovered in the future.