bluuebunny/crossref_metadata_2025 huggingface dataset:
Drugs in aerospace medicine
Authors: Perry Carlos J. G.
Published: January 2016

Primary variables of aerospace are altitude, radiation, motion, thermal extremes, and weightlessness. With respect to drug studies, only the first four have been explored directly. Secondary variables include the general nonspecific stress of the aerospace situation and operational performance considerations. These have been studied with respect to pharmacologic questions. Finally, another variety of compounds has been tested under one or more aerospace variables. Therapeutic and prophylactic usefulness for conditions unrelated to environmental stress have made this broad group of drugs available for inclusion in this review.
Antidepressant drug therapy
Authors: Friend Dale G.
Published: January 2016

Medicine had very little to offer in the treatment of the mentally depressed patient until the advent of shock therapy and the first monamine oxidase inhibitor, iproniazid. Unquestionably, the rather striking effects of iproniazid on mentally depressed individuals did much to stimulate interest in chemotherapy for this widespread and severely incapacitating mental condition. A large proportion of those with depression have a spontaneous remission 3 to 6 weeks after onset, but the situation may be serious during that period. In some, the condition does not undergo remission, grows steadily worse, and in others, leads to suicide. Continuous severe depression bringing about severe withdrawal of the individual from the main stream of life, ultimately leads to untreatable deteriorated states. It is, therefore, important that diagnosis be made as early as possible and treatment initiated promptly. Fortunately, drug therapy is now available which has much to offer these patients and even in the hands of the non psychiatrically oriented physician, oftentimes affords such relief as to return a patient to a much more useful and satisfactory existence.
The chemotherapy of malaria
Authors: Powell Robin D.
Published: January 2016

Malaria remains a formidable global problem. Although substantial progress has been made in efforts to combat and to eliminate this protozoan scourge, much remains to be done. This review dealing with the chemotherapy of malaria presents: a brief resume of historical aspects relating to the development of synthetic antimalarial drugs; a discussion of apposite considerations with respect to parasites that cause human malaria, classification of antimalarial drugs, and terminology; a summary of available information concerning the uses and effects of quinine and widely employed synthetic antimalarial drugs; a short account of certain other antimalarial agents, some developed recently, that are of considerable experimental interest; and a discussion of resistance of malaria parasites to drugs, with particular emphasis on recently detected parasites that are resistant to chloroquine and to other synthetic antimalarial drugs.
The relevance of preclinical assessment of carcinogenesis
Authors: Roe F. J. C.
Published: January 2016

Evidence for the carcinogenic activity of various pharmaceutical agents and preparations is reviewed and the relevance of laboratory tests for carcinogenicity on animals discussed. A rating system for carcinogenicity is proposed and the need for balancing risk, including carcinogenic risk, with the severity of the condition under treatment and the benefit to be expected from treatment, stressed. It is suggested that the following have a high carcinogenicity rating: biological alkylating agents, urethan, isonicotinic acid hydrazide (INAH), arsenic, coal tar and creosote preparations, phenylbutazone, estrogens (especially when administered continuously over long periods), large implants of materials such as plastic sponge in the course of plastic or reconstruction surgery, and combinations of 131I with goitrogens. Recommendations on the future use of these agents in therapy are made. The immediate need for a large scale epidemiologic survey of patients treated with INAH is strongly emphasized.
Clinical pharmacology of the new penicillins: I. The importance of serum protein binding in determining antimicrobial activity and concentration in serum
Authors: Kunin Calvin M.
Published: January 2016

The effect of human serum binding on free and total concentrations and urinary excretion of penicillins G, V, and ampicillin, oxacillin, cloxacillin, dicloxacillin, and methicillin achieved after administration in man is reported. In vitro studies comparing minimal inhibitory and bactericidal activity of these penicillins in 100 per cent human serum and trypticase soy broth revealed a close relation of inhibition of antimicrobial action to the extent of binding to serum. Quantitative data were obtained by use of arithmetic linear dilutions, in small steps, rather than the usual twofold dilution method. Extensive binding to serum proteins was demonstrated by equilibrium dialysis and ultrafiltration methods utilizing serum obtained from human volunteers receiving therapeutic doses of each penicillin analogue. Dicloxacillin, cloxacillin, oxacillin, and nafcillin were most highly bound in descending order. Penicillin G and V were intermediate, while methicillin and ampiCillin were least bound. Serum binding appears to be an important determinant of the high serum concentrations achieved with some of the new orally absorbed penicillinase‐resistant compounds. The uncritical use of the term “absorption curve” to describe concentrations of drugs which differ in distribution, metabolism, and excretion, after oral administration is deplored since the term implies that serum concentrations are the resultant of efficiency of gastrointestinal absorption alone. Alternate methods to assess absorption are illustrated. The customary twofold dilution broth assay of serum antibacterial activity may be misleading when employed with highly bound antibiotics. It is proposed that reports of studies of serum concentrations achieved with highly bound antimicrobial agents include data not only on total drug levels, but of free as well. This approach permits a more realistic correlation of serum concentration with minimum effective levels determined in the usual broth assays.
Clinical pharmacology of the new penicillins: II. Effect of drugs which interfere with binding to serum proteins
Authors: Kunin Calvin M.
Published: January 2016

