bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous infusions of arabinosyl cytosine in patients with neoplastic disease
Authors: Ellison R. R. , Carey R. W. , Holland J. F.
Published: January 2016

A study was undertaken of the effects of continuous infusion of arabinosyl cytosine in a group of patients with advanced cancer. Initially all patients received the drug for 7 days. The dose was increased in successive patients. Megaloblastosis occurred with doses as low as 3 mg. per square meter per day for 7 days, although no other hematopoietic effects of consequence occurred at doses less than 30 mg. per square meter per day. Depressions of leukocytes and platelets after 7 days of 30 mg. per square meter of arabinosyl cytosine were comparable to those reported by Talley after a much greater total dose. Compression of the total dose of 210 mg. per square meter into 3% instead of 7 days resulted in hematopoietic depression equivalent in degree and timing to that noted after the 7 day course. Further decrease of the length of the infusion of 210 mg. per square meter to 1.75, 0.875, or 0.44 days significantly decreased the hematopOietic depressant effects although megaloblastosis was again seen in all. Gastrointestinal toxicity was minor with one week infusions but occurred more frequently when the same total dose was given over a shorter period of time. No therapeutic activity was seen during this study.
Hypnotic activity of placebo in relation to severity of insomnia: A quantitative evaluation
Authors: Nicolis F. B. , Silvestri L. G.
Published: January 2016

Data obtained in a controlled clinical trial, carried out on 78 psychiatric patients, are presented as a contribution to the quantitative evaluation of the relationship between the effects of placebo and drugs at a given dose and the severity of the clinical condition being treated. In these patients, suffering from insomnia of different severities, satiofactory sleep after administration of placebo was demonstrated to decrease significantly with increasing pretreatment severity of the symptom. Furthermore, the differences in hypnotic activity between placebo and 100 mg. phenobarbital were almost nil in mild insomnia and increased significantly with increasing severity of insomnia. On the basis of these data, it is felt that some cases of mild insomnia may be better treated with placebo than with active drugs. Furthermore, clinical trials of hypnotic drugs appear to be more generally efficient if carried out with patients suffering from severe insomnia.
A note from the Editor
Authors: Modell Walter
Published: January 2016

During the past year original contributions well worthy of publication have been coming to the Editor's desk in increasing number. Obviously this is a most encouraging and rewarding development, but now the rate of their acceptance has begun to exceed the rate of their publication.
Effect of nicotine and vasopressin on the terminal vascular bed of the heart
Authors: Rakusan Karel , du Mesnil de Rochemont Wolfgang , Hanlon Jon , Braasch Wolfgang , Tschopp Hans , Bing Richard J.
Published: January 2016

The effect of nicotine and vasopressin on the capacity of the terminal vascular bed in heart and skeletal muscle of dogs was investigated. In normal heart muscle highest values were obtained in the apex. Nicotine had no significant effect unless the blood pressure increased to very high values. After vasopressin no significant changes were found in heart muscle, but vasoconstriction was present in skeletal muscle. Capillary blood flow determined in heart, lungs, and kidneys of rats increased in all organs after nicotine. In control rats, a slightly but significantly higher capillary blood flow was found in the right ventricle. This difference disappeared in nicotine‐treated animals and became more pronounced after injection of vasopressin.
The tolerance of coffee drinkers to caffeine
Authors: Colton Theodore , Gosselin R. E. , Smith Roger P.
Published: January 2016

To decaffeinated coffee powder was added either caffeine or lactose, each in an amount of 150 mg. per dose. Prepared packets were issued to second‐year medical students, who served as subjects. When consumed at bedtime, this modest dose of caffeine was significantly more effective than the lactose placebo at inducing a reduction in pulse rate in noncoffee drinkers, but not in those who habitually consumed caffeinated beverages. Small but significant differences were demonstrated in both frequency and intensity of response. Only non coffee drinkers reported disturbances in sleep patterns, most consistently a delay in the onset of sleep. The relative insensitivity of coffee drinkers to these actions of caffeine presumably represents an acquired tolerance. Like that previously demonstrated to the diuretic and salivary‐stimulating actions, this tolerance is probably low grade. Some of the cardiovascular effects of caffeine are reviewed. Heightened vagal tone appears to be responsible for the bradycardia, which is reportedly masked after high doses of caffeine by direct excitatory actions on the heart. Bradycardia has not been observed regularly after small doses of caffeine in man, apparently in large measure because most investigators failed to separate the responses of habitual and occasional coffee drinkers.
Magnesium pemoline: Stimulant effects on performance of fatigued subjects
Authors: Gelfand Sidney , Clark Lincoln D. , Herbert Emily W. , Gelfand Donna M. , Holmes Elaine D.
Published: January 2016

Magnesium pemoline, 100 mg., as compared to placebo, facilitated performance of fatigued subjects required to do repetitious arithmetic problems for 5 hours. It acted like methylphenidate hydrochloride, 20 mg., and d‐amphetamine, 15 mg., by maintaining speed and accuracy near a predrug base line. Smaller doses of magnesium pemoline, 25 and 50 mg., were not significantly different from placebo.
The acetylation of sulfamethazine and sulfamethoxypyridazine by human subjects
Authors: White T. A. , Evans D. A. Price
Published: January 2016

