bluuebunny/crossref_metadata_2025_split huggingface dataset:
PRESCRIBING AIDS FOR GENTAMICIN
Authors: MAWER G.E. , AHMAD R. , DOBBS SYLVIA M. , McGOUGH J.G. , LUCAS S.B. , TOOTH J.A. 
Published: July 2012

A nomogram and a digital computer program have been developed to calculate dosage schedules of gentamicin for individual patients. The minimum input data consist of the patients' age, sex, body weight and serum creatinine concentration.
These prescribing aids have been evaluated in 36 patients with severe Gram negative infections. Renal function ranged from normal to complete anuria. Nomogram dosage schedules gave serum concentrations of gentamicin within the chosen therapeutic limits. Physician dosage schedules gave serum concentrations which sometimes exceeded and sometimes fell below these limits. The validity of the computer program was demonstrated by its ability to predict serum concentrations of gentamicin whatever the dosage schedule.
Half the patients recovered from the bacterial infection but seven remained infected and eleven died. Pseudomonas aeruginosa was the most difficult organism to eradicate.
Four of the patients who survived developed ataxia and two developed hearing loss at high frequencies. The risk of ototoxicity was a function of mean trough serum gentamicin concentration and duration of treatment. Ototoxicity was only detected in patients with serum creatinine concentrations above 3 mg/100 ml who tended to have higher trough concentrations. When treatment was prolonged beyond 8–10 days the risk of ototoxicity was increased without evidence of further substantial therapeutic benefit.
ACUTE EFFECTS OF VARYING DOSES OF PROPRANOLOL UPON OXYGEN HAEMOGLOBIN AFFINITY IN MAN
Authors: BRAIN M.C. , CARD R.T. , KANE J. , LYONNAIS J. , DOLLERY C.T. 
Published: July 2012

The effect of propranolol 2 h following doses of 10, 30, or 100 mg upon the blood oxygen‐haemoglobin dissociation curves has been studied in four normal subjects.
The pO2 at 50% saturation (p50) was not changed significantly under control conditions or after 10 and 100 mg doses. There was a just significant increase of 2 mmHg in the p50 value after the 30 mg dose.
There was no significant change in red cell adenosine triphosphate or 2, 3‐diphospho‐glycerate nor in plasma phosphate. 4 There was no correlation between plasma propranolol concentration and changes in blood p50.
AVAILABILITY OF METHAQUALONE FROM COMMERCIAL PREPARATIONS: in vitro AND in vivo STUDIES IN MAN
Authors: WILLIAMS M.E. , KENDALL M.J. , MITCHARD M. , DAVIS S.S. , POXON R. 
Published: July 2012

The plasma profiles of methaqualone obtained from different commercially available preparations have been compared. Tablets were absorbed more efficiently than capsules. Mandrax preparations achieved much higher plasma levels than Melsedin tablets or the Melsed or Sedaquin capsules. These differences appear to be due to formulation factors.
The efficacy of the different drugs as hypnotics corresponded well with the blood levels achieved.
There was a significant correlation between the in vitro 1/t50% and the in vivo peak plasma levels. Thus in vitro dissolution studies can be used to predict the efficiency of absorption of different formulations in man.
INDOMETHACIN OR AMYLOBARBITONE SODIUM FOR SLEEP IN RHEUMATOID ARTHRITIS, WITH SOME OBSERVATIONS ON THE USE OF SEQUENTIAL ANALYSIS
Authors: HUSKISSON E.C. , GRAYSON M.F. 
Published: July 2012

