bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical pharmacology in industrial medicine
Authors: Warshaw Leon J.
Published: January 2016

The industrial medical department provides a satisfactory setting for research in clinical pharmacology. It offers an opportunity not only for evaluating the therapeutic efficacy of many drugs but also for the study of their effects on “normal” subjects. Among its advantages is the availability of suitable human subjects who can participate in these studies without loss of income, who are readily accessible for any necessary follow‐up, and whose work performance may provide a satisfactory index of the effects of certain drugs. The scientific requirements and standards for clinical pharmacologic research in industry are no different from those governing similar research in other settings. Certain problems, however, arise out of the necessity of conducting the research within the framework of the primary objective of the occupational health program: to maintain optimal productivity hy the promotion of better employee health.
Nerve iniury from intramuscular barbiturate iniection
Authors: Richards Richard K.
Published: January 2016

Intramuscular injection of drugs is usually considered a safe procedure. Occasionally, however, nerve damage, particularly to the sciatic nerve, has been reported following various drugs. There has been same dispute regarding the role which the chemical nature of the drug, the simple physical pressure effect, and technique play in such incidents.

A case is reported in which definite sensory damage to the sciatic nerve occurred in a patient after the intragluteal administration of amobarbital sodium. Experiments were undertaken in which amobarbital sodium solution was iniected along the course of the sciatic nerve in guinea pigs. Hypalgesia and decrease of muscle tone developed in all instances, and in same of the animals trophic changes of the feet appeared. The need for careful technique in placing the intramuscular iniection outside the course of the sciatic nerve is discussed.
Factors affecting the absorption and biliary excretion of erythromycin and two of its derivatives in humans
Authors: Hammond James B. , Griffith R. S.
Published: January 2016

The oral administration of the propionyl ester of erythromycin and the lauryl sulfate salt of the ester produces higher serum concentrations than the parent antibiotic, erythromycin. Lee explained this by his findings in rats that the biliary excretion of erythromycin was relatively high while that of the two derivatives was low. We extended his work to humans.

In 16 patients, with bile fistula propionyl erythromycin administered orally was followed by relatively high serum and low bile antibiotic activity, as compared to erythromycin. The lauryl sulfate salt form followed a pattern similar to the ester. Diverting antibiotic‐containing bile from the intestine lowered the serum antibiotic concentration during treatment with erythromycin. However, this procedure had little effect on the two derivatives, since they appear in the bile in only a minimal amount.

The clinical findings support the animal data.
Clinical pharmacology of hypnotics and sedatives
Authors: Shideman F. E.
Published: January 2016

If there is any tendency to become complacent about the adequacy of knowledge in a given area, a review of the subject usually serves to dispel this attitude. Although there exists a formidable body of knowledge on the pharmacology of the hypnotics and sedatives, that which remains unknown is even more formidable. Many of the experiments which have yielded information on the pharmacodynamics and disposition of these drugs in laboratory animals do not have their counterparts in human studies. In such instances, only a logical guess can be made in an effort to bridge this gap. The known effects of the barbiturates, bromides, paraldehyde, chloral hydrate, and newer hypnotics and sedatives in man are presented and an attempt is made to compare these with findings in other species. Where data of a critical nature with respect to the human pharmacology of these drugs are lacking, the fundamental features of their actions on other animals are presented.

In addition to the more classic aspects of their pharmacodynamics, the more significant alterations in behavior produced by these agents are summarized. Studies dealing with their pharmacology in both the normal and pathologic states and in therapeutic and toxic dosages are outlined. Finally, the disposition of these compounds in the body is considered, inasmuch as this aspect of their pharmacology may have important bearing on the responses elicited by them in the organism.
III. The interaction of thiopental and oxymorphone during surgical anesthesia
Authors: Keeri-Szanto M. , Knaff M. , Rondeau Y.
Published: January 2016

An equipotent mixture of thiopental and oxymorphone was used with very satisfactory results to supplement nitrous oxide anesthesia in 44 cases of major surgical operation. The mixture proved easy to prepare and to handle.

The mean anesthetic time/dose curve was established for this mixture and compared with corresponding data obtained earlier for the component drugs. According to the mathematical analysis, the anesthetic action of the thiopental‐oxymorphone mixture is additive rather than synergistic.

A technique is presented for the semiquantitative rating of various anesthetic agents, and by these criteria, the thiopental‐oxymorphone mixture is a better intravenous anesthetic agent than either of the components.
Diseases of medical progress
Authors: Moser Robert Harlan
Published: January 2016

Because of its well‐founded and penetrating significance, the publication of “Diseases of Medical Progress” in the New England Journal of Medicine in 1956 attracted a great deal of attention in well‐informed medical circles. A monograph which surveyed the growing and increasingly serious subject was published by the author in 1959 (Charles C Thomas, Publisher). The present review brings the subject up to date. How long it will remain so is an open question. In any event, it was considered that the subject is of sufficient importance to devote half of an entire issue of this journal to it.
Clinical trials based on patients' preferences A new test of statistical significance
Authors: Acland J. D.
Published: January 2016

