bluuebunny/crossref_metadata_2025 huggingface dataset:
Disappearance of phenobarbital and diphenylhydantoin from serum of children
Authors: Garrettson L. K. , Dayton P. G.
Published: January 2016

Children were treated for epilepsy with phenobarbital and diphenylhydantoin. In 2 cases, diphenylhydantoin could not be detected in the serum when combined with doses of phenobarbital above 1 mg. per kilogram per day. Other cases showed either a lowering of hydantoin levels or no change in the presence of phenobarbital. A method is presented which permits the quantitation of these two drugs and primidone from the same 0.5 ml. sample of serum. Serum half‐life of phenobarbital in 6 children was in the range of 37 to 73 hours. This is a lower range than that published for adults
Pemoline and methylphenidate in mildly depressed outpatients
Authors: Rickels Karl , Gordon Paul E. , Gansman David H. , Weise Charles C. , Pereira‐Ogan Jorge A. , Hesbacher Pefer T.
Published: January 2016

Pemoline and methylphenidate hydrochloride were compared to placebo in a double‐blind stUdy of mildly to moderately depressed outpatients with target symptoms of fatigue, apathy, anorexia. Patients attended either the psychiatric clinic of a large city hospital or the offices of several general practitioners and private psychiatrists. Clinic patients had Significantly lower educational and occupational levels than the middle‐ class private practice patients. At 2 and 4 weeks, both pemoline and methylphenidate produced significantly more improvement than placebo in clinic and general practice patients. Private psychiatric patients, however, improved as much or even slightly more on placebo than on either drug. A number of explanations are put forward.
Effects of a single large intravenous dose of methylprednisolone sodium succinate
Authors: Novak E. , Stubbs S. S. , Seckman C. E. , Hearron M. S.
Published: January 2016

A randomized double‐blind study with placebo control revealed that single large intravenous doses of methylprednisolone sodium succinate produced no serious systemic effects. The effects of a dose of 30 mg. per kilogram given over a 10 minute period were studied. A battery of tests given before, during, and after administration indicated that the physiologic changes are similar in kind and degree to those after oral administration. An ACTH stimulation test suggested that the ability of the adrenal gland to respond is preserved after the single large doses. On the basis of this study it was concluded that, when indicated, doses of up to 30 mg. per kilogram of methylprednisolone sodium succinate were safe for use.
Comparison of glaphenine and codeine in postoperative dental pain
Authors: Ruedy John , Bentley Kenneth C.
Published: January 2016

A double‐blind crossover study comparing glaphenine 400 mg., a new anti‐inflammatory analgesic drug, with codeine 30 mg. was performed on 98 outpatients suffering from postoperative dental pain. Of the 74 patients completing the trial, 84 per cent had successful analgesia with glaphenine as first drug compared with 36 per cent who had successful analgesia with codeine as first drug (X2 = 11.5, p < 0.0005). Similar results were observed comparing drugs on second administration in 59 patients requiring additional analgesia. The onset of analgesia with glaphenine occurred in one hour with a peak effect between 2 and 4 hours after intake. Side effects in patients who took glaphenine were frequent (19 per cent of patients) but mild.
Effect of intensive occupational exposure to DDT on phenylbutazone and cortisol metabolism in human subiects
Authors: Poland Alan , Smith Donald , Kuntzman R. , Jacobson M. , Conney A. H.
Published: January 2016

The effect of intensive occupational exposure to DDT on drug and steroid metabolism was studied. The concentration of DDT‐related substances in the serum and fat of DDT factory workers was 20 to 30 times that in a control population. The serum half‐life of phenylbutazone was 19 per cent lower (p < 0.01) and the urinary excretion of 6ß‐ hydroxycortisol was 57 per cent higher (p < 0.01) in the DDT factory workers. There were considerable variations in the phenylbutazone half‐life in different people, and there were also individual differences in the urinary excretion of 6ß‐hydroxycOrfisol. The variability in these parameters found in the DDT factory workers or in the control population was, however, not correlated with the concentration of DDT in the serum. Although we do not know whether DDT storage in the general population is sufficient to increase phenylbutazone metabolism or the urinary excretion of 6B‐hydroxycOrfisol, our results suggest that the extent of possible changes in these parameters would be small.
Effects of large and small doses of hydrochlorothiazide in hypertensive patients
Authors: Mcleod Peter J. , Ogilvie Richard I. , Ruedy John
Published: January 2016

The ceiling diuretic dose of hydrochlorothiazide (HCT) is 200 mg. per day. To investigate the antihypertensive effect of doses of HCT greater than that producing maximal diuresis, 21 hypertensive outpatients were studied. These patients were selected from a large group and included only those who, on previous occasions, had failed to obtain adequate blood pressure control from diuretic therapy alone. After stabilization on placebo, all patients received HCT 150 mg. per day for 12 weeks. The dose was increased to 450 mg. per day in the 19 patients whose hypertension was inadequately controlled on the lower dose, and they were followed for a further 20 weeks. At regular intervals, measurements were made of biochemical and hematologic indices as well as serum magnesium and HCT concentration. Despite doubling of serum HCT concentration with the higher dose, the patients had no greater blood pressure lowering and no changes in biochemical measurements when the dose of HCT was tripled.
V. The architecture of clinical research (concluded)
Authors: Feinstein Alvan R.
Published: January 2016