A double blind crossover trial in patients with rheumatoid arthritis showed that indomethacin given at night was superior to a hypnotic in providing sleep and relieving morning stiffness.
In a second trial, the combination of a hypnotic with indomethacin was not superior to indomethacin alone as judged by patients' preference, but further analysis suggested that the combination improved sleep without affecting morning stiffness.
It is argued that the use of a small closed sequential design produced too small a sample in the first trial. In the second trial, the sample was relatively large but the result was inconclusive; measurement of the response in terms of preference alone obscured the effect of treatment on one aspect of the symptomatology studied.
RATE OF ELIMINATION OF TRACER DOSES OF PHENYTOIN AT DIFFERENT STEADY‐STATE SERUM PHENYTOIN CONCENTRATIONS IN EPILEPTIC PATIENTS
Authors: HOUGHTON G.W. , RICHENS A. 
Published: July 2012

Serum phenytoin concentration, the serum half‐life of a tracer dose of carbon‐labelled phenytoin, and the ratio of the major metabolite of phenytoin to unchanged drug in urine (p‐HPPH: DPH ratio) were measured in epileptic patients on chronic anticonvulsant therapy.
A significant correlation was found between serum phenytoin concentration and half‐life, the slope of the regression line being dose dependent.
A significant negative correlation was found between serum phenytoin concentration and p‐HPPH: DPH ratio.
Increasing the daily dose of phenytoin lead to a lengthening of the half‐life and a reduction in the p‐HPPH: DPH ratio. The reverse occurred on lowering the dose.
These changes indicate that phenytoin hydroxylation is saturable.
Difficulty in achieving a stable serum phenytoin concentration within the therapeutic range may result.
THE EFFECTS OF SALBUTAMOL AND TERBUTALINE ON PHYSIOLOGICAL TREMOR, BRONCHIAL TONE AND HEART RATE
Authors: WATSON JUDITH M. , RICHENS A. 
Published: July 2012

The effects of oral doses of the bronchodilator drugs, salbutamol (4 and 8 mg) and terbutaline (5 and 10 mg), on physiological tremor, bronchial tone, heart rate and blood pressure were studied in six normal subjects.Both drugs produced a significant increase in physiological tremor, compared with placebo. Terbutaline, but not salbutamol, produced a dose related response. No significant differences were observed between drugs.Terbutaline (5 and 10 mg) and salbutamol (8 mg) produced a significant bronchodilatation compared with placebo. Dose related responses were obtained with both drugs, although this reached significance only with terbutaline.Both doses of each drug produced a tachycardia, although this was only statistically significant with the high doses.No significant change in blood pressure was observed with either drug.Peak effects of salbutamol occurred between 1 and 3 h and terbutaline between 1 and 4 hours. Both drugs were still active at 6 hours.
THE INFLUENCE OF URINARY pH ON THE ELIMINATION OF MEXILETINE
Authors: KIDDIE MOIRA A. , KAYE CM. , TURNER P. , SHAW T.R.D. 
Published: July 2012

The plasma elimination half‐life of mexiletine was measured in four subjects when the urine was rendered (a) acidic and (b) alkaline.
Urinary acidification (pH 5.0) was associated with a plasma elimination half‐life of 2.8 h and 57.5% of the intravenous dose was excreted in the urine within 48 hours. When the urine was alkaline (pH 8.0) the half‐life increased to 8.6 h with negligible amounts of drug appearing in the urine.
Urinary pH varies widely in cardiac patients and should be controlled or monitored to provide better therapeutic precision with mexiletine.
THE EFFECT OF PREDNISONE TREATMENT ON THE HALF‐LIFE OF INTRAVENOUS HYDROCORTISONE
Authors: SHENFIELD GILLIAN M. , PATERSON J.W. , COSTELLO J.F. , IJADUOLA O. 
Published: July 2012

The half‐life of hydrocortisone (Cortisol) has been measured in six patients before and after a three‐week course of prednisone given for asthma.
There was considerable variation in peak plasma level of Cortisol both within and between patients, but on both occasions the plasma half‐lives were the same.
It was concluded that short courses of prednisone have no effect on the handling of hydrocortisone.
THE PERSISTENCE OF ADRIAMYCIN IN MAN AND RAT
Authors: WILKINSON P.M. , MAWER G.E. 
Published: July 2012