When patients' preferences are used. to assess the value of alternative treatments in a comparative clinical trial, tied preferences are often obtained as a result of the poor discriminatory ability of the experimental subiects. It is maintained that the weight attached to a given preponderance of positive choices for one treatment should decrease as the number of tied preferences increases. However, tied preferences are neglected altogether in two recommended sequential statistical tests, while the correction for ties used in another statistical test, based on the coefficient of concordance, actually causes the significance leoels to increase with the number of ties. A new test of statistical significance is described which can be used in clinical trials based on paiients' preierences, if large numbers of ties are recorded. The presence of tied prejerences louiers markedly the significance leoels obtained in this test, The errors which may be caused by neglecting tied preferences are shoum to be quantitatively important.
Effect of methionine sulfoximine in man
Authors: Krakoff Irwin H.
Published: January 2016

Flour bleached with nitrogen trichloride (agene) has been known to cause canine hysteria or “running fits” in dogs and other animals but not in man. Methionine sulfoximine, the active toxic material in flour so treated, was shown in this study to produce toxic psychosis in man, associated in one instance with reoersible electroencephalographic changes. The toxicity of methionine sulfoximine was prevented in 1 subject hy the simultaneous administration of large doses of methionine.
Influence of previous therapy on anesthesia
Authors: Elliott Henry W.
Published: January 2016

The ever‐increasing number of potent new drugs with multiple actions and the rapidity with which they come into widespread use pose new problems in therapeutics. One of primary concern is the influence of drug therapy on other therapeutic measures. This review is concerned with those agents which have been found to influence anesthesia, including pituitary‐adrenal agents, insulin, tranquilizers and other central nervous system depressants, cardiovascular agents, and antibiotics. The actions of these drugs which may affect anesthesia and methods of dealing with them are discussed. It is concluded that the therapeutic status of all surgical patients should be known to their anesthetists if they are to undergo anesthesia and surgical operation under optimal conditions.
Some fallacies and errors in the application of the principle of consent in human experimentation
Authors: Beecher Henry K.
Published: January 2016

Fallacies and difficulties in the application of the principle of consent will be considered here. More questions will be raised than answers given; questions must be stated before answers can be expected.
The hypothesis in clinical pharmacology
Authors: Greiner Theodore
Published: January 2016

The hypothesis, which is scientific thought put into words, sets forth a speculation that is tentative and sometimes thought provoking. It is largely because new and exciting possibilities can be inferred from an original hypothesis that a great deal of experimental effort is devoted to confirming it.
Behavioral patterns of anti barbituric action after 5‐phenyl‐2‐imino‐4‐oxo‐oxazolidine, amphetamine, and caffeine
Authors: Dureman Ingmar
Published: January 2016

A battery of objective behavioral tests was used to assay the differential patterning of antibarbituric effects of 5‐phenyl‐2‐imino‐4‐oxo‐oxazolidine (PIO), amphetamine, and caffeine. The test battery included a difficult code‐tracking operation performed under forced speed conditions, a 40 minute monotonous test of clerical speed (simple arithmetic operations), reaction time, two tests of fine motor coordination, aiming accuracy (moving targets rotated at three different speed levels), and the Archimedes spiral. Pulse rate and systolic blood pressure were recorded before and after each session on the code‐tracking test.

Two types of barbiturates (amobarbital and neopentylallylbarbituric acid) administered at two different dose levels (200 and 400 mg.) were given orally as hypnosedative premedication 150 minutes before the intake of the stimulant drugs. When compared with barbiturate plus placebo, PIO was found to differ from amphetamine and, to a slightly lesser degree, from caffeine in (1) having no antagonistic influence on residual pulse and blood pressure effects induced by barbiturate premedication, (2) having a less‐pronounced effect on variables related to visual motion aftereffect and finger‐hand dexterity, (3) being more effective in preserving a high level of operational skill against speed stress both in rotor aiming and a difficult learning variant of the code‐tracking test, and (4) being free of adverse effects from the subjective point of view.
A possible mechanism of action of the antidiuretic effect of benzothiadiazine derivatives
Authors: Díes Federico , Rivera Alfonso
Published: January 2016

Acute experiments were performed on normal subfects to examine the mechanism of the antidiuretic effect of the benzothiadiazine diuretics which has been observed in animals and confirmed in patients with diabetes insipidus. In essence, the influence of dihydroflumethiazide on water loading was determined. On the basis of the data, it is suggested that the drug increases the permeability of the collecting tubule to water.
Part IV. Placebos: Problems and pitfalls
Authors: Wolf Stewart
Published: January 2016

Recently, the head of a clinical department in a medical school was heard to observe: “We very much hope that our young men will do research. Basic research is encouraged, clinical research is tolerated, therapeutic research is frowned upon.” Perhaps this conference will explain what it is about therapeutic research that arouses such an attitude, why it has become fashionable to be snobbish about this very difficult and exacting line of study. It may be that scientists in other areas are offended by the welter of uncritical therapeutic literature and the almost countless cacophonous names, worthy of Jonathan Swift, which the pharmaceutical houses have attached to their products. Until recently, the serious investigator had only a still, small voice in this whirlwind of drug promotion.
Toxic Hazards
Authors: Modell Walter
Published: January 2016

