bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cigarette smoking on blood coagulation
Authors: Ambrus Julian L. , Mink Irving B.
Published: January 2016

Eighteen medical students who were not smokers were asked to smoke a cigarette, inhaling as much as possible. Blood samples were obtained before and 5 minutes after smoking. A significant increase was observed in platelet adhesiveness. Whole blood coagulation time, recalcified plasma coagulation time, platelet count, partial thromboplastin time, thromboplastin generation time, and tensile strength of the clot showed changes compatible with increased coagulability; however, these were statistically not significant.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

This is an analysis and discussion of 34 reports which have appeared in recent years relating to analgesics and renal disease. The author reviews the known pharmacology and potential renal toxicity of acetophenetidin and other drugs, notably, acetylsalicylic acid, caffeine, aminopyrine, and antipyrine, which are usually incorporated into the analgesic complex. The author deplores the inferential association of phenacetin with specific nephrotoxicity, since this drug has rarely been used alone in the series reported. He relates that as experience was gained “it was found that the vast majority of alleged cases of analgesic‐induced renal disease consist of a rather typical bacterial pyelonephritis characterized by an unusually high incidence of papillary necrosis.” This could be related to several mechanisms: (1) analgesics could cause primary damage to the kidney, with secondary bacterial invasion; (2) analgesics could render the kidney less resistant to infection, and consequently “analgesic nephrotoxicity” could be an accelerated form of bacterial pyelonephritis; and (3) in many cases pre‐existing renal disease could be the reason for the excessive ingestion of analgesics. This could explain the divergent lesions that have been related to use of analgesic combinations.
The monitoring of hospital patients, with remarks on radio techniques
Authors: Davis David A.
Published: January 2016

In the continuous analysis of clinical events, termed “monitoring,” progress has not kept apace of possibilities. Present equipment is subject to much criticism; the capabilities of competent phYSical scientists have not been utilized. Attitudes of usefulness have not created a market for instrumentation which could be designed and utilized. Little effort has gone into the design of instruments for a particular purpose; much effort has been devoted to forcing instruments to accept information for which it is not prepared. The physcian has been lax in setting standards which are acceptable to modern data processing systems. Confronted with masses of information, utilization of these facts may complicate matters. Radio techniques, utilized for many years in meteorology, aircraft control, and space efforts, have not been exploited in clinical monitoring. The present advantages are those of convenience and relative freedom from AC interference. Complexity and cost may not be added to the cost of data collection, provided there is proper engineering. Results in certain areas of electrocardiography, electroencephalography, electromyography, and GSR measurements suggest that radio telemetry may be the method of choice, prOVided its limitations are recognized.
Therapy and management of paroxysmal pulmonary edema
Authors: Luisada Aldo A.
Published: January 2016

The causes of paroxysmal pulmonary edema are discussed. It is emphasized that, in the presence of left ventricular failure or mitral block, any increase of pulmonary flow may be followed by edema of the lungs. It is also stated that redistribution of the blood, secondary to systemic vasoconstriction, may be a factor. Pulmonary venoconstriction is another possible contributory cause. Two clinical syndromes are separated. In the first, increase of cardiac dynamics is present, and “relative” left ventricular failure may occur; in the second, decrease of cardiac dynamics is the rule, and shock may be easily precipitated. Treatment of pulmonary edema involves pharmacologic and physical means. The most effective are those which decrease venous return through central sedation, ganglion blocking effect, venous pooling, or bloodletting. The importance of oxygen and the part played by the foaming process are stressed. Defoaming agents effectively increase oxygen intake by decreasing surface tension and breaking bubbles and can be of help.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

A 22‐year‐old white man was admitted for evaluation of renal failure. Approximately 4 years before, after a diagnosis of primary pulmonary coccidiomycosis had been established, he was given amphotericin B, 2.5 Gm. in 36 divided doses intravenously, which resulted in clinical improvement, but with elevation of blood urea nitrogen from 5 mg. per 100 ml. to 28 mg. per 100 ml. Three months later the subject was admitted for headache, stiff neck, and fever. Complement fixing antibodies to Coccidioides immitis were identified in the cerebrospinal fluid. He was given amphotericin B, 9.2 Gm. intravenously and 49 mg. intrathecally, over a 6 month period. The patient was completely asymptomatic but had a persistent complement‐fixing antibody. Blood urea nitrogen, which had been 8 mg. per 100 ml. at the onset of the second course, rose to 47 mg. per 100 ml. Serum creatinine was 2.2 mg. per 100 ml. During a period of 5 months, spinal fluid remained clear, blood urea nitrogen fell to 22 mg. per 100 ml., and creatinine descended to 1.8 mg. per 100 ml.
Some aspects of the pathophysiology of spasticity and rigidity
Authors: Rushworth Geoffrey
Published: January 2016