Individuals can be phenotyped as either rapid or slow “acetylators” by means of a sulfamethazine test. Sulfamethoxypyridazine is acetylated in the human being much less than sulfamethazine. A greater percentage of the sulfamethoxypyridazine in the urine is in the acetylated form in rapid acetylators than in slow acetylators. This indicates that the acetylation polymorphism does influence the acetylation of sulfamethoxypyridazine. Acetyl sulfamethoxypyridazine, unlike acetyl sulfamethazine, was not detectable in the serum under the conditions of the present experiment. The serum concentration of free (i.e., nonacetylated) sulfamethoxypyridazine 30 hours after drug ingestion was not different in the two phenotypes. Possible reasons for the differences in metabolism between the two sulfonamide drugs and also implications for the predilection to sulfamethoxypyridazine toxicity are discussed. Individuals tend to acetylate sulfamethazine to a quantitatively similar extent when tested on two separate occasions. There seems to be significant variability between individuals within a given acetylator phenotype and it is suggested that this may be due to the operation of further genetic factors.
Respiratory and subjective effects of d‐ and I‐pentazocine
Authors: Bellville J. Weldon , Forrest William H.
Published: January 2016

The relative respiratory depressant potencies of the d‐ and l‐isomers of pentazocine were determined in a crossover study. The l‐isomer was found to be a potent respiratory depressant (13 mg. ≎ 10 mg. morphine). The response to 30 and 60 mg. of the d‐isomer did not differ significantly from placebo. The possibility that higher doses of d‐pentazocine might produce significant respiratory depression cannot be dismissed, however. Sub;ective effects similar to those produced by morphine were noted, although there appeared to be qualitative differences. Lightheaded and dreamy reactions were noted more frequently, for instance, after l‐pentazocine. Some effects, such as anxiety, were reported after d‐pentazocine while their opposites, stich as relaxation, were reported following administration of the l‐isomer.
The interaction of morphine and nalorphine on respiration
Authors: Bellville J. Weldon , Fleischli Gerald
Published: January 2016

A study was carried out in volunteers to determine the relative potency as respiratory depressants of nalorphine and morphine and their interaction when administered together. The relative potency of nalorphine when compared to morphine was found to be 0.74 (13.5 mg. nalorphine ≎ 10 mg. morphine). The data are consistent with the hypothesis that antagonism of the respiratory effects of morphine by nalorphine is related primarily to differences in intrinsic activity of the drugs and not solely in their receptor affinity. Thus, their interaction could be classified as competitive dualism.
Evaluation of botulinum antitoxin, supportive therapy, and artificial respiration in monkeys with experimental botulism
Authors: Oberst Fred W. , Crook James W. , Cresthull Paul , House Michael J.
Published: January 2016

A diagnosis for botulism in man probably would not be made until after signs and symptoms developed. In this study the critical time for initiation of treatment was emphasized. Rhesus monkeys were given 2.5 to 5 LD50 of botulinum toxin, type A, intravenously. As soon as toxic signs were observed, therapy was initiated. Some animals received bivalent botulinum antitoxin, types A and B, 1,000 to 2,700 U., with and without supportive treatment of liquid foods, vitamins, and antibiotics during the period of aphagia. Others also received artificial respiration (AR) and antitoxin only when respiration became inadequate. All untreated monkeys died. Antitoxin administered soon after the appearance of the very first toxic signs resulted in complete recovery in 8 out of 10 animals with supportive treatment but only 1 out of 6 when no supportive treatment was given. In monkeys with respiratory paralysis, treatment with AR and antitoxin prolonged life. Continued long‐term AR, however, may cause irreversible lung damage. It is concluded that treatment is useful even after toxic signs and respiratory paralysis occur.
Antagonism of the subjective, behavioral, pupillary, and respiratory depressant effects of cyclazocine by naloxone
Authors: Jasinski Donald R. , Martin William R. , Sapira Joseph D.
Published: January 2016

Naloxone is an opioid antagonist with little, it any, agonistic activity. Cyclazocine, on the other hand, in addition to antagoniZing the effects of morphine, produces agonistic effects in man, some of which resemble the effects produced by morphine and some of which do not. The interaction between naloxone and cyclaZOcine Wll8 assessed in 8 subjects. Naloxone antagonized the miotic and respiratory depressant as well as the behaVioral and subjective effects of cyclazocine.
Glucose tolerance prior to and during therapy with contraceptive steroids
Authors: Danowski T. S. , Sabeh G. , Alley R. A. , Robbins T. J. , Tsai C. T. , Sekaran K.
Published: January 2016

Oral glucose tolerance remained within the pretherapy range during cyclic administration of norethynodrel and ethinyl estradiol 3‐methyl ether (mestranol) in a single tablet to 17 women for 5 to 48 months. Our data and those in the literature indicate that in evaluations of oral contraceptive agents the pretherapy glltcose tolerance, the particular steroids prescribed, the schedule of dosage, and the dmation of therapy and other variables may be critical in establishing effects on glucose tolerance.
Effects of chronic administration of the amphetamines and other stimulants on behavior
Authors: Kosman Mary Ellen , Unna Klaus R.
Published: January 2016

