bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgery and pharmacology
Authors: Simeone F. A.
Published: January 2016

Until two centuries ago, surgery had been an empirical mechanical art. The surgeon, unlike the physician, achieved his objectives by use of his hands, hence the origin of the word from chirurgien, one who works with his hands. Even after Hunter had begun to dispel empiricism and to place surgery on a scientific basis, manual dexterity and speed of action were essential characteristics of the successful surgeon. The introduction of anesthesia, and later the development of asepsis as opposed to antisepsis made speed and dexterity less important. However, even today the successful surgeon, while not dramatically rapid in his actions, does not waste time as he performs a surgical procedure. And this is as it should be, for the pharmacology of anesthesia and the intricate mechanisms of the iatrogenic coma of anesthesia are not sufficiently well understood to render the duration of an operation truly insignificant. Therefore, technical skill and inborn manual dexterity are still important qualities which distinguish the surgeon from his colleagues.
Evaluation of antipruritic drugs in normal volunteers
Authors: Joglekar G. V. , Balwani J. H. , Mutalik G. S.
Published: January 2016

The antipruritic effect of trimeprazine and ergotamine was evaluated in medical students by use of the double‐blind technique. Itch was induced by Mucuna pmriens (cowage) ointment. Ergotamine tartrate was found to be ineffective, whereas no definite opinion could be formed regarding trimeprazine tartrate.
Nitrofurantoin in patients with hepatic dysfunction
Authors: Strauss Waiter , Jawetz Ernest
Published: January 2016

Individuals with varying degrees of hepatic dysfunction received sodium nitrofurantoin intravenously for active urinary tract infection. Repeated multiple laboratory examinations were performed in addition to careful clinical observations in an attempt to evaluate the possible hepatotoxicity of intravenous nitrofurantoin.

In 2 of 12 patients receiving a total dose of 3.6 to 6.5 Cm. nitrofurantoin in from 7 to 9 days by the intravenous route, liver function tests suggested possible hepatocellular insultby the drug. In these individuals test values returned to pretreatment levels soon after the drug had been discontinued. In 2 other patients liver function te5ts moved from abnormal toward normal values during nitrofurantoin administration, which might be interpreted as "improvement" of hepatocellular function. All of these changes probably only reflect fluctuations in values of liver function tests which are part of the natural history of hepatic disease.

One individual with alcoholic cirrhosis and esophageal varices developed violent retching, nausea, and vomiting on two occasions 10 days apart after the intravenous injection of only a few hundred milligrams of nitrofurantoin. However, there was no evidence of hepatic insult in that hyperreactive person. It is concluded that hepatotoxicity is neither a frequent nor a predictable event after the administration of intravenous nitrofurantoin.
A controlled trial with an antihistamine drug
Authors: Bouhuys A.
Published: January 2016

The effect of a small dose (5 mg. orally) of an antihistamine drug, methdilazine, on dyspnea and ventilation changes on Monday in hyssinotic cotton workers has been 5tudied in a douhle‐hlind trial. The decrease of ventilatory capacity during work on Monday was prevented by methdilazine in workers without evidence of irreversible lung function loss. Drowsiness from the drug was prevented by simultaneous administration of a caffeine beverage (Coca‐Cola). These results SUpp,Jrt the view, derived from previous experimental work on pharmacological effects of cotton dust, that ventilation changes during work on Monday in byssinosis are caused by release of histamine in the bronchial walls.
Comparison of benzphetamine, phenmetrazine, d‐amphetamine, and placebo
Authors: Patel Natoo , Mock David C. , Hagans James A.
Published: January 2016

Subjects wishing to lose weight were matched into groups on the basis of degrees of excess weight. One of four treatments‐phenmetrazine d‐amphetamine, placebo, and benzphetamine ‐were then assigned at random to each of the matched groups. The first 4 weeks were the control periods for all subjects. From the fifth through the twelfth weeks, all subjects took one tablet of one of the code‐labeled medications 3 times daily. Careful serial observations were made on weight change, caloric intake, therapeutic and side effects. No dietary re5trictions were imposed. Results were analyzed statistically before the code was broken.

Treatment with each of the three amphetamines induced about the same weight losses for each, but these were Significantly different from that after placebo. The reduction in caloric intake was not significant. Side effects were noted in all four treatment groups.
Radioactive pharmaceuticals
Authors: Wagner Henry N.
Published: January 2016

Diagnostic radiopharmaceuticals are administered to provide information rather than to induce pharmacologic response. Therefore, one cannot translate pharmacologic principles established for stable compounds directly to radioactive compounds. If radioactive materials are to be used safely and effectively, certain principles must be followed. Radiation to the patient must be minimized. Radiation detection instruments must be sensitive enough to yield statistically significant data with small doses of radiopharmaceuticals. Radionuclides with a rapid rate of physical decay are preferred, although, if a radioactive material is excreted rapidly and completely, the exposure to mdiation may be low despite long physical half‐life. It is important to use radioactive isotopes with no beta raciiations, or with low energy beta radiations. Because scintillation detectors which effectively measure only gamma radiation are most often used, beta radiation contributes to radiation dosage but provides no data. Special pharmaceutical problems associated with radiopharmaceuticals are: (1) problems of carrier‐free state, ie., those arising because of the extremely small chemical quantities; (2) problems of self‐decomposition, produced by the effect of radiation on the compound itself or on its solvent; (3) problems resulting from isotope effect, i.e., differences in reaction rates that sometimes result from differences in atomic weight of isotopes; and (4) problems resulting from chemical differences betwecn labeled and naturally occurring compounds.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