New discoveries in relution to the histology and electrophysiology of the muscle spindle show that the stretch reflexes are much more complex at the segmental level than was previously thought, and these must be taken into account in explaining various clinical hypertonias. Thus, the gamma‐1 fibers are believed particularly hyperactive in mild spasticity, while the gamma‐2 system may account for the large tonic stretch reflexes; in the “clasp‐knife” reactions sudden motoneuron inhibition occurs, while ordinarily, as stretch proceeds, more and more motoneurons are recruited. In some types of spasticity, alpha motoneuron hyperexcitability occurs and not the gamma, so that this type is resistant even to dorsal root section. Parkinsonian rigidity, characteristically mild and plastic, is relatively independent of the velocity of stretching, though the response of rigid muscles to fast stretch may be of the “cogwheel” type. Parkinsonian rigidity may be governed by gamma fibers and not maintained by the alpha system, which may account for the rapid and dramatic effect obtained with intramuscular procaine. Complex physiologic work on gamma systems of muscle spindles provides a working hypothesis to account for both spasticity and rigidity as well as for differential action of certain agents. Further work on the dual alpha and gamma systems is urgently needed, as is the development of methods for recording reflex action in man to quantitate spasticity and rigidity.
Integrators as measuring devices of bioelectric output
Authors: Tursky Bernard
Published: January 2016

It is difficult to quantify gross muscle spasms from the clinical electromyogmphic record. The use of integmtion techniques simplifies this task. Three such techniques are described: continuous avemging, voltage compamtor, and time reset. The use of integrators to convelt the high‐frequency EMG potentials to a slowly changing analogue voltage makes it possible to employ a data sampling concept based on experimental rather than physiologic band width. This reduces the problems of sampling and storage of information if data processing is being done by computer.
Problems in the clinical estimation of rigidity (hypertonia)
Authors: Schwab Robert S.
Published: January 2016

This paper is concerned entirely with problems involving the clinical estimation of rigidity, specifically in patients who have Parkinson's disease or are suspected of having this condition. By clinical estimation is meant the various manipulations and techniques used by the neurologist in the standard neurological examination and some speCial tests particularly designated to measure rigidity. It does not concern any of the techniques involving apparatus for measuring resistance of muscles passively or any of the computer or electronic equipment reported in other sections of this volume for the quantitative measurement of this state.
Evaluation of chronic cervical muscle spasm
Authors: Clark Glenn M.
Published: January 2016

Evaluation of disability involving pain and limitation of motion of the neck in such conditions as “whiplash in;ury,” fibrositis, rheumatoid arthritis, cervical disc disease, gout, “bursitis,” cervical osteoarthritis, as well as in anxiety reactions, coronary disease, neuromuscular disorders, hysteria, and “secondary gain syndrome” is extremely complicated and often the sub;ect of controversy, especially medicolegal. The diagnostic “tools” are discussed, and a simple technique for testing range of motion is described as a means for establishing the presence of cervical muscle spasm. Appropriate management is based on classification of cervical muscle spasm in six broad etiologic categories. In a 15 month pilot study 60 patients evaluated by the testing procedure and classification were treated with diazepam. The findings were a measurable increase in neck motion in patients in whom anxiety was a component of the cervical muscle spasm. Those with organic disease showed no consistent change by objective testing of motion range, but most of these sub;ects reported feeling better.
Adrenal function after topical steroid therapy
Authors: March Cyril , Rea Thomas H. , Porter Michael J.
Published: January 2016

Suppression of pituitary‐adrenal axis activity was observed in one of a series of 4 patients with psoriasis during treatment with topical fluorinated corticosteroids applied under occlusive dressings. The patient who showed suppression had a normal metyrapone test immediately after therapy. All 4 subjects had normal adrenal‐pituitary axis function, as measured by the metyrapone inhibition test, before treatment, but one showed impaired function after treatment, despite absence of adrenal suppression during therapy. With the conditions employed in this study, concentration of the medicament appears to be a significant factor in the production of adrenal suppression. From similar studies by other authors it is evident that extent of body area occluded and the status of the skin barrier are also important variables in influencing the presence or absence of percutaneous absorption sufficient to produce adrenal suppression.
Clinical studies of dichloromethotrexate (NSC 29630)
Authors: Frei Emil , Spurr Charles L. , Brindley Clyde O. , Selawry Oleg , Holland James F. , Rall David P. , Wasserman Louis R. , Hoogstraten Barth , Shnider Bruce I. , McIntyre O. Ross , Matthews Louis B. , Miller Sherwood P.
Published: January 2016

Dichloromethotrexate (DCM) is much superior to methotrexate (MTX) in inhibiting L1210 leukemia and C3H lymphosarcoma in mice. This greater effectiveness obtains for parenterally administered DCM and is much less apparent when DCM is given by mouth. The toxicity of DCM in animals is qualitatively similar to that produced by MTX. DCM is fifty to one hundred fold less toxic than MTX in rats and mice but only tenfold less toxic in dogs. It is concluded from clinical studies reported in this paper that: (1) The tolerated dose of DCM is fivefold that of MTX and the toxic manifestations are similar. (2) The tolerated doses of oral and iniramuscular DCM are equivalent. (3) Equitoxic, and presumably optimal, doses of oral DCM, oral MTX, and intramuscular DCM produce comparable antitumor effects in adults with lymphosarcoma and Hodgkin's disease. There is complete tumor regression in 10 to 20 per cent and partial regression in another 20 to 30 per cent of patients. These tumor regressions are, in general, short‐lasting. (4) The dose response relationship is steep. A twofold difference in dose of DCM or MTX results in a significant difference in toxicity and antitumor effect. (5) There are at least four other more effective modalities of treatment for lymphoma which should be employed before conventional folic acid antagonist therapy is considered.
Is DNA the “secret of life”?
Authors: Commoner Barry
Published: January 2016