Toxic Hazards I and II are soft cover, stapled collections of brief articles which appear monthly in the New England Journal of Medicine. Concise case reports usually serve as the text for the discussion of particular hazards, which range from reports of deaths from antifreeze to Xmas poison hazards. Included also are considerations of beryllium, dusts and fumes, ultra high frequency radiation, insecticides, expoxy resins, and other hazards present in home and field as well as industry.
Antihypertensive drugs
Authors: Friend Dale G.
Published: January 2016

Drug therapy for essential hypertension is now firmly established. Agents presently available, if used wisely, are capable of controlling hypertension in almost every patient requiring such treatment. There are certain important factors which must be carefully evaluated before patients are started on long‐term antihypertensive therapy. Since these factors in large measure determine the value and predicate the success of any drug therapy program, it is essential that they be thoroughly explored and understood at the outset.
Pharmacologic discovery by anesthesiologists
Authors: Vandam Leroy D.
Published: January 2016

The discovery of anesthesia in the 1840s has been said to be the first great contribution of pharmacology: yet pharmacology at the time was hardly in a formative stage. It was only after the Franco‐Prussian War that Schmiedeberg established the first laboratory of pharmacology at Strassburg. It is not as simple to discern when the roots of anesthesiology took hold. John Snow, the first physician to devote all of his time to this field, possessed the intellectual qualities, but at a time when it was not possible to benefit from advances in basic science that would have made experimentation possible. Anesthesiology became a true specialty only when its adherents looked beyond mere technical procedure to engage in teaching and investigation. If a time were to be cited for this transition, it would be the late 1920s when Ralph Waters laid the groundwork for the first academic department of anesthesia at Wisconsin. What have been the anesthesiologic contributions to pharmacology since then? One is at first beset with the problem of definition, to define anesthesiology's role in pharmacology. The contribution of anesthesiology may be found largely in the area of applied pharmacology with an emphasis not unlike that of Claude Bernard on the use of drugs to elucidate physiologic processes. But anesthesiology has not overlooked two other traditional pharmacologic aims: to define the safe limits of usage of drugs and to discover and assist in the evaluation of new agents.
Clinical and experimental pharmacology of parenteral spiramycin
Authors: Back N. , Ambrus J. L. , Velasco H. , Stutzman L. , Sokal J. E. , Klein E.
Published: January 2016

Spiramycin, an antibacterial chemotherapeutic agent, was found effective against a series of transplantable rodent tumors and neoplastic tissue culture lines. Acute and subacute toxicity was studied in mice and dogs. Large intravenous doses produced hypotension, increased intestinal motility, hyperactivity, increased neuromuscular irritability, salivation, and retching or vomiting in dogs. Animals which died after daily intravenous injections of large doses showed lymphoid involution, inhibition of mitosis, and degenerative changes in the intestinal epithelium, respiratory tract, liver, pancreas, salivary glands, and proximal renal tubules. There was no significant bone marrow depression.
Part VIII. Potential drug toxicity to the liver
Authors: Popper Hens
Published: January 2016

The problem of drug toxicity to the liver has two different aspects‐the effect of known poisons or agents that have foreseeable consequences and the unpredictable sequelae of therapy with drugs, especially new ones. Carbon tetrachloride intoxication illustrates the first aspect. Like other poisonous substances occasionally given as medicines or used in various life situations, it produces characteristic hepatic changes. These changes, either fatty metamorphosis or necrosis or both, usually involve a circumscribed zone of the liver lobule. The lesion can be produced at will in experimental animals. Its extent is fairly well correlated with the dose and is only modified by predictable circumstances such as alcohol consumption. Hepatic tests in both human and experimental animals indicate incipient liver damage. The main clinical problem is detection of the exposure.
Part IX. Research on psychopharmacology
Authors: Merlis Sidney
Published: January 2016

One might think that the conditions for research would be ideal when the subjects for study are continuously hospitalized and under complete and constant supervision. While in theory this may be so, in practice a number of problems exist which are of particular concern in the field of mental disease. For many reasons both good and bad, psychiatry has long been a stepchild of medicine. Its position, straddling the organic mental syndromes which are fairly well understood by our medical colleagues and the "functional psychologic disturbances" which frequently evoke explanations and theories bordering on the metaphysical, has often been quite confusing to physiCians trained in the hard practicalities of somatic disease. Another problem creating obstacles for psychiatrists is the continued and progressive influence of nonmedical scientists in the roles of diagnosticians and therapists Indeed, the field of psychiatry has in the past been placed in a medical limbo with no firm connection to any of the recognized medical specialties.
The eye as a pharmacologic laboratory
Authors: Leopold, Irving H.
Published: January 2016