Photosensitivity, Loosening of the Nails, and Discoloration of the Nails and Teeth in Association With Demethylchlortetracycline (Declomycin): Report of a Case With Review of Other Reported Cases by L. L. de Veber. Canad. M. A. J. 86:168‐172, 1962.
Treatment of diabetes insipidus with orally administered compounds
Authors: Dies Federico , Suarez Ma. Antonieta , Rivera Alfonso
Published: January 2016

Thirty‐five studies were done with oleous vasopressin and several antidiuretic drugs orally administered in 9 patients with idiopathic diabetes insipidus. Vasopressin was by far the most effective drug for controlling urine fiow. Benzothiadiazine derivatives, aminopyrine, and to a lesser degree spironolactone, exerted antidiuretic effects of clinical significance, especially when they were combined. The suggested mechanisms of action of thiazides and spironolactone are discussed. It is thought that the antidiuretic effect of aminopyrine is due to the decreased glomerular filtration rate.
Alcohol accumulation in humans after prolonged drinking
Authors: Forney Robert B. , Hughes Francis W.
Published: January 2016

Alcoholic beverages were consumed by adults during scheduled periods. Blood alcohol concentrations were determined from breath samples obtained every half hour from the beginning of the drinking period until one‐half hour after the last drink. One ounce of 100 proof bourbon could be consumed hourly for five hours without reaching blood levels associated with measured impairment. With the consumption of 2 ounces of 100 proof bourbon hourly, within one and one‐half hours blood levels considered prima facie evidence of alcoholic intoxication were reached.
A new antihypertensive agent
Authors: Janney James G. , Pierre Gerard D. , Thurmann Manfred , Utley James H. , Aykent Yavuz , Castro Juan
Published: January 2016

The double blind method was used in the evaluation of mebutamate in 20 cases of hypertensive vascular disease. A minimal effect was found upon the systolic and no effect upon the diastolic blood pressure. Drowsiness did not permit attainment of the maximum recommended doses of the drug in many instances.

A correlation was also made between the blood levels of the drug and the blood pressure response to a single large dose of mebutamate in 15 cases. A moderate fall in average systolic pressure and a minimal fall in average diastolic pressure resulted, associated with a high incidence of drowsiness.
The clinical pharmacology of THAM [tris(hydroxymethyUami nomethane]
Authors: Nahas Gabriel G.
Published: January 2016

Experimental and clinical studies have demonstmted that THAM is an effective titrating agent because of its buffering capacity, low toxicity, and mpid elimination. THAM has been used for the correction of acute acidosis during cardiac operation and extra corporeal circulation, cardiac arrest, and massive transfusions with ACD blood. Its use in chronic espiratory acidosis should be restricted to the acute decompensated phase and should be accompanied by mechanical ventilation. Other clinical indications for THAM administration include salicylate and barbiturate intoxication and the metabolic acidosis of diabetes. It is most effective when administered intravenously as a O.3M solution in amounts calculated to titrate excess acid in extracellular fluid.

THAM can be given orally as a salt in combination with a weak acid such as citrate. In this form, it is a gastric antacid and will also produce systemic alkalinization.
The effect of drugs on the electroencephalogram of man
Authors: Brazier Mary A. B.
Published: January 2016

In the study of the electroencephalogram of man and in the search for the clues this may give to the working of his brain, drugs have frequently been used as the exploring agent. In the following pages the EEG concomitants of four maior categories of drug action are reviewed.
Aids to wise choice among new drug products marketed in the United States
Authors: May Charles D.
Published: January 2016

A collection of reference sources is described that provides authentic information and expert opinion on new drug products, as evaluated by professional groups. Any doctor would profit by a modest investment in these tools (maximum of about $50.00 per year) to help him keep his storehouse of drug therapy in good repair. The combination of sources described constitutes one practical way of acquiring sounder appraisal of the newest drugs, reasonably promptly and without excessive personal expenditure of time, effort, and money—throughout an active professional career. Many other valuable source materials exist; some are designed for deeper inquiries, no one source answers all purposes, and different combinations may be preferred by various authorities as aids to wise chaise among new drug products.
Nethalide, a beta adrenergic blocking agent
Authors: Schröder G. , Werkö L.
Published: January 2016

In ten patients with arterial hypertension and 8 with no cardiovascular disease, the influence on the circulation of a peroral administration of Nethalide, a beta adrenergic blocking agent, was studied.

Heart rate, intra‐arterial blood pressure, cardiac output, and oxygen consumption were determined with the subject at rest and during standardized exercise on a bicycle ergometer before and after about one week's treatment.