In considering the design of a project in clinical research, we have thus far passed through five stages of biostatistical architecture. The first stage, concerned with the paramount principles of specifying the objective of the investigation, 19 contained the components and logic used for planning the sequence of initial state, maneuver, and subsequent state. The next four stages contained procedures for implementing the stated objective by delineating the intake, maintenance, initial identification, and subsequent identification of the population.20 This paper begins with the sixth stage of the design and continues through the remaining four operational principles that conclude this outline of biostatistical architecture for clinical research. Subsequent papers in this series will be devoted to additional methodologic issues that have been raised during the architectural discussions.
Formula for approximating plasma concentration
Authors: Roth Harold P. , Caron Herbert S. , Hsi Bartholomew P. , Clark Richard E.
Published: January 2016

The footnote on p. 231 of our article (this JOURNAL 11:228‐237, 1970) was to indicate the primacy [of Dr. John G. Wagner] in providing a formula for approximating plasma concentrations and was not meant to imply that our formula was superior. We regret that our method of expressing this was ambiguous.
Adverse drug reactions: A pharmacist‐based monitoring system
Authors: Gardner Pierce , Watson L. Jeannine
Published: January 2016

Virtually all recognized adverse drug reactions result in discontinuation or dose reduction of the suspected drug. In a study of adverse drug reactions, a pharmacist‐based surveillance system was used to monitor changes in drug orders. Drug reactions prompted 7.3 per cent of drug discontinuations or dose reductions. Compared with a physician‐based system of daily monitoring, the pharmacist‐based system detected more drug reactions, provided a more uniform method of study, and had greater acceptance by house physicians. Among 939 patients studied on the medical service of a university hospital, 48 (5.1 per cent) had adverse drug reactions on admission, and 99 (10.5 per cent) developed adverse drug reactions in the hospital.
The enterohepatic circulation in glutethimide intoxication
Authors: Chary tan Chaim
Published: January 2016

The role of the enterohepatic circulation in glutethimide (Doriden) metabolism and toxicity was investigated in patients and dogs undergoing biliary drailwge. Bile collected after the oral or parenteral administration of glutethimide contained insignificant quantities of active and unmetabolized drug. Oral administration of glutethimide both before and after complete biliary diversion revealed that this procedure had no effect on the absorption, excretion, or clinical manifestations of the active form of the drug. It is concluded that the enterohepatic circulation does not have a significant effect on the handling of active unmetabolized glutethimide and that there is no indication for biliary drainage in glutethimide intoxication.
The accumulation and metabolism of dopamine by the human platelet
Authors: Solomon Harvey M. , Spirt Nena M. , Abrams William B.
Published: January 2016

Human blood platelets incubated for one hour at 37° C. with dopamine‐l‐14C (DA) accumulated the amine against a gradient. Such accumulation was markedly reduced by cold and by various metabolic inhibitors including iodoacetate, dinitrophenol, and sodium cyanide. Increasing the concentration of DA caused a decrease in the steady‐state distribution ratio which suggests that the uptake process is saturable. Various compounds which inhibit or compete for the amine pump in the platelet membrane, including desmethylimpromine (DMI), diphenhydramine, serotonin, debrisoquin, and guanethidine, depress the accumulation of DA. Uptake of DA was also reduced by benztropine, trihexyphenidyl, and haloperidol. Less than 10 per cent of the DA which accumulates in the platelet during one hour is metabolized. DA is a relatively poor substrate for platelet MAO and in addition the cell does not appear to contain dopamine β‐hydroxylase.
Plasma protein binding of diphenylhydantoin in man; Interaction with other drugs and the effect of temperature and plasma dilution
Authors: Per Knut M. Lunde , Rane Anders , J. Yaffe Summer , Lund Lars , Sjöqvist Folke
Published: January 2016

Plasma protein binding of diphenylhydantoin (DPH) in normal plasma was investigated with an ultrafiltration technique (at room temperature) with the use of 14C‐labeled DPH. DPH was 92.6 per cent bound. There was no marked difference between sexes or individuals. In blood donor plasma the bound fraction was 93 per cent at a concentration of DPH of 16 μg per milliliter (therapeutic concentration). The binding was less at 37° C. than at wom temperature. The effect on DPH binding of some other drugs, including various anti‐epileptics, was investigated. Of these only salicylic acid, sulfafurazole and phenylbutazone (in concentrations which may be obtained clinically) decreased DPH binding. The effects of plasma dilution and of dilution of both plasma and DPH were investigated. In the former case unbound concentrations increased but were fairly constant in the latter. The clinical significance of these findings is discussed.
Vicissitudes in research: The twenty‐four hour urine collection
Authors: Turner William J. , Merlis Sidney
Published: January 2016

Often much depends in metabolic studies upon the accuracy of 24 hour urine collections. In the belief that many common sources of error occur and lead to faulty conclusions, this report of some experiences in a psychiatric hospital is presented as a cautionary tale. Difficulties described are due to inadequate communication, patient resistance, personnel variables, and medication errors.
The influence of alcohol and marihuana on motor and mental performance
Authors: Manno Joseph E. , Kiplinger Glenn F. , Scholz Norman , Forney Robert B. , Haine Susan E.
Published: January 2016