Adriamycin was administered as a single intravenous dose. The plasma concentration in man and rat decayed as a double exponential function of time.
A two compartment model was used to predict plasma and tissue concentrations in man and the rat. The validity of the tissue concentration predictions was confirmed experimentally in the rat.
Tissue components had a high capacity for the drug. There was evidence in the rat of preferential accumulation in the liver, spleen and bone marrow.
The large tissue capacity and the prolonged half time for elimination predispose to accumulation. This may be responsible for the greater toxicity of treatment schedules with short intervals between consecutive doses.
ETHOSUXIMIDE: LIVER ENZYME INDUCTION AND D‐GLUCARIC ACID EXCRETION
Authors: GILBERT J.C. , SCOTT A.K. , GALLOWAY D.B. , PETRIE J.C. 
Published: July 2012

A study has been carried out to determine if ethosuximide induces liver enzymes.
Ethosuximide did not affect the urinary excretion of D‐glucaric acid by healthy adult subjects nor was the mean daily D‐glucaric acid excretion of three epileptic children on long term ethosuximide therapy different from that of three matched controls.
Ethosuximide (10 mg/kg or 50 mg/kg daily) did not influence D‐glucaric acid excretion or liver microsomal protein and cytochrome P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it increased liver microsomal protein and cytochrome P450 without altering D‐glucaric acid excretion.
These results suggest that at anticonvulsant doses ethosuximide is unlikely to induce liver enzymes. The precise relationship between D‐glucaric acid excretion and liver enzyme induction remains in doubt.
URINARY d‐GLUCARIC ACID EXCRETION AND PLASMA ANTIPYRINE KINETICS DURING ENZYME INDUCTION
Authors: DAVIS M. , SIMMONS C.J. , DORDONI BETINA , WILLIAMS R. 
Published: July 2012

Changes in urinary D‐glucaric acid excretion following a 14 day course of antipyrine to produce enzyme induction have been compared in normal volunteers with changes in plasma half lives and steady state levels of antipyrine.
Urinary D‐glucaric acid excretion for the group rose significantly with induction, while there was a significant fall in the mean plasma antipyrine half life and steady state levels. The extent of the increase in urinary D‐glucaric acid excretion was inversely related to the pre‐induction level, and this also applied to the change in antipyrine half lives.
Although in individuals, urinary D‐glucaric acid excretion and plasma levels of antipyrine changed in parallel, there was no numerical correlation in the group as a whole between these two tests either before or after enzyme induction.
These findings are consistent with other recently reported evidence that plasma drug kinetics and other microsomal enzyme functions are not necessarily affected to the same degree by agents with enzyme inducing properties.
INVESTIGATION OF SALBUTAMOL TOLERANCE
Authors: SIMS B.A. 
Published: July 2012

A double blind cross‐over study was carried out on patients with reversible airways disease attending an out‐patient clinic.
Twenty patients were given either salbutamol (200 μg) or propellant by aerosol for two week periods and in another study twelve patients were given identical tablets containing either salbutamol (4 mg) or placebo for four week periods. Both forms of therapy were taken four times per day but stopped the evening before attending the clinic.
The improvement in FEV1 10 min following salbutamol (200 μg) by aerosol was measured after previous treatment with either salbutamol or placebo administered by aerosol and orally and the results were compared statistically. This failed to show a significant difference and suggests that regular treatment with salbutamol does not lead to a decreased response.
BIOAVAILABILITY OF COMMERCIAL TETRACYCLINE PRODUCTS
Authors: BARNETT D.B. , SMITH R.N. , GREENWOOD N.D. , HETHERINGTON C. 
Published: July 2012