Nethalide did not produce any changes in normal subjects at rest. In the hypeltensive patients, heart rate, brachial arterial pressure, cardiac output, and left ventricular work were lower during treatment than before. Heart rate, brachial arterial pressures, and left ventricular work were lower after tmatment in both groups. In the patients with arterial hypertension, the stroke volume was higher and the peripheral resistance lower after treatment with Nethalide.
Psychopharmacology of chlorphentermine and d‐amphetamine: A comparative study of their effects in normal males
Authors: DiMascio Alberto , Buie Dan H.
Published: January 2016

This study is mainly concerned with the actions of chlorphentermine and d‐amphetamine, other than those influencing appetite. A double‐blind comparison was made of the effects of a placebo and two presumably equiactive doses of the two drugs in 20 normal college males. The modes and speed of actions and the relative potencies of the two drugs were determined. Measures of drug actions were made on the autonomic nervous system activity, psychomotor behavior, cognitive perfm‐mance, affective states, and other subjective experiences. Except for the smaller dose of d‐amphetamine, the time of peak action for all drug conditions was found to be 2½ hours after administration. Peak activity of drug effects was compared. For both doses of d‐amphetamine there was a mild autonomic stimulation, but neither psychomotor activity nor cognitive performances was changed. There were reports of mild stimulation, well‐being, restless agitation, detached and unreal feelings, and lightheadedness. After administration of chlorphentermine, autonomic changes were slight and there were no changes in psychomotor and cognitive functionings. Chlorphentermine produced drowsiness, relaxation, lightheadedness, dizziness, numbness and weakness of extremities, detached and unreal feelings, and restless agitation. While these actions were perceived as being of a mild degree, they lasted longer than those of d‐amphetamine. Although effect on appetite was not specifically examined, 20 per cent of the subjects reported an increase in appetite after the higher dose of chlorphentermine, while 20 per cent reported a decrease after the lower dose of d‐amphetamine.
Primaquine and methemoglobin
Authors: Cowan W. K. , Evans D. A. Price
Published: January 2016

Methemoglobin formation occurring as a toxic manifestation of primaquine was studied in volunteers to determine whether or not it is an example of genetic polymorphism. No evidence of polymorphism was found.
Cutaneous effects of a new butyrophenone drug
Authors: Simpson G. M. , Blair J. H. , Cranswick E. H.
Published: January 2016

A new butyrophenone preparation produced ichthyosis in a small sample of white patients but not in any of the Negro patients receiving it. Hair loss, which was total in 2 of the subiects with ichthyosis, was reversible. Cholesterol values were cOnsistently lower during therapy than in four separate postdrug samples. Although the effects closely resemble those of triparanol (MER/29), the two are not chemically related.
Addiction to nonbarbiturate sedative and tranquilizing drugs
Authors: Essig Carl F.
Published: January 2016

Increasing numbers of nonbarbiturate sedative drugs are being introduced into medical practice. Despite their nonbarbiturate chemical structure and regardless of designations other than “sedative‐hypnotic,” at least six of the newer depressant drugs can cause states of intoxication and physical dependence that are clinically similar to those induced by barbiturates. These drugs are meprobamate (Miltown, Equanil), glutethimide (Doriden), ethinamate (Valmid), ethchlorvynol (Placidyl), methyprylon (Noludar), and chlordiazepoxide (Librium). The behavioral effects of these drugs and their combination with ethanol may become an increasingly important public hazard. The abstinence syndromes that can result from the abrupt withdrawal of excess dosages of these drugs include convulsions and psychotic behavior. Death has been attributed to withdrawal of meprobamate and methyprylon. Office or ambulatory withdrawal of any of these drugs after use in large dosage is not recommended. Gradual dosage reduction or barbiturate substitution prior to its gradual withdrawal during hospitalization is suggested. Substitution of diphenylhydantoin (Dilantin) or any of the phenothiazines as the sole means of support during sedative‐hypnotic drug withdrawal is a questionable practice.
Halothane
Authors: Cullen Stuart C.
Published: January 2016

In 1954 Beecher and Todd2 published an article in which they presented evidence that muscle relaxants increased mortality. This article and a few well‐placed speeches about the substance of the article precipitated a tremendous emotional reaction to the well‐established use of muscle relaxants. Anesthetists and surgeons alike, with somewhat more response from the latter, banned the use of muscle relaxants until more sober and more scientific reflection took place. (It is possible, also, that surgeons accustomed to profound muscle relaxation were so inconvenienced by the ban that reconsideration of the hazards of muscle relaxants was accelerated. ) Although there was a high level of correlation between morbidity and mortality in patients and the administration of muscle relaxants, there were many other factors that could have contributed to morbidity and mortality. Although the article and speeches created a reaction out of proportion to the hazard that existed and Received for publication March 12, 1964. although it is possible to question the validity of some of the data incriminating the muscle relaxants, there is no doubt that misuse of muscle relaxants was taking place and contributing to morbidity and mortality. The remedy applied was more vigorous than required by the disorder, but it did serve to compel users of muscle relaxants to re‐evaluate their practice with the drugs, and undoubtedly more patients were subjected to less hazard not because the drugs became safer but because they were better applied.
Clinical trials of hydroxyurea in patients with cancer and leukemia
Authors: Fishbein William N. , Carbone Paul P. , Freireich Emil J. , Misra Dwijendra , Frei Emil
Published: January 2016