A series of compounds were found to be effective in vitro inhibitors of serum protein binding of penicillins G, V, ancillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin when used at a molar concentration of 1 x 10−3 versus the penicillins at 1 x 10−4 M. Three of these compounds, sulfamethoxypyridazine, sulfaethylthiadiazole, and acetylsalicylic acid were employed in volunteer studies to determine their effect on serum concentrations and binding of the various penicillin analogues in vivo. it was possible to reduce serum binding of the penicillins in man by this approach with all of the penicillin analogues studied, including the very highly bound drug, dicloxacillin. When effective, binding inhibitors tended to lower concentrations in serum of total penicillin and in almost all instances significantly increased the concentrations of unbound antibiotic. Sulfonamides interfered with the oral absorption of oxacillin. The limitations of this approach to current therapy with penicillins are presented together with a brief description of the features of a desirable new penicillin analogue.
Species differences and the clinical trial of new drugs: A review
Authors: Koppanyi Theodore , Avery Margaret A.
Published: January 2016

In recent years a great deal of new information has been published on the effects of drugs and poisons on different strains of the same species and on different species of animals. Strains and different species, including Homo, may differ in the rate of turnover and metabolic degradation of drugs. These differences can be measured by the methods of essential elimination, as well as by chemical or biochemical techniques. Such studies may permit a limited extrapolation from experiments on lower animals to drug effects in the human species.
Response of experimental pain to analgesic drugs: II. Codeine and placebo
Authors: Wolff B. Berthold , Kantor Thomas G. , Jarvik Murray E. , Laska Eugene
Published: January 2016

Twenty‐four paid healthy human volunteers participated in a study of two algesimetric methods of measuring experimental pain, one employing cutaneous electrical stimulation of two fingers with one touch and two pain response parameters, the other utilizing immersion of the hand in ice water, yielding three pain response parameters. A double‐blind balanced randomized block design was used. Both permissive and nonpermissive instructions were employed with the electrical stimulation. It was found that tolerance to experimental pain consistently increased significantly with codeine for both methods and with both sets of instructions. On the other hand, codeine exerted a smaller and only occasional significant effect on pain threshold.
Kinetics of pharmacologic effects
Authors: Levy Gerhard
Published: January 2016

Mathematical expressions derived from models based on the exponential decline of drug levels in the body and/or on a linear relationship between the intensity of the elicited effect and the logarithm of the dose can frequently be used to describe the rate of decline of a pharmacologic effect, the relationship between dose and duration of pharmacologic activity, and the effect of repeated drug administration. Pharmacokinetic analysis of pharmacologic activity data can lead to better understanding of the relationship between dose and the multiple pharmacologic effects elicited by a drug, and it can facilitate the assessment of factors which account for individual variations in the response to drugs. Under certain conditions, rate constants for drug absorption and drug elimination may be determined from pharmacologic activity rather than from blood levels or urinary excretion rates of the drug. Examples are presented which illustrate the application of these concepts.
Oral analgesic studies: Pentazocine hydrochloride, codeine, aspirin, and placebo and their influence on response to placebo
Authors: Kantor Thomas G. , Sunshine Abraham , Laska Eugene , Meisner Morris , Hopper Mary
Published: January 2016

In an analgesic study of 244 patients with postsurgical pain, doses of placebo, 600 mg. aspirin, 60 mg. codeine, and 35 and 50 mg. of pentazocine were compared. Two drug presentations were used, the second one always placebo, in this “double unknowns” design. Pentazocine, 50 mg., was found to be equivalent to 60 mg. of codeine in analgesic potency; 600 mg. aspirin was superior to the 35 mg. dose of pentazocine. The analgesic potency of placebo as a second dose was functionally dependent on the preceding medication. When placebo followed placebo, responses were identical. This finding is interpreted to be a serious drawback to crossover designs in clinical trials of analgesics.
A new progestogen: The 18‐homologue of norethisterone
Authors: Greenblatt Robert B. , Jungck Edwin C. , Puebla Ruben A. , Ward Mary Carolyn
Published: January 2016

A new agent with progestational, anabolic, and antiestrogenic properties in man is the 18‐homologue of norethisterone. On clinical examination it proved to be more potent than norethisterone (17‐ethinyl‐19‐nortestosterone). The progestational potency was considered to be quite high since as little as 1.25 mg. given with 100 μg of ethinyl estradiol delayed the onset of menses in 100 per cent of the trials. Like norethisterone, anabolic and mildly androgenic characteristics were in proportion to doses. The drug was markedly antiestrogenic and readily neutralized the effect of endogenous estrogens on the vaginal mucosa of children with precocious puberty and of menopausal women with evidence of persistent estrogenic activity. Because of its multifaceted properties, the 18‐homologue of norethisterone may be useful in the management of endometriosis and also gynecomastia in adolescent males.
Hypolipidemic effect of chlorophenoxyisobutyrate in adult‐onset diabetes mellitus
Authors: Danowski T. S. , Novak J. F. , Saul R. W. , Vester J. W. , Moses C.
Published: January 2016

