bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of drugs on ocular counterrolling
Authors: Miller Earl F. , Graybiel Ashton
Published: January 2016

To determine the temporal effect of several drugs and placebo on ocular counterrolling, a specific indicator of otolith activity, measurements under controlled conditions were made before and at various times after oral administration. Nine normal subjects participated, and from 4 to 6 subjects participated in each experimental trial. Alcohol, 1 c.c. per pound of body weight, had a marked and progressive depressant effect on the amount of eye roll during the intoxication period; complete recovery was recorded 6 hours after its ingestion. Scopolamine, meclizine, acetylsalicylic acid, meprobamate, chlordiazepoxide hydrochloride, d‐amphetamine, and diphenidol, given in twice the usually recommended doses, had little or no effect.
Clinical use of psychotherapeutic drugs: Current status
Authors: Hollister Leo E.
Published: January 2016

The clinical efficacy of present psychotherapeutic drugs varies among the various types. Antianxiety agents are most controversial, as a great many confounding, metapharmacological variables influence the results obtained. The use of such drugs in traditional doses and dosage schedules also may not employ them to best advantage. Antidepressants must increasingly be considered in relation to the clinical type of depressive reaction being treated. Tricyclic drugs are clearly indicated for retarded or endogenous depressions; in exceptional cases, monoamine oxidase inhibitors may merit a trial in such patients. Depressions characterized by much attendant anxiety may respond better to phenothiazines or to antianxiety agents. Consequently, the scope of “antidepressants” may be larger than simply one or two drug classes. Antipsychotics are clearly effective. A large number of peer drugs are available, although it seems clear that, for reasons still to be elucidated, individual patients may respond better to one than to another. Drug therapy of other types of psychiatric disorder, such as mental retardation, childhood and adolescent behavior disorders, alcoholism, and psychoses associated with old age, is of limited value. Lithium salts may represent a significant advance in the management and prevention of manic attacks.
Response of experimental pain to analgesic drugs; III. Codeine, aspirin, secobarbital, and placebo
Authors: Wolff B. Berthold , Kantor Thomas G. , Jarvik Murray E. , Laska Eugene
Published: January 2016

In previous studies16, 17 we demonstrated that the response to experimentally induced pain in man could be modified by morphine and codeine, but we were unable to show any significant effects of aspirin. In both studies, electrical stimulation of two fingers and ice‐water (cold‐pressor) stimulation of each hand were used to induce pain. Both techniques permit the direct observation of two pain response parameters, pain threshold (minimal pain) and pain tolerance (maximal stimulus intensity tolerated). A third parameter, pain sensitivity range (PSR), the difference between pain tolerance and pain threshold, can also be calculated.
Cephaloglycin: Crossover absorption studies and clinical evaluation
Authors: Perkins Robert L. , Glontz Gary E. , Saslaw Samuel
Published: January 2016

Studies with volunteers on oral administration of cephaloglycin resulted in low serum but higher urinary concentrations. Although some absorption was observed with orally administered cephaloridine, serum levels were shorter in duration and urine concentrations were lower than those observed with cephaloglycin. Clinical evaluation indicated that cephaloglycin was effective in only 13 of 20 patients with acute lower respiratory infections, and the treatment failures observed in the present study suggest that it should not generally be used as a primary antibacterial agent for such infections. Despite the relatively high urinary concentrations observed after oral administration of cephaloglycin, 10 of 14 patients with chronic urinary tract infections exhibited treatment failures, possibly related in part to the presence of obstructive uropathy, urinary retention, or calculi.
Comparative evaluation of Rauwolfia whole root and reserpine
Authors: Smith W. M. , Thurm R. H. , Bromer L.
Published: January 2016

To compare the antihypertensive effect of a Rauwolfia whole root‐chlorothiazide combination with reserpine plus chlorothiazide, subjects were selected who had average diastolic pressures of 90 mm. Hg or more at home, in the sitting position. In a double‐blind study providing 3 months on each regimen with a 6 week placebo period intervening, no significant difference in antihypertensive effect was demonstrated between the whole root Rauwolfia‐chlorothiazide combination and the reserpine plus chlorothiazide.
request for quack treatment
Authors: Mainland Donald
Published: January 2016

About three years ago I received the following request from a pathologist:
Metabolic disposition of diphenylhydantoin in normal human subiects following intravenous administration
Authors: Glazko A. J. , Chang T. , Baukema J. , Dill W. A. , Goulet J. R.
Published: January 2016

Plasma levels of diphenylhydantoin and the urinary excretion of its hydroxylated metabolite were studied in 6 normal adults following single intravenous doses of 0.25 Gm. DPH‐sodium. The high initial plasma levels dropped rapidly to a mean value of 6.3 µg per milliliter 20 minutes after dosing and 5.2 µg per milliliter in one hour; the plasma half‐life in later time periods was about 15 hours (range 11 to 29 hours). Urinary excretion of free and conjugated HPPH in 5 of the 6 subjects, measured by a new gas‐chromatography procedure, accounted for 76 per cent of the dose (range 65 to 81 per cent) over a period of 5 days. Approximately one third of the administered dose was accounted for by urinary excretion in the first 24 hours, with diminishing amounts being excreted thereafter over periods of 4 to 5 days or more. The maximum excretion rate of HPPH was found to occur about 6 to 8 hours after the intravenous dose, presumably due to an initial delay in the enzymatic processes of hydroxylation or conjugation prior to excretion of the metabolite.
Urinary drug excretion in man during oral dosage of different nitrofurantoin formulations
Authors: Conklin John D. , Hailey Francis J.
Published: January 2016