There is at this time a widely held belief that, with the discovery of certain molecular attributes of deoxyribonucleic acid (DNA), the chemical basis of inheritance has at last been elucidated. However, a recent re‐examination of the data which have been advanced to support this conclusion1 and of a wider range of evidence relative to the problem2, 3 suggests strongly that DNA is neither a self‐sufficient genetic “code” nor the “master chemical” of the cell. This re‐evaluation of the problem suggests instead that inheritance depends on multimolecular interactions which occur in no system less complex than that in an intact cell; self‐duplication is, therefore, not a molecular attribute of DNA, but a property of the whole cell. These considerations lead to the proposal that DNA plays two distinctive roles in the complex chemistry of inheritance; one is related to a template function and the other to the influence of DNA synthesis on the metabolic availability of free nucleotides in the cell.
Demethylchlortetracycline therapy in acute gonococcal urethritis
Authors: Sokoloff Burton
Published: January 2016

In 232 male military personnel with acute gonococcal urethritis, 100 per cent cure rates followed oral demethylchlortetracycline after an initial dose of 900 mg. plus 150 mg. 4 times daily for 5 days (60 patients); 90 per cent cure rates after 900 mg. plus 150 mg. 4 times daily for 3 days (60 patients); and 64 per cent cure rates after a single dose of 900 mg. (113 patients). The incidence of adverse effects with these dosage regimens was 21.6,15.0, and 23.0 per cent, respectively. The effects consisted of mild gastrointestinal disturbances, developing usually within a few hours after the 900 mg. dose. The possible reasons for the relatively poorer results with a single 900 mg. dose than those reported by other investigators may include the varying rates of follow‐up and reinfection. Results may also be affected by the type of patients used.
Principles and practices of prescription writing
Authors: Friend Dale G.
Published: January 2016

The art of prescripiton writing is an ancient inheritance. Through many centuries the time‐honored custom of the prescription has played a vital role in the practice of medicine and pharmacy. Its origin is lost in antiquity but its importance through the centuries has made it one of the most significant written communications of the human race. The ancients started their prescriptions with an appeal to the gods for its success. The ancient symbol, “R” signifying this appeal, was established centuries ago and has been carried down to the present time.
Ethanol and urinary catecholamines in man
Authors: Anton Aaron H.
Published: January 2016

By measuring the main urinary catabolites of the catecholamines and serotonin, an attempt was made to elucidate which step in the metabolism of the amines is affected by ethanol in man. There was a Significant increase in urinary norepinephrine, dopamine, and metanephrine following the ingestion of a moderate dose of ethanol. Several possible enzymatic steps in the metabolism of the catecholamines where ethanol might act are discussed. The possibility that the results may have been complicated by the effect of ethanol on other physiologic functions is also considered.
Hypoxia in anesthesia: A review
Authors: Bendixen H. H. , Laver M. B.
Published: January 2016

Hypoxia associated with anesthesia and surgery has an etiology which ranges from simple though rare accidents, such as airway obstruction, to the complicated but common disturbances in the intrapulmonary relation of ventilation to perfusion. Anesthetic agents, properly used, do not give rise to hypoxia; rather, the impaired oxygenation is caused by such factors as pre‐existing disease or trauma, the position of the patient, other mechanical interferences with ventilation, a less than optimal pattern of ventilation, and an inadequate oxygen carrying capacity. The response to hypoxia in anesthesia differs from that encountered in the healthy and conscious individual primarily by being tremendously variable. Not only is the response to hypoxia modified by age and disease, but anesthetic agents and a variety of other drugs so interfere with circulatory and ventilatory compensation in hypoxia that no well‐defined pattern can be described. The symptoms of hypoxia in anesthesia vary from the “normal” response, consisting primarily in tachycardia and mild hypertension, to the response seen in patients who are unable to provide a compensatory increase in cardiac output and ventilation. Under such circumstances hypoxia will lead to bradycardia and hypotension.
Abstracts
Authors: Moser Robert Harlan
Published: January 2016

Case 1. A 68‐year‐old man was admitted with mid‐epigastric pain for the preceding 48 hours and three episodes of hematemesis. He had suffered a myocardial infarction 11 months previously and had been maintained on anticoagulant therapy. (Information regarding dosage was not available at the time of admission.)
Antihistaminics: Tailoring dosage to suit patients
Authors: Harter John G.
Published: January 2016

With the hayfever season approaching, it seems appropriate to comment on antihistaminics and their use. Every physician who tries these drugs for symptomatic relief of hayfever, urticaria, pruritus associated with atopic dermatitis, contact dermatitis, or other pruritic eczemas, or drug or transfusion reactions is soon aware of the marked variability in response. This variability is in terms of the therapeutic response as well as in the incidence and severity of adverse effects.
Chronic chlorpromazine administration: Some pharmacological and psychological effects in man
Authors: Sletten Ivan W. , Lang William J. , Brown Marjorie L. , Ballou Susan R. , Gershon Samuel
Published: January 2016