The administration of ethyl‐alpha (p‐chlorophenoxy) isobutyrate (CPIB, Atromid‐S) to 16 patients with adult‐onset diabetes mellitus was generally associated with decreases of 10 to 40 per cent or more in the serum total cholesterol and triglycerides, irrespective of normal or high pretherapy values. The alpha and beta lipoprotein cholesterol and triglycerides also decreased. Retinal exudates disappeared completely from one or both eyes in 2 out of the 3 patients with hard and soft exudates. Glucose tolerance generally did not change.
Newer anesthetics end their uses
Authors: Dobkin Allen B. , Po‐Giok Su Jane
Published: January 2016

Most anesthetics in general use ten years ago had important undesirable properties which limited the seope of their usefulness or were inherently dangerous in the seriously ill patient. New inhalation, intravenous, and loeal anestheties have been synthesized sinee then which more closely fill the needs of the clinical anesthesiologist and the patient. Halothane and methoxyflurane have obvious advantages over cyclopropane and diethyl ether because they are nonexplosive and cause less metabolic disturbance. We would welcome a new gaseous anesthetic more potent than nitrous oxide, less potent than cyclopropane, and completely free from adverse effects on the myocardium and the liver. Of the intravenous anesthetics, only methohexital appears to have even slight advantages over thiopental. We still need an intravenous anesthetic that is more rapidly detoxified or exereted, is a potent hypnotic and analgesic, and is free from adverse effects on the medulla and neuromuscular apparatus. The quest for less toxic and more potent or longer‐acting local anesthetic agents has resulted in the development of prilocaine and mepivacaine. Laboratory and clinical studies of both of these agents have failed to demonstrate any clear advantages over older ones.
What is the status of knowledge of the toxic effect of lead on identifiable groups in the population?
Authors: Hardy Harriet L.
Published: January 2016

Knowledge of lead poisoning is very old. It was known in Roman days for Pliny the Elder includes it among “the diseases of slaves.” Ramazzini, considered the father of industrial medicine, described the colic and palsy caused by lead. A century later, Tanquerel des Planches, called the Columbus of lead poisoning, made the observation that plumbism never followed the handling of solid lead but only a sick worker's exposure to “emanations.” In the United States, Dr. Alice Hamilton as late as 1912 found instances of serious overexposure to lead, in contrast to European countries where control of the hazard was reasonably complete by 1910. She writes: “From my own experiences I can unfortunately testify to the fact that, thanks to the lack of prophylactic measures, [lead poisoning] … is not even a vanishing condition, for new instances of lead tabes are being added to the number every year.”* In more recent years the lead worker has been protected from poisoning in most industries. Great strides in engineering control plus knowledge of the fate of lead in the body have changed the worker's fate, except in some small foundries and storage battery manufacturing plants. An entirely new set of questions is posed by the increase in the amount of lead introduced into United States urban air by leaded gasoline.28 Some authors claim that the decrease in lead in food and water supplies offsets the potential hazard implied. A recent article by Patterson,19 a geochemist, has forced review of present knowledge and ignorance of the possible damage consequent to steady exposure to levels of lead not associated with recognizable poisoning. One approach to examining Patterson's accusation is consideration of the potential hazard of low level lead intake from the environment on such identifiable groups in the population as infants and workers in lead‐using industries.
A comparison of the analgesic effects of pentazocine and morphine in patients with cancer
Authors: Beaver W. T. , Wallenstein S. L. , Houde R. W. , Rogers A.
Published: January 2016

A double‐blind crossover evaluation of the relative analgesic potency of graded intramuscular doses of pentazocine and morphine was carried out in patients with chronic pain due to cancer. The analgesic potency of pentazocine, based on “total” effect, is estimated to be approximately one sixth that of morphine. An analysis of the analgesic response of patients in relation to their prior narcotic experience suggests that cross‐tolerance between pentazocine and narcotics is low. Doses of from 10 to 80 mg. of pentazocine preCipitated acute narcotic withdrawal reactions in some patients with substantial prior narcotic experience. Other adverse effects produced by pentazocine were qualitatively similar to those of morphine.
Clinical pharmacology of drugs which influence uric acid production and excretion
Authors: Krakoff Irwin H.
Published: January 2016

The hyperuricemia which occurs in primary gout can be demonstrated in a large proportion of cases to be due to overproduction of uric acid, i.e., an increase in rate and amount of de novo biosynthesis. In myeloproliferative diseases there is also consistent overproduction of uric acid, in this case due to an exaggeration of cell “turnover” and degradation of nucleic acid purines. Several compounds are available which can increase the urinary excretion of uric acid with beneficial effects on chronic gout, both primary and secondary. The recent availability of allopurinol, an effective inhibitor of uric acid biosynthesis, provides a highly effective means for controlling hyperuricemia with less risk of toxicity and adverse effects than is present in the use of the uricosuric drugs. Other compounds are discussed which block uric acid excretion or increase uric acid biosynthesis. These are of interest from a pharmacologic standpoint and as models for the study of uric acid metabolism.
Clinical pharmacology of general anesthetics
Authors: Dundee John W.
Published: January 2016