Nitrofurantoin, a urinary tract antibacterial agent, was administered orally to human subiects in a therapeutic dose regimen for 7 days in microcrystalline form in a tablet or in macrocrystalline form in a capsule. The urine consistently contained substantial amounts of nitrofurantoin in each case, although the drug was not detectable in any of the blood samples collected during the study. Even though significantly greater urinary drug recoveries were obtained after the tablet than after the macrocrystalline drug, both formulations yielded adequate amounts of the drug in urine for potential antibacterial effectiveness. The differences in urinary drug recovery and in urinary drug‐excretion patterns between the two formulations suggests a slower rate of absorption of the macrocrystals in a capsule than of the microcrystalline form in a tablet.
Effect of antimalarial drugs and collection methods on urinary and plasma 17‐hydroxycorticosteroid determinations
Authors: Gilliland Paul F. , Brooks Marion H. , Bruton Joseph , Barry Kevin G.
Published: January 2016

Quinine, chloroquine, pyrimethamine, and sulforthodimethoxine, in concentrations comparable with levels observed in human plasma during therapeutic administration of these drugs, do not interfere with the Peterson method of determination of plasma 17‐hydroxycorticosteroids. Quinine concentrations achieved during administration to human beings do not interfere with determination of urinary 17‐hydroxycorticosteroids by a modified Porter‐Silber method.
The relationship between the plasma concentration of free nicotinic acid and some of its pharmacologic effects in man
Authors: Svedmyr Nils , Harthon Lennart , Lundholm Lennart
Published: January 2016

Nicotinic acid was infused intravenously in healthy human beings in doses between 0.01 and 0.1 mg. per kilogram per minute for 20 to 180 minutes. The relationship between pharmacologic action and blood concentration of nicotinic acid was investigated. An increase of free nicotinic acid in plasma by 0.1 to 0.4 µg per milliliter was accompanied by increased blood flow through the hand, which maximally amounted to 75 per cent, and a 100 per cent increase in blood flow through the muscle. The pulse rate increased, but there was no change in blood pressure. The blood concentrations of free fatty acids and glucose decreased. Flushing of the face and neck persisted as long as the plasma nicotinic acid increased but disappeared when a constant level was reached. The intensity of the remaining pharmacologic effects were only initially correlated to the flushing. A fivefold increase of the dose of infused nicotinic acid (0.05 to 0.07 mg. per kilogram per minute) induced a proportional increase of the plasma concentration. The muscle blood flow was considerably increased (200 per cent) by the higher dose, but the other effects were not significantly changed. The total concentration of pyridine compounds in whole blood increased during the infusion, parallel with plasma nicotinic acid, but decreased more slowly than the free nicotinic acid after the infusion, still being elevated when the pharmacological effects had disappeared. The mechanism of the vasodilating effect of nicotinic acid is discussed.
Interactions of levallorphan and meperidine
Authors: Rouge Jean‐Claude , Banner Marc P. , Smith Theodore C.
Published: January 2016

The respiratory effects of meperidine and levallorphan mixtures were studied in 5 healthy volunteers. The majority of pulmonary function tests and gas uptake studies gave either no evidence of change or only changes typical of opioids in general. Meperidine, 1.65 mg. per kilogram, intramuscularly, increased the end‐tidal CO2 tension by 6 torr with concommitant reduction in minute ventilation. Addition of levallorphan, 0.01, 0.02, or 0.04 mg. per kilogram caused only greater sedation. Even the sensitive test of ventilatory response to carbon dioxide challenge failed to distinguish mixtures of meperidine and levallorphan. During periods of controlled, elevated alveolar CO2 tension (48 ± 1 torr), meperidine, 1.1 mg. per kilogram, intravenously, depressed respiration 8 L. per minute. This depression was not significantly prevented or antagonized by levallorphan (0.014 mg. per kilogram). Levallorphan, 1.0 mg., produced respiratory depression equivalent to that produced by 40 mg. of meperidine. The interaction of the two is compatible with the hypothesis of competitive dualism.
Metabolism and excretion of pentazocine in man
Authors: Berkowitz Barry , Way E. Leong
Published: January 2016

A spectrophotofluorometric method has been developed which allows estimation of pentazocine in the urine in the presence of a fluorescent metabolite at drug concentrations as low as 0.2 µg per ml. Urinary excretion of the drug was followed for 24 hours after oral and intramuscular doses of pentazocine. Pentazocine was found to be extensively metabolized; less than 13 per cent of the dose appeared in the urine as unchanged pentazocine. Between 12 and 30 per cent was excreted as a glucuronide coniugate, and at least one other unidentified polar metabolite was detected. The maior portion of pentazocine and metabolites was excreted in the first 12 hours. Prolonged side effects noted in 2 subiects did not appear to correlate with the excretion of pentazocine or its metabolites.
The human platelet as a pharmacologic model for the adrenergic neuron
Authors: Abrams William B. , Solomon Harvey M.
Published: January 2016