Twelve healthy male volunteers smoked marihuana cigarettes calibrated to deliver 0, 2.5, or 5 mg. of delta‐9‐tetrahydrocannabinol (THC) either alone or in combination with either a plain fruit‐flavored beverage or the same beverage containing 15 ml. of alcohol per 50 pounds of body weight. Each subject received all 6 possible combinations in a double‐blind randomized block experiment. The parameters measured were four pursuit meter tests (motor performance), nine delayed auditory feedback tests (mental performance), pulse rate, conjunctival injection, and subjective effects (Cornell Medical Index). It was found that the high dose of THC produced Significant impairment in performance of both mental and motor tasks and that alcohol induced an additional effect. There was little difference between the response to 2.5 and 5.0 mg. of THC on these parameters. Conjunctival injection, ptllse rate, and subjective effects were dose dependent and alcohol was additive.
The polymorphic acetylation of dapsone in man
Authors: Gelber Robert , Peters John H. , Gordon G. Ross , Glazko Anthony J. , Levy Louis
Published: January 2016

The characteristics of the acetylation of dapsone (avlosulfon) were found to parallel those of isoniazid and sulfamethazine in 19 subjects, thereby establishing the genetic polymorphism for the acetylation of dapsone. This polymorphism was revealed by the distribution of the ratios of the plasma concentration of acetylated to parent drug. The acetylation capacity for dapsone was shown to be a reproducible, individual characteristic. Acetylation of dapsone and deacetylation of monoacetyl dapsone occurred concurrently. Constant plasma ratios of acetylated to parent drug characteristic for the individual were attained immediately after administration of dapsone but only after several hours following administration of monoacetyl dapsone. The available data suggest that acetylation rather than deacetylation is the primary determinant of these ratios. Rates of disappearance of dapsone and monoacetyl dapsone from the plasma were the same regardless of which of the two was administered or of the acetylator phenotype of the subject. After dapsone, no differences between rapid and slow acetylators were found in the 24 hour urinary excretion of dapsone and its conjugates hydrolyzed by mild or strong acid treatment. Rapid acetylators excreted significantly more monoacetyl dapsone and its acidlabile conjugates than slow acetylators. Because these compounds accounted for only a very small fraction of the dose, it was not possible to phenotype individuals by these measurements. More dapsone and acid‐hydrolyzable conjugates of dapsone were found in 120 hour urine collections after monoacetyl dapsone than after dapsone in both phenotypes.
The effect of methylphenidate and prolintane on the metabolism of ethyl biscoumacetate
Authors: Hague David E. , Smith Marva E. , Ryan Jerome R. , McMahon F. G.
Published: January 2016

Following the oral administration of ethyl biscoumacetate to 12 patients and the determination of the half‐life of the drug and the plasma prothrombin time, either prolintane, methylphenidate, or placebo were orally administered in double‐blind fashion to the same patients for a period of 4 days. Twelve hours following the last administration, an identical dose of ethyl biscoumacetate was again administered and the half‐life and plasma prothrombin time again determined. The results presented here did not confirm a previous report that methylphenidate inhibits the metabolism of ethyl biscoumacetate. No significant difference could be found in the plasma half‐life of ethyl biscoumacetate before and after the 3 treatments. It is concluded that neither prolintane nor methylphenidate inhibit the metabolism of ethyl biscoumacetate in man.
Clinical laboratory abnormalities
Authors: McDowell Fletcher
Published: January 2016

Data on repeated laboratory findings in 974 patients from 25 collaborative centers conducting studies on levodopa in parkinsonism have been analyzed in an attempt to evaluate the significance of laboratory abnormalities. The hematologic tests included hemoglobin, hematocrit determinations, white cell count, and Coombs test; the blood chemistry tests consisted of blood urea nitrogen, serum glutamic oxalacetic transaminase and other standard liver function tests, fasting blood sugar, uric acid, and protein‐bound iodine. The data show that, to date, there has been no significant interference with the hematologic system, renal function, liver function, or endocrine function. Occasional abnormalities in blood urea nitrogen, the serum glutamic oxalacetic transaminase test for liver function, fasting blood sugar, and protein‐bound iodine were found. The percentages of abnormalities for each of the tests are tabulated. Also studied were electrocardiogram, repeated 1,209 times and found abnormal in 28 per cent, and the electroencephalogram 334 times, found abnormal in 150. In general, few, if any, abnormalities could be clearly related to the ingestion of levodopa. Minor elevations in liver function test values returned to normal spontaneously within a month or two without discontinuation of levodopa. Continued careful monitoring by laboratory tests is nonetheless urged, because patients with Parkinson's disease tend to develop other illnesses.
Cardiovascular effects of levodopa
Authors: Goldberg Leon I. , Whitsett Thomas L.
Published: January 2016

The patient with Parkinson's disease under treatment with levodopa may be subject to potentially hazardous cardiovascular effects. The most serious side effect of levodopa in patients is ventricular arrhythmia which is unlikely to occur in a subject with normal heart but a risk in patients with myocardial irritability or ischemia. Patients with such a history of ventricular ectopic activity should be treated with caution and monitored electrocardiographically. Levodopa dosage should be increased gradually; if ectopic activity is observed the drug should be discontinued or administered together with an antiarrhythmic agent, the most rational being β‐adrenergic blockers. If these are contraindicated, other antiarrhythmic agents may be successful. Orthostatic hypotension, more common and usually not symptomatic, should be monitored by frequent blood pressure measurements in the standing position, and exercise should be restricted.
Central nervous system and cardiovascular effects of lorazepam in man
Authors: Elliott H. W. , Nomof N. , Navarro G. , Ruelius H. W. , Knowles J. A. , Comer W. H.
Published: January 2016