The past decade has seen great interest in the clinical pharmacology of general anesthetics. Recently introduced drugs, such as halothane or methoxyflurane, have already been studied in more detail than ether or nitrous oxide had been during the first century of their clinical use. This review discusses some aspects of the actions of anesthetics of immediate clinical significance to the practicing anesthesiologist. Uptake and distribution of anesthetics in the body follows certain well‐defined laws and is a continuously changing process. Volatility and the blood to gas partition ratio are the main factors influencing the onset of inhalation anesthetics, while a high blood to tissue ratio will aid recovery. Lack of ionization and high lipoid solubility explain the rapid onset of the useful intravenous agents. With these drugs the clinical “depth” of anesthesia is often unrelated to the blood level, their action being markedly influenced by dosage and premedication. Most general anesthetics are direct myocardial depressants and cause a variable degree of peripheral vasodilation, but those which increase blood catecholamine levels cause less hypotension. Hypercarbia is a major cause of cardiac arrhythmias during anesthesia, particularly with cyclopropane and halothane. Contrary to some opinions, liver dysfunction is probably no more common after halothane than after other agents, although there may be a particular danger associated with its repeated administration. Many factors other than the general anesthetic itself increase the incidence of postoperative vomiting; opiate premedication is the main factor which is under the direct control of the anesthesiologist.
What is a biomedical computer center?
Authors: Brandt Edward N.
Published: January 2016

As the importance of medical computer applications increases, many medical investigators will use them. This will require the medical personnel to deal with computer centers and their personnel. It, therefore, seems important for physicians and investigators to be familiar not only with computers but also with the organization and staff of biomedically oriented computer centers as well. The goals of each center as well as the environment within which it is established dictate the specifics of its organization, but certain features are common to all. Computer centers should be a dynamic force in the educational, research, and patient care activities of any medical institution. They can be so only if they are readily accessible to all personnel, both physically and administratively.
Computers in physiological analysis and simulation
Authors: Stauffer William M.
Published: January 2016

Physiological problems demand the capacity for handling analogue data as weil as for providing answers from calculations in “real‐time.” The biocomputation facility of the University of Utah has been designed for these problems. This system permits simultaneous usage from several remote stations. Problems which have utilized this system include: the distribution of transit times for dye in the circulatory system, beat‐to‐beat calculation of cardiac output, heart rate, stroke volume, and other parameters from the aortic pulse pressure, image processing of radiopaque dye injections, and an electrocardiographic diagnosis program.
Use of computers in pharmacokinetics
Authors: Wagner John G.
Published: January 2016

Analogue, digital, and hybrid computers may be used in two principal ways in the analysis of data from pharmacokinetic studies: (1) for rapid numerical analysis of data and (2) for pharmacokinetic simulation. Simulation may be defined as the act of building a model of a system and observing its performance. In pharmacokinetics, the equations and models elaborated are always oversimplifications and their appropriateness can only be iudged by their ability to describe the observed data and the accuracy with which they make predictions of future observed data. Five examples are employed to illustrate the use of computers; the paths from the original observed data to the final answers are shown in detail. The examples are as folIows: (1) the relationship between the area under the lincomycin serum concentration curve and the dose of lincomycin administered intramuscularly; (2) the distribution of the half‐lives of the antibiotics lincomycin and novobiocin; (3) prediction of multiple dose serum levels of lincomycin observed after constant rate intravenous infusions with an analogue computer; (4) the fitting of serum levels of tetracycline observed after a single oral dose with a two‐term exponential equation; (5) simulation of serum levels produced by depointramuscular preparations of lincomycin with a digital computer.
Effects of methyldopa in fifty hypertensive patients
Authors: Horwitz David , Pettinger William A. , Orvis Harold , Thomas Raymond E. , Sjoerdsma Albert
Published: January 2016

Satisfactory blood pressure control was obtained in two thirds of a group of fifty hypertensive sub;ects receiving methyldopa under highly controlled conditions. It was well tolerated by most, yielded uniform effects during the course of the day, and showed sustained effectiveness during six months of therapy. Low grade lactation associated with elevated plasma prolactin levels occurred in four women and reversible abnormalities of liver function tests, in three other patients.
A new guanidine diuretic, amipramizide: Reduction of the kaliuretic effect of ethacrynic acid in man
Authors: Alter Sheldon , Cushman Paul , Hilton James G.
Published: January 2016

Metabolic balance studies were carried out in four patients with refractory edema with the use of the guanidine diuretic, amipramizide (MK 870), and ethacrynic acid. MK 870 caused limited natriuresis and little or no weight loss. In all patients ethacrynic acid induced natriuresis and weight loss. With ethacrynic acid and MK 870, potassium balance in the cardiac patient remained at control values. One cirrhotic patient was maintained in normal potassium balance with normal serum electrolytes. In the other cirrhotic patients there was negative potassium balance but it was of lesser magnitude with milder degrees of hypokalemic alkalosis. In all patients the natriuresis and weight loss were greater than after ethacrynic acid alone.
A study of cross‐tolerance to circulatory effects of organic nitrates
Authors: Schelling Jean-Louis , Lasagna Louis
Published: January 2016