Hydroxyurea (HU) was studied in 53 patients with malignant disease. Toxicity at the tolerated dose of 25 to 50 mg. per kilogram (0.75 to 1.5 Gm. per square meter) was mainly myelosuppression and was rapidly reversible upon drug withdrawal. HU or its metabolites interfere with normal as well as leukemic hemopoietic cells. HU can produce beneficial effects in chronic myelogenous leukemia (CML) as manifested by a fall in white blood count, decrease in hepatosplenomegaly, improvement in anemia and M/E ratio. In patients with acute leukemia, HU regularly causes a decrease in leukemiG cells, but rarely induces remission. No significant antitumor activity was seen in the 13 patients with nonleukemic neoplasms. From this study, it is suggested that the drug has potential application in the treatment of C M L and for the rapid lowering of the high white blood cell count of patients with blastic crisis and acute leukemia. Studies pertaining to the made of action of the drug are briefly reviewed.
The physiologic disposition of 5‐fluorouracil and 5‐fluoro‐2′‐deoxyuridine in man
Authors: Clarkson Bayard , O'Connor Annabel , Winston LaReine , Hutchison Dorris
Published: January 2016

The plasma concentration and the urinary excretion of 5‐fluorouracil (FU) and 5‐fluoro‐2′deoxyuridine (FUdR), administered to patients with cancer, were determined by microbiologic assay; following regional administration, both local and systemic concentrations were measured. Rapid intravenous injections of usual clinical doses resulted in relatively high initial plasma concentrations (100 to 750 mμM per milliliter) which fell below a detectable level by 3½ hours in all patients. Generally, less than one fifth of the dose was excreted in the urine and almost all of this occurred in the first hour. The renal clearance of both drugs exceeded the glomerular filtration rate, and the clearance of FUdR was greater than FU. Gastrointestinal absorption of FU was unpredictable; FUdR was very poorly absorbed. Both drugs were degraded more completely when given by continuous infUSion, as indicated by reduced urinary excretion. After intravenous injection, the drug concentration in the cerebrospinal fluid and in neoplastic effusions was only one‐fiftieth or less that of the plasma concentration. After direct injection into neoplastic effusions, the concentration in the fluid was over 100 times that reached in the effusion after intravenous injection of the same dose. Long‐term infusion of low doses of FU into small arteries resulted in 100 or more times greater local than systemic plasma concentrations, while regional perfusion of FUdR resulted (briefly) in up to 1,000 or more times the concentration in the perfusion circuit compared to the general circulation.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

Six pregnant young women were admitted with signs and symptoms of acute pyelonephritis, and died of hepatic insufficiency. The clinical courses were remarkably similar. All were characterized by rapid progression, with nausea, vomiting, cyclic temperature swings, jaundice, acidosis, azotemia, hematemesis, melena, and terminal hypotenSion. All received tetracycline intravenously in doses higher than those usually recommended. Average doses varied from 2.4 Gm. per day to 4.0 Gm. per day with the extremes being 1.0 to 6.0 Gm. per day. Tetracycline was given for periods ranging from 3 to 9 days. In 2 women this was followed by oral tetracycline. Urine cultures were positive in 4 of the 6 patients. The organism was sensitive to tetracycline in 3. On the third to fifth day after the institution of tetracycline therapy, jaundice was noted in each patient. It was soon learned that this was a grave prognostic sign. All 6 women died 5 to 13 days after the start of tetracycline therapy.
Drugs for peripheral vascular disease
Authors: Friend Dale G.
Published: January 2016

The problem presented by inadequate peripheral circulation is exceedingly common and at times serious. Consequently there has been a search for more and better agents for the treatment of various peripheral obstructive states. As a result, there are now several agents promoted for the treatment of peripheral vascular disease.
A comparison of the value of 200,000 I. U. tetanus antitoxin (horse) with 20,000 I. U. in the treatment of tetanus
Authors: Vakil B. J. , Tulpule T. H. , Armitage P. , Laurence D. R.
Published: January 2016

Patients were allotted at random, after diagnosis, to receive either 200,000 I.U. or 20,000 I.U. antitoxin. The results were analyzed sequentially and the trial was stopped after 300 patients had been treated. There was no significant difference between the mortality rates in the two dosage groups.
Further studies on the absorption of chymotrypsin
Authors: Avakian S.
Published: January 2016

The proteolytic enzyme, chymotrypsin, was administered orally to 27 patients, each of whom had previously been subiected to the same experimental procedure without chymotrypsin. A statistically significant increase in plasma chymotrypsin levels was found 4 hours after administration. This experiment was designed primarily to determine whether chymotrypsin was absorbed from the intestinal tract of man. Quantitative data necessary to speculate on the clinical significance of these findings are not available.
A modified (once a day) corticosteroid dosage regimen
Authors: Demos Christopher H. , Krasner Frank , Groel John T.
Published: January 2016