A group of 15 healthy adult men was divided into three groups for a double‐blind study of the sedative‐hypnotic activity of single oral doses of lorazepam, a new member of the benzodiazepine series. Premedication procedures included complete blood counts, liver function tests, urinalyses, electroencephalograms, electrocardiograms and observations of central nervous system activity, as well as response to CO2, cardiac output, and peripheral vascular resistance. Three subfects received 100 mg. of sodium pentobarbital, 4 subfects received 2.5 mg., 4 subiects, 5.0 mg., and the remaining 4, 7.5 mg. of lorazepam. The same observations were repeated on all at intervals throughout the day of the test. There were no significant changes in laboratory findings or electrocardiograms and no severe impairment of respiratory and cardiovascular centers. The compound probably acts indirectly on vasomotor reflexes by way of the central nervous system. The serum concentrations of lorazepam reached a peak between 2 and 6 hours and then declined slowly. Clinical recovery occurred in 6 to 8 hours in all but one subject, even though serum levels were appreciable at 24 hours. About two thirds of the doses were recovered in urine as glucuronide within 96 hours.
Studies of the dependence‐producing properties of GPA‐1657, profadol, and propiram in man
Authors: Jasinski Donald R. , Martin William R. , Hoeldtke Robert
Published: January 2016

GPA‐1657, profadol, and propiram are proposed as analgesies of low abuse potential since none will suppress but each will precipitate abstinence in morphine‐dependent monkeys. GPA‐1657 is not an antagonist in man but a typical morphine‐like compound and is fudged to have significant abuse potential. Profadol and propiram act as antagonists in man and precipitate abstinence in subiects dependent on 240 mg. of morphine per day. As agonists, profadol and propiram resemble morphine‐like rather than nalorphine‐like drugs, since both produce morphine‐like subjective effects and physical dependence and suppress abstinence in subiects dependent on 60 mg. per day of morphine. Both were judged to have abuse potential. Propiram was judged to have somewhat less abuse potential than profadol, since it produces less euphoria and less physical dependence. The morphine antagonist properties of profadol and propiram are thought to be caused by the fact that they are morphine agonists with less intrinsic activity than morphine.
Antilipidemic effect of nafenoic acid
Authors: Russo Carlo , Mendlowitz Milton
Published: January 2016

Nafenoic acid, an antilipidemic compound, was tested in a double‐blind study in 14 patients with essential hypertension. It decreased serum triglycerides but had no significant effect on total lipids or cholesterol. No side effects were observed.
Some cardiovascular effects of marihuana smoking in normal volunteers
Authors: Johnson Stephen , Domino Edward F.
Published: January 2016

Marihuana smoking caused a significant increase in heart rate in 25 normal male volunteers. The degree of techycardia was significantly related to the dose of Δ‐9‐ tetrahydrocannabinol (Δ‐9‐THC). The marihuana smoked contained 0.5 and 2.9 per cent Δ‐9‐THC and was compared to extracted marihuana as a control in a single‐blind experimental design. Dose of Δ‐9‐THC was expressed as the total amount available in the number of cigarettes smoked under standard conditions. The tachycardia reached a maximum within 30 minutes and persisted longer than 90 minutes. Systolic and diastolic blood pressures were significantly elevated after total doses of marihuana containing more than 10 mg. of THC, but blood pressure was better correlated to heart rate than to dose. Changes in the electrocardiogram were minimal, but there were premature ventricular contractions in some subjects.
The fate of SU‐13197, a new antiarrhythmic drug, in rat and man
Authors: Shand D. G. , Cavanaugh J. H. , Oates J. A.
Published: January 2016

The fate of 14C‐labeled SU‐13197 was investigated in rat and man. In both, the drug was almost completely metabolized and the radioactivity excreted in the urine and feces. The half‐life of the parent drug was shorter than that of the total of the radioactive metabolites, two of which were recognized as maior components. A glucuronide coniugate was present in rat and human urine and excreted in rat bile. In the six subiects investigated, this excreted con;ugated metabolite had a half‐life similar to that of SU‐13197 (16 hours), while the other metabolite had a longer half‐life (44 hours). In 3 sub;ects who received the drug by oral and intravenous administration, more unchanged SU‐13197 was excreted in the urine following intravenous than oral administration, despite comparable absorption of the radioactive label. This suggests that significant amounts of the drug are metabolized during the process of transfer from the gut to the systemic circulation. The data suggest that following oral administration plasma levels may vary as much as tenfold between individuals. A suitable therapeutic regimen is predicted from the data.
Studies on anabolic steroids. IV. The effects of oxandrolone on height and skeletal maturation in uncomplicated growth retardation
Authors: Limbeck George A. , Ruvalcaba Rogelio H. A. , Mahoney C. Patrick , Kelley Vincent C.
Published: January 2016