Recently, 5‐iodo‐2'‐deoxyuridine has been demonstrated by Kaufman, Nesburn, and Maloney to be effective in controlling a human virus disease. It is a readily available, relatively nontoxjc compound that acts by interference with the virus‐directed synthesis of desoxyribonucleic acid. The compound had been found only partially effective against experimental virus infections in tissue culture and against anomalous desoxyribonucleic acid synthesis in cancer, but successful trials were performed on herpetic infections in the cornea of the experimental animal and human eye. Demonstration in the eye may have wide applicability for desoxyribonucleic acid virus diseases, and subsequent investigations may‐lead to effective antiviral chemotherapy in body areas distant from the eye.
Suppressive therapy of chronic bronchial infections
Authors: Dowling Harry F. , Lepper Mark H. , Jackson George Gee
Published: January 2016

The studies of long‐term antibiotic therapy reported in the literature are reviewed. The best clinical and bacteriologic results were obtained with 1 to 2 Gm. of tetracycline administered each day. Lesser degrees of improvement were reported when smaller doses were given, when the antibiotic was administered twice a week, or when therapy was given for a portion of the year only. Penicillin therapy was considerably less effective, erythromycin therapy appeared totally ineffective, and oleandomycin‐penicillin therapy was more effective than penicillin but less so than tetracycline.

Untoward reactions occurred in all regimens but, prOvided patients reported them promptly, were not serious. Tetracycline‐resistant staphylococci appeared in the sputum of an occasional patient during therapy with that antibiotic but did not cause any complications, except possibly the development of pneumonia in 1 patient.
Symposium on chemical carcinogenesis
Authors: Shimkin Michael B.
Published: January 2016

Seven members of the staff of the National Cancer Institute have prepared a series of five reviews on chemical carcinogenesis for this journal.
Are sitosterols atherogenic?
Authors: Lawn Bernard , Portman Oscar W. , Stare Fredrick J.
Published: January 2016

In the editorial which appeared in the July‐August, 1962, issue of this journal, the untoward effects and possible danger of various cholesterol‐lowering agents were discussed, and only dietary modifications were considered a safe approach. In the discussion of sitosterols, the authors of the editorial stated that no toxic effects had as yet been reported. However, they made reference to a report by Curran and Costello in 1956 and stated: “There is evidence that [sitosterols] can induce atherosclerosis in experimental animals.” The implication that this may also be the case in man is apparent from the leitmotiv of the editorial.
Quantitative electroencephalographic analysis of naturally occurring (schizophrenic) and drug‐induced psychotic states in human males
Authors: Goldstein Leonide , Murphree Henry B. , Sugerman A. Arthur , Pfeiffer Carl C. , Jenney Elizabeth H.
Published: January 2016

Analysis of the quantified electroencephalogram of the left occipital lead (Drohocki's integrative method) of 21 normal male subjects revealed an average coefficient of variation in electrical energy of 15.4 per cent. In 25 male chronic schizophrenic patients, the mean coefficient of variation was 8 per cent. Placebo administration did not produce any significant change in either group. In the normal men, oral dosage with 0.3 p.g per kilogram of D‐N, N diethyllysergamide (lysergic acid diethylamide, LSD‐25) produced a 33 per cent decrease in variability without significant change in the mean energy content of the electroencephalogram. When the dose of lysergic acid diethylamide was increased to 1 p.g per kilogram, a 25 per cent decrease in variability and 23 per cent reduction of the energy content of the electroencephalogram followed. In schizophrenic patients, lysergic acid diethylamide at 1 μg per kilogram orally did not affect the mean energy content but produced a 47 per cent increase in variability. The findings indicate that the electroencephalogram of male institutionalized chronic schizophrenics tends to be hyperregulated. Similar hyperregulation is produced in normal volunteers by threshold and larger doses of lysergic acid diethylamide.
Pathologic physiology, pharmacology, and therapeutics of tetanus
Authors: Laurence D. R. , Webster, R. A.
Published: January 2016

Experimental evidence for the routes of tramport of tetanus toxin from the site of its formation to the central nervous system is reviewed. The possible sites and mechanisms of action of toxin are discussed, and an attempt is made to correlate the mode of action with that of drugs used to suppress convulsions.

Despite the total absence until recently of any valid therapeutic comparisom, an attempt is made to evaluate the principal controversial therapeutic techniques, including antitoxin, care of the wound, chemotherapy, central anticonvulsants, neuromuscular blocking agents, tracheostomy, and adrenocortical steroids.
Part II. Carcinogenesis associated with foods, food additives, food degradation products, and related dietary factors
Authors: Kraybil H. F.
Published: January 2016