After a brief survey of effects in man, the authors review behavioral studies in animals on the effects of chronic administration of dl‐amphetamine, d‐amphetamine, methamphetamine, cocaine, pipradrol, methylphenidate, phenmetrazine, and caffeine. The areas covered include: food and water intake, general behavior, self‐administration of drugs, activity, fatigue, and performance of learned responses. The review is primarily concerned with changes in various parameters of behavior which develop during the course of chronic drug administration. These changes include both increases and decreases in the magnitude of response, reversal of effects, and the appearance of new patterns of behavior. The effects observed after cessation of chronic drug administration are discussed with reference to withdrawal symptoms and to persistent effects which are revealed by observation of general behavior and by tests of activity, performance, learning ability, and response to various drugs. Areas in which further research is needed are mentioned throughout the review. Emphasis is placed on the need for more comparative studies on the amphetamines, as the available data suggest that, under conditions of chronic administration, the effects of methamphetamine differ significantly from the effects of dl‐ and d‐amphetamine.
Apparent effect of probenecid on the distribution of penicillins in man
Authors: Milo Gibaldi , Schwartz Michael A.
Published: January 2016

Pharmacokinetic analysis of literature data on drug serum levels after administration of ampicillin, ancillin, nafcillin, and cephaloridine, with and without probenecid, suggests a new mechanism of action of probenecid. The results indicate that while probenecid markedly diminishes tubular secretion of the drugs, this effect is not the principal one in accounting for the enhanced serum levels of drug. More important, is the fact that a significant decrease in the apparent volume of distribution of each drug in the presence of probenecid has been observed. The decrease in distribution volume results in a larger fraction of drug in the body in the central compartment and gives rise to higher serum levels. A number of possible effects of probenecid aTe explored to explain the observed phenomenon.
Methylhistamine excretion during treatment with a monamine oxidase inhibitor
Authors: Fram D. H. , Green Jack Peter
Published: January 2016

Relative levels of methylhistamine in urine increased in patients taking isocarboxazid, a monamine oxidase inhibitor.
Clinical uses of metal‐binding drugs
Authors: Chenoweth Maynard B.
Published: January 2016

To summarize the current position of metal‐chelating drugs in medicine is not difficult. Arsenic and mercury poisonings call for immediate systematic treatment with dimercaprol; symptoms of chronic lead poisoning respond well to systemic calcium disodium edetate; Wilson's disease is ameliorated by oral D‐penicillamine and all the other situations discussed are still experimental and sub iudice. Many of the observations reported on the effects of these drugs do not seem to be clearly related to metal binding. Certain toxic metals such as cadmium, thallium, beryllium, and manganese have, as yet, no notably effective antidotes.
Retention of inhaled sarin vapor and its effect on red blood cell cholinesterase activity in man
Authors: Oberst Fred W. , Koon William S. , Christensen Milton K. , Crook James W. , Cresthull Paul , Freeman Gustave
Published: January 2016

This study was conducted to determine whether retention and absorption of sarin vapor differ in (1) resting men breathing exclusively through the nose (2) or the mouth, and (3) in exercising men breathing exclusively through the mouth. Inhibition of red blood cell cholinesterase (R.B.C.‐ChE) activity was the criterion used to measure absorption. We found that the resting men retained approximately the same percentage of the vapor inhaled, but exercising men retained a significantly lower percentage. This does not mean that in an uncontrolled exposure sedentary people would receive a higher dose than active people. In fact, iust the opposite would be true because minute volume is much higher in exercising people and their total retained dose would be much higher. We also found that, regardless of route of inhalation (oral or nasal) or level of physical activity, inhibition of R.B.C.‐ChE activity was directly related to the retained dose of sarin.
Inhibition of monoamine oxidase in man by furazolidone
Authors: Pettinger William A. , Soyangco Florlisa G. , Oates John A.
Published: January 2016

Furazolidone (Furoxone) was found to be a potent inhibitor of monoamine oxidase (MAO) in man. It produced marked supersensitivity to tyramine and amphetamine, inhibition of intestinal MAO and increased urinary excretion of tryptamine. Continued administration of furazolidone produced a cumulative inhibition of MAO to the extent that chronic therapy would be expected to carry a significant risk of hypertensive crisis. However, a brief period of furazolidone administration should be free from this hazard. A safe method of quantifying changes in pressor sensitivity to tyramine is described. There is a semilogarithmic correlation between changes in response to tyramine and monoamine oxidase activity measured biochemically.
The control of viral diseases, with special reference to mumps, rubella, and interferon
Authors: Hilleman Maurice R.
Published: January 2016

The approaches to specific control of viral infectious diseases are immunologic, chemical, and host resistance (interferon). Immunologic control is discussed in reference to latest advances and progress toward control of measles, mumps, and rubella by vaccines. Mumps vaccine was recently licensed for general use and rubella vaccine should become generally available in the foreseeable future. Chemical agents offer the only significant hope for treating the cell once infected and offers some promise for prophylaxis as well. To date, the rewards have been meager considering the effort, and few chemicals of clinical usefulness have been developed. Interferon per se shows little promise as a means for preventing or treating human viral disease, primarily because of source, yield, and cost. By contrast, inducers of interferon show great promise. The recent discovery of interferon induction by double‐stranded RNA has opened a new era of possibility for utilization of the interferon mechanism and is being actively pursued.
Ethambutol hydrochloride (Myambutol tablets)
Authors:   Lederle Laboratories
Published: January 2016