Data are reported on oxandrolone as a growth‐promoting agent in children with uncomplicated growth retardation. The effects on height and skeletal maturation suggest that it has advantages over other anabolic agents. The mean rate of linear growth was approximately doubled, and the mean advance in height age was accelerated more than was the mean advance in skeletal maturation. The former observation demonstrates that oxandrolone is an effective growth‐promoting drug, while the latter suggests that the children's ultimate adult heights may not be compromised because of the administration of this anabolic steroid.
Comparison of thioridazine and chlorpromazine in doctor's choice research design
Authors: Kimbel Isham , Overall John E. , Winkelman George W. , Hughes Waunell M.
Published: January 2016

A series of 156 patients selected by doctor's choice for treatment with either chlorpromazine or thioridazine was studied. The purposes of the investigation were to examine feasibility and utility of statistical control over extrinsic sources of variance in nonexperimental clinical research, to further the development of an adequate model for clinical research in natural treatment settings, and to evaluate possible specific differences in therapeutic indications of two widely used phenothiazine derivatives. From statistical analyses of the data, the results indicated that response to treatment depends on a number of nonspecific factors, some of which interact significantly with drtlg treatments. In the treatment of certain types of patients who have been reported in other studies to have generally favorable prognosis or to evidence good placebo response, chlorpromaZine and thioridazine appeared equally effective. In the treatment of types of patients that have not been reported to evidence such favorable nonspecific response, thioridazine appeared more effective. While both drugs are effective antipsychotic medications, the results from this study suggest that thioridazine may have a broader spectrum of activity.
New approach to the treatment of hypercalcemia The effect of short‐term treatment with mithramycin
Authors: Slayton Robert E. , Shnider Bruce I. , Elias Elias , Horton John , Perlia Charles P.
Published: January 2016

An intravenous bolus injection of mithramycin (25 μg per kilogram) was given to patients with malignancy‐related hypercalcemia persisting after hydmtion. In most instances a gradual but steady fall in the serum calcium occurred within the next 48 hours, accompanied by a fall in serum inorganic phosphate and 24 hour urinary calcium excretion. Patients with head and neck cancer, cancer of the lung, and multiple myeloma were somewhat less responsive as a group than patients with cancer of the breast or kidney. Aside from transient nausea and vomiting, side effects were minimal. Small doses of mithramycin inhibit bone resorption; dactinomycin and other RNA inhibitors block the action of vitamin D in vitro. The hypocalcemia following administration of these agents may be an expression of their antivitamin D action.
Effects of guancydine on systemic and renal hemodynamics in arterial hypertension
Authors: Villarreal Herman , Arcila Heriberto , Ramirez Miguel Angel , Sierra Pedro
Published: January 2016

The effect of 1‐cyano‐3‐tert‐amylguanidine (guancydine) on systemic and renal hemodynamics was studied in patients with arterial hypertension. Antihypertensive drugs were withheld for 15 days prior to beginning of investigation. Average sodium intake was 105 mEq. per 24 hours in some patients and 25 mEq. per 24 hours in others. Patients were first on placebo during a control period averaging 14 days. Guancydine was given for 7 to 18 days at an average dose of 21 mg. per kilogram of body weight. Although mean arterial blood pressure decreased significantly in all patients, in only two did it reach normal levels. There was no change in cardiac output. Glomerular filtration rate and renal plasma flow remained unchanged while urinary sodium excretion diminished, suggesting a tubular effect. A substantial gain in body weight was noted. Nausea, vomiting, constipation, somnolence, restlessness, mental confusion, asthenia, and urine retention were observed. The antiangiotensin effect of guancydine described in animals was nut observed.
XII. On exorcising the ghost of Gauss and the curse of Kelvin
Authors: Feinstein Alvan R.
Published: January 2016

At any era in the history of science, the further advance of science has been retarded by certain fundamental concepts that were enlightcning when introduced, but that later, after persisting too long, became barriers to future progress.
Lithium and leukocytosis
Authors: Shopsin Baron , Friedmann Richard , Gershon Samuel
Published: January 2016

Peripheral blood specimens from 22 hospitalized psychiatric patients and one outpatient were examined for white blood cell (WBG) count changes during treatment with lithium carbonate. Significant leukocytosis occurred during periods of lithium ingestion; this phenomenon was reversible, apparently innocuous, and not related to psychiatric diagnosis or the many variables of hospitalization. While elevations in WBG count are likely the result of a drug effect, they were not dose related or dependent on the concentration of lithium in the peripheral blood. A trend toward neutrophilia and lymphocytopenia emerged for the group but cannot be said to account for the global change in total WBG.
Effects of boxidine on human serum sterols and neoplasms
Authors: Gailani Salman , Holland James F. , Glick Aaron
Published: January 2016

Thirteen patients with neoplasms which had progressed beyond conventional means of therapy were given boxidine, a hypocholesteremic agent, in daily doses of 60 mg. and 120 mg. from 17 to 62 days. An adrenal carcinoma regressed in one patient who had received 120 mg. of boxidine daily for 50 days. A definite decrease in serum chalesterol was observed in 9 of the 13 patients, and 7‐dehydrocholesterol appeared in the serum of all the patients tested. Measurement of serum sterols in 3 patients after the discontinuation of boxidine showed persistence of high level of 7‐dehydrocholesterol. Substantial amounts of 7‐dehydrocholesterol were found in the tissues of a patient who died 129 days after the discontinuation of boxidine. Side effects included anorexia, nausea, and vomiting, severe at times, which were associated with the higher dose only.
The nonpharmacologic basis of therapeutics
Authors: Mazzullo John
Published: January 2016

