bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARISON OF THE THERAPEUTIC EFFECTIVENESS OF APRINDINE, PROCAINAMIDE AND QUINIDINE IN CHRONIC VENTRICULAR DYSRHYTHMIAS
Authors: VAN DURME J.P. , BOGAERT M.G. , ROSSEEL M.T. 
Published: July 2012

A cross‐over study with aprindine (100 mg daily after a loading dose of 200 mg), procainamide (4 times 1000 mg daily) and quinidine bisulphate (2 times 750 mg daily), all given orally, was performed in seventeen patients with stable chronic premature ventricular contractions following healed myocardial infarction.
The effectiveness of the treatment was evaluated during three consecutive weeks by continuous ambulatory tape recording of the electrocardiogram and repeated determinations of plasma levels were done.
The results showed that aprindine was more effective than procainamide and quinidine.
For the three drugs the therapeutic plasma levels varied markedly from patient to patient, but for each patient taken individually, the therapeutic activity could be correlated with the plasma levels.
BIOAVAILABILITY OF DIFFERENT PREPARATIONS OF PARACETAMOL
Authors: RICHTER ANNA , SMITH S.E. 
Published: July 2012

Plasma drug concentrations in eight volunteer subjects following oral administration of six preparations of paracetamol have been studied.
Significant interindividual differences in plasma paracetamol concentration were found within 1 h but there were no consistent differences between the different drug preparations. The results indicate that all the preparations have equivalent bioavailability.
In four subjects, tested with the same preparation on two occasions, the findings suggest that drug absorption may differ from one occasion to another.
ALTERED DISTRIBUTION OF DIGOXIN IN RENAL FAILURE—A CAUSE OF DIGOXIN TOXICITY?
Authors: ARONSON J.K. , GRAHAME‐SMITH D.G. 
Published: July 2012

Three cases are described in which renal failure was accompanied by a lowered apparent volume of distribution of digoxin. In two cases this resulted in frank digoxin toxicity and in one equivocal toxicity. In all three cases digoxin plasma levels were greater than 2 ng/ml.
The possible causes of the abnormal distribution of digoxin in renal failure are discussed.
Recommendations are outlined for the use of digoxin in patients with renal failure aimed at circumventing the problem raised by a lowered apparent volume of distribution of the drug.
DRUG ADVERTISING IN MEDICAL JOURNALS
Authors: MORGAN A.H. , JEFFERS T.A. , PETRIE J.C. , WALKER W. 
Published: July 2012

One hundred different drug advertisements from each of seven leading medical journals have been assessed.
Information about drug interactions, adverse reactions, mode of action, absorption, distribution, metabolism, excretion and cost was seldom provided in UK journals.
A requirement should exist that drug advertisements include such clinically important information. Only a few pharmaceutical companies are attempting to educate doctors through their marketing and promotional material in advertisements in medical journals.
CONTROLLED TRIAL OF FRUSEMIDE AS AN ANTIEPILEPTIC DRUG IN FOCAL EPILEPSY
Authors: AHMAD S. , CLARKE LESLEY , HEWETT A.J. , RICHENS A. 
Published: July 2012

The antiepileptic activity of oral frusemide (120 mg daily) was compared with that of an identical placebo in a double‐blind crossover trial in fourteen patients with severe focal epilepsy who were receiving long‐term therapy with established antiepileptic drugs.
A statistically significant reduction in the frequency of focal fits was seen with the active drug.
Marked drowsiness occurred in three patients during frusemide therapy, causing their withdrawal from the trial.
A slight, but significant, rise in serum phenobarbitone concentrations was observed during frusemide therapy, but no change was seen in serum primidone or phenytoin concentrations.
Frusemide significantly lowered plasma sodium and potassium concentrations, and increased plasma bicarbonate.
A CONTROLLED STUDY ON THE ANTIHYPERTENSIVE EFFECT OF A NEW β‐ADRENERGIC RECEPTOR BLOCKING DRUG, METOPROLOL, IN COMBINATION WITH CHLORTHALIDONE
Authors: JÄÄTTELÄ A. , PYÖRÄLÄ K. 
Published: July 2012