Myambutol (Ethambutol) Ledede is an oral chemotherapeutic agent which is specifically effective against actively growing microorganisms of the genus Mycobacterium, including M. tuberculosis.1
The effect of disease, drugs, and dilution on the binding of sulfonamides in human plasma
Authors: Anton Aaron H.
Published: January 2016

The plasma protein‐binding capacity for sulfonamides (and presumably other drugs and endogenous substances) was found to be decreased more than 10 per cent in 4 of 16 hospitalized patients. 1n other experiments it was found that a combination of drugs significantly interfered with the protein binding of sulfonamides under conditions in which each drug by itself had only slight displacing activity. The drugs decreased the binding of the sulfonamides more when diluted plasma was used, and the interference was more marked when the drugs were tested against a less highly bound sulfonamide. It is suggested that a binding defect may contribute to the incidence of adverse reactions to drugs by making available unanticipated amounts of drug. In another series of experiments the binding of sulfonamides in human plasma was determined under the following conditions: (1) dilution of plasma protein while keeping sulfonamide concentration constant, and (2) dilution of a sulfonamide‐containing solution of plasma so as to maintain a constant ratio between protein and sulfonamide. As predicted by the law of mass action, the fraction of bound sulfonamide decreased in both situations as the protein was diluted. These results may explain the erroneous conclusion of several investigators who reported that the binding of sulfonamides in human serum did not interfere with antibacterial activity.
A clinical comparison of the effects of oral and intramuscular administration of analgesics: Pentazocine and phenazocine
Authors: Beaver W. T. , Wallenstein S. L. , Houde R. W. , Rogers A.
Published: January 2016

The relative analgesic potency of oral and intramuscular pentazocine was evaluated in a double‐blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both intensity and duration of effect are considered (total effect), oral pentazocine was one third as potent as the intramuscular form. In terms of peak effect, however, oral pentazocine was only one fourth as potent. Single oral doses of 240 mg. caused psychotomimetic reactions 4 out of 23 times. These reactions were transient and, with the possible exception of one equivocal reaction to the 60 mg. intramuscular dose, were not seen after the intramuscular or lower oral doses. Exclusive of these reactions, adverse effects were not significantly different for equianalgesic doses of oral and intramuscular pentazocine, and were, in general, similar to those associated with the administration of narcotic analgesics. Assuming that the repeated administration of oral pentazocine does not produce adverse effects unanticipated on the basis of this study of single dose administration, the oral form of the drug should be useful in treating moderately severe or severe pain which is now being treated with potent oral or parenteral narcotics.
Correlation of performance test scores with “tissue concentration” of lysergic acid diethylamide in human subiects
Authors: Wagner John G. , Aghajanian George K. , Bing Oscar H. L.
Published: January 2016

Previously published plasma concentrations of LSD‐25, observed following intravenous iniection of 2 mcg. per kilogram of LSD‐25, have been found to be explained by the two‐compartment open model. Performance scores on arithmetic tests were shown to be highly linearly correlated with the concentration in the “tissue” (outer) compartment. The estimated volume of the plasma (inner) compartment was 16.3 per cent of body weight, which is approximately the value reported for extracellular water; the estimated volume of the tissue compartment was 11.5 per cent of body weight. The estimated half‐life for loss of LSD‐25 from the plasma compartment, based on the model, was 103 minutes compared with a half‐life of 180 minutes calculated directly from plasma concentrations.
Liver disease in narcotic addicts II. The role of the needle
Authors: Sapira J. D. , Jasinski D. R. , Gorodetzky C. W.
Published: January 2016

A liver disease is described among narcotic addicts examined at the Addiction Research Center. The clinical picture is described and discussed in light of the pertinent literature. It is suggested that many narcotic addicts have a long‐term intermittent serum hepatitis, chronic addiction serum hepatitis. There is a correlation between evidences of this liver disease and the duration of exposure to hypodermic equipment.
Growth hormone and insulin during oxandrolone therapy of stunting
Authors: Danowski T. S. , Morgan Carl R. , Mintz Daniel H. , Sabeh George , Alley Richard A. , Weir Thomas F.
Published: January 2016

In a group of growth‐retarded children, generally of the constitutional type with height below the tenth or the third percentile, the mean increases in serum growth hormone ohserved between the ½‐ and 2‐hour points of an intravenous tolbutamide tolerance test were ab out the same as those recorded in a control group of normal children. Differences present in the 0 and 15 minute growth hormone values of the 2 groups were not outside the range recorded in control subjects. Also, the mean fasting and posttolbutamide levels of serum insulin, blood sugar, and serum inorganic phosphorus were of the same magnitude in the growth‐retarded and the control groups. Administration of oxandrolone, a protein anabolie steroid with relatively low virilizing properties to growth‐retarded children, at a dosage of 2.5 to 30 mg. per day for 3 months or longer, did not affect the fasting levels of serum insulin, serum inorganic phosphate, or blood sugar, nor the changes in these indices induced by tolbutamide. Growth hormone levels measured during the fasting state also remained unaltered during oxandrolone therapy. Infusion of tolbutamide or of arginine during oxandrolone treatment did not enhance growth hormone responses to these stimuli. Indeed, the peak growth hormone responses to tolbutamide and to arginine were lower during oxandrolone ingestion. In the arginine tests, the decrease in the peak growth hormone response was accompanied by lower peak levels of serum insulin.
Plasma levels and urinary excretion of hexamethylmelamine following oral administration to human subjects with cancer
Authors: Bryan George T. , Worzalla John F. , Gorske Arnold L. , Ramirez G.
Published: January 2016