The uptake of norepinephrine (NE) by the human platelet resembles that of the adrenergic neuron. Platelets incubated with d1‐14C‐NE (2.1 x 10−6M) for one hour at 37° C. concentrated the amine to a distribution ratio of 5.1 ± 0.1. Uptake was markedly reduced by cold and metabolic inhibitors such as cyanide, fluoride, dinitrophenol, and PCMB. NE uptake was also diminished by ouabain, quinidine, and substitution of lithium for sodium in the medium, suggesting the uptake mechanism is related to a sodium pump. Drugs which interfere with the uptake of NE by the neuron have a similar effect on the platelet. Uptake of 14C‐NE was impaired by serotonin (5HT), tryptamine, tyramine, amphetamine, bretylium, debrisoquin, guanethidine, desmethylimipramine, and various antihistamines. 14C‐NE accumulated in the platelet by a preliminary incubation was released by reserpine, tyramine, phenylephrine, and debrisoquin, less by guanethidine, but not by ephedrine or mephentermine. 14C‐5HT was released by reserpine, tyramine, debrisoquin, and mephentermine, less by ephedrine, but not by guanethidine or phenylephrine. Thus, release or failure of release of NE or 5HT from platelets will not necessarily reflect the action of a drug on sympathetic neurons.
Inhibition of aspirin absorption by activated charcoal and apomorphine
Authors: Decker Walter J. , Shpall Robert A. , Corby Donald G. , Combs Harold F. , Payne Carl E.
Published: January 2016

Oral administration of 30 Gm. of activated charcoal to adult male volunteers 30 minutes after they had received 50 grains of aspirin resulted in a serum salicylate concentration 50 per cent of that of a control group. Vomiting induced by apomorphine also resulted in a similar difference. The use of both charcoal and induced emesis simultaneously caused a greater reduction in serum salicylate concentration than either measure alone.
Pathogenesis of hypertension and implications for its therapeutic management
Authors: Grollman Arthur
Published: January 2016

Excluding elevations in blood pressure secondary to primary hemodynamic changes and the relatively rare disorders in which hypertension is an accompaniment of extrarenal disturbances, hypertensive cardiovascular disease is attributable to dysfunction of the kidney. In a small group of patients, the elevation in blood pressure is mediated or intensified by a circulating pressor agent secreted by the kidney and detectable in the untreated plasma of the renal venous effluent. This unidentified pressor agent differs from renin and angiotensin, neither of which plays a primary role in the pathogenesis of renal hypertension. Most cases of chronic hypertension, including essential hypertension, are attributable to the loss of a normal renal function concerned in the maintenance of the normotensive state. This fuction appears to be humoral in nature, and replacement therapy with this humoral agent affords the prospect of a rational approach to the effective therapy of essential and related forms of hypertensive cardiovascular disease.
Clinical pharmacology of beta‐receptor‐blocking drugs
Authors: Dollery C.T. , Paterson J.W. , Conolly M.E.
Published: January 2016

In the short period of time since their introduction into clinical practice, almost 1,000 scientific papers have been written concerning beta‐receptor‐blocking drugs. This review does not cover the whole of this literature as it is particularly concerned with the effects of beta‐blocking drugs in man. To simplify presentation the review is divided into six main sections. The first deals with the nature of beta blockade and the second with structure activity relationships among beta‐blocking drugs. The third section is an account of the pharmacology of beta‐blocking drugs, mainly from the standpoint of their action on vascular, bronchial, and cardiac muscle and is chiefly derived from animal data. The fourth section deals with the clinical pharmacology, particularly circulatory and metabolic aspects, but it also includes some relevant animal data, especially that concerned with metabolic effects. The fifth and largest section deals with the clinical use of beta‐blocking drugs. The final section summarizes the adverse reactions so far reported with these drugs.
EMTP in obesity
Authors: SedgWick J. P.
Published: January 2016

I have just completed reading the paper "Toxic and therapeutic effects of EMTP in obesity," by Hollingsworth and Amatruda, in your JOURNAL (10:540‐542,1969).
Cytarabine (Cytosar)
Authors:   The Upjohn Company
Published: January 2016

Warning. Only physicians experienced in cancer chemotherapy should use Cytosar. For induction therapy patients should be hospitalized in a facility with laboratory and supportive resources sufficient to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The main toxic effect of Cytosar is bone marrow suppression with leukopenia, thrombocytopenia and anemia. Less serious toxicity includes nausea, vomiting, diarrhea and abdominal pain, oral ulceration, and possibly hepatic dysfunction. The physician must judge possible benefit to his patient against known toxic effects of this drug in considering the advisability of therapy with Cytosar. He should be familiar with the following text before making this judgement or beginning treatment.
The effect of heat, cold, and work on the central actions of scopolamine
Authors: Safer Daniel J.
Published: January 2016

Forty‐eight healthy male volunteers were tested in drug‐alone (D), drug‐and‐work (D‐and‐W), and work‐alone (W) groups at 40°,70°,85°, and 95° F. and in a drug‐alone group at 1050 F. to measure the separate and combined effects of work and temperature stress on the central actions of scopolamine hydrobromide. The dose of scopolamine was the same for all drugged men, 10 mg. per kilogram. The degree of work (walking a 10 per cent inclined treadmill at 3 miles per hour for 2 hours) was also the same for all subjects tested under stress. Performance and rating tests were used to measure memory function, behavioral variations, attention, and manual dexterity. MaioI' findings were as follows: Mental and motor impairments induced by a low deliriant dose of scopolamine were significantly increased in ambient temperatures of 95° F. and 105° F.; work increased the psychotomimetic effects of scopolamine only at 95° F. (the highest temperature tested with drug‐and‐work group); an initial 90 minute period of elevated ambient temperature (1050 F.) was decisive for the accentuation of the central effects of scopolamine. 1t was also noted that the increase in peripheral blood flow caused by scopolamine was most apparent at temperature extremes and that the central effects of the heat‐drug stress showed no relationship to body temperature.
Effects of SU‐13437 on serum lipids in hyperlipoproteinemic patients
Authors: Weiss Peter , Dujovne Carlos A. , Margolis Simeon , Lasagna Louis , Bianchine Joseph R.
Published: January 2016