This study was undertaken to determine whether there were changes in the pharmacological profile of chlorpromazine when it was given over a long period of time and in view of these findings to examine claims that chlorpromazine is clinically useful as an antidepressant. Fifteen patients with chronic mental illness were given infusions of epinephrine, norepinephrine, histamine, and yohimbine before and at 1, 10, 30, and 90 days during a course of chlorpromazine therapy. Psychological measurements by observers unaware of drugs given indicated that the anxiety‐arousing effects of epinephrine were reduced by chlorpromazine but that the anxiety‐like effects of yohimbine were potentiated. Histamine and norepinephrine had no significant psychological effect. Treatment with chlorpromazine reduced manifestations of mental illness. Base‐line blood pressure was reduced Significantly early in chlorpromazine therapy but only slightly later on. The systolic pressor effects of epinephrine were reduced by chlorpromazine but to a lesser extent late in the 90 day period. Norepinephrine systolic blood pressure effects were not Significantly altered by chlorpromazine. The cardiovascular effects of histamine were potentiated by chlorpromazine throughout as were the cardiovascular effects of yohimbine. In a parallel dog study chlorpromazine augmented norepinephrine pressor effects. It is concluded that, in view of its tendency to potentiate yohimbine and norepinephrine, chlorpromazine has some characteristics similar to those of the antidepressant drug imipramine. These results are discussed in relation to findings that chlorpromazine and imipramine alter storage and release of catecholamines
Proteolytic enzymes in clinical medicine
Authors: Colman Robert W.
Published: January 2016

The explosive expansion of our knowledge of the basic properties of the mammalian proteolytic enzymes has stimulated a parallel growth in their applications to clinical medicine. The outcome of this research has been significant advances in the therapy, diagnosis, and pathogenesis of disease processes in almost all fields of medicine. The enzymes discussed in this paper are pepsin, the pancreatic endopeptidases (chymotTypsin, trypsin, kallikrein, and elastase), the blood proteolytic enzymes (thrombin and plasmin), the pancreatic exopeptidases (leucine aminopeptidase and carboxypeptidases), and the tissue proteases (cathepsins). After a brief summary of the physical and biochemical properties of each enzyme, a critical appraisal is made of its potential and limitations as the enzyme is used in clinical medicine. This review concentrates on a delineation of the more important of the recent contributions, a discussion of certain controversial areas, with speCial emphasis on the therapeutic applications and the suggestion of certain fields of investigation which may require more attention in the future.
Comparison of cyclophosphamide and 5‐fluorouracil in the treatment of patients with metastatic breast cancer
Authors: Talley R. W. , Vaitkevicius V. K. , Leighton G. A.
Published: January 2016

Sixty‐two patients with metastatic breast cancer were treated randomly with either cyclophosphamide or 5‐fluorouracil. The patients were classified as haVing either an objective remission or a failure of treatment by accepted techniques. Eleven of 30 patients responded to 5‐fluorouracil, and 7 of 32 responded to cyclophosphamide. These differences are not significant. Subsequently, each patient was treated with the other agent, and 4 of 32 responded to 5‐fluorouracil, and 7 of 30 responded to cyclophosphamide. Thus, a total of 14 patients experienced clinical remissions of their disease with cyclophosphamide, and 15 had remissions with 5‐fluorouracil. Of the 18 patients responding to the first agent, 7 experienced objective regressions with the second agent, whereas only 4 of the 44 patients failing to respond to the first agent experienced objective remissions with the second agent. This difference was significant at p < 0.02. Factors such as menopausal age of patient, site of the dominant lesion, and response to prior hormonal therapy were of no value in predicting response to these two agents. Survival of the patients after the start of chemotherapy was 14.7 ± 10.2 months for patients responding to both agents, 10.5 ± 9.0 months for patients responding to the first agent only, 6.2 ± 12.8 months for patients responding to the second agent only, and 5.2 ± 4.5 months for patients responding to neither agent. Subjective improvement correlated well with objective improvement, but some patients failing to respond to therapy experienced temporary subjective improvement.
Interaction between some anticholinergic agents and phenothiazines: Potentiation of phenothiazine sedation and its antagonism
Authors: Gershon Samuel , Neubauer Harry , Sundland Donald M.
Published: January 2016

Chlorpromazine and promazine were found to potentiate certain effects of JB‐329 and atropine in a group of psychiatric patients. These effects were measured by a JB‐329 rating scale, 80 items grouped to yield nine cluster scores. This scale allowed a differenrtiation of the particular aspects potentiated by chlorpromazine and promazine. This potentiation was observed on three scores: neurological impairment, loss of consciousness, and impaired performance on the Bender‐Gestalt test. Imipramine did not show any such potentiation on this scale and was similar in effect to a saline control. THA and yohimbine were found to antagonize the effects produced by the combination of an anticholinergic and a phenothiazine compound. The effects of these drug combinations were similar to those observed in dogs, but not to the findings in smaller animals (mice and rats).
Excerpts from the Federal Register
Authors: Harvey John L. , Larrick Geo. P.
Published: January 2016