An ultraviolet spectrophotometric analytical method was used to study the plasma levels and urinary metabolites of cancer patients following oral administration of the antineoplastic agent hexamethylmelamine (HMM). Maximum plasma levels varied directly with the dose administered and occurred 2 to 3 hours after drug ingestion. At clinically employed dosage levels no intact HMM was present in the plasma, but two metabolites of this drug were detected. Hemolyzed erythrocytes contained no HMM or drug metabolites. Nearly 19 per cent of a single oral dose of HMM was excreted in the urine 0 to 24 hours after administration, with an additional 12 per cent appearing between 24 and 48 hours. Following prolonged continual daily administration of HMM, 50 to 65 per cent of a daily dose was recovered from the urine as drug metabolites. At least 3 maior urinary metabolites of HMM were found in urine, but no unmetabolized HMM was recovered. These data suggest that the metabolism of HMM may be significantly different from that of its structural analogue triethylenemelamine.
Cephaloridine (Loridine)
Authors:   EH Lilly and Company
Published: January 2016

Because of nephrotoxicity (e.g., tubular necrosis) of cephaloridine at closes above 4 Gm. daily (see Warnings and Adverse Reaction), recommended doses should not be exceeded. Patients with known or suspected impairment of renal function should be under close clinical observation for changes in renal function, or be hospitalized. If impaired renal function develops during therapy, cephaloridine should be discontinued. Cephaloridine should not be used in patients with azotemia.
Drug misuse and physician education
Authors: Palmer Roger F.
Published: January 2016

There is little doubt that drugs, old and new, have reduced morbidity and mortality rates and continue to do so. It is dis‐concerting, however, to find that improper medication, polypharmacy, and adverse drug reactions are increasing to the point where drugs, either because of their pharmacologic effects, side reactions, or economic impact on the family unit, constitute what is approaching a national health problem. 2 In some reported series, adverse reactions occurred in 14 per cent of hospitalized patients and 7 per cent of these reactions were fatal or life‐threatening.4 In 5 per cent of admissions to a general hospital, drug reactions were a major factor leading to hospitalization.4
Stimulatory effect of cigarette smoking on the hydroxylation of 3,4‐benzpyrene and the N‐demethylation of 3‐methyl‐4‐monomethylaminoazobenzene by enzymes in human placenta
Authors: Welch R. M. , Harrison Y. E. , Gommi B. W. , Poppers P. J. , Finster M. , Conney A. H.
Published: January 2016

Cigarette smoking markedly increases the activity of enzymes in human placenta which hydroxylate 3,4‐benzpyrene and N‐demethylate 3‐methyl‐4‐monomethylaminoazobenzene. No detectable benzpyrene hydroxylase or aminoazo dye N‐demethylase activity was observed in 17 human placentas obtained after childbirth from nonsmokers, but these enzymes were found in the placentas obtained from 17 smokers. Considerable variability in benzpyrene hydroxylase activity was observed in placentas that were obtained from women who smoke the same number of cigarettes. Several polycyclic aromatic hydrocarbons which are present in cigarette smoke were tested for ability to induce benzpyrene hydroxylase in rat placenta. Treatment of pregnant rats with 3,4‐benzpyrene, 1,2‐benzanthracene, 1,2,5,6‐dibenzanthracene, chrysene, 3,4‐benzofluorene, anthracene, pyrene, fluoranthene, perylene, or phenanthrene increased benzpyrene hydroxylase activity in the placenta.
Statistical ward rounds—13
Authors: Mainland Donald
Published: January 2016

During October and November, 1968, I had some of the most encouraging and stimulating experiences in classroom teaching that I have ever had. A rather full account of them is being prepared for the "Notes on biometry in medical research," mentioned in the footnote on this page, beginning with Note 43 which will probably be published early in 1969. My excuse for alluding to the subject here is that the experience is likely to provide some "cases" for the Rounds.
The influence of debrisoquin on the accumulation and metabolism of biogenic amines by the human platelet, in vivo and in vitro
Authors: Solomon Harvey M. , Ashley Constance , Spirt Nena , Abrams William B.
Published: January 2016

Although the platelet has a specialized function in the control of hemostasis,13 its membrane resembles that of many other cells. For example, the platelet maintains hydrogen ions against a concentration gradient24 and actively transports certain amino acids and sugars. 23, 25 In addition its membrane is permeable to several relatively large, lipid‐insoluble organic compounds. 23 The membrane of the platelet also shares certain characteristics with that of the adrenergic neuron; both cells actively accumulate such drugs as guanethidine4, 7 and debrisoquin.5, 9 In addition, desmethylimipramine inhibits the active uptake of serotonin by the platelet20 and the active uptake of norepinephrine by the neuron.1, 12
Comparison of clorexolone, a new diuretic, with hydrochlorothiazide
Authors: Russell R. Patterson , Macaraeg Placido V. J. , Schrogie John J.
Published: January 2016