The ability of a tetralin phenoxy isobutyrate, SU‐13437, to lower serum lipids was compared with that of a matching placebo in a double‐blind crossover study. Treatment with SU‐13437 for 4 weeks lowered serum cholesterol by 23 per cent in hypercholesterolemic patients, and it lowered serum triglycerides by 68 per cent in hypertriglyceridemic patients. None of the patients failed to respond to treatment. Gastrointestinal upset was seen in 2 of the 29 patients, and one patient had transient elevation of serum glutamic oxaloacetic transaminase.
Chloramphenicol‐associated encephalopathy
Authors: Levine Paul H. , Regelson William , Holland James F.
Published: January 2016

Three cases of toxic delirium associated with oral chloramphenicol are reported. In two of the cases, symptoms disappeared with cessation of chloramphenicol and reappeared when treatment was resumed. The appearance of chloramphenicol‐associated encephalopathy after oral but not after parenteral medication at the same dosage suggests that altered hepatic function related to higher‐portal drug concentration may be responsible. Such dysfunction may depend on inhibition of synthesis of hepatic enzymes involved in biochemical processes necessary for normal brain function. An alternative possibility is a direct effect on brain cells.
Atropine metabolism in man
Authors: Kaiser Sarah C. , McLain Paul L.
Published: January 2016

Administration of two ¼C‐tropine‐labeled atropines to man shows the urinary excretion of 77 to 93 per cent of the injected dose in 24 hours. Only the N‐methyl‐¼C but not the 2,4‐14C‐atropine shows oxidation to HCO, with arespiratory elimination of 3 per cent in 3 hours. Atropine disappears very rapidly from the blood. Urinary excretion 01)er the first 24 hours occurs at two rates; a fast rate occurring first with a t½. of about 2 hours and a slow rate with a t½ of ab out 13 to 38 hours. The early urine samples show the major fraction of the HC existing as a chromatographic component which is a α‐glucuronide., The urines collected at later periods (4 to 8 hours) contain little, if any, of this component. The chromatographically distinguishable ¼C‐containing urinary components do not differ between the two HC‐atropines.
Gentamicin sulfate distribution in body fluids
Authors: Rodriguez Victorio , Stewart Oorothy , Bodey Gerald P.
Published: January 2016

Pharmacological studies were conducted on patients receiving gentamicin sulfate intravenously. The mean peak serum level was 4.5 P,g per milliliter after the administration of 40 mg. per square meter gentamicin sulfate. The serum half‐life was approximately 2 hours and the decrease was exponential. There was no evidence of drug accumulation when administered at a dose of 30 mg. per square meter every 6 hours over a 10 day period. The concentration of gentamicin in thoracic duct lymph paralleled the simultaneous serum concentration. The drug did not diffuse readily into the cerebrospinal fluid. The intravenous administration of gentamicin was well tolerated and no unexpected toxicity was observed.
Book reviews
Authors: Modell Walter
Published: January 2016

Introduction to General Phannacology, T. Z. Csaky. New York, 1969, AppletonCentury‐ Crofts, Inc., 249 pages. $5.95.
Effect of tetracycline, polymyxin B, and rifampin on phagocytosis
Authors: Hoeprich Paul D. , Martin Catherine H.
Published: January 2016

Tetracycline, polymyxin B, and rifampin (an investigational, semisynthetic antibiotic) did not affect engulfment or intraleukocyte killing of bacteria by leukocytes derived from the peripheral blood of normal volunteers. The augury of unimpaired phagocytic function in the infected human being under treatment with either of these agents has clinical support.
Reply to a short‐sighted Editorial and to an odd stance
Authors: Wolff Frederick
Published: January 2016

Things have come to a sorrow pass when two of the foundling fathers of Clinical Pharmacology turn against the very basis of their discipline, and if one of them issues a vituperative attack on the strongest support, albeit imperfect, which this discipline has so far received.
Comparisons of effects of morphine, meperidine, fentanyl, and fentanyl‐droperidol
Authors: Ordy J. M. , Kretchmer H. E. , Gorry T. H. , Hershberger T. J.
Published: January 2016

The specific aims of the double‐blind study were to compare the analgesic effectiveness of morphine (10 mg. per milliliter), meperidine (75 mg. per milliliter), fentanyl (0.1 mg. per milliliter), and fentanyl‐droperidol (0.1 to 2.5 mg. per milliliter) in patients subjected to routine medical and dental procedures at a metropolitan general hospital. The (4 x 3) analysis of variance design included the 4 drugs with observations on analgesia, vital signs, and blood chemistry 15, 30, or 45 minutes after drug infection. No significant differences in degree of relief from pain were observed among the 4 drugs or the 3 postinjection intervals. There was a significant interaction in the degree of relief by the 4 drugs with the 3 postinjection time intervals. The fentanyl‐droperidol combination provided a greater and more prompt degree of relief at 15 than at 30 or 45 minutes. Significant differences were not observed in manifest anxiety or frequency of nausea among the patients. No Significant differences were observed in vital signs, blood protein, glucose, cholesterol, or corticosterone levels among the 4 drug groups. Significant differences in blood glucose, cholesterol, and corticosterone were noted among the 3 postinjection time intervals.
Displacement of warfarin from human albumin by diazoxide and ethacrynic, mefenamic, and nalidixic acids
Authors: Sellers Edward M. , Weser Jan Koch
Published: January 2016

