bluuebunny/crossref_metadata_2025 huggingface dataset:
Local and systemic hemodynamic effects of nylidrin
Authors: Frohlich Edward D. , Schnaper Harold W.
Published: January 2016

The hemodynamic effects of nylidrin were observed in a group of normal human subjects and in the constantly perfused dog forelimb. In the human, heart rate and cardiac output increased following acute intra‐arterial administration of the drug; total peripheral resistance, mean circulation time, and arterial blood pressure decreased. The plasma and central blood volumes and hematocrit remained unchanged, whereas blood volume decreased; stroke volume and venous pressure showed no consistent change. In the dog forelimb, acute local elevation of plasma nylidrin concentration greatly decreased resistance to blood flow in the small vessels over a wide dose range. It appears that there are two primary effects of this agent following its intra‐arterial administration: one, to decrease total peripheral resistance; and two, a direct effect on the heart to increase cardiac output. In the dosage used and the route administered, there were no clinically significant effects on heart rate or blood pressure. These results suggest that nylidrin exerts these local vascular and myocardial actions by stimulation of the beta‐adrenergic receptor sites.
Drug combinations‐uses, dangers, and fallacies
Authors: Jick Hershel , Chalmers Thomas C.
Published: January 2016

The use of many drugs for the treatment of a single disease or symptom complex has been a prevalent practice throughout history. Indeed, William Withering's clinical description of “dropsy” published in 1785 advocated treatment which included “medicines of the de‐obstruent tonic, antispasmodic, diuretic and evacuate kinds.” In the best tradition of multiple component therapy, he advised the use of “pills of Myrrh and white vitriol; and if costive, a pill with calomel and sloes.” Now as then, the psychological appeal of prescribing “not just one but a combination of medically proven ingredients” is apparently hard to resist, presumably on the basis of “more” being necessarily better than “less.”
Enhancement of blood antibiotic levels through the combined oral administration of phenethicillin and chymotrypsin
Authors: Avakian S. , Kabacoff B. L.
Published: January 2016

To determine the effect of the proteolytic enzyme, chymotrypsin, on phenethicillin blood levels, both drugs were administered orally to a group of subiects. The same subiects previously had received phenethicillin and a placebo. On both test days blood samples were drawn at frequent intervals and assayed for penicillin activity. The test procedure was repeated, under double‐blind conditions, in a second group of patients. The oral administration of crystalline chymotrypsin was found to increase substantially phenethicillin blood levels without affecting the half‐life of the antibiotic in the blood. The clinical significance has yet to be established through clinical trials.
State of knowledge on human exposures and biologic effects of economic poisons
Authors: Kay Kingsley
Published: January 2016

Concern over the toxic potential of economic poisons developed around 1950 following widespread reports of ill‐effects from two main classes of these chemicals, the chlorinated hydrocarbons and organic phosphates. The large number of cases appears to have resulted from the increasing use of the pesticides in agriculture and by vector control personnel untrained in safety procedures. At the same time the development of resistance by many species of pests‐ has necessitated higher dosages and new compounds. Toxicity assessment, primary to measures for controlling use hazard, has been required under the Food and Drug act but largely in terms of life and death data from laboratory animals subjected to oral, parenteral, skin, and inhalation exposures. A new trend emphasizes the investigation of psychophysiologic factors, storage in body fat depots, tumorigenicity and carcinogenicity, effect on reproductivity and related genetic COnsiderations, potentiation by associated substances, antagonism, and therapeutics. The problem of impurities of high tOXicity in commercial products appeared early in production of aldrin and has been met with subsequently in connection with production of other materials. Vehicles and solvents have been found to play a role in tOXicity. Currently there is a difference between the evaluation basis commonly used in the U.S. and U.S.S.R. In the U.S.S.R. functional changes are frequently adopted as an index of toxicity. Cultural and climatic considerations play a significant role in determining the ultimate hazard.
Introduction
Authors: Levine Irving M.
Published: January 2016

Beginning with the latter part of the nineteenth century, many outstanding contributions have been and continue to be made, which enlarge our understanding of neuromuscular and musculoskeletal function. Largely through the efforts of several of the participants of this symposium, much has been learned regarding central and peripheral mechanisms involved in both the regulation and control of normal muscle tone, and their disruption, which results in hypertonia.
The extrapyramidal system and postural mechanisms
Authors: Denny-Brown D.
Published: January 2016

Extrapyramidal disorders, which include a wide range of disturbances involving loss of ability of movement, and muscle stiffness of either the plastic or springy type, are distinguished from those of “spastic paralysis” due to lesions of some part of the corticospinal tract. The most obvious features of the former are disturbances of postural attitude. Other features‐tremor, rigidities, exaggerated deep reflexes, and resistance to stretch‐are discussed in terms of the mechanisms (facilitatory and inhibitory) involved. Data from classical experiments, ahlation and stimulation of the supplementary area and other cortical extrapyramidal postural regions, are reviewed, interpreted, and related to the clinical manifestations of spasticity and dystonias. Current experimental evidence (decorticate monkey) reveals the interdependence between proiected types of motor reactions served hy the pyramidal system and the more elementary reactions such as the grasp reflex and traction reactions, and points to the involvement also of mechanisms at the cortical level in dysionias, previously descrihed as symptoms of basal ganglia diseases.
Skeletal muscle spasms and spasticity: Clinical considerations
Authors: Kane Charles A.
Published: January 2016