A double‐blind crossover evaluation of the antihypertensive effect of metoprolol v. placebo was carried out in a series of twenty‐three patients with mild or moderate essential hypertension who were receiving chlorthalidone (25 mg daily) as their basic treatment. An individually titrated metoprolol dosage (75–300 mg) was used. The double‐blind crossover study consisted of two 3‐month periods during which the patients received either metoprolol or placebo in addition to chlorthalidone.Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. Normotension was achieved during metoprolol‐chlorthalidone treatment in twenty‐two of the twenty‐three patients, but during placebo‐chlorthalidone treatment in only twelve of the twenty‐three patients.During the double‐blind crossover study mild side‐effects occurred during metoprololchlorthalidone treatment in fourteen patients during first month, in twelve patients during second month and seven patients during third month. During placebo‐chlorthalidone treatment side effects occurred in seven, six and seven patients, respectively.In conclusion, metoprolol caused a significant fall in blood pressure when given to patients already receiving chlorthalidone. Metoprolol in combination with chlorthalidone appears to be an effective and well‐tolerated treatment for mild and moderate hypertension in those patients not responding to chlorthalidone alone.
COMPARISON OF THE BRONCHODILATOR EFFECTS OF SALBUTAMOL INHALED AS A DRY POWDER AND BY CONVENTIONAL PRESSURISED AEROSOL
Authors: DUNCAN D. , PATERSON I.C. , HARRIS D. , CROMPTON G.K. 
Published: July 2012

A double‐blind placebo controlled comparison of the bronchodilator effects of salbutamol inhaled as a dry powder and by conventional pressurized aerosol was carried out in 20 patients with chronic bronchial asthma.
No significant difference in the bronchodilator response between 400 μg and 600 μg of dry powder and 200 μg from the aerosol was detected.
Even with the highest dose of 600 μg dry powder salbutamol no subjective or objective side‐effects were observed and the inhalation of salbutamol in a lactose base was well tolerated by all the patients.
RESPONSES OF HUMAN SKIN BLOOD VESSELS TO SYNTHETIC HISTAMINE ANALOGUES
Authors: ROBERTSON I. , GREAVES M.W. 
Published: July 2012

The vascular responses of human skin to two synthetic analogues of histamine, 2‐methyl histamine (an H1‐receptor agonist) and 4‐methyl histamine (an H2‐receptor agonist) have been studied in vivo.
Both compounds evoked dose‐related erythema, 2‐methyl histamine but not 4‐methyl histamine causing erythema mediated by an axon reflex, thus suggesting that the axon reflex and direct vasodilator action of histamine are due to H1 and H2 actions respectively.
The H1‐receptor antagonist chlorpheniramine inhibited erythema due to 2‐methyl histamine. Cimetidine, an H2‐receptor antagonist, had no effect on the reaction to 2‐methyl histamine. In contrast, the erythema reaction to 4‐methyl histamine was suppressed by both cimetidine and chlorpheniramine.
Although both histamine analogues caused wealing, this was not dose‐related within the dose range used, and neither chlorpheniramine nor cimetidine caused detectable suppression of wealing responses to either histamine analogue.
These results lend further support to the view that human skin blood vessels possess H2 as well as H1 receptors.
THE EFFECT OF LITHIUM TREATMENT ON ERYTHROCYTE MEMBRANE ATPase ACTIVITIES AND ERYTHROCYTE ION CONTENT
Authors: HESKETH J.E. , LOUDON J.B. , READING H.W. , GLEN A.I.M. 
Published: July 2012

ATPase activities were studied in erythrocyte membranes prepared from blood of patients suffering from affective disorders.
Long‐term (9–12 months) administration of lithium led to an increase in the erythrocyte membrane Na/K ATPase activity (54%) when studied on an age and sex matched basis or when the patients were studied before and after treatment. The Mg ATPase activity was also increased (38%) but there was no consistent effect of lithium treatment on Ca stimulated ATPase activity in the membranes. It is suggested that the effect of lithium treatment on Na/K ATPase was due to recovery of the patients rather than an effect of the drug.
MgATPase activity increased regardless of clinical condition. Short‐term lithium treatment (2–4 weeks) led to increased Mg ATPase activity (43%). These results suggest that lithium treatment itself causes an increase in Mg ATPase activity and that this effect is not dependent on changes in protein synthesis.
Lithium treatment (long‐term) increased the erythrocyte sodium content by 15%. No effect on plasma sodium, magnesium, potassium or erythrocyte magnesium and potassium was observed.
PLASMA, BONE, HIP CAPSULE, AND DRAIN FLUID CONCENTRATIONS OF CEPHAZOLIN DURING TOTAL HIP REPLACEMENT
Authors: PARSONS R.L. , BEAVIS J.P. , DAVID JILL A. , PADDOCK GILLIAN M. , TROUNCE J.R. 
Published: July 2012