Large doses of drugs that are highly bound to proteins can displace coumarin anticoagulants from plasma proteins and thereby potentiate anticoagulation. Mefenamic acid, ethacrynic acid, nalidixoic acid, and diazoxide displace significant amounts of warfarin from human albumin in vitro by a noncompetitive mechanism. The relative potency of these displacing agents is: mefenamic acid > ethacrynic acid > diazoxide > nalidixic acid. If this effect occw's in vivo, clinical use of these drugs would cause an increase of 66 to 400 per cent in free active warfarin and make it necessary to reduce anticoagulant dosage in order to prevent excessive hypoprothrombinemia and hemorrhage.
Comparative beta‐blocking activities and effects on sodium excretion of sotalol and propranolol
Authors: Rice A. J. , Ferguson R. K. , Delle M. , Wilson W. R.
Published: January 2016

This study compares beta‐blocking effects and effects on urinary sodium excretion of propranolol and sotalol, a new beta blocker. All subjects received a liquid, 100 mEq. sodium diet. Acute effects were studied in 4 normal men who received graded daily doses (5 to 1,280 mg. orally) of the 2 beta blockers after a control period in a crossover design. Subacute effects were studied in 2 groups of 6 men who received 2 doses of each drug for 4 days. Both propranolol and sotalol produced dose‐related attenuation of the increases in heart rate and decreases in diastolic blood pressure during isoproterenol infusions. Neither drug appreciably altered 24 hour urinary sodium, potassium, or creatinine excretion. Both drugs reversed the day‐night ratio of urinary sodium excretion, but propranolol produced this effect at a lower dose level than sotalol. Reversal of the day‐night ratio was not dose related with either drug and could not be directly correlated with beta blockade.
Penetration of clindamycin into synovial fluid
Authors: Plott Michael A. , Roth Henry
Published: January 2016

The new antibiotic, clindamycin, was administered to 15 patients with joint effusions. Synovial fluid samples obtained at various intervals were analyzed for clindamycin. Results indicate good penetration of clindamycin into the synovial space which appears to be independent of local inflammation.
Procarbazine hydrochloride capsules (Matulane)
Authors:   Roche Laboratories
Published: January 2016

A new type of chemotherapeutic agent for the palliative treatment of Hodgkin's disease
Role of corticosteroids in the treatment of circulatory collapse states
Authors: Lefer Allan M. , Verrier Richard L.
Published: January 2016

Corticosteroids are hormones which exert effects on virtually every organ and tissue and thereby play a key role in preserving and maintaining homeostasis. 154 In particular, corticosteroids exert prominent effects on the cardiovascular system. 65, 66 The circulatory effects of the orticosteroids have been under investigation since 1849 when Addison 2 recognized that cardiovascular collapse was a prominent feature of adrenal insufficiency. However, it has only been within the last twenty years that corticosteroids have been available in pure form, thereby permitting an investigation of their effects. The cardiovascular effects of corticosteroids are of considerable interest because hypotension is a prominent feature in adrenocortical insufficiency, and hypertension occurs in hypersecretion of adrenal corticosteroids. Furthermore, corticosteroids have been widely used in the treatment of a variety of states of circulatory shock. The particular emphasis of this review will be to discuss, in terms of recent developments in the field, the basic physiologic and pharmacologic mechanisms by means of which corticosteroids exert their cardiovascular effects in shock states. Several new findings necessitate a significant shift in our thinking about the circulatory effects of the corticosteroids.
Effect of L‐dopa alone and in combination with an extracerebral decarboxylase inhibitor on blood pressure and some cardiovascular reflexes
Authors: Watanabe A. M. , Chase T. N. , Cardon P. V.
Published: January 2016

L‐Dopa produced a significant reduction in recumbent and standing blood pressure in patients with neurologic or psychiatric disorders. The addition of an extracerebral decarboxylase inhibitor potentiated this effect. Reflex forearm arteriolar and venous constriction was present during therapy with L‐dopa alone or in combination with the decarboxylase inhibitor, but there was an attenuation of reflex forearm arteriolar constriction. It is suggested that the hypotensive effect of L‐dopa may be mediated through the central nervous system.
Ketamine hydrochloride (Ketalar)
Authors: Davis Parke
Published: January 2016

Ketalar is a nonbarbiturate anesthetic chemically designated dl 2‐ ( o‐chlorophenyl) ‐2‐ (methylamino) cyclohexanone hydrochloride. It is formulated as a slightly acid (pH 3.5–5.5) solution for intravenous or intramuscular injection in concentrations containing the equivalent of either 10 or 50 mg. ketamine base per ml. and contains 1: 10,000 Phemerol (benzethonillm chloride) as a preservative. The 10 mg. per ml. solution has been made isotonic with sodium chloride.
Closed designs for sequential clinical trials
Authors: Becktel Jack M.
Published: January 2016

A collection of new closed sequential designs applicable to clinical trials with the paired preference technique is presented. The designs are simple, consisting of two intersecting straight lines. No advantage other than simplicity is claimed over designs such as those of Bross and Armitage when comparable designs are available, but a broader selection of risk and probability levels is prOVided.
I‐Dopa in the treatment of parkinsonism
Authors: Calne D. B.
Published: January 2016