Under appropriate conditions, virtually any striated muscle can develop painless or painful clonic or tonic spasms, leading to a wide range of clinical syndromes, from the rare “stiff‐man syndrome” to very common athletic injuries. The pathogeneses of hypertonias are legion, involving, among others, central nervous system lesions, e.g., basal ganglia disease, traumatic lesions of the spinal cord and nerve roots, encephalopathies of the “stimulus‐sensitive” type (myoclonus, hypsarrhythmia), true muscular cramps associated with electrolyte abnormalities (tetany), infections (tetanus, rabies), neurotoxins (venoms), and hereditary absence of muscle phosphorylase (McArdle's syndrome). Also, treatment involves a wide variety of modalities, from relief of spasm by local physical ameliorants to destructive surgical procedures. Intrathecal steroid injections in patients with spastic paraparesis due to multiple sclerosis produced a striking reduction of incapacitating lower limb spasticity in 3 of 10 patients treated. While responses were inconsistent and unpredictable, further careful testing is deemed warranted.
Skeletal muscle cramps
Authors: Geschwind Norman
Published: January 2016

The different clinical conditions characterized by the presence of cramps (intense, often painful, localized contractions of skeletal muscle) were surveyed. These clinical conditions are varied and include certain primary diseases of muscle metabolism, disorders of the muscle membrane, and various affections of nerve. In addition, certain widespread metabolic disorders may lead to cramps, probably in most cases by mechanisms affecting firing in peripheral nerves. The problem of cramps of functional origin is also briefiy discussed. Some of the physiologic mechanisms of cramps are outlined briefiy.
Controls in clinical research
Authors: Greenblatt Milton
Published: January 2016

The problems of controlled experiments in the human subiect are by no means solved by the balanced group method and double‐blind procedures‐a fact to be co!1JSidered in attempts to reduce error and raise confidence levels in clinical results. Among the sources of experimental error, particularly in psychiatry, may be the personality uf the investigator himself, affecting physiologic rapport ("concordance") with the patient, not to mention the premises he selects for establishing criteria. The vagaries uf the placebo reactor, the position of the placebo in the series of drugs tested, what the patient is told concerning the drug, the attitude uf the staff, the types of communication received from other patients in the group, the subiect's “set," his interest and ability in responding to his environment are among the factors which determine reliability of the results and the validity of the conclusions. “Love of truth" and “plain horse sense" remain the mainstays in sound clinical evaluation.
Quantification of the electromyogram in neurospastic disorders
Authors: Levine Irving M. , Jossmann Paul B. , DeAngelis Vincent , Kane Madeleine
Published: January 2016

A procedure for direct recording of the electromyogram in the polygraph laboratory, integration of the raw data, and distant monitoring of the EMG is presented in graphic form. A telephone telemetry system known as telmedography or telemedography, especially useful for obtaining EMG and ECG and EEG data from nonambulatory patients from their homes, is also described. The accompanying figures serve to illustrate the equipment involved in laboratory and telephone telemetry recording, its uses in monitoring bedridden patients with neurospastic disorders, and obiective recording of the data obtained.
Cerebral palsy‐a pharmacologic approach
Authors: Denhoff Eric
Published: January 2016

Rehabilitation of the cerebral palsied child demands a multiplicity of modalities to deal with the complex disabilities: neurological dysfunction, behavioral difficulties, perceptual distortion, emotional disturbances, and learning disabilities. Pharmacologic agents represent but one of many aids in a comprehensive program of effective rehabilitation. A practical drug approach is presented as an adjuvant to physical therapy and other modes of treatment. The electroencephalic photo‐Metrazol technique was used for objective differentiation between behavior symptoms of organic origin and those of emotional disorders in 192 children with cerebral palsy and related disorders. ApprOXimately 60 per cent had abnormal or borderline photo‐Metrazol thresholds, indicating diencephalic dysfunction. These were candidates for amphetamine therapy; those with narmal levels despite hyperkinetic behavior were nat. In a double‐blind study, diazepam was tested in 25 children with cerebral palsy, with an over‐all improvement in 36 per cent; in those who were nonambulatory, with rigidity and moderate degrees of mental retardation, a 60 per cent improvement was observed.
Summary: Thirty years' progress in hypertonic quantifications
Authors: Doshay Lewis J.
Published: January 2016

It was very good of you to take time from all your pressing duties to come here to contribute your experiences toward a better understanding of hypertonic quantification.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

A 35‐year‐old man developed swelling and discomfort over the left elbow. Two years before, he had experienced stiffness and edema of the fingers. Salicylate therapy had been helpful. Shortly thereafter he had a brief episode of what had been considered “mild anicteric hepatitis” which subsided within a month.
Drugs used in the treatment of glaucoma. Part I
Authors: Leopold Irving H. , Keates Edwin
Published: January 2016

Glaucoma, an ocular disorder, is characterized by increased intraocular pressure, excavation and degeneration of the optic disc, and typical defects in the field of vision. The disease may progress to blindness. It is generally held that ocular hypertension is due to some form of obstruction to the outflow of aqueous humor from the anterior chamber. Surveys indicate at least 2 per cent of the population of the United States over 40 years of age has this condition.42 More than one half of those afHicted are unaware of its presence.
Aldosterone and its antagonists
Authors: Ross E. J.
Published: January 2016