Thirteen commercial tetracycline products were assessed for bioavailability by in vitro and in vivo tests. Three failed the B.P. disintegration test and three products in a dissolution test released less than 50% of their stated potency by 3 hours.
In vivo bioavailability was assessed by serum and urinary data. Six products were tested by serum data over 48 h and their bioavailability profiles varied but their ranking correlated well with in vitro dissolution in water; three were better than the others. In a further study, based on urinary excretion alone, the thirteen products showed considerable variation in bioavailability. One product gave an extremely poor result (6 mg excreted in 24 hours).
These findings of generic non‐equivalence illustrate the need for adequate standards of bioavailability testing.
BIOAVAILABILITY OF DIGOXIN FROM RAPIDLY DISSOLVING PREPARATIONS
Authors: JOHNSON B.F. , LADER SUSAN 
Published: July 2012

Intestinal absorption of digoxin was assessed by determination of peak plasma concentrations, areas under plasma concentration curves over 80 h, and 10 day urinary excretion. Absorption was equal after ingestion of single doses of standard Lanoxin (Wellcome) tablets, tablets and capsules of ultra‐rapid dissolution rate material, or an oral solution of digoxin in water.
Mean plasma concentrations and dosage‐interval urinary excretion were highly similar during 14 day courses of either Lanoxin or ultra‐rapid dissolution tablets. Increased bioavailability does not result from encapsulation of solid dosage presentations, nor from increasing tablet dissolution rate beyond 75% in 15 minutes.
Fourteen day courses of tablets of slow dissolution rate produced lower and less consistent mean plasma concentrations and urinary excretion. Slow dissolution rates are associated with greater individual variability in absorption.
LITHIUM TREATMENT STRONGLY INHIBITS CHOLINE TRANSPORT IN HUMAN ERYTHROCYTES
Authors: LEE G. , LINGSCH C. , LYLE P.T. , MARTIN K. 
Published: July 2012

The influx of [14C] ‐choline and the efflux of 22Na in human erythrocytes were measured in vitro using blood from patients treated with lithium, patients not on lithium and healthy individuals.
The administration of lithium to patients significantly reduces the transport of choline; during the first 6 weeks of treatment the influx of choline is about half the normal rate, later it falls to around 10%.
This inhibition of choline transport is not dependent on the presence of lithium in the incubation medium. 4 The active and passive efflux of sodium are apparently not affected by lithium treatment.
A CONTROLLED TRIAL OF PRACTOLOL IN MILD HYPERTENSION
Authors: CHAPUT D.M. , SAINTONGE DE , ROBERTS C.J.C. , STRICKLAND I.D. , VERE D.W. 
Published: July 2012

Fifteen patients with diastolic blood pressures between 90 and 120 mmHg were admitted to a trial comparing placebo with practolol at doses up to 500 mg 12 hourly.
The trial was a double blind cross over study. Treatments were allocated at random and each treatment block lasted 12 weeks.
Ten patients completed the trial, and none of those who withdrew experienced serious unwanted effects. 4 Practolol caused significant falls in standing systolic and diastolic pressures and the supine diastolic pressure.
A COMPARISON OF THE EFFECTS OF PROSTAGLANDIN E2 AND SALBUTAMOL BY INTRAVENOUS INFUSION ON THE AIRWAYS OBSTRUCTION OF PATIENTS WITH ASTHMA
Authors: SMITH A.P. 
Published: July 2012

The effects of intravenous infusion of prostaglandin E2 (PGE2) on forced expiratory volume in 1 second (FEV1) were studied in ten asthmatic patients and compared with the effects of intravenous salbutamol.
PGE2 at infusion rates of 5, 10 and 20 μg/min for three 15 min periods resulted in a small bronchodilator effect in four patients, bronchoconstriction in four, and had no measurable effect on FEV1 in two patients; side effects were frequent and it was concluded that PGE2 was unsuitable for use in the management of attacks of asthma.
In the same subjects bronchodilatation occurred during infusion of salbutamol at flow rates of 5, 10 and 20 μg/min (six patients), 10, 20 and 40 μg/min (two patients) and 20, 40 and 80 μg/min (two patients). Serious cardiovascular effects were not encountered at flow rates of less than 20 μg/minute.
A PRELIMINARY STUDY OF THE EFFECT OF NORFENFLURAMINE ON LIPOGENESIS BY HUMAN ADIPOSE TISSUE In vitro
Authors: ASHWELL MARGARET 
Published: July 2012