Clinical experience over the last decade indicates that 1‐3,4‐dihydroxyphenylalanine (l‐dopa, levodopa) may replace other forms of medical and surgical treatment in a substantial proportion of parkinsonian patients. This therapeutic development has arisen from the application of new concepts derived from a wide range of neuro‐pharmacological investigations. In this review the subject will be considered in the following stages: pharmacological background; therapeutic effects; adverse reactions; pharmacokinetics; other drugs modifying dopaminergic function.
Standard oral water load to determine the site of action of diuretics in man With data on metolazone, a new diuretic
Authors: Michelis Michael F. , DeRubertis Frederick , Beck Nama P. , McDonald Robert H. , Davis Bernard B.
Published: January 2016

Two male volunteers were given metolazone, a new diuretic, intravenously during a stable protracted water diuresis. The drug caused a mean decrease in CH2O of 2.8 c.c. per minute, a mean increase in sodium excretion of 419.5 μEq. per minute and no Significant change in urine flow rate or clearance of either inulin or PAH. The data suggested that metolazone affects the diluting segment of the nephron reducing the ability to clear free water. Five volunteers were given a standard water load with and without metolazone 10 mg. orally. The data revealed that total free water cleared in the 4 hours following the administration of water decreased (387.6 C.c. S.E. ± 73.9, P < 0.02), while osmols cleared increased (546.6 C.c., S.E. ± 106.7, P < 0.01) and sodium excretion increased (60.6 mEq., S.E. ± 10.5, P < 0.01). Urine volumes and potassium excretion were unchanged. Similar studies with oral water loads given to 4 volunteers who were also given 50 mg. of hydrochlorothiazide, which acts on the diluting segment of the nephron, produced changes such as those seen with metolazone. The data suggest, therefore, that metolazone, like hydrochlorothiazide, acts on the diluting segment of the nephron and that the standard oral water load is an accurate and convenient means of determining the site of action of diuretics.
Comparative clinical therapeutic trial with two hypolipidemic drugs: Clofibrate and nafenopin
Authors: Dujovne Carlos A. , Weiss Peter , Bianchine Joseph R.
Published: January 2016

The effects of clofibrate and nafenopin were compared in hyperlipidemic patients. Each patient was randomly assigned to take one of the drugs first for 12 weeks followed by the other drug for approximately the same period. The two drugs reduced serum cholesterol and triglyceride in all 15 patients who completed the study. No statistically significant differences in the effects of the two drugs were seen. With nafenopin the maximum hypotriglyceridemic effect was at one month; subsequently there was a slight but progressive increase in serum triglycerides. Clofibrate progressively decreased serum triglycerides. One subject developed marked hypertransaminasemia while receiving nafenopin and was withdrawn from the study. Changes from base Zine in the serum transaminases and alkaline phosphatase in some patients are described and discussed.
A Companion To Medieal Studies
Authors: Modell Walter
Published: January 2016

R. Passmore, M.A., D.M., and J. S. Robson, M.D., F.R.C.P., editors. Philadelphia, 1969, F. A. Davis Company, vol. 1, Anatomy, Biochemistry, Physiology, and Related Subjects. 1142 pages. $16.00. vol. 2, General Pathology and Pharmacology. 700 pages. $16.00.
Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine
Authors: Hollister Leo E.
Published: January 2016

Two separate experiments indicated that in most subjects, after oral administration of marihuana, total food intake, as well as reports of hunger and appetite, are increased. Drugs, such as dextroamphetamine and, to a lesser extent, alcohol reduced food consumption and appetite. Stimulation of appetite by marihuana is by no means invariable, occurring in only slightly more than half the subjects. Similar variations between individuals were observed in the case of responses to dextroamphetamine and alcohol.
The influence of urinary pH on the plasma half‐life of pseudoephedrine in man and dog and a sensitive assay for its determination in human plasma
Authors: Kuntzman Ronald G. , Tsa Irene , Brand Leonard , Mark Lester C.
Published: January 2016

A sensitive method has been developed which allows estimation of pseudoephedrine in plasma at drug concentrations as low as 0.05 fLg per milliliter, making possible, for the first time, the measurement of pseudoephedrine in human plasma. In 3 normal volunteers, the plasma ty, of pseudoephedrine was 5.2,7.6, and 8.0 hours, respectively. When urinary pR was decreased by the administration of NR,Cl, the plasma ty, of pseudoephedrine decreased markedly. In contrast, when urinary pR was increased by the ingestion of NaRCOs, the plasma ty, of pseudoephedrine increased.
The pharmacokinetics of daunomycin in man
Authors: Alberts David S. , Bachur Nicholas R. , Holtzman Jordan L.
Published: January 2016