Since its isolation in 1952, the understanding of the function of aldosterone in mineral metabolism has grown by leaps and bounds. This review explores and summarizes the present state of knowledge concerning aldosterone and of a relatively new group of drugs which antagonize the action of aldosterone.
Objecfive evaluation of antitussive agents
Authors: Sevelius Hilli , Lester Patrick D. , Colmore John P.
Published: January 2016

Subjective evaluation of antitussives is unreliable. In the search for an ideal procedure for evaluation, several methods have been developed which use bronchial irritants for artificial cough production in selected subjects. The currently popular citric acid and the acetylcholine methods with healthy volunteers were re‐evaluated and in our hands were unsatisfactory. Abrief discussion of the use of electronic cough recorders in subjects with spontaneous coueb as the only other presently available objective procedure for evaluating the efficacy of antitussive agents is presented.
D‐Lysergic acid diethylamide (LSD): A review of its present status
Authors: Hoffer A.
Published: January 2016

This is a review of an important but controversial subject, written by one of the important figures involved in the controversy. It was not possible to get a review in depth by someone who was not also involved in the controversy. With this in mind, this review was accepted for publication because it was written by an authority actively engaged in the problem and because it was thought important to bring details of the subject to the attention of a large readership. Correspondence is invited.
Drugs used in the treatment of glaucoma. Part II
Authors: Leopold Irving H. , Keates Edwin
Published: January 2016

Parasympathomimetic drugs act like acetylcholine. This naturally released neurohormonal agent promptly loses potency in solution and is rapidly inactivated in tissues by the enzyme, cholinesterase. For these reasons it is not generally used in the management of glaucoma. Corneal penetration by acetylcholine is very poor, but it can be increased by use of a wetting agent such as benzalkonium chloride.
Pharmacologic effects of CI‐581, a new dissociative anesthetic, in man
Authors: Domino Edward F. , Chodoff Peter , Corssen Guenter
Published: January 2016

Pharmacologic actions of CI‐581, a chemical derivative of phencyclidine, were determined in 20 volunteers from a prison population. The results indicate that this drug is an effective analgesic and anesthetic agent in doses of 1.0 to 2.0 mg. per kilogram. With intravenous administration the onset of action is within 1 minute and the effects last for about 5 to 10 minutes, depending on dosage level and individual variation. No tachyphylaxis was evident on repeat doses. Respiratory depression was slight and transient. Hypertension, tachycardia, and psychic changes are undesirable characteristics of the drug. Whether these can be modified by preanesthetic medication was not determined in this study. Recovery from analgesia and coma usually took place within 10 minutes, although from electroencephalographic evidence it may be assumed that subiects were not completely normal until after 1 to 2 hours. No evidence of liver or kidney toxicity was obtained. CI‐581 produces pharmacologic effects similar to those reported for phencyclidine, but of shorter duration. The drug deserves further pharmacologic and clinical trials. It is proposed that the words “dissociative anesthetic” be used to describe the mental state produced by this drug.
Thalidomide (N‐phthaloylglutamimide> in the treatment of advanced cancer
Authors: Olson Kenneth B. , Hall Thomas C. , Horton John , Khung Christiaan L.
Published: January 2016

Thalidomide (N‐phthaloylglutamimide) was administered to 21 patients with fourteen types of cancer for periods of 1 to 34 weeks, with total doses ranging from 4.2 to 354.0 Gm. There were mild hemologic and neurological untoward effects. Notumor regression was noted but there was significant subjective palliation in 7 patients. Further study of this drug in patients with advanced cancer is warranted. Palliation was noted to be chiefly improved sedation in disturbed and elderly persons. There was possible arrest of previously rapid growth of tumor in 2 cases.
Thalidomide in the treatment of lepra reactions
Authors: Sheskin J.
Published: January 2016

In 6 consecutive cases of lepromatous leprosy, acute severe lepra reactions were qUickly resolved with disappearance of symptoms as well as signs after the use of thalidomide as a sedative. No exceptions were noted. Concurrent therapy with sulfones and arsenicals did not appear to be involved. The cases are reported at this early stage because of the obvious importance of corroborating these findings.
Studies of sulfamethoxydiazine
Authors: Kaplan Kenneth , Chew William H. , Weinstein Louis
Published: January 2016

Studies are reported comparing the antibacterial activity and chemical levels of sulfamethoxydiazine, a new long‐acting sulfonamide, in serum and plasma of humans. Eleven subjects were treated with various dose schedules for 7 to 10 days; blood samples were taken at the expected daily low and high sulfonamide concentrations. Serum and plasma antibacterial activity was the same. A tendency for each subject to show a positive linear correlation between sulfonamide concentration and antibacterial titer of serum or plasma was noted. This could be demonstrated whether drug levels were compared with antimicrobial activity or whether the sulfonamide concentration was studied at selected titers of antibacterial activity. The 95 per cent confidence limits for the group, however, were very broad and indicated that prediction of either antibacterial activity or sulfonamide concentration from knowledge of the other was not possible. In general, the administration of 1.5 to 2.0 Gm. of sulfamethoxydiazine initially and 0.5 Gm. daily produced blood levels of 7 to 12 mg. per 100 ml. and bacterial inhibition at titers of 1:32 and 1:64. On this basis, this dose of sulfamethoxydiazine is recommended tor therapy.
A clinical comparison of the antipyretic potency of aspirin and sodium salicylate
Authors: Seed John C.
Published: January 2016