Norfenfluramine is thought to be the major active metabolite of fenfluramine in man. Therefore its in vitro effect on lipogenesis in human adipose tissue from twelve patients was investigated.
Although inhibition of lipogenesis was demonstrated, the concentrations of norfenfluramine necessary (>1 mM) were much higher than normal blood levels of the drug.
There was no correlation between the degree of inhibition by norfenfluramine in vitro and fat cell size, age or relative weight of the subject. Greater degrees of inhibition were however associated with samples of tissue from patients with higher blood glycerol concentrations and lower blood triglyceride concentrations.
THE CLINICAL PHARMACOLOGY OF VILOXAZINE HYDROCHLORIDE—A NEW ANTIDEPRESSANT OF NOVEL CHEMICAL STRUCTURE
Authors: BAYLISS P.F.C. , DUNCAN S.M. 
Published: July 2012

The clinical pharmacological properties of viloxazine hydrochloride (ICI 58, 834, Vivalan), a new antidepressant of novel chemical structure, have been investigated in a series of double‐blind randomized studies comparing it with placebo and imipramine. Throughout the studies, viloxazine hydrochloride was given in single doses of 100 mg (expressed as base), and imipramine hydrochloride was given in single doses of 50 mg (expressed as salt).
The effect of viloxazine upon the following parameters was measured: pulse rate, blood pressure, forced expiratory volume, reaction time, critical flicker frequency, salivary flow, pupil size and palpebral fissure size. In addition, the possible interaction between viloxazine and alcohol was investigated using measurements of reaction time.
Both viloxazine and imipramine produced a transient tachycardia, but no consistent effect on blood pressure was seen. Neither drug had any effect upon forced expiratory volume.
The differences that emerged between viloxazine and imipramine were that viloxazine depressed critical flicker frequency whereas imipramine did not, and imipramine prolonged reaction time whilst viloxazine did not. Imipramine reduced salivary flow and increased the size of the pupil and palpebral fissure. Viloxazine did neither.
Imipramine was shown to potentiate alcohol whereas, at the doses used, viloxazine did not.
It is concluded that viloxazine appears to have less anticholinergic and possibly less sympathomimetic properties than imipramine. It is also concluded that viloxazine, unlike imipramine, does not potentiate alcohol.
THE EFFECT OF FRUSEMIDE ON INDOMETHACIN PLASMA LEVELS
Authors: BROOKS P.M. , BELL M.A. , LEE P. , ROONEY P.J. , DICK W.C. 
Published: July 2012

The pharmacokinetic and clinical effects of concurrent oral indomethacin and frusemide administration were determined in eight patients with rheumatoid arthritis.
Oral frusemide significantly reduces the plasma level of indomethacin following concurrent administration of the two drugs orally.
A profile of pain index, articular index and grip strength following oral indomethacin (50 mg) was determined and although the decrease in articular index was less when frusemide and indomethacin were given together it did not reach statistical significance.
THE ALIMENTARY ABSORPTION OF DIAMORPHINE AND MORPHINE IN MAN AS INDICATED BY URINARY EXCRETION STUDIES
Authors: TWYCROSS R.G. , FRY D.E. , WILLS P.D. 
Published: July 2012

Urine was collected over 24 h from 40 patients with advanced malignant disease who had received a known four‐hourly oral dose of either diamorphine or morphine in an elixir or of diamorphine by injection for at least 3 days.
Samples were assayed for total urinary morphine (free and conjugated) by gas‐liquid chromatography.
The percentage of the administered dose recovered as morphine was:

diamorphine hydrochloride by injection: 70% (s.d. 25)
diamorphine hydrochloride by mouth: 77% (s.d. 27)
morphine sulphate by mouth: 56% (s.d. 21)