The object of this study was to compare the metabolic and hypotensive effects of clorexolone, a new diuretic which is structurally similar to benzothiadiazines and phthalimidines. Twentythree hypertensive outpatients were randomly allocated and treated for three 6 week periods with clorexolone or hydrochlorothiazide and clorexolone or hydrochlorothiazide with supplements of potassium. The treatment periods were preceded by a 3 week placebo period. Clorexolone and hydrochlorothiazide significantly reduced recumbent and standing blood pressure, weight, and serum potassium and chloride and significantly increased serum carbon dioxide‐combining power and serum uric acid and urea nitrogen levels. Hydrochlorothiazide significantly increased the fasting blood glucose; clorexolone increased the 2 hour blood glucose. The addition of potassium chloride prevented a significant reduction in serum potassium and ameliorated carbohydrate impairment only in the clorexolone‐treated group.
A statistical solution to an ethical problem
Authors: Bross I. D. J. , Schmidt M. L. , Dao T. L. , Nemoto T.
Published: January 2016

Ethical considerations sometimes preclude the use of the optimum design for a given clinical trial. Sometimes, however, it is possible to find alternative lines of statistical analysis which are ethically acceptable to the investigator and which will provide useful information on clinical issue, though less information than the optimum design. A study of adrenalectomy and chemotherapy in patients with recurrent breast cancer provides an example of a possible statistical solution to a difficult ethical problem. The effects of adrenalectomy are estimated by delaying the operation rather than withholding it entirely. Such a procedure requires that a mathematical model be developed to describe the specific experimental situation‐not, in general, an easy task. When feasible, however, the approach enables an investigator to circumvent what would otherwise be an ethical roadblock to research.
A comparison of the analgesic effects of profadol and morphine in patients with cancer
Authors: Beaver W. T. , Wallenstein S. L. , Houde R. W. , Rogers Ada
Published: January 2016

The relative analgesic potency of profadol (CI‐572) and morphine was evaluated in a double‐blind crossover comparison of graded, single intramuscular doses in patients with chronic pain due to cancer. Profadol was found to be about one fourth as potent as morphine. The time‐effect curves of the 2 drugs were similar. Profadol produced more injection‐site pain than morphine, but other effects observed after the 2 drugs were similar in kind and occurrence.
Comparison of absorption, disposal, and activity of soluble and repository corticosteroid esters
Authors: Melby James C. , Dale Sidney L.
Published: January 2016

Plasma concentrations of H3 dexamethasone and C14 dexamethasone were maximal at one and 8 hours, respectively, following the intramuscular iniection of 1,2,4‐H3‐ dexamethasone phosphate or 16‐methyl‐C14‐dexamethasone acetate. Urinary 17‐hydroxy‐corticosteroid levels return to normal 3 to 4 and 7 to 8 days following iniection of the phosphate ester and acetate ester, respectively. The minimal plasma concentration of dexamethasone for maximal suppression of the pituitary‐adrenal axis appears to be between 0.5 and 1.0 µg per cent. The slower rate of appearance in blood and the more delayed excretion of C14 compared with H3 probably reflect the slower rate of absorption of the acetate ester.
Analgesic and side effects of pentazocine and morphine in a large population of postoperative patients
Authors: Paddock Richard , Beer E. George , Bellville J. Weldon , Ciliberti Benjamin J. , Forrest William H. , Miller Elliott V.
Published: January 2016

The analgesic and side effects of pentazocine were compared with those of morphine in 1,074 surgical patients. Three separate three‐point assays were conducted. Standard doses used were 5 mg. and 10 mg. of morphine and 10 mg., 20 mg., and 40 mg. of pentazocine. The relative analgesic potency, based on a 225 minute time period for analgesic effect, was 0.28 (36 mg. of pentazocine ≃ 10 mg. of morphine). For peak pain intensity difference, the relative potency was found to be 0.38 (27 mg. of pentazocine ≃ 10 mg. of morphine).
Analgesic and other effects of the d‐ and l‐isomers of pentazocine
Authors: Forrest William H. , Beer E. George , Bellville J. Weldon , Ciliberti Benjamin J. , Miller Elliott V. , Paddock Richard
Published: January 2016

The d‐ and l‐isomers of pentazocine were compared with morphine for analgesia and other effects in two randomized, double‐blind assays involving 889 treatments in 478 patients, given principally for postoperative pain. Response to 60 mg. of d‐pentazocine was less than that to 5 mg. of morphine. Relative potency for l‐pentazocine based on effects measured up to 255 minutes was found to be 0.35 to 0.40 (25 to 29 mg. ~ 10 mg. of morphine). Sedation and sweating were common with the l‐isomer. It appears that analgesia resides principally in the l‐isomer
Psychotropic effects of caffeine in man. III. A questionnaire survey of coffee drinking and its effects in a group of housewives
Authors: Goldstein Avram , Kaizer Sophia
Published: January 2016