The therapeutic results obtained in 345 patients with various allergic, dermatologic, and rheumatic diseases with a once a day dose of triamcinolone, a corticosteroid with a long plasma half‐life, are presented. Two hundred and seventy‐three of the patients were on a divided dose regimen immediately prior to being transferred to a once a day regimen with the corticosteroid equivalent total dose. Of these 273, 237 had been receiving triamcinolone in a divided dose. This modified dosage regimen was, for the most part, therapeutically comparable with the corticosteroid divided daily dosage schedule. It was effective in 164 (82 per cent) of 200 patients with dermatoses, 42 (78 per cent) of 54 patients with allergies, and 58 (64 per cent) of 91 patients with rheumatoid arthritis and connective tissue diseases. With the exception of rheumatoid arthritis, most patients under control with conventional divided daily doses of corticosteroids could be easily transferred to once a day dosage with triamcinolone. In the 58 patients with allergies and dermatoses who had not received prior divided dose therapy, but were treated initially with a single daily dose of triamcinolone starting at a suppressive dose and arriving at a maintenance dose, this regimen was effective in 91 per cent. The possible advantages of once a day corticosteroid administration given in the morning are discussed. The necessity of maintaining continuous blood levels of exogenously administered corticosteroids is questioned. The theoretical advantage of minimizing disturbance of the diurnal rhythm of the adrenal glands is discussed.
Further studies on the therapeutic value of sodium dextrothyroxine
Authors: Starr Paul
Published: January 2016

Sodium dextrothyroxine has been used (1) to maintain a euthyroid state in hypothyroid patients; (2) to lower serum cholesterol in euthyroid patients having idiopathic hypercholesterolemia without producing hyperthyroidism; (3) to lower serum cholesterol in diabetic patients without increase in insulin requirement; (4) to counteract the hypercholesterolemia due to male hormone therapy; (5) to lower serum cholesterol in patients with coronary artery occlusive disease without increasing, and sometimes with decrease of, angina pectoris; and (6) in conditions due to endogenous thyroid stimulating hormone (TSH) action, such as gaiter, thyroid cancer growth, and malignant exophthalmos.
Introductory remarks
Authors: Kane Charles A.
Published: January 2016

Ladies and Gentlemen:

As Chainnan of this symposium, it is my pleasure and privilege to extend a cordial welcome to you all, especially to our foreign guests and participants.
The gamma (γ) loop in the mediation of muscle tone
Authors: Granit Ragnar
Published: January 2016

Two types of rigidities‐the gamma and alpha rigidities or exaggerations of striated muscle tone‐are revealed by single fiber records from dorsal roots. Tentative ideas concerning the role of the two kinds of spindle receptors‐spindle primaries and spindle secondaries innervated by two kinds of fibers‐are put forth. Both function as length‐measuring instruments in the muscle, and both are essential in the bombardment of the motoneurons and the control of the setting of length for coordination within the muscular apparatus. The gamma release makes the intrafusal muscle too short relative to the extrafusal one and so the latter is forced by the loop to follow suit. In the intact decerebrate cat the extensors are stretched by forced bending of the knee; the secondary spindles check extensor tension, augmenting flexor tension, thus fixing the limb in a state of “plasticity.” It is suggested that spindle control is far better developed in the forelimbs than in the hind limbs, the subject of most previous studies. Recent work on respiratory movements shows the gamma loop cooperating with the alphas also in respiratory muscles. Differential diagnosis of both hyperresponsive and hyporesponsive states must take into account this alpha‐gamma linkage of the efJerents.
Evaluation of hypertonia with the use of a gravity‐driven ergograph
Authors: Timberlake William H.
Published: January 2016

A gravity‐driven ergograph is described for recording movement at a joint to which constant torque force is applied by various weights. The joint to be tested is put in a horizontal position to eliminate the effect of gravity. The force of gravity of varying weights suspended by a cable supplies a constant, reproducible acceleration which moves the limb, stretching the muscle. The amount of movement in response to the force applied reflects the amount of spasticity. Even in the relatively stable environment of hospitalized patients, marked variations in spasticity have been recorded from day to day. The changes with oral medications so far have been well within variations during control periods. The technique has potential value in quantitating spasticity.
Clinical application of quantitative methods in the study of spasticity
Authors: Leavitt Lewis A. , Beasley Willis C.
Published: January 2016

Instrumentation and methods are described for measuring and recording in an eight‐channel system a variety of muscular and electromyographic variables that are regarded as appropriate to the objective study of spasticity and other related neurophysiologic responses. These variables include resistive forces developed in extensor and flexor muscles elicited by passive stretching through the full arc of motion, tensive forces developed in response to tendon tap in eliciting deep muscle myotatic reflexes, and angle of swing in unrestricted responses of the same type. Correlated electromyographic potentials are recorded in both extensor and flexor muscles concurrently with the muscular resistive forces and the angle of motion. A case study is presented to illustrate the sen8itivity and Consistency of the procedures in detecting effects from spasmolytic medication in altering the responses of a patient with clinically evident spasticity. Conclusions are particularized for the individual case presented. Numerous problems, including statistical methods and experimental designs, are being studied with a view toward planning systematic investigation of medication effects in patients with clinical manifestations of hypertonicity and hyperreflexia.
On the use of natriuretic drugs in the treatment of edema due to renal disease
Authors: Kessler Richard H.
Published: January 2016

The management of edema that develops in the course of intrinsic renal disease is challenging and often unsuccessful. As with other difficult‐to‐treat syndromes, a common error is to overtreat. This is another circumstance in which treatment is prescribed for the needs of the physician, not the patient. The information needed to make a reasonable choice of therapy is available. Inherent in this opinion is the fact that no treatment is sometimes the treatment of choice. I will state what I believe to be the facts of the formation of edema in renal disease and the mechanism of natriuretic therapy. The purpose of this discussion is to equip the reader with information I think essential to the natriuretic therapy of renal disease.
Protection studies with sodium thiosulfate against methyl bis (β‐chloroethyllamine hydrochloride (HN2) and its ethylenimonium derivative
Authors: Bonadonna Gianni , Karnofsky David A.
Published: January 2016