A notice of a proposal by the Commissioner of Food and Drugs to repeal the tolerances for chlordane and to establish a tolerance of zero for residues of chlordane for each of the raw agricultural commodities named in § 120.122 was published in the FEDERAL REGISTER of December 5, 1963 (28 F.R. 12938). Within the time limit specified in the notice Velsicol Chemical Corp., 330 East Grand Avenue, Chicago, Ill., 61611, requested that the proposal be referred to an advisory committee, in accordance with section 408 (e) of the Federal Food, Drug, and Cosmetic Act.
The Burroughs Wellcome Fund Clinical Pharmacology Award program
Authors: Creasy William N.
Published: January 2016

For many years Burroughs Wellcome & Co.—which was founded in 1880 by two enterprising young Americans—has had as its objective the discovery, the development, manufacture, and distribution of drugs that would be of use to the physician in his diagnosis, prevention, and treatment of diseases. At a very early date in its history (the early 1900's), as a result of Henry Wellcome's insight into the problem of drug safety and drug toxicity, the Company became concerned with the effect of chemical compounds on the body's physiology. Because Henry Wellcome was prepared to pioneer in drug research and sought to improve the standardization and quality of drugs, he was able to persuade Henry Dale, the distinguished physiologist and pharmacologist, to join Burroughs Wellcome & Co. in the early 1900's.
Amitriptyline in childhood enuresis
Authors: Poussaint Alvin F. , Ditman Keith S. , Greenfield Richard
Published: January 2016

In a double‐blind, placebo‐controlled study with cross‐over, 50 outpatient enuretic children (aged 5 to 15) were treated for 8 weeks. It was found that amitriptyline in doses of 25 or 50 mg. (for children aged 12 and over) was superior clinically (P < 0.0005) to a placebo in decreasing the frequency of nights with enuresis. Adverse effects from the amitriptyline were found to be minimal. After the 8 week treatment period, the dosage of amitriptyline at bedtime was manipulated over a range of 25 to 75 mg. and the clinical response was improved in some instances. Five children (10 per cent) became completely dry and remained dry after the drug was gradually withdrawn. Thirty children (62 per cent) showed various degrees of improvement with a small percentage of relapses when the drug was withdrawn. Fourteen (28 per cent) failed to benefit from treatment.
Response of experimental pain to analgesic drugs: I. Morphine, aspirin, and placebo
Authors: Wolff B. Berthold , Kantor Thomas G. , Jarvik Murray E. , Laska Eugene
Published: January 2016

Two methods of inducing pain experimentally in man have been investigated as possible laboratory instruments for evaluating analgesic efficiency; one uses electrical stimulation of two fingers, yielding one touch and two pain response parameters, the other, thermal stimulation of the hand by immersion in ice water, yielding three pain response parameters. Sixty paid healthy volunteers were divided into three groups of 20 each. One group received placebo in all four experimental sessions, the second received morphine twice and placebo twice, and the third received aspirin twice and placebo twice. The results indicated significant changes occurring during morphine conditions for both the pain, but not the touch, response parameters produced by electrical stimulation; and for pain tolerance and pain sensitivity range, but not for pain threshold, obtained with ice‐water stimulation. Aspirin failed to produce Significant changes in any response parameter with either technique, but in some subiects lowered the pain threshold. Some laterality differences between the dominant and nondominant hands were observed which were occasionally significant.
Bacillus subtilis protease in the digestion of burn eschar
Authors: Prytz Bo , Connell James F. , Rousselot Louis M.
Published: January 2016

The activity of a Bacillus subtilis protease on burn eschar was studied. The protease is a broad‐spectrum proteolytic enzyme active between pH 5.4 and 7.8. The enzyme digests denatured necrotic human skin but is practically inactive toward nOlmal viable skin. In the course of its digestive activity, it breaks down burn eschar to acid‐soluble peptides and amino acids; the latter predominating in comparison with the activity of some other enzymes. About 40 per cent of burn eschar is broken down in 24 hours. By applying fresh enzyme and extending the time to 48 to 72 hours, 60 per cent of the eschar may be broken down. The residue is left in a condition which is easily removed. The release of the enzyme from a fatty base is satisfactory.
Methylquinazolone and hepatic function
Authors: Breslow Irwin H. , Haidri S. Z.
Published: January 2016

The effects of methylquinazolone on hepatic functions were studied. In the initial phase of the investigation, 200 mg. was administered daily for 4 weeks to 29 normal subjects at the end of their working day. In the second phase of the study, 7 subjects were given 400 mg. daily for 4 weeks. No evidence of any hepatic dysfunction connected with the use of methylquinazolone was found.
Ultra‐short‐acting barbiturates as oral hypnotic agents in man
Authors: Bush Milton T. , Berry Geoffrey , Hume Arthur
Published: January 2016