In a study on adult patients with cancer and low‐grade fevers due to chronic infection, aspirin appeared to be 1.5 times as potent as sodium salicylate as an antipyretic. The difference in potency is probably due to the difference in pKa of the two acids.
Studies with acetylsalicylic acid
Authors: Krumholz Wilhelm V. , Sheppard Charles , Merlis Sidney
Published: January 2016

In this communication we report an attempt to verify the findings of a previous report comparing the “rtranquilizing and antidepressant” effects of aspirin, an aspirin compound, a mild tranquilizer, and a placebo on 20 volunteer subjects. In a double‐blind, Latin‐square comparison, slightly different from the first design, the “antidepressant” effects of aspirin were verified. Some comments are made on the problems of subject selection in psychopharmacologic studies. The need for further study of the “tranquilizing and antidepressant” effects of aspirin is indicated.
Folates and megaloblastic anemia: A review
Authors: Johns D. G. , Bertino J. R.
Published: January 2016

In recent years, a great deal of new information on the identity and distribution of the naturally occurring folates, on the adult daily requirement for folic acid, and on folate‐vitamin B12 interrelationships has been published. The compound, 5‐methyltetrahydrofolate, has been found rfo be present in significant amounts in human serum, red cells, and liver, and to be involved in the synthesis of methionine from homocysteine, a reaction which appears to require vitamin B12. In vitamin B12,‐deficiency states, such as pernicious anemia, 5‐methyltetrahydrofolate cannot be demethylated to yield rtetrahydrofolate, and as a consequence a secondary defiCiency of tetrahydrofolate develops. These and other recent studies concerning folates and the megaloblastic anemias are re1Jiewed.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

This is a brief report of eight mothers whose offspring were found to have unilateral or bilateral cataracts of unknown origin. Three women had taken tetracycline or oxytetracycline “during pregnancy or while breast‐feeding.” One had received tetracycline alone at 10 weeks' gestation; another, oxytetracycline alone at 6 weeks; the third, sulfisoxazole at 7 weeks followed by chloramphenicol and tetracycline; the fourth received meclizine, doxylamine, and dicyclomine at 10 weeks, progesterone from the eighth to twentieth week, and tetracycline and oleandomycin for 2 weeks after parturition. (No doses or exact duration were provided.) Of the remaining women, one took no drugs, another promazine alone, the third received acetylaminophenol alone at 10 to 12 weeks, and the fourth took thenalidine tartrate at 12 weeks, phenylbutylamine and acetozolamine at 24 weeks, and sulfamethoxypyridazine at 10 weeks. (Doses and duration not provided.)
The effects of tris (hydroxymethyl) aminomethane on the composition of extracellular fluid, skeletal muscle, and cardiac muscle
Authors: Talso Peter J. , Cutilletta Anthony F.
Published: January 2016

Tris (hydroxymethyl) aminomethane in a dose of 44 ml. per kilogram of a O.3M solution was administered to a series of dogs anesthetized with pentobarbital sodium. Seven received THAM alone and seven received THAM with supplementary sodium and potassium chloride. Electrolyte determinations were performed on serum and on samples of skeletal and cardiac muscle. A significant increase in serum pH and total CO2, followed the infusions while serum Cl‐ and Nw decreased significantly. No significant changes in serum potassium concentration were observed. The content of extracellular and intracellular water together with the concentration of intracellular electrolytes in both skeletal and cardiac muscle did not change significantly following the infusions. Thus, THAM is capable of inducing marked changes in extracellular ph and total CO2, without significantly altering tissue water and electrolyte composition.
A short‐acting monoamine oxidase inhibitor, Ro 5‐1025
Authors: Feldstein Aaron , Freeman Harry
Published: January 2016

A clinical, physiologic, and biochemical study was made of Ro 5‐1025, a short‐acting MAO inhibitor. Ro 5‐1025 did not show antidepressant properties and did not lower blood pressure at 20 to 60 mg. per day. The radioactioe serotonin test for MAO showed that Ro 5‐1025 was a weak MAO inhibitor without accumulative effects at the doses indicated.
How reliable are enteric‐coated aspirin preparations?
Authors: Clark Richard L. , Lasagna Louis
Published: January 2016

Uncoated aspirin and two brands of enteric‐coated aspirin were given to eight patients and two healthy volunteers in multiple‐dose experiments designed ,to achieve relatively “steady‐state” conditions with regard to the various preparations. Satisfactory and reasonably consistent blood concentrations of salicylate were obtained with ordinary aspirin and one enteric‐coated brand. Results with the second enteric‐coated brand indicated capricious and generally poor absorption. The findings are discussed in terms of the problem of devising satisfactory enteric‐coating and of reliance on in vitro studies for predicting biologic activity.
The clinical status of low molecular weight dextran: A critical review
Authors: Couch Nathan P.
Published: January 2016