Since the genesis of tumors may be influenced to a lesser or greater degree by the nutrient environment furnished the host, frequent reference is made to the role of nutrition and dietary factors in carcinogenesis. A current and comprehensive review of nutrition and cancer has been presented by Tannenbaum. While the obvious association of cancer and nutrition was recognized earlier, a comprehensive assessment of the role of food and diet in the induction of neoplasms must more accurately be viewed in relation to the ingestion of food additives, food contamif!ants, processing degradation products, and other dietary components.s, Rapid advances in modem food technology have focused attention on dietary components other than essential nutrients such as food additives and processing degradation products. The utilization of agricultural chemicals as soil fumigants, plant growth regulators, and pesticides which may remain on fruits and vegetables if not adequately removed also contributes food contaminants to the diet of man. More recently, the nuclear detonations in weapons‐testing programs as well as the expanded industrial and medical applications of radiOisotopes have introduced radionuclides into the diet as food contaminants. While many of these materials and identified chemical compounds appearing either as additives, contaminants, or degradation products may not be labeled as poisons toxicologically, their latent effect must be assessed in terms of their potential contribution to induction of cancer.
Part III. Chemistry, host entry, and metabolic fate of carcinogens
Authors: Falk Hans L. , Kotin Paul
Published: January 2016

The skin, respiratory tract, and gastrointestinal tract are the organ systems through which environmental carcinogenic agents gain entry into the host. Of the several sources of carcinogenic agents, this report is concerned with the two most common in the respiratory environment—urban polluted air and cigarette smoke. Carcinogenic polycyclic aromatic hydrocarbons (PAH) are the most ubiquitous and are present in the highest concentrations. Certain exogenous and endogenous factors significantly modify the biologic action of carcinogenic hydrocarbons. Exogenous factors includes (1) the simultaneous presence and action of anticarcinogenic agents in the environment, (2) their occurrence in a physical state compatible with inhalation and deposition in the respiratory tract, and (3) the presence of factors modifying the host response, particularly in relation to the normal physiologic defenses. The endogenous factors include: (1) the vehicle serving the carcinogenic agents as it affects persistence at site of entry and rate of systemic distribution, (2) the rate of metabolism in the hepatobiliary system, and (3) the existence of anatomic or metabolic abnormalities modifying the tissue response.

The metabolism of carcinogenic P AH is, in the truest sense, a pharmacologic detoxification process since the metabolites are either weakly or, as is more common, wholly noncarcinogenic. This suggests that carcinogenic PAH, as they occur in the environment, are the proximate carcinogens. The complexity of the carcinogenic process is emphasized by the multiplicity of factors, many of them noncarcinogenic in themselves, that are concerned with the pathogenesis of neoplastic disease.
Comparison of acetophenazine with perphenazine in schizophrenics: Demonstration of differential effects based on computer‐derived diagnostic models
Authors: Overall J. E. , Hollister L. E. , Honigfeld G. , Kimbell I. H. , Meyer F. , Bennett J. L. , Caffey E.
Published: January 2016

Acetophenazine was compared with a closely related phenothiazine tranquilizer, perphenazine, under controlled conditions in 98 schizophrenic men newly admitted to five Veterans Administration hospitals. Clinical response was evaluated by two separate rating scales, the Inpatient Multidimensional Psychiatric Scale (IMPS) and the Brief Psychiatric Rating Scale (BPRS).

Improvement was noted in most factors of both rating devices from either treatment, with no evidence of any difference between the drugs on the basis of mean score changes. Rather marked differences were fmmd between the two drugs in relation to the spread of mean score changes, those from acetophenazine varying more than those from perphenazine. To determine whether there was any specificity of patient type which might influence reaction to drugs, further analyses were made after patients were classified as “paranoid” and “core schizophrenic” by computer analysis of initial ratings on the BPRS. Acetophenazine was found to be clearly the more efficacious drug in patients claSSified as “paranoid,” while the converse was true in the case of perphenazine.

Reactions and complications of treatment were mild, not impairing the study to any extent. Perphenazine induced more extrapyramidal disturbances than acetophenazine. Abnormal laboratory findings were relatively frequent before treatment and occurred sporadically during treatment. Their significance depends entirely on accompanying clinical findings.
Preliminary clinical trials of hadacidin, a new tumor‐inhibitory substance
Authors: Ellison Rose Ruth
Published: January 2016

Hadacidin retards the growth of human tumors in embryonated eggs and the rat. This report deals with the initial clinical trials of this compound which were terminated when the drug was no longer available. In 17 patients hadacidin caused leukocyte depression in 11, platelet depression without leukocyte fall in 1, and gastrointestinal tract abnormalities (stomatitis, diarrhea, nausea and vomiting) in 6. While falls in the leukocyte count occurred regularly in chronic granulocytic leukemia, the trials were not sufficient to determine whether or not clinical benefit will result from use of hadacidin. In view of the ability of this compound to inhibit the formation of adenylic and deoxyadenylic acids, further clinical study of hadacidin, both alone and in combination with other agents capable of inhibiting nucleic acid metabolism, is indicated.
Quantitative comparisons of the electroencephalographic stimulant effects of deanol, choline, and amphetamine
Authors: Pfeiffer Carl C. , Goldstein Leonide , Muiioz Carlos , Murphree Henry B. , Jenney Elizabeth H.
Published: January 2016