Ten hospitalized volunteer subjects were given pentaerythrol tetra nitrate (PETN) daily in divided doses over a period of four weeks. Before and during PETN treatment, the subjects were challenged with 0.3 mg. sublingual nitroglycerin (NTC). The changes in blood pressure and heart rate after NTC were significantly decreased while subjects were receiving PETN. Reports of NTC‐ and PETN‐related headache also decreased during PETN administration. Since long‐acting nitrates may carry within them the seeds of their own therapeutic failure via the development of tolerance, it is suggested that animal studies on such agents routinely include repeated pharmacological testing designed to detect and measure the development of tolerance to cardiovascular and other effects.
Assessment of the dependence‐producing properties of dihydrocodeinone and codoxime
Authors: Jasinski Donald R. , Martin William R.
Published: January 2016

Dihydrocodeinone and a new narcotic antitussive, codoxime, were compared in single doses with morphine in a crossover study to compare their ability to produce opiate‐like euphoria. In addition, both drugs were substituted for morphine in 7 chronically addicted subjects to determine their capacity to produce physical dependence. Results indicated both drugs definitely produced drug dependence of the morphine type.
Evaluation of a new photographic method for assessing pupil diameters
Authors: Jasinski Donald R. , Martin William R.
Published: January 2016

To assess opiate effects, photographic methods have been utilized for an objective, precise measure of pupil size.1, 2 These methods require elaborate, stationary mechanisms for proper focusing, Recently, a Polaroid close‐up camera has been modified to allow its use for photographing pupils of bed‐confined patients.4 The present communication deals with the reliability of this method when used to assess changes in pupil size during the precipitated morphine‐abstinence syndrome.
Salicylates
Authors: Moser Robert Harlan
Published: January 2016

Six healthy adult subjects and 8 patients with rheumatoid arthritis were given acetylsalicylic acid, 1.0 Gm. 3 times a day, in the form of tablets dissolved in water. Vascular, plasma, and platelet factors were studied before and during the second week of acetylsalicylic acid ingestion. There was no difference in response between normal subjects and rheumatoid arthritis patients; acetylsalicylic acid in the doses employed in this study induced prolongation of bleeding time, prothrombin time, and increased platelet stickiness. These defects were “ … definitely not sufficient to cause major hemorrhage, and, if this occurs, individual susceptibility to acetylsalicylic acid must be assumed.”
Statistical ward rounds‐2
Authors: Mainland Donald
Published: January 2016

The cases in this round will be concerned chiefly with statistical significance in a drug trial and the question, “How little better may the better drug be?”
Midwest Cooperative Group evaluation of piposulfan (A‐20968) in cancer
Authors: Nelson N. A. , Talley R. W. , Reed M. L. , Evans A. M. , Isaacs Bertha L. , Huffman Philip , Louis John
Published: January 2016

Piposulfan (Ancyte), a methanesulfonate, alkylating derivative of piperazine, was administered to 594 patients with various types of cancer. The ohjectives of the study were to determine the optimal dose and to evaluate the therapeutic efJicacy of the drug. After preliminary trials with doses ranging from 3 to 1 mg. per kilogram per day, it was decided to use 1 mg. per kilo gram per day as an initial dose in the majority of patients. Various degrees of therapeutie remissions were seen in patients with malignant lymphomas, acute and chronic leukemia, polycythemia, multiple myeloma, adenocarcinomas, epidermoid carcinomas, and various types of sarcomas. However, the magnitude of the therapeutic response appeared to be quantitatively inferior to that obtained with current antitumor drugs in wide usage. Bane marrow depression or gastrointestinal disturhances occltrred in 118 patients, hut the patients responded to dosage ad;ustments.
The relative effectiveness of antihypertensive drugs in Caucasians and Negroes
Authors: Howard Jan , Tiedeman Gary
Published: January 2016

A secondary analysis of 133 clinical trials of antihypertensive drugs was conducted for the purpose of assessing the relationship between race and drug effectiveness. The race categories were whites and nonwhites (all or almost all of whom were Negroes). Effectiveness and ineffectiveness were generally defined in terms of reduced blood pressure. Two different methods of analyzing the data were used: the Fisher Exact Test approach and the logit approach. The analyses showed a consistent tendency for the whites to be more responsive to antihypertensive therapy than were the nonwhites. The race difference in average successrates was fairly small and not consistently significant at the 0.05 level, but the trend in favor of whites merits reporting. Three possible explanations for the race difference are suggested: a differential cooperation hypothesis, a differential severity of illness hypothesis, and a genetic hypothesis.
The use of a discriminant function in the assessment of analgesic drugs
Authors: Hill G. B. , Loan W. , Dundee J. W.
Published: January 2016