Although dextran of molecular weight 75,000 has established clinical value as a plasma expander, dextran of molecular weight 40,000 remains under study, Because of its alleged effects on microvascular flow, there has been renewed interest in changes of suspension stability of blood and of erythrocyte aggregation, Several workers have observed that low molecular weight dextran reverses aggregation of red blood cells in various disease states, but quantitative evidence to date is too sparse to determine the fme therapeutic value of the compound. If it can be shown to have important effects beyond those resulting from plasma expansion and dilution of erythrocytes and plasma macromolecules, it is hoped that the benefots will outweigh the very serious disadcantage of rapid renal excretion. Considerably more data are needed, including comparisons with equivalent amounts of other common plasma expanders; these data should be sequential and should include viscosity, hematocrit, fobrinogen, globulin, and peripheral flow determinations.
One drug‐one name
Authors: Friend Dale G.
Published: January 2016

The dilemma in which the medical profession finds itself regarding drug terminology is causing considerable confusion. Many in the pharmaceutical industry are certain that the trade‐name program is absolutely essential for its well‐being. They feel that it is essential to protect them from inroads on their products by other pharmaceutical firms which have not devoted the expense, time, and effort that go into research and development of useful new entities. Furthermore, drug manufacturers with a certain degree of pride and good reason feel that a trade name on which they have spent a great deal of effort also places them in a position of responsibility in that the product put out under their trade name must be of the highest quality or they are likely to suffer in competition, particularly if the trade name becomes discredited by imperfect or poor products. On the other hand, there is a large and rapidly growing group who feel that the use of the trade name leads to a certain amount of abuse in that it permits the manufacturer to continue to receive rather excessive profits on trade name drugs, through protection by copyright of the names of drugs, which for the most part have long since been made available to others in the industry and which can usually be sold cheaper than the trade‐named article. This group feels that all prescriptions should be written in nonproprietary or generic terminology, thereby permitting the pharmacist to dispense the drugs as the usually less expensive non‐trade named item. For this reason, in some places, the proponents of nonproprietary terminology have actually gone so far as to insist that welfare prescriptions be written in that terminology.
Forced diuresis in the management of barbiturate intoxication
Authors: Strickler James C.
Published: January 2016

The renal excretion of barbiturates is increased in both experimental animals and in patients heavily overdosed with these sedative drugs by enhancing the urine flow. The greatest increases in excretion as a function of urine flow occur with those long‐acting and intermediate‐acting barbituric acid derivatives which are, in therapeutic dosages, eliminated in part by the kidney. Alkalinization of urine further augments the renal excretion of the compounds with relatively low pKa values. Hemodialysis and to a lesser extent peritoneal dialysis more rapidly eliminate barbiturates, particularly the short‐acting derivatives, than does any diuretic regimen.
Physiologic combinations of synthetic thyroid hormones in myxedema
Authors: Wool Marvin S. , Selenkow Herbert A.
Published: January 2016

Physiologic combinations of synthetic L‐thyroxine and L‐triiodothyronine, the two naturally occurring thyroid hormones, have been formulated to produce full thyroid hormone replacement in athyreotic patients and at the same time give levels of protein‐bound iodine (PBI) and other thyroid parameters consistent with the patient's metabolic status. The optimal combination contains approximately 175 meg. sodium L‐thyroxine and 50 mcg. L‐triiodothyronine and is calorigenically equivalent to about 180 mg. of a potent porcine preparation of desiccated thyroid, USP. This mixture has the clinical advantage of not requiring standardization, therefore obviating fluctuations in hormonal potency. In addition, it mimics all the metabolic effects of normal thyroid hormone secretions and produces PBI levels commensurate with the patient's metabolic state. It is recommended as a reliable, physiologic, synthetic hormonal combination for use wherever thyroid replacement is indicated.
Increased sensitivity of the heart to catecholamine‐induced arrhythmias following guanethidine
Authors: Muelheims Gerhard H. , Entrup Richard W. , Paiewonsky Donald , Mierzwiak Donald S.
Published: January 2016

Guanethidine was administered orally to normotensive subjects and the responsiveness of the cardiovascular system to a norepinephrine infusion in increasing concentrations was examined. After guanethidine the infusion of norepinephrine resulted in a higher mean arterial blood pressure and a lower heart rate; cardiac arrhythmias appeared after lower doses of norepinephrine with greater frequency and occasionally were of a type having more serious implication. The almost exclusive development of A‐V nodal beats and A‐V nodal rhythm before as well as after guanethidine suggests the importance of vagal activity reflexly produced by stimulation of the sinoaortic baroreceptors through the rise in blood pressure. However, a direct effect of guanethidine sensitizing the myocardium to norepinephrine cannot be ruled out. It seems advisable to administer norepinephrine to patients receiving guanethidine with even greater caution than usual.
The “induction” of leukocyte and erythrocyte dihydrofolate reductase by methotrexate
Authors: Bertino J. R. , Cashmore A. , Fink M. , Calabresi P. , Lefkowitz E.
Published: January 2016

A study of the phenomenon of “induction” of the enzyme dihydrofolate reductase that occurs in leukocytes and erythrocytes after methotrexate administration has been made with the dog as an experimental model as weU as man. The “induction” has been shown to be specific for 4‐amino analogues of folate that are strong inhibitors of dihydrofolate reductase. Attempts to block induction with possible end products of dihydrofolate reductase activity and an inhibitor of protein synthesis, actinomycin D, were unsuccessful. Based upon studies of the enzymeinhibitor interaction as a function of pH, the rise in enzyme activity observed is explained by an accumulation of methotrexate‐bound enzyme that occurs as a result of protection of the enzyme from normal catabolic processes; free enzyme is observed because of the in vitro conditions employed for enzyme assay.
Overdoses of psychotherapeutic drugs
Authors: Hollister Leo E.
Published: January 2016