Quantitative electroencephalography is a sensitive method for assaying stimulant and depressant effects of drugs. This method was utilized to study the stimulant effect of deanol in rabbits and human subjects as compared with the efJect of amphetamine. Choline and placebo controls were applied. In both species, both deanol and amphetamine had statistically significant stimulant effects. In rabbits, deanol reversed the depressant effect of pentobarbital as did amphetamine. Amphetamine acted immediately but deanol acted only after a latent period. In humans, deanol did not show a significant latent period and appeared to act through mechanisms which can be acutely saturated.
Systemic and coronary hemodynamic effects of an amine oxidase inhibitor and of serotonin
Authors: Rowe George G. , Afonso Skoda , Castillo Cesar A. , Kyle John C. , Leicht Thomas R. , Crumpton Charles W.
Published: January 2016

The systemic arul corolUlry hemodYlUlmic e{fects of administration of pheniprazine were studied in dogs both on acute intravenous administration arul after aperiod of approximately 18 hours' pretreatment with the drug. No significant hemodYlUlmic changes occurred, although the arterial hemoglobin arul hernatocrit rose arul the body oxygen consumption teruled to be higher after pheniprazine. The hemodYlUlmic e{fects of serotonin were slightly increased after pheniprazine pretreatment in that the cardiac rate increased more, the arterial pressure decreased further, arul left ventricular work was reduced. When injected in the same dose into the left atrium of control animals, serotonin produced aresponse qualitatively similar to that during its right atrial administration. The relation of the present observations to the pathogenesis of the carcinoid syndrome and the therapy of angilUl pectoris is discussed.
Clinical applications of sequential analysis: An introductory review
Authors: Rümke Chr. L.
Published: January 2016

Sequential designs can be used and have been applied in a wide variety of clinical trials. The general principles Q/ul advantages of the method are reviewed, and references to trials designed in this way are provided.
The General Practitioner Research Group
Authors: Wheatley David
Published: January 2016

The General Practitioner Research Group is an organization of 150 general practitioners undertaking clinical trials in Great Britain.

Many diseases are treated solely by the general practitioner and he is best qualified to evaluate new drugs in these conditions. Also, different stages of the same diseases are seen in domiciliary and in institutional practice, and evaluation of therapy may be totally different in these stages. Drugs which are better tolerated from the point of view of adverse efJects and convenience of medication may become the treatment of choice in general practice.

The members of the Group are classified according to their own special interests and types of practice and are divided into smaller sections of 8 to 10 for each individual trial. On occasion, the full resources of the Group may be employed when information is required on a large number of cases in a short space of time.

Although the Group receives financial support from the pharmaceutical industry and academic institutions, there is no direct contact between the physicians taking part in a trial and the supplier of the drug concerned. Neither do the members of the team know one another until the end of the trial, when the results are analyzed centrally. Shortened versions of the reports of the Group are published in a regular monthly series in the Practitioner.

The usual design of trial is a comparison of the new drug to a "standard" preparation, on the "double‐blind" basis, with random seleetion of patients.
Proposed aims, organization, and activities of a division of clinical pharmacology
Authors: Carr Edward A.
Published: January 2016

The general aim of a division of clinical pharmacology is to provide opportunity for the work of present clinical pharmacologists, to encourage the development of improved methods of research, and, in particular, to foster the training of young men in this discipline. Specific areas of research, teaching, and service can already be foreseen. The best administrative home of the division will probably be a department of pharmacology, although special arrangements regarding budget, personnel, and appOintments will probably be necessary. Training in clinical pharmacology should be from 1 to 3 years. The trainee should have already received a background of clinical experience, and this may be further strengthened during his specific training in clinical pharmacology. Courses in advanced pharmacology and statistics are obviously necessary. Each division will probably find it necessary to create at least one new course dealing with the special problems of human pharmacology, discussed preferably in an informal seminar environment.
Untoward reactions to radiodiagnostic contrast media
Authors: Crocker Dean , Vandam Leroy D.
Published: January 2016

Untoward reactions to radiodiagnostic contrast media have been known since these techniques were first employed. Unless the reaction is of a maior systemic nature, detection is difficult and the over‐all incidence is unknown. Mortality is said to be as high as 1 in 1,000 during intravenous pyelography and 4 in 1,000 on whom cerebral angiograms are performed. The organic iodides are associated with the highest number of reactions, but there is no satisfactory means of predicting toxicity from chemical structure. Results of experimental studies are not readily applicable to man because of variations in experimental design and species differences. Monitoring of physiological function during diagnostic studies in man would provide not only more information but greater safety. History taking and pretesting are not universally reliable in preventing reactions. Efforts should be made to detect reactions at the earliest moment and to apply resuscitative measures as soon as possible.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

Upper Abdominal Pain and Intrahepatic Cholestasis as Manifestations of Sensitivity to Ilosone, by E. L. Cittler. Am. J. Castroenterol. 38:691‐692, 1962.
Some experimental and clinical studies on cephalothin
Authors: Herrell Wallace E. , Balows Albert , Becker Jean
Published: January 2016