Administration to man of about 10 mg. per kilogram of thiopental sodium, hexobarbital sodium or methohexital sodium can produce rapid, intense sedation of only an hour or two's duration, with substantial recovery, including return of mental clarity within 3 to 4 hours. Quantitative determinations of barbiturate concentrations in the blood are closely correlated with clinical effects. From these and other results, we infer that to achieve the rapid absorption necessary for these results, the stomach must be empty at the time of administration and the drug must be in solution or in a form which is qUickly soluble in the aqueous medium in the stomach. Correlations between chemical structure and physical properties, on the one hand, and lipid solubility and rapidity of absorption on the other are discussed.
Some side effects of heparin, heparinoids, and their antagonists
Authors: Coon William W. , Willis Park W.
Published: January 2016

Effects of heparin, heparinoids, and their antagonists, other than actions on blood coagulation and lipemia clearing, are described. Many, if not all, of these properties are probably related to the unusual structure and high‐charge density of these macromolecules. Some may have therapeutic utility.
Sequential experimentation and multivariate analysis in the evaluation of a treatment for postoperative intestinal symptoms
Authors: Cattaneo Angelo D. , Lucchelli Paolo E. , Bona Nelly , Maccacaro Giulio A.
Published: January 2016

A mixture of iodochlorhydroxyquinoline and phenanthrolinedione was tested for its action on postoperative intestinal symptoms in man. The double‐blind technique was adopted, and a sequential approach was chosen showing that the preparation is significantly more active than the placebo. The results were confirmed by a discriminatory analysis carried out on the data collected.
Failure of chlorpromazine to prevent barbiturate‐withdrawal convulsions
Authors: Essig C. F. , Fraser H. F.
Published: January 2016

In dogs, as well as in men, addicted to barbiturate, withdrawal may be associated with convulsions, delirium, and even death. Withdrawal at a rate not exceeding 0.1 Gm. daily is a safe and effective method of overcoming the barbiturate abstinence syndrome. Chlorpromazine has been advocated for the treatment of this serious withdrawal phenomenon. Dogs were used in this study to test the effects of chlorpromazine at various dose levels on barbital‐withdrawal convulsions. Chlorpromazine in dosages ranging from 1 mg. per kilogram every 4 hours to 32 mg. per kilogram every 12 hours failed to suppress the convulsions. Chlorpromazine also failed to suppress the restlessness, tremulousness, twitching, and increased startle response that occur during the week following withdrawal of barbiturate in the dogs. On the basis of these observations in the dog, it is recommended that chlorpromazine not be used in the treatment of barbiturate‐withdrawal manifestations in man.
Effects of drugs on the coronary circulation of man
Authors: Rowe George G.
Published: January 2016

The literature on the effects of pharmacologic agents on the human coronary circulation has been reviewed. It seems probable that the resistance vessels in the myocardium, rather than the maior coronary arteries, control myocardial blood flow. This is generally accepted for other areas of the body. If this is true in the heart, considerable changes in the lumen of the large coronary arteries may produce no significant difference in flow through the myocardium. This could explain the gross discrepancy between the severe coronary artery disease which has been demonstrated by coronary arteriography and the normal values for coronary flow obtained utilizing the nitrous oxide method or the radioactive gas methods. As it now stands, methods for measuring coronary blood flow have been of no value in detecting coronary artery disease and of very little value in predicting which drugs will be effective in relieVing angina pectoris. A general rule would seem to be that an agent which reduces cardiac work is apt to be effective in relief of anginal pain. Clearly, further information is desirable.
New uses for an old hormone
Authors: Selenkow Herbert A. , Wool Marvin S.
Published: January 2016

Hypothyroidism is no longer a rare disease. Widespread therapeutic use of radioactive iodine has increased the incidence of progressive thyroid failure to unexpected proportions, and this insidious complication has necessitated critical reappraisal of isotopic therapy for hyperthyroidism. In view of the recognized deleterious effects of hypothyroidism and the well‐known difficulties and delays attendant on its diagnosis, some observations on prevention of thyroid insufficiency by the administration of thyrOid hormones seem justifiable and timely. The indiscriminate or injudicious use of thyroid hormone therapy as a metabolic cure‐all is to be deplored. However, under circumstances which are known to produce a high incidence of thyroid insufficiency, for example, following radioactive iodine therapy or subtotal thyroidectomy for lymphoid thyroiditis, selective use of full therapeutic doses of thyroid hormones to prevent hypothyroidism is indicated.
The drug treatment of arterial hypertension
Authors: Page Irvine H.
Published: January 2016

Some of the important events in the contemporary history of the drug treatment of arterial hypertension are discussed. The many kinds of hypertension are beginning to be recognized and defined, and attempts are being made to fit the treatment to the mechanism. Although only a limited number of mechanisms causing hypertension are involved in the drugs employed, still normal or almost normal blood pressures can be achieved. Physicians and patients must be trained to use these drugs more effectively.
Hypotensive action of propranolol
Authors: Waal Hendrika J.
Published: January 2016