A rapid intravenous bolus injection of cephazolin (4.0 g) was administered immediately before induction of anaesthesia to seven patients having total hip replacement.
The plasma, bone, hip capsule and drain fluid concentrations of cephazolin following rapid intravenous injection of cephazolin were all well above the minimum bactericidal concentration of this antibiotic against a wide range of organisms, in particular, the penicillin resistant Staph. aureus, most Gram negative rods and Bacteroides species that cause postoperative infections in these patients.
These results suggest that an intravenous bolus injection of cephazolin (4.0 g) given during induction of general anaesthesia should provide safe, effective prophylactic cover against all the organisms that cause postoperative wound infections in patients who undergo total hip replacement. This pharmacokinetic finding needs to be confirmed in a larger clinical trial of cephazolin.
The optimum empirical prophylactic mode of administration of cephazolin that provides high plasma and tissue concentrations during this procedure appears to be a rapid intravenous bolus injection before induction of anaesthesia.
The intravenous injections of cephazolin were well tolerated in every patient. No cases of thrombophlebitis occurred and no other side or toxic effects were reported.
PHARMACOKINETICS AND METABOLISM OF VARIOUS BENZODIAZEPINES USED AS HYPNOTICS
Authors: BREIMER D.D. 
Published: July 2012

In the management of insomnia with drugs, any action should be restricted to the duration of the night and residual effects should be absent during the day‐time. The intermittent type of drug action desired is fundamentally different from drug treatment where a constant effect is sought.
Duration of drug action is dependent on the kinetics of distribution and elimination of the parent drug and its effective metabolites. In addition biopharmaceutical factors, such as those which promote a rapid rate of absorption, are important.
These considerations serve as a guide for a review of the kinetics and metabolism of various benzodiazepines.
PHARMACOKINETICS OF CLOSELY RELATED BENZODIAZEPINES
Authors: CURRY S.H. , WHELPTON R. 
Published: July 2012

It is commonplace for drugs to vary by only minor chemical differences. This is particularly so for those seven benzodiazepines discussed in this paper which are related both as precursors and as metabolites. However, minor chemical differences may cause major differences in physicochemical and pharmacodynamic properties.
Although the physicochemical differences are difficult to relate to effect, the influence of structure on absorption, distribution and elimination is of considerable importance in governing duration of effect, as shown by studies in monkeys and in man. This in turn dictates the suitability of a particular drug as a day or night sedative, as an anticonvulsant, or as an anxiolytic.
Structure affects the relative potency of the compounds as anticonvulsants, anxiolytics or sedatives so that judicious choice of a particular compound for a particular patient and condition will lead to improved therapy. It is fallacious to consider all benzodiazepines as similar.
BIOAVAILABILITY OF TEMAZEPAM IN SOFT GELATIN CAPSULES
Authors: FUCCELLA L.M. 
Published: July 2012

Healthy volunteers received single doses of temazepam 30 mg in conventional gelatin capsules, suppositories or in solution. They experienced marked sedation and sleepiness. The onset of sleepiness was prompt after the administration of the solution; this latter showed the fastest absorption and gave the highest peak plasma levels. This observation led to the development of the soft gelatin capsule.
To assess bioavailability of the formulation, plasma levels of temazepam were determined in healthy volunteers after single oral administration of soft and hard capsules, and after seven consecutive night‐time doses of the soft capsule. Absorption from the soft gelatin capsule was faster and produced earlier and higher peak plasma levels. There were no differences in relative availability.
The apparent half‐life of temazepam after night‐time administration was shorter than after morning administration, but no change was observed between the first and seventh night‐time doses.
EFFECTS OF HYPNOTIC AND SLEEP‐INDUCING DRUGS ON OBJECTIVE ASSESSMENTS OF HUMAN PSYCHOMOTOR PERFORMANCE AND SUBJECTIVE APPRAISALS OF SLEEP AND EARLY MORNING BEHAVIOUR
Authors: HINDMARCH I. 
Published: July 2012

An acute dose comparison against placebo of the effects of nitrazepam 5 mg and temazepam 15 and 30 mg on measures of arousal and performance and on subjective assessment of sleep was carried out in 20 subjects with a history of using night‐time medication for insomnia.
Amylobarbitone (100 mg) was included as an active control and each drug was given in hard gelatin capsules. Subjects reported improved sleep with nitrazepam 5 mg and temazepam 30 mg, but there was evidence of impaired performance the next day with temazepam 30 mg.
The effect of temazepam 20 mg prepared in the Scherer formulation was compared against placebo in a further ten subjects. The subjects reported improved sleep without evidence of impaired performance the next day.
DIAZEPAM AND ITS HYDROXYLATED METABOLITES: STUDIES ON SLEEP IN HEALTHY MAN
Authors: BARBARA M. STONE 
Published: July 2012