Every physician who has contact with outpatients has on occasion had his grandest therapeutic regimen hopelessly confounded by a patient's bewilderment over which little white pill comes next. Every physician has also experienced the frustration of trying to extract from a new patient information on what pills he has been taking: "I have been taking a little white pill for nerves and pressure." (phenobarbital, hydrochlorthiazide, or reserpine?)
Effect of route of administration on the relationship between β‐adrenergic blockade and plasma propranolol level
Authors: Cleaveland Clifton R. , Shand David G.
Published: January 2016

The antagonism of isoproterenol‐induced tachycardia by orally and intravenously administered propranolol was measured in 5 subjects and related to the plasma propranolol concentration. Two hours after oral administration of a single dose of propranolol, the degree of beta blockade associated with a given plasma propranolol concentration was greater than that seen with the same concentration achieved by intravenous administration. After 6 hours, this disparity was no longer apparent. During long‐term 6 hour administration, the effect of the twenty‐first dose both 2 and 6 hours after administration was the same as that resulting from similar plasma levels achieved by intravenous administration. These findings can be explained by the formation after single oral doses of an active metabolite, 4‐hydroxypropranolol, which has a shorter half‐life than does the parent drug. This metabolite is not produced during intravenous administration of single doses. However, at the end of a 6 hour dosage interval and after chronic oral administration, the effects of propranolol could be attributed entirely to circulating levels of the parent drug.
Effect of methylphenidate on plasma anticonvulsant levels
Authors: Kupferberg Harvey J. , Jeffery William , Hunninghake Donald B.
Published: January 2016

The effect of the oral administration of 30 mg. of methylphenidate daily on serum levels of phenobarbital, diphenylhydantoin, and primidone was evaluated in 11 patients. One group of patients was assigned to an 18 week treatment period of 6 weeks each for control, methylphenidate, and control; another group was studied in similar fashion for methylphenidate, control, and methylphenidate. Plasma anticonvulsant levels were determined at weekly intervals. No significant differences in plasma anticonvulsant levels were noted during methylphenidate administration.
Seminal acid phosphatase content in the clinical bioassay of androgens and antiandrogens
Authors: Kent J. R. , Hill M. , Huix F. J. , Segre E. J.
Published: January 2016

The lack of methods for quantifying androgen activity in man has made it difficult to validate anabolic‐androgenic dissociation and antiandrogen activity of experimental compounds. We assessed drug‐induced changes in seminal fructose, citric acid and acid phosphatase content, and efaculate volume in hypogonadal males. Of these four indices of androgen target gland function, acid phosphatase was most suitable for bioassay purposes. Androgens studied included fluoxymesterone, oxymetholone, methyltestosterone, and testosterone propionate. A reasonable dose response was noted. Simultaneous administration of an antiandrogen partially blocked the androgen effect. The system developed may be useful for quantifying the potency of androgens in human subjects and also to demonstrate antiandrogen activity.
Effect of triamterene on the renal clearance of calcium, magnesium, phosphate, and uric acid in man
Authors: Walker Barry R. , Hoppe Robert C. , Alexander Fred
Published: January 2016

Triamterene administered for 2 weeks to 16 normal volunteers increased the renal clearance of sodium and magnesium without affecting calcium or phosphate excretion. It decreased the uric acid clearance in proportion to the decrease in creatinine clearance. Triamterene induced no significant change in serum calcium, phosphate, or uric acid, but there was a slight increase in serum magnesium. The results support the hypothesis that sodium transport in the distal tubule can be inhibited without affecting calcium reabsorption. The mechanism for the increased blood and urine magnesium is not known but could be both renal and extrarenal. There was no evidence for an inhibition of tubular secretion of uric acid. On the basis of these data, it seems unlikely that triamterene could produce clinically significant hypercalcemia or hyperuricemia in nonazotemic patients. However, magnesium depletion could result from long‐continued use, especially when triamterene is combined with other diuretics which also increase magnesium excretion.
Thrombelastography of human blood after aspirin
Authors: Hawkins Rosemary I.
Published: January 2016

Blood samples from 17 sub;ects were analyzed with the use of the thrombelastograph. After 600 mg. aspirin there was a significant prolongation of the reaction time, initial clotting speed, and total coagulation time. There was no alteration either in the maximum clot elasticity or in the time taken to reach this value, nor was there any change in clot retraction.
Comparison of crystalline and amorphous asparaginase in treatment of acute leukemia in children
Authors: Pratt Charles B. , Verzosa Manuel
Published: January 2016

Crystalline and amorphous preparations of asparaginase were compared with regard to toxicity and capacity to induce remission of acute leukemia in children. Both preparations were administered in a dosage of 5,000 international units (I.U.) per square meter of body surface area twice weekly for 4 doses. Thirty‐one children with acute lymphocytic leukemia (ALL) and 6 with acute myelocytic leukemia (AML) refractory to conventional antileukemic drugs were admitted to this study. All were in complete relapse. Four of 11 children with ALL receiving crystalline asparaginase and 10 of 20 receiving the amorphous preparation developed complete‐remission bone marrow status. None of the children with AML responded. Hepatic and renal toxicity were more frequent in the patients receiving amorphous asparaginase, but not significantly so. None of the patients developed pancreatitis, and there were no toxic deaths with either preparation. Crystalline asparaginase has no apparent advantage over amorphous asparaginase in treatment of leukemia in children.
Influence of nitrazepam on oral anticoagulation with phenprocoumon
Authors: Bieger Robert , de Jonge Hendrik , Loeliger Emil A.
Published: January 2016