Coronary heart disease together with sudden cardiac death is now the main cause of death in patients being treated for hypertension at the Wellcome Medical Research Institute, probably because of a reduction in deaths from heart failure and stroke. A hypotensive agent with antiarrhythmic properties might, therefore, be valuable. This work confirms the hypotensive action of the antiarrhythmic agent propranolol in hypertensive patients. In subiects with mild to moderate hypertension, propranolol controlled the hypertension adequately in 30 to 40 per cent. The dose was higher than that necessary for antiarrhythmic effects. The hypotensive effect of propranolol was fully estahlished after one day; no cumulation but rather mild tolerance developed.
The effect of reserpine on catecholamine metabolism and behavior in retarded children
Authors: Anton Aaron H. , Greer Melvin
Published: January 2016

The clinical and biochemical effects of reserpine were studied in a group of retarded children whose diet, activity, and environment could be rigidly controlled. A single intramuscular iniection of reserpine induced the following significant changes in urinary catecholamines: (1) a decrease in norepinephrine and its metabolite normetanephrine, (2) an increase in epinephrine and its metabolite, metanephrine, (3) a decrease in dopa, the first catechol on the biosynthetic pathway to the other amines, and (4) an increase in vanilmandelic acid, the mator product of norepinephrine and epinephrine metabolism. The chronic administration of reserpine to two children caused a similar trend in urinary catecholamines but with some minor differences. No consistent change was observed in serotonin metabolism in either the acute or chronic study as reflected by the random day‐to‐day fluctuation in urinary 5‐hydroxyindoleacetic acid. The physiologic changes, pmticularly the onset and cessation of sedation, appeared to coincide more with changes in vanilmandelic acid, epinephrine, and metanephrine than with any of the other substances. The retarded patients excreted significantly more of all the catechols than did the normal children, but this study does not delineate the basis for this difference.
Effects of pesticides on drug and steroid metabolism
Authors: Conney A. H. , Welch R. M. , Kuntzman R. , Burns J. J.
Published: January 2016

Treatment of experimental animals with small amounts of halogenated hydrocarbon insecticides stimulates the activity of oxidative enzymes in liver microsomes that metabolize drugs and steroid hormones. The enhancing effect of these pesticides on drug metabolism alters the duration and intensity of drug action in animals and also markedly influences drug toxicity. The minimum exposure to DDT required to decrease the hypnotic action of pentobarbital in rats gives rise to 10 to 15 μg of DDT per gram of fat, a concentration approaching that reported to occur in the human population. The physiological significance of pesticide‐induced increases in steroid hydroxylases in liver microsomes is not known, and further studies are necessary to elucidate the importance of this effect. In contrast to the stimulatory effect of halogenated hydrocarbon insecticides on hepatic steroid hydroxylases, treatment of rats with organophosphate insecticides, such as chlorthion, inhibits the liver microsomal metabolism of several steroid hormones. Chlorthion has a greater inhibitory effect on the 16α‐hydroxylation of testosterone than on the 6β‐ or 7 α‐hydroxylation of this steroid, suggesting that separate enzyme systems are required for the various hydroxylation reactions. Since the stimulatory effects of several drugs on drug and steroid metabolism in animals is paralleled by enhanced drug and steroid hydroxylation in man, further studies should be carried out to determine whether the chronic environmental exposure of humans to pesticides is sufficient to alter their metabolism of drugs and steroids.
A comparative clinical trial of guanoxan and guanethidine in essential hypertension
Authors: Ruedy John , Davies R. O.
Published: January 2016

Guanoxan and guanethidine were studied in 52 patients with essential hypertension using a double‐blind crossover technique. No difference was seen in the hypotensive effects of the two drugs. Blood pressure in the standing position (systolic/diastolic) was decreased by 30/25 mm. Hg and in the recumbent position, by 20/15 mm. Hg; postexercise blood pressure was decreased by 45/40 mm. Hg. Fatigue was a more common complaint after administration of guanethidine, but otherwise guanoxan and guanethidine were similar in efficacy and in adverse effects. Twenty‐four hour urinary excretion of norepinephrine, but not epinephrine, was decreased during therapy with both drugs.
Computers in public health
Authors: Binder Sidney , Simmons Walt R.
Published: January 2016

The United States Public Health Service has 17 computers active in all phases of health activities. Analysis of vital statistics is one such activity. Advances in computer technology have indicated a complete reappraisal in approach to vital records systems. Developments of major significance in health applications include optical character recognition equipment, more rapid printers, and remote stations. Integration of the vital records data management system and application of computer methods would permit rapid retrieval of data needed for program development and evaluation, as well as for the study of changes over short time periods. Computers have made it possible to plan for such an integrated system.
Computers in biomathematical applications
Authors: Ackerman Eugene , Strickland E. Hardin , Hazelrig Jane B. , Gatewood Laël C.
Published: January 2016

Electronic computers of both the digital and the analogue varieties have made possible many studies with the use of mathematical models of physiological systems. This area of biomathematics has grown rapidly in the last decade. The general aims, limitations, and problems of such mathematical models are reviewed in this paper. Techniques for the conformation of such mathematical models to experimental data by the application of electronic computers are discussed. Finally, three specific examples are presented briefiy: the regulation of the concentration of glucose in the blood, the metabolism of calcium by bone, and the stimulation of mitochondrial respiration. These examples are presented, rather than an encyclopedic list of uses or a technical set of computer pro grams, in the hope that they will better illustrate some of the applications of electronic computers in biomathematics.
Medical records and computers
Authors: Yoder Richard D.
Published: January 2016