A comparative clinical trial of analgesic drugs in postoperative pain following upper abdominal surgery produced data on the effects of morphine, 10 mg., placebo, and two doses of a new analgesic, pentazocine. Three assessments of analgesia, derived from the patient's subjective opinion, the observer's subjective opinion, and the patient's peak‐flow rate were combined into a single score by calculating a discriminant function with respect to the morphine and placebo groups. With the use of this combined score to assay the analgesic effect of pentazocine, it was found that 20 mg. of pentazocine was as effective as 10 mg. morphine, and 40 mg. pentazocine was significantly more effective. The discriminant function provides a useful method of analYZing clinical trial data of this type.
Studies on beta‐aminopropionitrile in patients with scleroderma
Authors: Keiser Harry R. , Sjoerdsma Albert
Published: January 2016

Single oral doses of β‐aminopropionitrile (BAPN) up to 3.5 Gm. and treatment for several days with doses as high as 2.0 Gm. per day were found to have no apparent pharmacologic or toxic effects in patients with scleroderma. As in the rat, cyanoacetic acid was found tobe the maior urinary metabolite of the drug. When four patients were treated with 1.0 to 3.0 Gm. of the drug per day for 22 to 67 days, distinct effects on collagen metabolism were observed, consisting of increases in urinary hydroxyproline and acid extractable dermal collagen and its a:β ratio. A reversible periosteal reaction occurred in one patient and untoward effects were observed in four other patients at a dose level which produced only moderate effects on skin collagen and no apparent therapeutic effect. Thus, future use of the drug as an inhibitor of collagen cross‐linking in man should probably be limited to short‐term trials.
The medical‐legal aspects of adverse drug reactions
Authors: Tozer Forrest L. , Kasik John E.
Published: January 2016

The unexpected, unfavorable response to a prescribed drug is a phenomenon of increasing familiarity to every physician. The constant addition of new and powerful drugs to therapy has led to the appearance of many new reactions of incredible diversity and an increase in the incidence of older, well‐recognized adverse reactions to drugs until the diagnosis and therapy of drug‐induced diseases has reached the status of a subspecialty of medicine.
How to stuff a stuffer and cook a wolf
Authors: Modell Walter
Published: January 2016

In our protest some months ago of what we considered highly improper use of the drug package stuffer by the FDA, we indicated that these practices had turned the stuffer into the Big Bad Wolf, and that we were afraid.
What are the possibilities for immunotherapy and immunoprophylaxis of cancer?
Authors: Southam Chester M.
Published: January 2016

There are valid reasons for the upsurge in interest in cancer immunology, but the obstacles to clinical application of immunologic methods for the treatment or prevention of cancer are formidable both in theory and in practice. Thus this is an exciting and challenging field to work in and to watch, and it is a field of research in which the observer and the investigator are well advised to have both an open mind and a critical attitude.
The antihypertensive effects of an imidazoline compound
Authors: Davidov Michael , Kakaviatos Nikos , Finnerty Frank A.
Published: January 2016

The antihypertensive properties of a new imidazoline compound, ST 155, were examined in man. Oral administration of 75 to 150 mcg. consistently produced an average fall of about 15 per cent in mean arterial pressure within one hour. Repeated administration was associated with drug resistance which was prevented by the simultaneous use of thiazide diuretics. The combination of ST 155 in a dosage of 450 mcg. with a diuretic in patients with moderately severe hypertension resulted in an average fall in mean arterial pressure of about 25 per cent. The only side effects were dryness of the mouth and sedation, whichdecreased after the first month of therapy.
A comparison of hydrolyzed L‐ and synthesized DL‐amino acids for complete parenteral nutrition
Authors: Peaston M. J. T.
Published: January 2016

Two comparable groups of patients received high calorie intravenous diets in which the nitrogen was supplied as one of two currently marketed preparations of amino acids. One group received hydrolyzed L‐amino acids and the other a similar nitrogen supply as synthesized DL‐amino acids. Each patient received 2,000 calories per day as soya bean oil fat emulsion in addition to the calories provided by the sugar solutions included with the amino acid preparations. The results confirmed that the hydrolyzed amino acid preparation provides a readily utilizable source of nitrogen for total parenteral nutrition but indicate that the synthesized amino acid preparation containing predominantly DL‐ forms of essential amino acids was not effectively metabolized. It is suggested that the present choice of amino acid preparation for total parenteral nutrition is one containing hydrolyzed L‐amino acids.
Effects of exogenous adenosine 3',5'‐monophosphate in man: I. Cardiovascular responses
Authors: Levine Robert A. , Dixon Leon M. , Franklin Robert B.
Published: January 2016

The cardiovascular response to administration of cyclic adenosine 3',5'‐monophosphate (3',5'‐AMP) was studied in 26 human volunteers. In relatively large doses (10 mg. per kilogram or 0.5 mg. per kilogram per minute), 3',5'‐AMP induced prompt cardioacceleration and increased cardiac output. In contrast to those receiving rapid 3',5'‐AMP iniection, all subiects receiving a constant infusion of the nucleotide showed a progressive and sustained elevation of systolic blood pressure. Responses to 3',5'‐AMP were demonstrated in the presence of attempts at pharmacologic blockade of beta adrenergic and cholinergic receptor sites by dl‐propranolol and atropine, respectively. Following production of marked hypotension by trimethaphan (Arfonad) and glyceryl trinitrate, with consequent blockade of sympathetically induced cardioacceleration, administration of 3',5'‐AMP promptly increased heart rate without any change in blood pressure. These findings suggested a direct cardiac action of the nucleotide rather than reflex alterations of the heart due to arterial pressure changes. The cardiac findings in man support in vitro data that 3',5'‐AMP may represent part of the biochemical basis for the myocardial response to catecholamines.
Prostaglandins
Authors: Euler Euler U. S.
Published: January 2016