In vitro sensitivity studies indicate that cephalothin is highly active against both penicillin‐sensitive and penicillin‐resistant strains of Staphylococcus aureus. Strains of beta hemolytic streptococci, streptococcus viridans, Diplococcus pneumoniae, Corynebacterium diphtheriae, Neisseria, and Actinomyces are quite sensitive to its action. Enterococci are relatively resistant. Approximately half of the strains of Klebsiella pneumoniae studied were sensitive. Some strains of Escherichia coli were sensitive. Some strains of Salmonella, Shigella, and Proteus were sensitive; others resistant. Strains of Pseudomonas aeruginosa were resistant to its action. Strains of Salmonella typhi tested were found to be sensitive. Serum inhibition studies indicate that the serum of patients receiving cephalothin is bactericidal for resistant and sensitive strains of Staphylococcus aureus and for strains of beta hemolytic streptococci and Klebsiella pneumoniae. Its action against the gram‐negative rods is highly selective. Infections due to organisms that are found to be sensitice respond favorably to treatment.
Ethamivan and the ventilatory responseto carbon dioxide in depressed man
Authors: Rockwell Gaylord H. , Greene Nicholas M.
Published: January 2016

Because the means by which analeptics stimulate respiration is generally unknown, a study was instituted to evaluate the effect of ethamivan (Emivan) on the threshold response of the human respiratory center to carbon dioxide. Alveolar carbon dioxide tensions and minute respiratory volumes were measured in normal subiects prior to the administration of any drug, folloWing elevation of the threshold of the respiratory center to carbon dioxide produced by meperidine and thiopental, and, finally, following the intravenous IUlministration of ethamivan. The effects of ethamivan were tested only in subiects whose respiration had been depressed because of the suggested use of analeptics in such states. The results showed that in the presence of respiratory depression, ethamivan produced a prompt and significant increase in ventilation but that with the dosage tested ethamivan did not fully restore ventilation to normal control value. Ethamivan produced this effect by lowering the previously elevated threshold response of the respiratory center to carbon dioxide rather than by inducing hyperventilation through other neurophysiologic mechanisms.
Studies on the mechanism of anaphylaxis: A possible basis for a pharmacologic approach to allergy
Authors: West G. B.
Published: January 2016

According to the latest and best estimates, 10 per cent of the population suffers from major allergic illness while 20 per cent more are affected with minor allergies. Allergy is largely an inherited disease, and an increase in the total number of cases in the future is possible. The introduction of thousands of new foods, drugs, synthetic materials, and consumer goods has multiplied the number of allergic victims, and more people than ever have household pets, which are also major sources of allergens. This review deals with some of the mechanisms involved.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

Hypoglycemic Coma During Change From Insulin to Tolbutamide, by 1. Fine, B. McLean, and D. F. Rickards. Brit. M. J. 2:1585, 1962.
Strychnine poisoning and its treatment
Authors: Swissman Neil , Jacoby Jay
Published: January 2016

Strychnine should not be forgotten or overlooked as a cause of poisoning. It is the principal alkaloid of a seed called nux vomica. It was first employed in medicine in 1540. The adult lethal dose is 60 to 90 mg., but now with adequate therapy recovery may take place following ingestion of doses exceeding 500 mg. It is still found in medications and pesticides.
Cloxacillin, a new oral synthetic penicillin: Comparisons with oxacillin
Authors: Sidell Sheldon , Bulger Roger J. , Brodie Jean L. , Kirby William M. M.
Published: January 2016

With antibiotics, as with other drugs, minor alterations in chemical structure are often responsible for significant differences in pharmacologic activity. In the present study, cloxacillin, differing in the addition of a single chloride atom, gave much higher blood levels following oral administration than those obtained with oxacillin. Other characteristics of the two compounds, including in vitro activity, development of resistance, and binding to serum proteins, were remarkably similar for the two compounds. The significantly higher blood levels obtained with cloxacillin suggest that this compound represents a useful advance in the oral therapy of infectiOns caused by penicillin G‐resistant staphylococci.
The comparative potency and effectiveness of topical anesthetics in man
Authors: Adriani John , Zepernick Richard , Arens James , Authement Enoch
Published: January 2016

Comparative data concerning the effects of topical anesthetics in man are not available. A technique with the use of electrical stimulation which permitted such a study was developed by the authors. The tip of the tongue is the most sensitive area in the body to this type of stimulation. Over 40 drugs with topical activity were studied with the tip of the tongue as the test site. The most potent and effective compounds are tetracaine, cocaine, dibucaine, lidocaine, and dyclonine. With the exception of dyclonine, these are toxic systemically if used in excess. The addition of vasoconstrictors, detergents, demulcents, cations, hyaluronidase, and other often suggested potentiating agents, does extend the period of activity.
The drug letter
Authors: Modell Walter
Published: January 2016

The drug letter is a new feature which appears on page 117 of this issue of the JOURNAL. Its purpose is to publish for those interested the concerns and decisions of outstanding hospitals over the country regarding new drugs, drug reactions, and drug problems as expressed in the communications of their Formulary Committees (or equivalents) to hospital staffs. In the main, local hospital drug letters deal with reasons for the addition of new drugs to the pharmacy list and for the deletion of those once considered acceptable. Warnings of drug reactions, deterioration, incompatibility, problems in handling, and use also appear in these communications.
Adverse reactions to drugs: Should we have formal programs for reporting them?
Authors: Carr Edward A.
Published: January 2016