By means of a questionnaire, information was gathered about coffee drinking and its effects in 239 young housewives. The group was divided into roughly equal parts with respect to daily coffee consumption: abstainers, light users (1 to 2 cups); moderate users (3 to 4 cups); and heavy users (5 or more cups). The respondents were asked why they drink coffee in the morning, what behavioral changes it produces, and what effects would ensue if morning coffee were omitted. They were also asked if coffee makes them wakeful at night. The results indicate substantial differences in the responses correlated with the extent of coffee use. Heavy users reported less wakefulness caused by coffee at night and less nervousness caused by coffee in the morning as compared with light users. On the other hand, heavy users reported more of the desirable stimulant and euphoriant effects than did light users. Heavy users also described a characteristic set of dysphoric symptoms attributed to omission of morning coffee: irritability, inability to work effectively, nervousness, restlessness, lethargy, and headache. The validity of these results was confirmed in an experimental study on some of the same subjects reported in the accompanying paper.
Differential effects of scopolamine and chlorpromazine on REM and NREM sleep in normal male subiects
Authors: Sagales Teresa , Erill Sergio , Domino Edward F.
Published: January 2016

The study compares the effects of scopolamine, methscopolamine, and chlorpromazine on the EEG and the EOG in sleeping subjects. Saline was used as a control. Scopolamine hydrobromide (0.006 mg. per kilogram) clearly retarded the onset of stage REM. No immediate rebound was seien in the analysis of the sleep pattern for two hours after the first recording of this stage. The total amount of REM sleep during the full period of recording was therefore diminished. The decrease in REM resulted in an increased amount of stages I and II. No significant changes were observed in stages III or IV or in the periods of wakefulness. A significant increase in body movements was noted. Methscopolamine bromide (0.0055 mg. per kilogram) did not produce any substantial modification in the pattern of sleep. Chlorpromazine hydrochloride (0.4 mg. per kilogram) produced an increase of stage III activity apparently at the expense of stage II sleep. The observed changes further support a role of cholinergic mechanisms in human REM sleep.
Toxic and therapeutic effects of EMTP in obesity
Authors: Hollingsworth Dorothy R. , Amatruda Thomas T.
Published: January 2016

EMTP (Fenfluramine), a new anorexigenic drug without properties that stimulate the central nervous system, was used as an ad;unct to an 800 calorie diet in a 120 day, double‐blind, randomized control study of 36 obese veterans. The greatest weight loss occurred in patients who were given the drug in Period 1 of the study and the least occurred in patients given placebo in Period 11. Although EMTP appeared more effective than the placebo, its results were not dramatic (nor statistically significant). The drug caused mild to moderately severe side effects in 25 of 36 patients whereas there were only mild complaints in 11 of 28 patients receiving the placebo. The large percentage of side effects may reflect the high dosage schedule in this drug trial. There was impotence in two men. Since most obesity drug evaluations are done in obese women, this effect might be missed.
Reduction or prevention of aspirin‐induced occult gastrointestinal blood loss in man
Authors: Leonards Jack R. , Levy Gerhard
Published: January 2016

The purpose of this study was to determine if the occult gastrointestinal blood loss produced by aspirin administered in the form of conventional tablets may be reduced or prevented by using aspirin in solutions. Fifty‐seven healthy subiects received 2.6 or 3.9 Gm. of aspirin daily for 8 day periods. Blood loss in the feces was determined by the Cr51 method. The average daily blood loss was 0.5 ml. during drug‐free control periods and 3 ml. above control values when aspirin tablets were taken. After calcium‐aspirin solution with low buffer capacity and a calcium‐sodium‐aspirin solution with medium buffer capacity, average daily blood loss was 48 and 32 per cent of that produced by aspirin tablets. Highly buffered sodium‐aspirin solutions, with or without acetaminophen and caffeine, caused no bleeding. Thus, aspirininduced occult gastrointestinal blood loss may be reduced significantly or prevented by administering the drug in a solution of sufficient buffer capacity to reduce appreciably the acidity of gastric fluids. Since aspirin in solution not only causes little or no bleeding but also is more rapidly absorbed and yields higher drug concentrations in the plasma than do tablets, it is concluded that aspirin‐induced gastrointestinal bleeding is a local rather than a systemic effect under the experimental conditions.
Sulfameter (Sulfa)
Authors: Robins A. H.
Published: January 2016

500 mg. tablets, Warning. Fatalities have occurred due to the development of Stevens‐Johnson syndrome (erythema multiforme exudativum) following the use of Sulla (sulfameter). Therefore, the patient must be closely observed, and should a rash develop during therapy with Sulla, the drug should be discontinued immediately. Sulla is a sulfonamide which maintains a long‐lasting blood level due to slow excretion. Because of the long‐lasting blood levels, a smaller dosage than is normally employed with shorter‐acting sulfonamides should be administered. Since the short‐acting sulfonamides are effective for the same conditions, their use should be ruled out before the long‐acting sulfonamides are employed.
Deferoxamine mesylate (Desferal mesylate); A specific iron‐chelating agent for treating acute iron intoxication
Authors:   Ciba Pharmaceutical Company
Published: January 2016

Desferal is a compound with a specific ability to chelate iron; thus, it is of particular value in treating acute iron intoxication. As a chelating agent, Desferal complexes with iron to form ferrioxamine, a stable chelate which prevents the iron from entering into further chemical reactions. This chelate is readily soluble in water and passes easily through the kidney, giving the urine a characteristic reddish color. Theoretically, 100 parts by weight of Desferal are capable of binding approximately 8.5 parts by weight of ferric iron. In studies thus far in man and animals, Desferal does not cause any demonstrable increase in the excretion of electrolytes and trace metals.
Debrisoquin, a selective inhibitor of intraneuronal monoamine oxidase in man
Authors: Pettinger W. A. , Korn A. , Spiegel H. , Solomon H. M. , Pocelinko R. , Abrams W. B.
Published: January 2016