Methyl bis (β‐chloroethyl)amine hydrochloride (HN2) and chlorimine picrylsulfonate derivative (CPS) were injected alone and with sodium thiosulfate (TS) in laboratory animals and in patients with widespread metastatic carcinoma in order to study the protective effect of TS on the bone marrow depression produced by HN2 and CPS. In rats and rabbits 1.0 Gm. per kilogram of TS gave complete protection against supralethal doses of CPS, whereas it provided little protection against lethal doses of HN2. In man, however, 200 mg. per kilogram of TS protected against daily doses of HN2 and CPS (2 to 3 times the usual daily dose) administered for several days to a total of 2 to 9 times the amount given in the usual course of treatment. Nausea and vomiting usually followed each injection of HN2 and CPS, and thus was not prevented by TS. With one exception, tumor regression in these metastatic carcinomas was not observed after the administration of either HN2 or CPS preceded by protective doses of TS. TS gives much better protection against CPS than against HN2 in rodents, but this difference, while suggested by our data, was not clearly defined in man.
The respiratory and subjective effects of pentazocine
Authors: Bellville J. Weldon , Green Jean
Published: January 2016

Pentazocine, a new potent analgesic, was studied to determine the respiratory depressant effects. It is a potent respiratory depressant whose dose‐effect curve slope is not significantly different from that of morphine. In respiratory depressant effect it is estimated that 21 mg. of pentazocine is equivalent to 10 mg. of morphine. However, the time‐effect curve for pentazocine appeared to be different from that of morphine for it achieved a higher initial peak effect and showed a more rapid decline.
An electroencephalographic study of the effects of meprobamate on human sleep
Authors: Freemon Frank R. , Agnew Harman W. , Williams Robert L.
Published: January 2016

The effect of meprobamate on human sleep and dreaming was assessed in a double‐blind, placebo‐controlled study by means of all‐night electroencephalography. On nights when meprobamate was ingested in a dose of 400 mg. at 9:00 P.M. and 800 mg. at 12:00 A.M., normal subiects spent significantly less time in sleep accompanied by low‐voltage fast EEG waves and more time in sleep manifested by spindling in the EEG than when receiving placebo. The time spent in rapid eye movement periods, which are related to visual dreaming, was decreased by meprobamate. This study shows that meprobamate characteristically alters the amount of time spent in each sleep stage and significantly decreases inferred oisual dreaming. Comparisons are made between the changes in the human electroencephalogram during sleep produced by meprobamate and those produced by the barbiturates.
Studies of sulfamethoxydiazine
Authors: Chew William H. , Kaplan Kenneth , Weinstein Louis
Published: January 2016

Serum, plasma, and urine concentrations resulting from the administration of sulfamethoxydiazine, a new long‐acting sulfonamide, were studied in twelve adults. A single dose of 0.5,1.0, or 2.0 Gm. was found to produce peak serum levels of free drug of 3.6,8.0, and 13.4 mg. per 100 ml. in 6 to 8 hours. Seventy‐five per cent of the peak remained after 24 hours and 50 per cent was still present after 48 hours. About 5 per cent of the drug in the blood was in the acetylated form. Twenty‐five per cent of a dose of SMOD was excreted in the urine during the first 24 hours and 50 per cent in 48 hours; 20 to 30 per cent of the drug in the urine was acetylated. After various “loading doses,” SMOD was administered at 24 to 48 hour intervals for 7 to 10 days. The administration of an initial dose of 1.0 to 2.0 Gm. followed by 0.5 Gm. once daily produced serum concentrations of 6 to 14 mg. per 100 ml.; slightly higher levels were produced in individuals given somewhat larger “loading doses.” The accumulation of SMOD in the blood levels which followed its administration were similar to those of other long‐acting sulfonamides. No untoward effects were observed.
Cardiovascular effects of rapid intravenous injection of synthetic oxytocin during elective cesarean section
Authors: Andersen Thorkild W. , De Padua C. B. , Stenger V. , Prystowsky H.
Published: January 2016

Synthetic oxytocin injected rapidly, intravenously in 22 patients during elective cesarean section caused a decrease ill blood presslIre and an increase in heart rate. In 16 patients, heart rate, cardiac output, and stroke volume increased while mean arterial pressure and total peripheral resistance decreased. All changes were pronollllced, rapid in onset, and of short duration. No serious electrocardiographic changr;s were found. Repeat injeotion in 5 patients caused similar changes. The type of anesthesia did not appear to matter.
The action of L‐dihydroxyphenylalanine in patients receiving nialamide
Authors: Friend Dale G. , Bell William R. , Kline Nathan S.
Published: January 2016