The strong right arm of therapeutics has made such benefits available to patients in recent years that few would wish to return to the past. Those who decry treatment with modern drugs should go to some area of the world where these drugs are not available and see how it is to live (or more often die) without them. But our patients still run the risk of falling into another sinister grip‐serious adverse reactions to the drugs we use. There has been a tendency for many physicians to accept too eagerly the immediate benefits of modern drugs, while a sour minority has stressed almost exclusively their adverse effects. It is time the right hand knew what the left hand is doing, and vice versa.
The therapeutic use of progestational steroids
Authors: Berczeller Peter H. , Young Iven S. , Kupperman Herbert S.
Published: January 2016

Although the progestins in common play an integral role in the endogenous synthesis of all steroids, precise definition of what a progestin is is nonetheless difficult, since the progestational steroids are ubiquitous steroids of multiple sources in the body and have many different effects and facets of action. The gonadal and metabolic effects of the progestins are discussed in detail. Uses in menstrual abnormalities, contraception, cancer, endometriosis, and habitual abortion are considered from the therapeutic point of view.
Excerpts from the Federal Register
Authors: Larrick Geo. P.
Published: January 2016

Within the 30‐day period provided in the order published in the Federal Register of December 29, 1962 (27 F.R. 12913), the Dow Chemical Company, Midland, Michigan, filed an objection stating that the regulation contained in §121.1111 may create the impression that a synthetic glycerin made by another process would be in conflict therewith. For the purpose of clarification, and since approvals for other processes for making synthetic glycerin were granted prior to the enactment of the Food Additives Amendments to the Federal Food, Drug, and Cosmetic Act, the Commissioner of Food and Drugs, pursuant to the provisions of the statute (sees. 409, 701, 52 Stat. 1055, 72 Stat. 1785; 21 U.S.G 348, 371) and under authority delegated to him by the Secretary of Health, Education, and Welfare (25 F.R. 8625), hereby amends §121.1111 to read as follows:
Adverse reactions to drugs
Authors: Friend Dale G.
Published: January 2016

During the past two decades an old problem has become so important as to demand the serious consideration of all physicians. At the turn of the century, few potent drugs were in use. Most of them had been in use for long periods of time and it was seldom that more than two or three new agents were introduced in one year. Physicians in practice were thoroughly familiar with the drugs they used and had a considerable experience with their adverse reactions. Because of the limited number of potent drugs, it was comparatively easy for the physician to understand thoroughly the complexities of dosage, pharmacologic effects other than the principal or desired effect, and many other aspects of the drug's activity in the human organism. He was therefore in a position to recognize and take proper measures promptly when an adverse reaction occurred.
Drug toxicity and its impact on drug evaluation in man
Authors: Abrams William B. , Bagdon Robert E. , Zbinden Gerhard
Published: January 2016

A necessary concomitant of the rapid expansion of therapeutics witnessed over the past decade has been the introduction of large numbers of new drugs into clinical trial. New expressions of drug toxicity have been the “biologic price” of this progress. In an attempt to meet this challenge, animal toxicologic procedures have been greatly expanded and the current methods are briefly outlined. It is clear, however, that, although these animal studies may eliminate frankly pOisonous material from human trial, “safety” in animals does not eliminate idiosyncrasy, allergy, and other more subtle reactions in humans. Thus, the adverse effects of new drugs must be actively sought as an integral part of clinical studies. A classification of drug toxicity organized to indicate the stages of clinical trials in which the specific types of reactions might be expected to appear is presented. On the other hand, tOXicity in animals is not conclusive evidence that a given drug will be toxic for man. Indeed, many important currently used medications are highly toxic in one or more species of animals. Thus, rigid interpretation of animal data could seriously hamper the progress which holds so much promise for the future.
Mephentermine and ephedrine in man: A comparative study on cardiovascular effects
Authors: Andersen Thorkild W. , Gravenstein J. S.
Published: January 2016

Mephentermine and ephedrine were given to healthy volunteers, and their cardiovascular effects were compared. In doses equally effective in raising systolic blood pressure, ephedrine caused significantly greater elevations of heart rate, stroke volume, and cardiac output than mephentermine. The calculated total peripheral resistance was significantly increased by mephentermine, and reduced or not changed by ephedrine.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

A 62‐year‐old woman with a long history of neurotic depression and vertex headaches had been taking trifluoperazine (Stelazine), 1 mg. twice a day for 3% years. This medication was stopped and a mixture of tranylcypromine (Parnate) and trifluoperazine, 1 tablet twice a day, was substituted because of the depression. On the sixth day the customary headaches became worse and localized in the occipital area. The medication was stopped the next day. Five days later there was nuchal rigidity, positive Kernig's signs, and fever. Blood pressure was 170/110. Lumbar puncture showed xanthochromic fluid. The subject's condition improved with bed rest, but the former headaches returned.