A double‐blind trial was carried out on 22 volunteer patients to observe the influence of nitrazepam on the course of long‐term anticoagulant therapy with phenprocoumon. Dosage of phenprocoumon remained unchanged for all patients during the 8 week trial. Nitrazepam or placebo, assigned at random, was taken every night for a 2 week period; a subsequent 2 week period without test drugs was followed by a second series with the other tablet. The last 2 weeks of the trial were without test drugs. There was no difference between the effects of the placebo and the nitrazepam on the hypocoagulability due to the oral anticoagulant therapy. It is concluded that nitrazepam can safely be prescribed as a hypnotic for patients on long‐term anticoagulant therapy.
Pharmacologic studies of indoramin in man
Authors: Royds R. B. , Coltart D. J. , Lockhart J. D. F.
Published: January 2016

The effects of indoramin, a new hypotensive drug with competitive α‐adrenergic receptor blocking properties, were studied in a double‐blind investigation in healthy human subjects. Indoramin (20 mg.) orally produced a significant fall in blood pressure at high exercise loads when compared with placebo. Indoramin (20 and 40 mg.) reduced erect blood pressures during a period of 6 hours when compared with placebo in another double‐blind study. Histamine skin wheals were also reduced in a dose‐related manner but no effect on critical flicker frequency was demonstrated. The pressor response to intravenous norepinephrine showed a parallel time‐related shift to the right after the intravenous administration of 20 mg. of indoramin. The effect of intravenous indoramin (10 mg.) on myocardial funcion was studied with noninvasive techniques. No effect was demonstrated on systolic time intervals, cardiac output, or eiection fraction. Indoramin (20 mg.) given orally twice daily for 2 weeks reduced erect and supine blood pressures without evidence of drug accumulation. No drug‐related effects on biochemical or hematologic values were detected.
Effect of some drugs on penicillin half‐life in blood
Authors: Kampmann J. , Hansen J. Mølholm , Siersbœk‐Nielsen K. , Laursen H.
Published: January 2016

The half‐life (T /2) of penicillin in blood was determined in 61 patients. An inverse relationship of penicillin T/2 and endogenous creatinine clearance was found. In a group of elderly patients with normal serum creatinine, penicillin T/2 was prolonged due to age‐dependent decrease in renal function. The effect of several drugs on the active renal tubular transport mechanism of penicillin was studied. Probenecid increased penicillin T/2 from an average of 40.4 to 104.3 minutes. Penicillin T/2 in the younger patients using probenecid was of the same order as penicillin T/2 in elderly individuals not using probenecid. Phenylbutazone increased penicillin T/2 almost as much as did probenecid. Sulfinpyrazone, acetylsalicylic acid, indomethacin, and sulfaphenazole in therapeutic doses increased penicillin T /2 to a smaller degree. There was no significant change in penicillin T /2 after therapeutic doses of chlorothiazide, sulfamethizole, and sulfamethoxypyridazine.
Analgesic and other effects of nalmexone in man
Authors: Forrest William H. , Shroff Phyllis F. , Mahler Donald L.
Published: January 2016

Analgesic and other effects of nalmexone, an n‐dimethylallyl derivative of oxymorphone, were compared with those of morphine in 451 surgical patients in 2 hospital members of the VA Cooperative Analgesic Study. Based on total analgesia for a 255 minute observation period, relative potency estimates indicated that 70 to 90 mg. of nalmexone was equivalent to 10 mg. of morphine. Sedation and, to a lesser extent, sweating were frequent effects of both drugs.
Effects of propranolol on marihuana‐induced cognitive dysfunctioning
Authors: Drew William G. , Kiplinger Glenn F. , Miller Loren L. , Marx Marilyn
Published: January 2016

Paid male volunteers were allowed to smoke marihuana cigarettes calibrated to deliver a dose of 25 µg per kilogram of delta‐9‐tetrahydrocannabinol (Δ‐9‐THC). All subjects were given propranolol or placebo (administered in a double‐blind fashion), in 4 divided doses beginning 24 hours before and ending 2 hours prior to smoking. Marihuana smoking resulted in significant disruption in the recall of narrative material and moderate impairment in performance on a modified version of the Reitan Trail Making test. Stroop‐Color Word performance was not affected by marihuana. Propranolol, a beta adrenergic blocking agent, failed to interact with marihuana to reduce its disruptive effects on any of the tests.
Plasma urea kinetics in urea infusion
Authors: Yarnell Philip R. , Bell Richard L. , Ng Paul , Gormley William T.
Published: January 2016

Seven patients undergoing an infusion of 30 per cent urea‐10 per cent invert sugar solution (Urevert) for treatment of cerebral edema were studied with regard to plasma urea kinetics. The 2 compartment (extracellular and intracellular fluid spaces) model has been applied to analysis of the plasma levels. On the average, the human data could be simulated with our standard canine correlation: 2 compartment urea transport coefficient K, (liters per hour)= 0.735 weight (kilograms)± 14 per cent.
Toxicity of a hepatotoxic laxative preparation in tissue culture and excretion in bile in man
Authors: Dujovne C. A. , Shoeman D.W.
Published: January 2016