Through the use of fluorescence assay methods, the plasma levels, urinary excretion, and tissue levels of daunomycin and its fluorescent metabolites were determined in patients treated with this drug for disseminated solid malignancies. The patients received daunomycin in a single rapid intravenous dose at 80 mg. per square meter and 120 mg. per square meter. Fluorescence studies showed the short plasma half‐life to be 0.75 hours, the long plasma half‐life to be 55 hours, the apparent volume of distribution to be ab out 1,000 L., and the relative volume of distribution to be 580 L. per square meter. Drug and fluorescent metabolites in urine averaged 13 to 14 per cent of the total dosage in 7 days. Tritiated daunomycin was used, but isotopic assay produced values different from those with fluorescence assay. These were interpreted to be the result of tritium exchange or metabolism of the daunomycin. Daunomycin fluorescence was detected in autopsy specimens 16 and 19 hours after administration, with the highest levels in kidney, spleen, liver, and lung. The fluorescent species extracted from both plasma and urine consisted predominantly of daunomycin (D1) and daunomycin metabolite (D2), although small amounts of the aglycones were detected. It is proposed that, because of the long half‐life of daunomycin, the current treatment schedule be revised to a single intravenous dose.
Genetic and environmental factors affecting ethanol metabolism in man
Authors: Vesell Elliot S. , Page John G. , Passananti G. Thomas
Published: January 2016

The relative contribution of genetic and environmental factors to maintaining twofold differences in rates of ethanol elimination from plasma was examined in 14 sets of nonmedicated, nonhospitalized healthy twins. After a single oral dose of 1 ml. per kilogram of 95 per cent ethanol, intrapair differences in rates of elimination were less in identical than in fraternal twins. Thew results indicate that individual differences in rates of ethanol elimination among the 28 twins were genetically controlled and that environmental factors played a negligible role. In 6 prisoners in solitary confinement, rates of ethanol metabolism increased in 3 but declined in the remaining 3 after 21 days of ethanol administration. Rates of antipyrine elimination from plasma were accelerated by ethanol administration in each of the 6 volunteers. Considerable individual variation occurred in the degree to which ethanol shortened plasma antipyrine half‐lifes; reduction ranged from 4 to 37 per cent of the initial antipyrine half‐life. These results suggest that ethanol administration for 21 days at this dosage fails to alter consistently the rate of its own metabolism but increases antipyrine metabolism in all subjects to varying extents.
Plasma DOPA response to levodopa administration in man: Effects of a peripheral decarboxylase inhibitor
Authors: Dunner David L. , Keith H. , Brodie H. , Goodwin Frederick K.
Published: January 2016

Plasma DOPA leveLy were determined in depressed patients at various times after oral administration of levodopa with and without a peripheral decarboxylase inhibitor, D,L‐alpha‐methyl‐dopa‐hydrazine (MK‐485). Pretreatment with MK‐485 caused an approximately tenfold increase in the peak plasma leveLs following a DOPA load. Equivalent plasma levels were achieved with 1/10 the dose of levodopa with use of MK‐485. A significant prolongation of the half‐life of the amino acid in the plasma was aLYo achieved. The increase of plasma DOPA leveLs with MK‐485 is in the same range as the potentiation of clinical effect with this inhibitor.
Imipramine metabolism: pH‐Dependent distribution and urinary excretion
Authors: Gram Lars F. , Kofod Bent , Christiansen Johannes , Rafaelsen Ole J.
Published: January 2016

The effect of ammonium chloride and sodium bicarbonate administration on urinary excretion of 14C‐imipramine in man and on tissue distribution of 14C‐imipramine in rats has been studied. Oral administration of ammonium chloride to man increased the total excretion of orally administered 14C‐imipramine about 10 to 40 per cent. This increase was due to a 50 to 100 per cent increase in excretion of nonconjugated metabolites. In particular the excretion of unchanged imipramine and desmethylimipramine was sensitive to changes in urinary pH. Compared to sodium chloride‐treated rats, in rats treated with ammonium chloride the uptake of 14C‐imipramine in brain was reduced some 15 per cent.
Predictors of chlordiazepoxide response in anxiety
Authors: Rickels Karl , Downing Robert W. , Howard Kay
Published: January 2016

A step‐search multiple‐regression procedure was employed in an effort to predict treatment response in a group of 111 patients treated with chlordiazepoxide and 201 patients treated with placebo, using as potential predictors several forms of demographic information, assessments of the severity of initial psychopathology, and measures of patient and physician attitude. Patients were drawn from 2 hospital clinic settings and the private practices of several general practitioners and psychiatrists. They participated in a double‐blind drug trial of 4 weeks' duration. All were psychoneurotic and most complained of moderately severe anxiety. Outcome criteria included both a global improvement measure, combining physician ratings of over‐all response to treatment after 2 and 4 weeks, and the 4 week change score of the 10 item physician questionnaire. Treatment differences were highly significant for both improvement measures. Also, for both improvement measures, greater drug‐placebo differences were found in patients who: (1) were more severely ill; (2) were of higher socioeconomic class; and (3) had an illness of 6 months' or more duration. Irrespective of treatment agent, greater improvement was seen in those patients receiving a more favorable prognosis. Several additional variables were predictive for one but not the other measure of improvement, and their implicatiOns, more tentative than those for the more consistent predictors, have been explored.
Lithium carbonate (Eskalith)
Authors:   Smith, Kline & French Laboratories
Published: January 2016

Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy.
Status of the clinical evaluation of levodopa in the treatment of Parkinson's disease and syndrome
Authors: Langrall Harrison M. , Joseph Clifford
Published: January 2016