Widespread use of the newer central nervous system depressants and stimulants has resulted in many instances of overdoses, either accidentally by children or purposely by adults. While many of the general principles of treatment of poisoning with these drugs are the same as for older sedatives and stimulants, some problems are different.
Cardiac and renal hemodynamic effects of debrisoquin sulfate in hypertensive patients
Authors: Onesti Gaddo , LaSchiazza Dominic , Brest Albert N. , Moyer John H.
Published: January 2016

Debrisoquin sulfate is a moderately potent antihypertensive agent with a predominant orthostatic antihypertensive action. The antihypertensive effect of the drug appears to be due primarily to a decrease in cardiac output. There is no consistent effect on total peripheral resistance. Renal hemodynamic functions are not affected significantly in the supine position; however, when more significant blood pressure reduction is produced with upright posture, consistent diminution in renal blood flow follows.
Trial of amantadine in epidemic influenza
Authors: Wendel Herbert A. , Snyder Merrill T. , Pell Sidney
Published: January 2016

Amantadine hydrochloride, a chemotherapeutic anti‐influenza compound, was tested for prophylactic and curative effects in double‐blind trials on 794 and 55 prisoner volunteers during an Asian influenza epidemic. Oral 200 mg. doses were given for 10 to 14 days. In the prophylactic trial, 5 of 439 (1.1 per cent) drug‐treated subjects became ill in contrast to 15 of 355 (4.2 per cent) placebo subjects, indicating significant protection. Among unselected drug‐treated subjects, fourfold or greater titer rises occurred in 30 per cent fewer subjects than in the placebo group (p < 0.05). Subjects with initial titers of 40 or less showed a 43 per cent titer rise difference (p < 0.02). Measured by the rises of mean titers, amantadine exerted a 52 per cent protection (p < 0.05). Reduced antibody titer rises accompanying therapeutic drug administration were not significant.
Treatment of pernicious anemia: Historical aspects
Authors: Castle William B.
Published: January 2016

Highlights in the history of the development of successful and specific treatment for pernicious and other megaloblastic anemias are reviewed. The evolution of knowledge concerning the clinical and physiological basis for their separation into those due to vitamin B12 and to folic acid deficiencies, respectively, is discussed, and the consequent biochemical abnormalities related to megaloblastic erythropoiesis are briefly presented. The importance of informed collaboration between the medical profession and the pharmaceutical industry for the future initiation, development, and appraisal of new drugs is emphasized.
Evaluation of a new bronchodilator aerosol and its components in pulmonary emphysema
Authors: Wilson Roger H. L. , Wilson Nancy L.
Published: January 2016

The effects of nebulized isoproterenol dispensed in the conventional Freon propelled cartridge were studied in a group of emphysematous patients. The components of the study included combination with a surfactant (thonzonium bromide), the surfactant alone, isoproterenol alone, propellant and solvent alone, an isoproterenol analogue, and a simulated preparation of room air. Seventeen patients in the group were completely studied in three separate series. A fourth series with differing concentrations of thonzonium bromide was included. Results show an enhancing effect with prolongation of improvement with the addition of thonzonium bromide, the possible importance of a rebound reaction at 30 minutes, a definite improvement with propellant and solvent, and that the best concentration of thonzonium bromide is at 0.1 per cent. The clinical implications are discussed.
Studies on the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone
Authors: Baba Walten I. , Lant Ariel F. , Wilson Graham M.
Published: January 2016

A study aimed at investigating the mechanism and characteristics of action of a new phthalimidine diuretic, clorexolone, has been undertaken in rats and in a group of twenty‐three normal human subiects under various experimental conditions. Hydroflumethiazide, a typical benzothiadiazine analogue, has been used as a standard of comparison. The pharmacological properties of clorexolone have been found to resemble closely those of hydroflumethiazide. Duration of clorexolone‐induced diuresis is, however, longer. At maximally effective doses, the natriuretic responses achieved by both drugs are not statistically different. Orally administered clorexolone is without effect on GFR and its action upon the nephron appears to be directed primarily at a tubular level. The cellular mechanism of clorexolone action does not involve significant inhibition of renal carbonic anhydrase in vivo since urinary bicarbonate excretion and pH remain unchanged after its administration. The natriuretic effect occurs independently of aldosterone antagonism and is, at least in part, due to selective inhibition of sodium reabsorption without water at the urinary diluting sites in the distal part of the nephron. The data do nat exclude the possibility of an additional interference with proximal processes of isoosmotic sodium reabsorption. The extent of the urinary potassium loss induced by clorexolone is linked to the degree of mineralocorticoid stimulation of the distal nephron K+‐H/Na+ competitive exchange system. In addition, significant increase in potassium excretion also occurs after clorexolone administration in adrenalectomized animals, a finding which implicates a direct action upon tubular handling of potassium ion independent of mineralocorticoid participation.
Gastric hemorrhage induced by nonnarcotic analgetic agents in dogs
Authors: Davison Clarke , Hertig David H. , DeVine Raylene
Published: January 2016