Indices of MAO activity were monitored during administration of debrisoquin to 4 patients with hypertension. That there was no inhibition of MAO was indicated by unaltered urinary tryptamine and tyramine excretion, no depression of intestinal mucosal MAO activity, and no decrease of intestinal inactivation of orally ingested tyramine. Inhibition of sympathetic neuronal MAO is suggested by increased sensitivity to intravenous tyramine with a slight increase in norepinephrine sensitivity, decreased urinary VMA, and increased NMN excretion. It is suggested that anatomic selectivity of enzyme inhibition is related to drug‐concentrating mechanisms in sympathetic neurons.
The effect of amphotericin B on the fungal flora in feces
Authors: Bodey Gerald P.
Published: January 2016

Doses of 600 mg., 3 Gm., and 6 Gm. of amphotericin B were administered daily in 28 clinical trials. Only 8 of the 26 (31 per cent) fungal strains present in initial stool specimens were eliminated. Fifteen new fungal strains appeared during therapy and only 3 of these were subsequently eliminated. The drug was most effective against species of Candida other than C. albicans and virtually ineffective against Saccharomyces sp. and Torulopsis glabrata. Maximum serum levels of amphotericin B in these patients were less than 0.25 p.g per milliliter. The concentration of amphotericin B in the stool specimens of patients receiving 3 Gm. per day was 6.0 to 27.8 mg. per gram. Failure to eradicate fungi from the stools was probably not due to the development of resistance to amphotericin B. Twelve patients experienced some nausea and vomiting and 2 developed cramping abdominal pain. Severe diarrhea and systemic toxicity did not occur.
Influence of repetitive dosing of tetracyclines on biologic half‐life in serum
Authors: Doluisio James T. , Dittert Lewis W.
Published: January 2016

The apparent biologic half‐lives of tetracycline, demethylchlortetracycline, methacycline, and doxycycline were found to increase from 6.3, 11, 7, and 8.3 hours to 10, 14.7, 11, and 14.5 hours, respectively, during 4 days of repetitive dosing (every 12 hours). Steady‐state serum levels predicted mathematically on the basis of the latter biologic half‐lives agreed with those observed experimentally, whereas steady‐state serum levels predicted on the basis of the biologic half‐life calculated from single‐dose studies did not. A method was developed for estimating the biologic half‐life from steady‐state serum level data; these estimates agreed well with the biologic half‐life estimated from semilogarithmic plots of serum level versus time data during the steady state and after dosing had ceased. Capsules of tetracycline phosphate complex, tablets of demethylchlortetracycline hydrochloride, capsules of methacycline hydrochloride, and capsules of doxycycline hyclate were found to produce comparable serum levels of antibiotic activity when administered at recommended doses every 12 hours.
An experimental model in dogs for studying interactions of drugs with bishydroxycoumarin
Authors: Welch R. M. , Harrison Y. E. , Conney A. H. , Burns J. J.
Published: January 2016

Experiments were carried out in dogs to investigate potentially dangerous interactions of drugs with bishydroxycoumarin that can occur in man. Dogs were treated orally with 1 mg. per kilogram of body weight of bishydroxycoumarin every other day for 39 to 44 days, and constant elevated prothrombin times and plasma levels of drug were obtained. When the dogs were given 10 mg. per kilogram of phenobarbital daily, the prothrombin time fell to normal and anticoagulant was no longer detectable in the plasma. If the dose of bishydroxycoumarin was then increased sevenfold, prothrombin times and plasma levels of drug were only slightly elevated. Phenobarbital administration was stopped, but bishydroxycoumarin was continued. Ten to 15 days after discontinuing phenobarbital, plasma levels of bishydroxycoumarin increased markedly, and all dogs developed severe hemorrhages. Administration of barbital also decreased the plasma level of bishydroxycoumarin and antagonized the activity of the anticoagulant, but barbital was less potent than phenobarbital. These effects can be explained by a stimulatory effect of the barbiturates on the metabolism of bishydroxycoumarin. When phenylbutazone and tolbutamide were given under the same conditions as the barbiturates, anticoagulant activity was first potentiated and then antagonized. This can be explained by initial displacement of bishydroxycoumarin from binding sites on plasma protein followed by a stimulatory effect of phenylbutazone and tolbutamide on the metabolism of bishydroxycoumarin.
Studies of interactions among drugs in man at the renal level: Probenecid and sulfinpyrazone
Authors: Perel James M. , Dayton Peter G. , Snell M. McMillan , Yü T. F. , Gutman Alexander B.
Published: January 2016

The interactions between the uricosuric agents probenecid and sulfinpyrazone were studied in subjects with gout by means of renal clearance experiments. It was found that in both acid and alkaline urine, probenecid markedly inhibited renal tubular secretion of sulfinpyrazone without significantly altering the maximal uric acid clearance observed with each drug alone. It was also observed that probenecid inhibits the tubular secretion of the p‐hydroxy metabolite of sulfinpyrazone. The implications of these findings are discussed in terms of multiple "cascade" renal interactions among administered drugs and their respective metabolites.