It is suggested that diamorphine hydrochloride is completely absorbed by the ***gastro‐intestinal tract but that morphine sulphate is only some two‐thirds absorbed.
BROMOCRIPTINE AND DOPAMINE RECEPTOR STIMULATION
Authors: DEBONO A. GALEA , MARSDEN CD. , ASSELMAN P. , PARKES J.D. 
Published: July 2012

The response to different doses of bromocriptine (12.5, 25, 50 and 100 mg) has been established in six patients with Parkinson's disease.
Bromocriptine, like levodopa, causes improved mobility in patients with Parkinsonism, emesis, hallucinations, a fall in supine and erect blood pressure, increase of plasma growth hormone and suppression of prolactin concentration.
Bromocriptine (50 or 100 mg) has as great an anti‐Parkinsonian effect as average therapeutic doses of levodopa, and a longer duration of action, 6–10 hours.
In the dose range studied, bromocriptine appears to be a complete dopamine agonist, although 100 mg was less effective than 50 mg in two patients.
The different actions of bromocriptine and other dopamine agonist drugs may result from stimulation of different types of dopamine receptor.
ADRENOCEPTOR RESPONSIVENESS IN BRONCHIAL ASTHMA: EFFECT OF ISOPRENALINE INHALATION ON PLASMA CYCLIC 3′,5′‐AMP LEVELS
Authors: TREMBATH P.W. , SHAW J. 
Published: July 2012

The effect of isoprenaline inhalation on plasma levels of cyclic AMP has been studied in a group of normal subjects and compared to a group of asthmatics.
The normal subjects had a prompt rise in their plasma cyclic AMP level, and when compared to the asthmatic group, had a significantly greater percentage rise in plasma cyclic AMP from the basal levels.
The markedly attenuated response to isoprenaline inhalation in the asthmatic group is consistent with the concept that asthmatics have a relative impairment of β‐adrenoceptor function.
These results support the in vitro studies demonstrating that lymphocytes from asthmatic subjects incubated with isoprenaline produce less cyclic AMP than those from normal subjects.
THE EFFECT OF METOPROLOL AND PRACTOLOL ON LUNG FUNCTION AND BLOOD PRESSURE IN HYPERTENSIVE ASTHMATICS
Authors: FORMGREN H. 
Published: July 2012

The effect of metoprolol, a new β1‐adrenoceptor blocking agent, was compared to practolol in the treatment of hypertension in seventeen asthmatics during concurrent optimum bronchodilator therapy with a selectiveβ2‐adrenoceptor‐stimulant.The two β‐adrenoceptor antagonists were given at two dose levels, practolol (200 mg and 400 mg) daily, and metoprolol (100 mg and 200 mg) daily, in a twice‐daily. dosage schedule, at 12 h intervals, for 17 days. The comparison was made double‐blind and a crossover design was used. The drugs were given in randomized order. The study started with a run‐in placebo period and there was a washout period on placebo between the treatment periods. Spirometry, blood pressures and heart rates were recorded in a standardized manner.At the lower dose levels no influence on FEV1was noted, and no difference was found between the two active drugs. At the higher dose level FEV1was reduced by both β‐adrenoceptor‐blocking drugs. Four out of twelve patients given the higher dose experienced exacerbation of their asthma. The heart rate fell with both drugs and at both dose levels. During the placebo period a marked increase of heart rate was noted. The blood pressure fell at both dose levels compared to placebo, no difference being recorded between the two drugs.Metoprolol and practolol are equally effective β1‐adrenoceptor blocking drugs. In this study it was found that metoprolol could be used in asthmatics who had indications for β‐adrenoceptor blockade, provided that the total daily dose did not exceed 100 mg. Optimal bronchodilator treatment with a bronchoselective β‐adrenoceptor agonist is an absolute prerequisite in order to avoid the risk of aggravation of asthma.