Observations from 1930 to 1934 have indicated autopharmacological effects of human seminal fluid. The active principle was shown to be an unsaturated lipid‐soluble acid. After isolation in 1960 of two closely related compounds, the chemical constitution was established. From the parent compound, called prostanoic acid, a numerous family of compounds have been derived and isolated. Prostaglandins are present in high concentrations in human and sheep scminal fluid, being formed in the seminal vesicles and in the vesicular gland. They also occur in low concentrations in a great variety of tissues, including lung, nervous tissue, and menstrual fluid. The chief component in seminal fluid, prostaglandin E., lowers blood pressure, stimulates various smooth muscle organs, inhibits uterine movements, lipolysis, and gastric juice secretion, and causes sedation when administered into brain ventricles. Prostaglandins exert well‐marked synergistic and antagonistic actions with catecholamines on some organs. it has been suggested that prostaglandins are of importance for male and female sexual functions, in addition to metabolic actions, primarily on lipid metabolism, and actions on the nervous system and blood pressure.
Thiothixene (Navane)
Authors:   J. B. Roerig Division
Published: January 2016

Navane (thiothixene) is a new, potent thioxanthene psychotherapeutic agent with clinical usefulness which parallels or exceeds that of most phenothiazine drugs. It is a major new antipsychotic agent. Navane (thiothixene) is effective in the management of acute or chronic schizophrenic patients either in a hospital or an outpatient setting. Particularly notable is the ability of the drug to improve alertness and increase the degree of purposeful effort and activity in chronically ill, apathetic psychotic patients. Patients in whom prior therapy has failed may respond significantly to Navane (thiothixene).
Evaluating side effects of analgesics in a cooperative clinical study
Authors: Bellville J. Weldon , Forrest W. H. , Elashoff Janet , Laska Eugene
Published: January 2016

Studies in large numbers of patients successfully identified incidence and severity of adverse effects of analgesic agents in patients with postoperative pain. In a series of studies, such data from 5 hospitals taking part in the Veterans Administration Cooperative Analgesic Study were pooled. The survey involved up to 1,000 patients receiving more than 2,000 medications in the comparison of a single drug with morphine. Statistical methodology and standardized training of nurse observers permitted pooling data from separate sources. For some side effects, it was possible to make relative potency estimates. The approach used overcomes many of the disadvantages of both the small, controlled study (in which too few patients participate to provide meaningful information about side effects) and the large, uncontrolled study (where bias in reporting and missing information seriously impair the data obtained).
Trifluperidol and cholesterol in man
Authors: Clark Mervin L. , Braun George A. , Hewson J. Robert , Serafetinides E. A. , Colmore J. P. , Rahhal Don K.
Published: January 2016

Trifluperidol, a butyrophenone compound with antipsychotic properties, was studied for its behavioral and hypocholesterolemic effects in psychotic male patients. Subiects receiving trifluperidol exhibited significant decreases in serum cholesterol concentration. Furthermore, quantities of a cholesterol precursor identified as 7‐dehydrocholesterol accumulated in the serum, suggesting that TFP acts as a △7‐reductase inhibitor interfering with the conversion of 7‐dehydrocholesterol to cholesterol.
Supersensitivity to tyramine during monoamine oxidase inhibition in man; Mechanism at the level of the adrenergic neuron
Authors: Pettinger William A. , Oates John A.
Published: January 2016

Studies were performed to determine whether inhibition of the metabolism of tyramine within the nerve ending was a maior mechanism in the supersensitivity to this amine during monoamine oxidase (MAO) inhibition. The enhancement of the pressor response to intravenously administered tyramine produced by MAO inhibition was compared with the enhancement of the response to amphetamine, an indirectly acting amine which is not a substrate for MAO. The responses to these two were found to be increased to approximately the same degree, indicating that the supersensitivity to tyramine at the neuron level during MAO inhibition occurs because interaction with the release mechanism in the neuron terminal increases release of norepinephrine.
The antihypertensive and diuretic effects of amiloride and of its combination with hydrochlorothiazide
Authors: Kampffmeyer Hermann , Conway James
Published: January 2016

The hypotensive effect as well as changes in serum electrolytes and uric acid of amiloride (AM) and of its combination with hydrochlorothiazide (HC) were studied. In five hypertensive patients over a five‐day period, AM and HC administered together produced more natriuresis than either alone. Potassium, chloride, and bicarbonate concentrations in the serum showed a smaller alteration from normal with the combination than with HC alone. Twelve additional outpatients with moderate hypertension were followed for twelve weeks with the use of randomized Latin squares in double‐blind fashion. A blood pressure‐lowering effect of AM by itself or when added to HC was not seen. AM had no discernible effect on serum glucose, uric acid, or chloride concentrations.
Disorders produced by anticoagulants
Authors: Moser Robert Harlan
Published: January 2016