Nialamide produces effective monamine oxidase inhibition resulting in a three‐ to fivefold increase in tryptamine excretion when administered in a dose of 100 mg. for 10 days. L‐Dihydroxyphenylalanine, given in a dose of 75 to 100 mg. to normal volunteers receiving nialamide in a dose of 100 mg. daily for 10 days, produces a prompt and prolonged elevation in the blood pressure. Flushing of the face, heat, and pounding of the heart were poduced in most subjects. The blood pressure elevation was considered to be secondary to the intake of large amounts of the potent precursor in the presence of effective monamine oxidase inhibition. The active amine was not identified but could have been dopamine, norepinephrine, or a mixture of the two.
Pancreatic collagenase therapy for severe, progressive systemic sclerosis: Effect on skin and on hydroxyproline content in urine
Authors: Nellas Constantine L. , Crawford Neville , Scherbel Arthur L.
Published: January 2016

A patient with severe, progressive systemic sclerosis was treated for 7 months with AL‐0534, a pancreatic collagenase preparation. With the measurement of hydroxyproline as an index, the results of the urinary output and skin biopsy content suggested that some in vivo enzymatic hydrolysis of body collagen took place during the first 2 months of treatment. Later in the treatment program, the results reverted to pretreatment levels. The failure to maintain improvement clinically, and according to laboratory tests, could be related to several theoretic factors: antibody inactivation of the enzyme, the presence of a small amount of soluble collagen, and low dosage of AL‐0534. Further clinical study is needed to evaluate the place of collagenase in the treatment of scleroderma.
Drug interactions in man
Authors: Cucinell S. A. , Conney A. H. , Sansur M. , Burns J. J.
Published: January 2016

Chronic treatment of experimental animals with phenobarbital resulted in accelerated metabolism of a variety of drugs such as bishydroxycoumarin, diphenylhydantoin, and antipyrine. Evidence for the ability of drugs to stimulate drug metabolism in man has come from the results of studies presented here, showing that phenobarbital decreases the plasma level of diphenylhydantoin and bishydroxycoumarin. The decreased plasma leGel of bishydroxycoumarin in man was correlated with a decreased anticoagulant action of the drug. The ability of a drug to stimulate its own metabolism or the metabolism of another drug appears to have important implications in clinical pharmacologic studies, as weU as to the problem of drug therapy in man.
Investigations with 5‐azaorotic acid, an inhibitor of the biosynthesis of pyrimidines de novo
Authors: Granat Pepi , Creasey William A. , Calabresi Paul , Handschumache Robert E.
Published: January 2016

Preclinical and clinical metabolic investigations of 5‐azaorotic acid, an inhibitor of the biosynthesis de novo of pyrimidine nucleotides, have suggested its possihle use as an antitumor agent in the therapy of liver and the kidney tumors. Tissue slice experiments indicated extensive utilization of orotic acid by the liver and kidney, and inhihition of this utilization by 5‐azaorotic acid. Tissue distribution studies in rats showed localization of the drug in these tissues. Metabolism to a compound resembling N‐formylbiuret tuas observed in human studies, and rapid urinary cxcmtion of unchanged 5‐azaorotic acid occurred. Effective blockade of the utilization of exogenous orotic acid by 5‐azaorotic acid was sustained in patients for 6 hours after intravenous administration of the compound. Renal toxicity, possibly secondary to crystalline deposits in the tubules, may restrict the clinical use of the compound.
The influence of prophylactic methicillin and oxacillin in the prevention of staphylococcal colonization and subsequent clinical infection in newborn infants
Authors: Shaw Russell F. , Riley Harris D. , Bracken E. C.
Published: January 2016

Two hundred randomly selected newborn infants were studied to determine the natural history of staphylococcal nasal colonization patterns. Methicillin and oxacillin were given prophylactically to 81 patients; rthe control group was of equal size. The effect of this treatment on infection and carrier rates after the infants had been discharged to the home environment was also studied. It teas found that prophylactic administration of Ithe synthetic penicillins significantly reduced the nasal staphylococcal colonization rates of newborns but was ineffectual in eradicating the carrier state once it was established. The regimen did not have any apparent long‐term effect on subsequent colonization rates or on the incidence of infection once the infant left the hospital nursery and was exposed to the environment of its home.
Some quantitative factors in topical corticosteroid therapy
Authors: Scholtz Jud R. , Nelson Don H.
Published: January 2016

Corticosteroids are presently the most widely used and effective agents in topical therapy of cutaneous disease. The use of plastic film dressings increases the effectiveness of treatment, but also increases absorption and the possibility of systemic corticosteroid effects, and raises the question of possible adverse effects on pituitary‐adrenal function. A summary of previously published studies on this question is presented, and criteria for distinguishing transient adrenal suppression from true adrenal insufficiency are outlined. Proved cases of adrenal insuffiCiency caused by topical corticosteroids have not been reported, but the number of properly studied cases is too small for firm conclusions. The question of “dosage” of topically applied corticosteroids has heretofore received scant attention. A dosage schedule, which is effective treatment for many steroid responsive lesions and is below the range which produces significant systemic effects, is presented. The results of pituitary‐adrenal function tests in specific cases treated with known amounts of topical corticosteroids are presented. Because of the importance and widespread use of topical corticosteroids, it is urged that further study of these questions be pursued.
Antidepressants‐A somewhat depressing scene
Authors: Hollister Leo E.
Published: January 2016