Dioctyl sodium sulfosuccinate (DSS), 100 or 200 mg., was given orally to patients with indwelling T‐tube biliary drainage. Concentrations of the drug in bile measured by gas chromatography ranged from 4 to 9 × 10−5M. Before recent modifications, DSS and oxyphenisatin were the components of a laxative preparation, Dialose Plus. The cytotoxic potential of both drugs on human liver cell cultures (Chang) was quantitated by loss of lactate dehydrogenase and ß‐glucuronidase into surrounding tissue culture media after exposure to concentrations of the drugs between 10−6M and 2 × 10−4M for 4 to 24 hours. At 4 hours and higher concentrations, only DSS or the 2 drugs together were cytotoxic; at 24 hours high concentrations of oxyphenisatin became cytotoxic. At most other lower concentrations the addition of the 2 drugs to the same cultures resulted in greater cytotoxicity than either did separately. These data suggest that clinical hepatotoxicity might be facilitated when patients achieve “critical” concentrations of one or both of these drugs in liver parenchyma.
Acute adverse reactions to prednisone in relation to dosage
Authors:   The Boston Collaborative Drug Surveillance Program
Published: January 2016

Among 718 consecutively monitored hospitalized medical patients who received prednisone, adverse reactions were recorded in 121 (16.9 per cent). Of these, 82 experienced acute reactions (11.4 per cent of the total series), and 39 (5.4 per cent) had a more gradual onset of the reactions. The daily dose of prednisone was analyzed in 594 patients in whom adverse reactions were not recorded and in the 82 patients with acute reactions. While there was a striking dose‐response relationship for acute psychiatric reactions, there was no correlation between dose and gastrointestinal side effects, diabetes, superinfections, and leukocytosis.
Introduction and opening remarks
Authors: Lasagna Louis
Published: January 2016

The volunteer subject, as a formal concept in drug research, is a relatively new phenomenon. It is also a uniquely human phenomenon. It was probably Hobart Reimann who once wrote that the adjective, human, before the noun, volunteer, was redundant, sinee Homa sapiens is the only species that could volunteer for anything. While some people who work with animals might dispute that statement, there is enough right about it to make its point.
A scientific rationale for choosing patients rather than normal subiects for Phase I studies
Authors: Oates John A.
Published: January 2016

The determination of safety and adverse effects in Phase I together with investigations on the disposition and bioavailability of the drug often provide a better scientific and ethical basis if conducted with knowledge of the dose required to produce the desired pharmacologic effect. Because certain pharmacologic effects are specific for the disease state, Phase I studies on stich drugs should be conducted only in carefully selected patients with the appropriate disease.
Summation of meeting
Authors: Lasagna Louis
Published: January 2016

Is there a moral imperative or a compelling sense of responsibility to volunteer? I'm not sure. One could also call it energetic altruism, and there's much to be said for such an attitude. But I think there's also a general tendency for people to want to let others undergo any risks inherent in volunteering. It is desirable that we try to reverse the notion that all volunteers are neurotic or psychotic, even though there is considerable evidence that the psychologic factors can be awfully important in volunteering. It is a pity that many oppose the use of prisoners under any circumstances. I suspect that American prisoner volunteers are probably less “captive” a group than most British or American patient volunteers. It's also important for us not to limit further the options of the prisoner by making it impossible for him to participate in activities that are highly important to his moral and psychologic well‐being.
XIX. Ambiguity and abuse in the twelve different concepts of “Control”
Authors: Feinstein Alvan R.
Published: January 2016

Sir Ronald Fisher began his classic book,8 The Design of Experiments, by pointing out that a critic who refuses to accept the conclusions of an experiment can take “two lines of attack.” In one approach, the critic believes that the results have received a faulty interpretation. In the second approach, the experiment itself is regarded as “ill designed.”
Uptake and distribution of thiopental after oral, rectal, and intramuscular administration: Effect of hepatic metabolism and injection site blood flow
Authors: Saidman Lawrence J. , Eger Edmond I.
Published: January 2016

The effects of hepatic metabolism and iniection site blood flow on blood and brain thiopental concentrations following oral, rectal, and intramuscular administration were evaluated using a digital computer programmed with input data from an idealized electrical model. Peak drug levels were increased with high injection site flow rates and decreased with high rates of metabolism. The position of the liver relative to the iniection site was important in decreasing drug levels approximately twice as much after oral than after intramuscular administration. Altered hepatic function (increased or decreased) will affect blood and tissue thiopental levels more after oral or rectal administration than after intramuscular or intravenous administration.
The effect of five per cent carbon dioxide on the response of muscle blood flow to isoproterenol in man
Authors: Xanalatos C. , MacDonell Lindsay , Larbi E. , James I. M.
Published: January 2016

Heart rate, muscle blood flow, and blood pressure were measured in 10 subjects. The administration of 5 per cent CO2 caused a fall in blood flow and an increase in mean arterial pressure without significant change in heart rate. An infusion of isoproterenol at a dose of 2 ug per minute caused an increase in flow, heart rate, and pulse pressure but no change in mean arterial blood pressure. The administration of 5 per cent CO2 during the isoproterenol infusion abolished the increase in muscle blood flow, produced an increase in mean arterial blood pressure, and caused an attenuation of the chronotropic effect of isoproterenol. These results suggest that certain cardiovascular effects of isoproterenol are altered during respiratory acidosis.