Do barbiturates influence the prothrombin‐proconvertin level during anticoagulant therapy?
Effects of trimethoprim on folate metabolism in man
Authors: Kahn S. Benham , Fein Sandra A. , Brodsky Isadore
Published: January 2016

Recent studies have demonstrated a synergistic effect of dihydrofolate reductase (DHFR) inhibitors and sulfonamides in the therapy of chronic urinary tract infections and malaria. Trimethoprim (TMP) (Ro‐56846, Hoffmann‐LaRoche) has 10,000 times more inhibitory effect on bacterial DHFR than on mammalian DHFR. Folate metabolism was evaluated in 10 normal patients treated with TMP alone for 4 weeks and 14 patients with chronic genitourinary infections treated with TMP and sulfonamides for periods up to 2 years. Parameters under study were complete blood count, bone marrow examination, serum and red blood cell folate levels, formiminoglutamic acid (FiGlu) excretion, and lobe counts of circulating neutrophiles. In order to measure folate activity a mutant strain of L. casei resistant to TMP was developed (Hitchings and Burchall, Burroughs Wellcome & Co. [U.S.A.] Inc.). In the short‐term group 1 patient developed thrombocytopenia and another anemia associated with transitional megaloblastosis, while 5 patients excreted FiGlu and all had significant elevation of lobe counts. When the drug was stopped these abnormalities disappeared in 2 weeks. One patient ingesting the combination of drugs demonstrated thrombocytopenia and leukopenia which disappeared when citrovorum factor was given despite continued administration of drugs. The dose of citrovorum factor needed to ensure hematologic normalcy was 400 µg. It is concluded that TMP has mild inhibitory effects On folate metabolism in man at the tissue level which can be overcome by administration of reduced folates.
Magnesium pemoline: Stimulant effects on performance of fatigued men
Authors: Herbert Emily W. , Gelfand Sidney , Clark Lincoln D. , Gelfand Donna M.
Published: January 2016

Compared to placebo, magnesium pemoline, 100 mg., facilitated performance of fatigued subjects in repetitious arithmetic problems for 3 to 8 hours after drug ingestion in a group of male subjects. There was a gradual decrement in performance; but performance after magnesium pemoline was superior to that after placebo during the entire 5 hour period. Subjects' judgments of their drug condition seemed unimportant.
The influence of dosage form on the activity of a diuretic agent
Authors: Tannenbaum Philip J. , Rosen Earl , Flanagan Thomas , Crosley Archer P.
Published: January 2016

Tablets and capsules of a combination product containing triamterene and hydrochlorothiazide in a 2:1 ratio were compared in a series of short‐term studies with male volunteers. The tablet caused approximately twice as much excretion of hydrochlorothiazide and 3 times as much triamterene as the capsule. These studies provide further evidence of the importance of the dosage forms in the effectiveness of drugs.
The hypnotic effects of ethchlorvynol and secobarbital in man
Authors: Bellville J. Weldon , Forrest William H. , Stevens Jeffrey , Beer E. George
Published: January 2016

Findings in a controlled double‐blind crossover clinical study in which secobarbital and ethchlorvynol were studied each at two dose levels are reported. The hypnotic relative potency was calculated from the patients' subjective reports of onset, duration, and quality of sleep. It is estimated in this way that 770 mg. of ethchlorvynol is equivalent to 100 mg. of secobarbital.
Pharmacologic alteration of steroid hormone functions
Authors: Gaunt Robert , Steinetz B. G. , Chart J. J.
Published: January 2016

A large number of compounds can modify the function, synthesis, or metabolism of steroid hormones. These are not necessarily otherwise related chemically or pharmacologically. The drugs used as examples in this review were selected to show the wide variety of potential sites and modes of action. While many compounds have been shown to interfere with one or another step in the biosynthesis of corticosteroids, the number of known substances having any profound effect on gonadal steroidogenesis is surprisingly few. On the other hand, many more compounds are known either to mimic or modify the end‐organ response to gonadal than to adrenal steroids. The field of endocrine pharmacology is being rapidly widened as systematic searches are now being made for drugs which affect endocrine function either as a primary or incidental action.
Propranolol hydrochloride (Inderal)
Authors:   Ayerst Laboratories Incorporated
Published: January 2016

This beta‐adrenergic blocker is a new approach in the management of cardiac arrhythmias.
Averages and individuals
Authors: Mainland Donald
Published: January 2016

A draft report of a small trial. After the completion of a blindfold two‐group trial, with random assignment of a drug and a placebo, I submitted the draft of areport to the clinical investigators. The numbers in the trial had been small (21 on placebo and 22 on the drug), largely because the drug had been widely used for a number of years and patients who had ever received it were disqualified from the trial. Of the very few previous controlled trials of the drug the largest, very carefully conducted, had revealed, in most of the criteria of assessment, a small average superiority of the drug over the placebo, “significant at the 5 per cent level.” The much sm aller trial, on which I reported, had shown similar average differences, but in none of the clinical criteria were the differences “significant.”