The effect of various nonnarcotic analgetic agents in producing gastric hemorrhage has been investigated in Pavlov‐pouch dogs. Of the compounds tested, only aspirin in suspension at pH 3.0 produced extensive bleeding. The same drug in solution, as well as salicylic acid, salicylamide, methylsalicylate, and acetaminophen, produced no significant effect. Intravenous aspirin in high doses failed to cause gastric effects.
Trends in the therapy of acute poisonings
Authors: Gosselin R. E. , Smith Roger P.
Published: January 2016

Attention has been focused on many new and old techniques for preventing and treating poisonings arising from the ingestion of substances against which no specific antidotes are established. Aside from symptomatic and general supportive care, the nonspecific measures of value in clinical toxicology are of two types: those employed to minimize absorption by terminating the toxic exposure and those designed to promote the excretion of poisons already absorbed. In the first category, the induction of emesis, gastric lavage, the ingestion of adsorbents, and the administration of cathartics are recognized. In the second category are techniques for accelerating renal and biliary excretion, as well as extracorporeal hemodialysis, peritoneal dialysis, gastric dialysis, and related procedures. Considerably more information is desirable about each of these measures, how and when it should he used, and what advantages and disadvantages can be anticipated in its adoption. On the basis of recent studies, specific topics of promise for future investigation are suggested. Developments in these areas will probably prove to be more important than new systemic antidotes in terms of improving patient care in clinical toxicology.
Evaluation of the nalorphine pupil diagnostic test for narcotic usage in long‐term heroin and opium addicts
Authors: E. Leong Way , Mo Benjamin P.N. , Quock Collin P. , Yap P. M. , Ou George , Chan S. C. , Cheng Jay
Published: January 2016

The usefulness of the nalorphine pupil test for diagnosing narcotic usage was established on 67 addicts physically dependent on heroin and on 12 opium addicts. Reversal of narcotic miosis was obtained with 3 mg. nalorphine subcutaneously (positive test) in all addicts for at least one testing interval during a 72 hour observation after narcotic administration. The most responsive period (95 per cent positive reactions) occurred during the first testing interval between 1 and 4 hours; with time, the incidence of positive responses gradually decreased and the pupillary responses became increasingly erratic. Heroin inhalers reacted most consistently at the testing intervals between 2 to 10 hours. Intravenous heroin addicts on high doses of heroin gave inconsistent pupillary responses to nalorphine particularly during the early phase after narcotic withdrawal. Individuals who smoked opium showed a fairly high percentage of positive reactions at 48 and 72 hours despite the fact that withdrawal signs and symptoms were mildest in this group. Nalorphine abstinence‐like signs were also induced, with maximum responses observable at about 16 hours in contrast to peak pupillary responses at about 4 hours and regular narcotic withdrawal effects at about 36 hours. The correlation between the pupil and urine tests for narcotics on the first day of withdrawal in these experiments was better than 95 per cent.
The role of vincristine in the treatment of childhood acute leukemia
Authors: Karon Myron , Freireich Emil J. , Frei Emil , Taylor Robert , Wolman Irving J. , Djerassi Isaac , Lee Stanley L. , Sawitsky Arthur , Hananian Juliet , Selawry Oleg , James David , George Phillip , Patterson Richard B. , Burgert Omer , Haurani Farid I. , Oberfield Richard .A. , Macy C. T. , Hoogstraten Barth , Blom Johannes
Published: January 2016

In a study of 117 patients under the age of 20 with acute leukemia, vincristine (VCR), at 2 mg. per square meter body surface per week, produced complete remissions in 55 per cent and partial remissions in 15 per cent. The drug also induced second remissions. Patients entering complete remission with VCR were randomly allocated to maintenance therapy with VCR or placebo. The median duration of remission was short: 9 weeks for VCR compared with 6 weeks for placebo. The probability of serious neurological toxicity computed according to the time of exposure to VCR, based on the supposition that VCR was not used for maintenance therapy, indicated that the minimal theoretical risk of toxicity for the highest complete remission rate occurred at 4 weeks (38 per cent remissions with 5 per cent toxicity). At 6 weeks, the corresponding probabilities were 54 and 16 per cent.
Observations in patients with metastatic malignancy treated with duazomycin A
Authors: Colsky Jacob , Shnider Bruce I. , Franzino Arthur , Perez Jesus
Published: January 2016

Duazomycin A a glutamine analogue, chemically similar to DON, was studied in 143 patients. An intravenous dose of 3 mg. per kilogram daily for 14 days appeared to be the tolerated dose in humans. Undesirable effects were nausea, vomiting, diarrhea, stomatitis, leukopenia, and thrombopenia. These effects cleared rapidly when the drug was discontinued. Tumor regression was noted in 6 patients but was evanescent and clinically beneficial to only 2.
A comparison of the analgesic effects of methotrimeprazine and morphine in patients with cancer
Authors: Beaver W. T. , Wallenstein S. L. , Houde R. W. , Rogers Ada
Published: January 2016