Feelings of sadness and depression are so common in human experience that most of us can easily identify with patients suffering from the manifold symptoms of depressive reactions. Judging from the great proliferation of antidepressant drugs in the past eight years, one might assume that depressions should be easily and effectively managed by drug therapy. Unfortunately, this is not the case.
The passage of THAM across the peritoneum during dialysis
Authors: Nahas Gabriel G. , Gjessing Jon , Giroux Jacques J. , Verosky Mariagnes , Mark Lester C.
Published: January 2016

The use of THAM during peritoneal dialysis for the extraction of CO2, and weak acids in dogs was compared with other dialyzing media. The rapid passage of THAM across the peritoneum is a limiting factor and to avoid reaching toxic levels, the total amount administered of a 0.075M THAM dialysate should not exceed 22 mM per kilogram per 24 hours. Dialysate pR and THAM concentration fell rapidly during the first 30 minutes and then more gradually, while dialysate CO2, content increased markedly, THAM dialysate acting as a “C02 trap.” After 3 hours 47 per cent of the THAM administered was excreted in the urine and there was a moderate diuresis of alkaline urine. After six 30 minute periods of dialysis the rate of passage of pentobarbital into the dialysate was three times greater with THAM solution than with Ringer solution and more than one and one half times greater than with NaHC03. Comparable results for the three media were obtained during the extraction of phenobarbital. The amount of sodium salicylate extracted into the three dialyzing media was similar, but the production of an alkaline urine with THAM administration enhanced salicylate excretion. Three times more salicylate was excreted in the urine during THAM administration than with Ringer solution and one and one half times more than with NaHCO3. Peritoneal dialysis with THAM should have clinical applications for the removal of exogenous or endogenous weak acids.
Hypertension and renal artery stenosis: Serial observations on 54 patients treated medically
Authors: Sheps Sheldon G. , Osmundson Philip J. , Hunt James C. , Schirger Alexander , Fairbairn John F.
Published: January 2016

Medical treatment of hypertension was undertaken in 54 selected patients with arteriographically proved stenosis of the renal artery (32 with atheromatous and 22 with fibromuscular lesions). At follow‐up study (average, 20.3 months), 65 per cent of 49 surviving patients were normotensive on a regimen of common antihypertensive drugs in usual doses. There also was improvement in the hypertensive changes noted in the optic fundus. In 13 patients, additional cardiovascular episodes complicated the hypertensive disease and 5 of these patients had died. The frequent long duration of hypertension and frequent bilateral involvement of the renal arteries necessitate caution in recommending surgical treatment when: (1) the situation technically demands nephrectomy; (2) there are renovascular lesions in the absence of significant hypertension; (3) arteriographic and renal function data are discordant; and (4) there is associated severe symptomatic cardiovascular disease, old age, or other infirmities.
Ethyl chlorophenoxyisobutyrate (CPIB) effects in juvenile‐onset diabetes mellitus
Authors: Danowski T. S. , Cohn R. E. , Limaye N. R. , Novak J. F. , Saul R. , Sunder J. H. , Moses C.
Published: January 2016

Ethyl‐α (p‐chlorophenoxy)isobutyrate (Atromid‐S or CPIB) was administered for three months to 18 patients with diabetes mellitus of juvenile onset. The intensity of the diabetes, ;udging by serial fasting blood sugar levels, glucose tolerance tests, 24 hour urine glucose excretion, and tests of fractional urine specimens for sugar and acetone did not change significantly. The drug did not produce a hypolipidemic effect but pretherapy values for serum lipoprotein cholesterol and triglycerides were almost always within the normal range. Several nonsustained increases in cephalin flocculation and one instance of prothrombin time prolongation were observed. Other hepatic function indices remained unchanged. A slight increase in serum total CO2, and a slight decrease in serum inorganic phosphorus were not statistically significant. Serum uric acid did decrease: the differences between pretherapy and therapy values were statistically significant. No other parameters of blood, serum, body fluids, hepatic, thyroid, adrenal, or pituitary function were discernibly affected.
A comparison of fentanyl, droperidol, and morphine
Authors: Gorodeizky C. W. , Martin W. R.
Published: January 2016

Single intramuscular doses of fentanyl, droperidol, fentanyl plus droperidol, morphine, and placebo were compared in a double‐blind, cross‐over study on 6 normal male postnarcotic addicts. Miotic effects were assessed by pupillography, opiate signs and symptoms, and liking by questionnaires. Fentanyl alone was foltnd to be similar to morphine in its pattern of signs and symptoms and its high frequency of identification as a narcotic. For equimiotic doses, fentanyl is at least as euphorogenic as morphine. In the combination of fentanyl plus droperidol, droperidol alters some of the morphinelike effects of the mixture, making the mixture similar to droperidol alone. However, if the dose of fentanyl in the mixture is increased, more of its morphinelike effects emerge. For equimiotic doses the combination is not more euphorogenic than morphine or fentanyl alone. The time courses of fentanyl, droperidol, and fentanyl plus droperidol are similar and differ from morphine in their shorter duration of action. All effects of the combination of fentanyl plus droperidol could be accounted for by the additive effects of each drug alone. Therefore, droperidol does not potentiate any of the effects of fentanyl. Extrapyramidal reactions were noted in 7 of 15 subjects who received single intramuscular doses of droperidol alone, and in one of 8 subjects who received single intramuscular doses of fentanyl plus droperidol in combination. These reactions were rapidly relieved by intramuscular administration of benztropine or diphenhydramine.