The effect of levodopa on Parkiruon's disease and syndrome was studied in a total of 1,533 patients according to a protocol for open clinical evaluation. The average daily dose to achieve maximum relief of clinical symptoms with tolerable side effects ranged from between 3.5 and 6.5 Gm. per day given in divided doses. The dosage of levodopa, sometimes administered concomitantly with other antiparkinson agents, was increased slowly in small increments, and dosage regimens were individualized for each patient according to his response. Approximately two thirds of the patients treated achieved a satisfactory resporue, while side effects occurred in over 90 per cent of the patients treated. Improvement in clinical symptomatology was sometimes delayed but continued on long‐term maintenance therapy. Laboratory abnormalities, though frequent, were rarely serious and, to date, are reversible. An additional 3,000 patients were monitored for severe and unusual reactioru and deaths. No death in any of the studies was attributed directly to the administration of the drug; however, experience showed that psychiatric changes masked by Parkinson's disease may manifest themselves in depression with suicidal tendencies as therapeutic doses are approached. It is concluded that, with proper care and careful management, levodopa appears to be a relatively safe and effective agent for the treatment of Parkinson's disease and syndrome.
Glucose, insulin, and free fatty acid metabolism in Parkinson's disease treated with levodopa
Authors: Woert Melvin H. Van , Mueller Peter S.
Published: January 2016

Metabolism of carbohydrate and insulin was evaluated in 24 patients with Parkinson's disease before and during L‐dihydroxyphenylalanine (levodopa) therapy. In the untreated state these patients had low rates of glucose utilization (k) and impaired release of insulin during an intravenous glucose tolerance test (GTT). These abnormalities could not be related to age, diet, or degree of neurological disability. In addition these untreated patients had high fasting serum glucose and free fatty acid (FFA), normal human growth hormone (HGH), and low fasting serum insulin levels. It is proposed that the primary abnormality in carbohydrate‐insulin metabolism observed in these parkinsonian patients is a deficit in pancreatic insulin release. Levodopa treatment did not alter the low k and impaired insulin release. A trend toward more normal fasting serum levels of glucose, insulin, and FFA during levodopa therapy was suggested.
Phenylalanine and tyrosine metabolism in Parkinson's disease treated with levodopa
Authors: Woert Melvin H. Van
Published: January 2016

Plasma levels of phenylalanine and tyrosine were measured before and after oral administration of either phenylalanine (phenylalanine tolerance test and phenylalanine conversion test) or tyrosine (tyrosine tolerance test) in patients with Parkinson's disease before and during L‐dihydroxyphenylalanine (levodopa) therapy. In the untreated parkinsonian patients there was no abnormality in the phenylalanine tolerance test, tyrosine tolerance test, or conversion of phenylalanine to tyrosine. The fasting plasma phenylalanine and tyrosine were normal in Parkinson's disease and were not altered by levodopa therapy. When the last dose of levodopa (1 Gm.) was administered half an hour before the phenylalanine tolerance tests, phenylalanine conversion tests, or tyrosine tolerance tests, the plasma levels of these amino acids were found to be lower at 0.5, 1, and 2 hours. Twelve hours after the last dose of levodopa, the tolerance and conversion tests were normal. Levodopa treatment did not alter the concentration of phenylalanine or tyrosine in the cerebrospinal fluid (esP) of parkinsonian patients. The competition of levodopa with phenylalanine and tyrosine for intestinal transport pathways is probably the maior effect of levodopa therapy on the metabolism of these amino acids.
Interaction of warfarin and nonsystemic gastrointestinal drugs
Authors: Robinson Donald S. , Benjamin David M. , McCormack John J.
Published: January 2016

The absorption and pharmacologic action of warfarin may be influenced by such factors as gut motility, pH, solubility, and chemical binding. To investigate the possible interaction of warfarin with nonsystemic gastrointestinal drugs in clinical use, (1) cholestyramine, (2) an antacid mixture containing magnesium and aluminum hydroxide, and (3) psyllium hydrophyllic mucilloid were studied in 6 normal subjects. In a series of experiments average therapeutic doses of each drug were administered concurrently with a single oral dose of warfarin 40 mg. Cholestyramine was found to decrease significantly mean plasma warfarin levels and the hypoprothrombinemic effect of warfarin even after a 3 hour interval between ingestion of the two drugs. Neither the antacid nor psyllium colloid was found to alter plasma concentrations or pharmacologic action of warfarin. In vitro experiments demonstrated significant binding of warfarin to cholestyramine at a pH above its pKa of 5.5.
Gas chromatography‐mass spectrometry of nortriptyline in body fluids of man
Authors: Hammar Carl-Gustaf , Alexanderson Balzar , Holmstedt Bo , Sjôqvist Folke
Published: January 2016

The application of the mass fragmentographic technique has aUowed accurate identification of a tricyclic antidepressant drug, nortriptyline, and some of its metabolites in biological fluids from patients treated with therapeutic doses and from one patient intoxicated with the same drug. Mass fragmentography in combination with the scanning of mass spectra of compoundy eluted from the gas chromatography column made it possible to identify nortriptyline and the metabolites, desmethylnortriptyline, 10‐hydroxynortriptyline, and, tentatively, 10‐hydroxydesmethylnortriptyline.
Once more‐On the extraordinary side effects of drugs
Authors: Kupfer David J. , Detre Thomas P.
Published: January 2016

A concise self‐administered questionnaire is described which elicits responses to 40 symptoms usually attributed to psychotropic drugs. The relationship of such symptoms to age, sex, and education leoels in a group of newly admitted psychiatrie outpatients is examined. The symptoms most frequently reported correlate significantly with a standardized self‐rating system form (KDS), suggesting that certain pretreatment symptoms may be somatic concomitants of the patient's illness. It is proposed that the determination of pretreatment incidence of all somatic and psychological symptoms that may be attributed to the administration of drugs is a necessary step in conducting clinical drug trials.