The effects of diazepam 5, 10 and 15 mg and its hydroxylated metabolites, 3‐hydroxydiazepam (temazepam) 10, 20 and 30 mg and 3‐hydroxy, N‐desmethyldiazepam (oxazepam) 15, 30 and 45 mg on sleep in healthy man were studied in young adulthood and in middle age. The effectiveness of the drugs for sleep during the day was also investigated.
In young adults diazepam and temazepam reduced sleep onset latencies and awake activity and increased total sleep time, and temazepam also reduced drowsy sleep. The activity of oxazepam was similar to that of temazepam except that it had no effect on sleep onset latencies. In middle age the effects of diazepam and temazepam were less pronounced than would be expected from studies in young adulthood. Essentially they reduced awake activity.
During the day diazepam increased total sleep time and reduced drowsy sleep in young adults, but temazepam and oxazepam had less activity than would be expected from their effect on night‐time sleep. With temazepam there was no increase in total sleep time, although there was reduced awake activity and drowsy sleep, and with oxazepam total sleep time was increased without changes in awake activity and drowsy sleep.
It is considered that these hypnotics provide a basis for the management of sleep disturbance in persons involved in skilled activity. In limited doses each drug has hypnotic activity without residual effects on performance.
β‐Adrenoceptor blockers and the blood‐brain barrier
Authors: Neil‐Dwyer G , Bartlett J , McAinsh J , Cruickshank JM 
Published: July 2012

1 This study on 21 neurosurgical patients was set up to investigate the extent to which four chronically administered β‐adrenoceptor blockers, propranolol, oxprenolol, metoprolol and atenolol, cross the blood‐brain barrier and enter the cerebrospinal fluid (CSF) and brain tissue. The concentration in the CSF of the three lipophilic β‐adrenoceptor blockers, propranolol, oxprenolol and metoprolol, approximated to the free drug concentration in the plasma, and was a poor predictor of brain concentration. These three lipophilic β‐adrenoceptor blockers appeared in brain tissue at concentrations 10‐20 times greater than that of hydrophilic atenolol. The approximate brain/plasma ratio for propranolol was 26, for oxprenolol 50, for metoprolol 12 and for atenolol 0.2.2 The low concentration of atenolol in brain tissue is possibly responsible for the low incidence of central nervous system‐related side effects in patients on this agent compared to lipophilic β‐adrenoceptor blockers.
CENTRAL α2‐ADRENOCEPTORS AND BLOOD PRESSURE REGULATION IN MAN: STUDIES WITH GUANFACINE (BS100‐141) AND AZEPEXOLE (BHT 933)
Authors: REID J.L. , RUBIN P.C. , HOWDEN C. W. 
Published: July 2012

The haemodynamic and sedative actions of guanfacine and azepexole, two α2 adrenoceptor agonists, have been examined in hypertensive patients and normotensive subjects, respectively.
After oral dosing both drugs lowered supine and erect blood pressure, reduced plasma noradrenaline and caused subjective drowsiness lasting for 6–8 h.
The duration of hypotensive action of a single dose of guanfacine was 24–30 h allowing single daily dosing in several patients, while the duration of effect of azepexole was shorter (8 h).
After 8–10 weeks treatment with guanfacine was stopped. There was a gradual return of blood pressure to pre‐treatment levels over 4 days.
Both the sedative effect and the centrally mediated fall in blood pressure appear to result from activation of adrenoceptors of the α2 subtype.
Disruption of redox homeostasis leads to oxidative DNA damage in spermatocytes of Wolbachia‐infected Drosophila simulans
Authors: Brennan L. J. , Haukedal J. A. , Earle J. C. , Keddie B. , Harris H. L. 
Published: July 2012