A double‐blind crossover evaluation of the relative analgesic potency of graded intramuscular doses of methotrimeprazine and morphine was carried out in patients with cancer. The configurations of the time‐effect curves of the two drugs appeared to be similar. Considering either “total” or “peak” effects, the analgesic potency of methotrimeprazine is estimated to be approximately one half that of morphine. A significantly larger number of patients had side effects with methotrimeprazine than with morphine, and this was largely due to the pronounced sedative effect of methotrimeprazine. Nausea and vomiting were much less frequent following administration of methotrimeprazine than morphine.
The effect of butoxamine on catecholamine‐inducedmetabolic changes in humans
Authors: Hunninghake Donald B. , Azarnof Daniel L. , Waxman David
Published: January 2016

Butoxamine (5 mg. per kilogram) inhibits the fasting as well as the epinephrine‐, norepinephrine‐, and isoproterenol‐induced rise in plasma free fatty acids in man. Although it also significantly lowers fasting plasma glucose levels, butoxamine does not inhibit the rise in plasma glucose induced by epinephrine or norepinephrine. The cardioaccelerator and blood pressure effects of epinephrine and isoproterenol are also decreased by butoxamine which has no significant effect on cardiovascular changes induced by norepinephrine.
Phenformin and lactic acidosis
Authors: Lacher John , Lasagna Louis
Published: January 2016

There is considerable evidence, both from animal studies and clinical reports, to suggest that the hypoglycemic agent phenformin interferes with lactate metabolism. Experimental data are reported which are consistent with a defiCiency in the ability of phenformin‐treated rats to handle endogenous and exogenous lactate. An interesting case of lactic acidosis simulating myocardial infarction is presented and discussed. It is concluded that phenformin can initiate or contribute to the clinical syndrome of lactic acidosis.
Serum lipids and glucose tolerance in diabetes during therapy with a thyromimetic agent
Authors: Danowski T. S. , Limaye N. R. , Cohn R. E. , Grimes B. J. , Narduzzi J. V. , Moses C.
Published: January 2016

Ingestion of a thyromimetic compound, beta‐diethylaminoethyl‐3, 5 diiodo‐4‐(3′ iodo‐4′methoxy phenoxy) phenylacetate HCL, in daily doses of 8 to 32 mg. during successive 4 week periods by 11 adults with diabetes mellitus of juvenile onset was accompanied by a decrease in serum cholesterol (Sperry‐Schoenheimer method). This effect appeared earlier and during smaller doses (8 mg. per day for 2 or 4 weeks) in patients with cholesterol levels in the lower range. In those with higher cholesterol levels the hypocholesterolemic action became evident at the 20 mg. per day dose. The serum total triglycerides and the alpha and beta lipoprotein partition of cholesterol and triglycerides were not affected. The serum total iodine, inorganic iodine, protein‐bound iodine (PBI), butanol extractable iodine (BEI), and the urinary total iodine all increased in proportion to the increased intake of this agent. The binding of T3 to blood cells was not affected. Thyroidal I131 uptake and the usual increase in uptake which follows thyrotropic hormone (TSH) were suppressed during drug ingestion. Slight tachycardia and limited weight loss occurred as the dosage was increased. Diastolic blood pressure decreased in the majority of cases during treatment with this compound. There were no clinically significant changes in the status of the diabetes mellitus, except for possible suppression of hyperglycemia follOWing a glucose load.
Single weekly doses of oral sulfamethoxypyridazine in preventing recurrences of rheumatic fever
Authors: Feinstein Alvan R. , Glazko Anthony J. , Spagnuolo Mario
Published: January 2016

A single weekly dose of sulfamethoxypyridazine (SMP), 3.0 Gm., provided rheumatic children and adolescents with higher blood levels of the drug through most of the week than peak values after single daily doses of sulfadiazine, 1.0 Gm. When tested in a program of prophylaxis against recurrences of rheumatic fever, the repetitive weekly dose of SMP was maintained continuously with about the same degree of fidelity given to a daily oral sulfadiazine regimen. The SMP regimen seemed more effective than daily sulfadiazine for preventing streptococcal infections but not for preventing rheumatic recurrences. Although no significant adverse effects of SMP were noted, the reports of severe reactions in other circumstances have discouraged further clinical trials with long‐acting sulfonamide preparations. When newer and safer long‐acting sulfonamides become available, their value in antirheumatic prophylaxis should be explored.
Antagonism of adrenergic neuron blockade in hypertensive subjects
Authors: Gulati O. D. , Dave B. T. , Gokhale S. D. , Shah K. M.
Published: January 2016

The effects of dextroamphetamine, methamphetamine, methylphenidate, nialamide, imipramine, and ephedrine in reversing the adrenergic neuron blocking action of guanethidine were investigated in 16 human hypertensive subiects, with the abolition of the cold‐pressor response and the fall of arterial blood pressure as evidence of the blocking action of guanethidine. Dextroamphetamine and methamphetamine totally reversed the blocking action of guanethidine on the cold‐pressor response and simultaneously antagonized the hypotensive effect of guanethidine. Nialamide, methylphenidate, and ephedrine had a similar but less pronounced effect. The probable mechanism of this antagonism is discussed. Imipramine did not reverse the circulatory guanethidine effect. These observations suggest that hypertensive patients taking dextroamphetamine for weight reduction will respond poorly to guanethidine, and that dextroamphetamine and methamphetamine would serve as effective antagonists of guanethidine in clinical situations where the drug has caused an excessive fall in blood pressure.