Information processing is an important aspect of health care. Clinical information occurs in various modes including numerical measurements, text, and codes. Considerations important in processing such data include the data collection or input documents, amount and type of processing to be done, and methods for displaying the collected information. A system for handling clinical information has been developed by the Division of Medical Computing Sciences at Tulane University. Although a system such as is described cannot now be iustified economically except for research purposes, hopefully it will soon be abasie component of clinical care.
Specific therapeutic actions of acetophenazine, perphenazine, and benzquinamide in newly admitted schizophrenic patients
Authors: Hollister Leo E. , Overall John E. , Bennett J. L. , Kimbell Isham , Shelton Jack
Published: January 2016

One hundred newly admitted schizophrenic men were treated with either acetophenazine, perphenazine, or benzquinamide in a controlled study. Each drug produced substantial and essentially equal improvement according to most criteria examined. Classification of patients according to standard nomenclature‐derived prototypes, as paranoid and nonparanoid, revealed no significant differences between drugs, all being somewhat more effective in paranoid patients. Regression analysis revealed a similar trend. The different response to antipsychotic drugs of paranoid as compared with nonparanoid schizophrenic patients provides still further evidence for a difference between these two schizophrenic clinical subtypes.
Persistent neuropathy following chronic use of glutethimide
Authors: Nover Robert
Published: January 2016

Glutethimide (Doriden) is one of the widely prescribed nonbarbiturate hypnotics in the United States. A recent case of a patient in a psychiatric hospital who abused the use of glutethimide gave evidence of sensory neuropathy which persisted after withdrawal of the drug.
Absorption of exogenous and endogenousproteolytic enzymes
Authors: Ambrus J. L. , Lassman H. B. , De Marchi J. J.
Published: January 2016

A method is described for estimating chymotrypsin and trypsin in circulating blood. Parenterally or orally administered chymotrypsin and trypsin resulted in speci[ic esterase activity changes in blood. This indicates absorption of the enzymes administered rather than release of secondary enzymes from the intestinal tract. Stimulation of pancreatic secretion did not cause demonstrable increases in blood esterase levels. Thus, the method described oes not seem to be useful as a pancreatic function test.
Oxandrolone therapy in stunting and in ovarian dysgenesis
Authors: Danowski T. S. , Weir T. F. , Girdany B. , Lee F. A.
Published: January 2016

Therapy of stunted children with oxandrolone has been associated with probable acceleration of vertical growth in 11 out of 20 patients. This was generally not accompanied by acceleration of skeletal maturation. One of three patients with proved gonadal dysgenesis grew faster during treatment. Sexual pseudoprecocity did not develop in the males nor were arrhenomimetic effects observed in the females.
The effect of phenyramidol on the metabolism of diphenylhydantoin
Authors: Solomon Harvey M. , Schrogie John J.
Published: January 2016

When phenyramidol was given to subiects taking diphenylhydantoin, the mean biologic alf‐life of diphenylhydantoin increased from 25 hours to 55 hours. In patients taking both drugs simultaneously, elevated plasma concentrations of diphenylhydantoin could account for the increased anticonvulsant effects observed.
The physiological disposition of the carcinostatic 1,3‐bis(2‐chloroethyU‐l‐nitrosourea (BCNU) in man and animals
Authors: DeVita Vincent T. , Denham Charlene , Davidson Jack D. , Oliverio Vincent T.
Published: January 2016

The pharmacology of BCNU, an active antitumor agent in animal and man, was studied with the use of the C14‐labeled drug. Radioactivity was excreted slowly in man and monkeys and rapidly in mice. Urinary excretion accounted for the maior portion of the isotope although as much as ten per cent was excreted as CO,. The compound is rapidly degraded and promptly after administration no intact drug is demonstrable, although plasma levels of the isotope are prolonged by protein binding of a portion of the drug. Part of the drug may be recirculated in the bile and partially accounts for the prolonged plasma levels. The drug is stable in an acid milieu and well absorbed orally. Its high lipid solubility allows it to readily cross the blood‐brain barrier. The active moiety of this agent is still unknown. The contrast of the short biologic half‐life of intact BCNU to the delayed clinical toxicity and prolonged plasma levels of carbon‐14 is interesting.
Placental transmission of colistimethate
Authors: MacAulay M. A. , Charles D.
Published: January 2016

When injected intravenously in a single 150 mg. dose, the polypeptide colistimethate passes from the mother to the fetus. No toxic effects were encountered with the single dose, in either the mothers or in the fetuses. Colistimethate is not found in the amniotic fluid within 3 hours after intravenous administration to the mother but later observations were not made. One fifth to one quarter of the total colistimethate injected into the amniotic fluid, of patients not in labor, is present after 18 hours; detectable maternal blood levels are notobtained until approximately 2 hours after injection. Barely detectable concentrations (ca approximately 0.45 /Lg per milliliter) of colistimethate are maintained in the mother from 2 to 7 hours, and similar levels have been found in newborns delivered 6 and 20 hours after injection into the amniotic sac. The possible use of colistimethate in the prevention of intrauterine infection and possible toxic effects are discussed.