AbstractMolecular interactions between symbiotic bacteria and their animal hosts are, as yet, poorly understood. The most widespread bacterial endosymbiont, Wolbachia pipientis, occurs in high density in testes of infected Drosophila simulans and causes cytoplasmic incompatibility (CI), a form of male‐derived zygotic lethality. Wolbachia grow and divide within host vacuoles that generate reactive oxygen species (ROS), which in turn stimulate the up‐regulation of antioxidant enzymes. These enzymes appear to protect the host from ROS‐mediated damage, as there is no obvious fitness cost to Drosophila carrying Wolbachia infections. We have now determined that DNA from Wolbachia‐infected mosquito Aedes albopictus (Aa23) cells shows a higher amount of the base 8‐oxo‐deoxyguanosine, a marker of oxidative DNA damage, than DNA from uninfected cells, and that Wolbachia infection in D. simulans is associated with an increase in DNA strand breaks in meiotic spermatocytes. Feeding exogenous antioxidants to male and female D. simulans dramatically increased Wolbachia numbers with no obvious effects on host fitness. These results suggest that ROS‐induced DNA damage in sperm nuclei may contribute to the modification characteristic of CI expression in Wolbachia‐infected males and that Wolbachia density is sensitive to redox balance in these flies.
Effects of chronic consumption of fruit and vegetable puree‐based drinks on vasodilation, plasma oxidative stability and antioxidant status
Authors: George T. W. , Paterson E. , Waroonphan S. , Gordon M. H. , Lovegrove J. A. 
Published: July 2012

AbstractBackgroundFruit and vegetable‐rich diets are associated with a reduced cardiovascular disease (CVD) risk. This protective effect may be a result of the phytochemicals present within fruits and vegetables (F&V). However, there can be considerable variation in the content of phytochemical composition of whole F&V depending on growing location, cultivar, season and agricultural practices, etc. Therefore, the present study investigated the effects of consuming fruits and vegetables as puree‐based drinks (FVPD) daily on vasodilation, phytochemical bioavailability, antioxidant status and other CVD risk factors. FVPD was chosen to provide a standardised source of F&V material that could be delivered from the same batch to all subjects during each treatment arm of the study.MethodsThirty‐nine subjects completed the randomised, controlled, cross‐over dietary intervention. Subjects were randomised to consume 200 mL of FVPD (or fruit‐flavoured control), daily for 6 weeks with an 8‐week washout period between treatments. Dietary intake was measured using two 5‐day diet records during each cross‐over arm of the study. Blood and urine samples were collected before and after each intervention and vasodilation assessed in 19 subjects using laser Doppler imaging with iontophoresis.ResultsFVPD significantly increased dietary vitamin C and carotenoids (P < 0.001), and concomitantly increased plasma α‐ and β‐carotene (P < 0.001) with a near‐significant increase in endothelium‐dependent vasodilation (P = 0.060).ConclusionsOverall, the findings obtained in the present study showed that FVPD were a useful vehicle to increase fruit and vegetable intake, significantly increasing dietary and plasma phytochemical concentrations with a trend towards increased endothelium‐dependent vasodilation.
Added value of a mandible movement automated analysis in the screening of obstructive sleep apnea
Authors: MAURY GISELE , CAMBRON LAURENT , JAMART JACQUES , MARCHAND ERIC , SENNY FRÉDÉRIC , POIRRIER ROBERT 
Published: July 2012

SummaryIn‐laboratory polysomnography is the ‘gold standard’ for diagnosing obstructive sleep apnea syndrome, but is time consuming and costly, with long waiting lists in many sleep laboratories. Therefore, the search for alternative methods to detect respiratory events is growing. In this prospective study, we compared attended polysomnography with two other methods, with or without mandible movement automated analysis provided by a distance‐meter and added to airflow and oxygen saturation analysis for the detection of respiratory events. The mandible movement automated analysis allows for the detection of salient mandible movement, which is a surrogate for arousal. All parameters were recorded simultaneously in 570 consecutive patients (M/F: 381/189; age: 50 ± 14 years; body mass index: 29 ± 7 kg m−2) visiting a sleep laboratory. The most frequent main diagnoses were: obstructive sleep apnea (344; 60%); insomnia/anxiety/depression (75; 13%); and upper airway resistance syndrome (25; 4%). The correlation between polysomnography and the method with mandible movement automated analysis was excellent (r: 0.95; P < 0.001). Accuracy characteristics of the methods showed a statistical improvement in sensitivity and negative predictive value with the addition of mandible movement automated analysis. This was true for different diagnostic thresholds of obstructive sleep severity, with an excellent efficiency for moderate to severe index (apnea–hypopnea index ≥15 h−1). A Bland & Altman plot corroborated the analysis. The addition of mandible movement automated analysis significantly improves the respiratory index calculation accuracy compared with an airflow and oxygen saturation analysis. This is an attractive method for the screening of obstructive sleep apnea syndrome, increasing the ability to detect hypopnea thanks to the salient mandible movement as a marker of arousals.