bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE INFLUENCE OF THIETHYLPERAZINE ON THE ABSORPTION OF EFFERVESCENT ASPIRIN IN MIGRAINE
Authors: WAINSCOTT GILLIAN , KASPI TASOULLA , VOLANS G.N. 
Published: July 2012

The absorption of effervescent aspirin was studied in three groups of patients during attacks of migraine. The first group received intramuscular thiethylperazine 10 min before effervescent aspirin; the second group received intramuscular metoclopramide 10 min before effervescent aspirin; and the third group received effervescent aspirin alone.
Where possible each patient was retested when headache‐free but under conditions which were otherwise as similar as possible to those during the acute attack.
Intramuscular metoclopramide corrected the impairment of drug absorption that occurred during a migraine attack, whereas thiethylperazine did not.
In the group of patients treated with thiethylperazine and aspirin, the impairment of absorption did not correlate with the duration of the symptoms, nor with the severity of the headache and nausea.
Patients treated with thiethylperazine and aspirin tended to take longer to recover than those patients treated with metoclopramide and aspirin. However, in the thiethylperazine treated group, the time to recover did not correlate with the salicylate level achieved.
ACETYLATOR PHENOTYPE AND THE CLINICAL PHARMACOLOGY OF SLOW‐RELEASE PROCAINAMIDE
Authors: CAMPBELL W. , TILSTONE W.J. , LAWSON D.H. , MUTTON I. , LAWRIE T.D.V. 
Published: July 2012

Slow‐release procainamide given 8‐hourly is shown to produce plasma levels generally accepted as giving effective prophylaxis against ventricular dysrhythmias occurring after recent myocardial infarction.
Patients can be classified into ‘slow’ and ‘fast’ acetylators of procainamide.
Knowledge of acetylator status is helpful in determining the dose of procainamide necessary to attain effective steady‐state plasma levels while avoiding toxic ones.
Acetylator status cannot be assessed accurately using sulphadimidine when the patients are also taking procainamide.
EFFECT OF PHENYTOIN THERAPY ON THYROID FUNCTION
Authors: FINUCANE J.F. , GRIFFITHS R.S. 
Published: July 2012

Serum total and free fraction of thyroxine and triiodothyronine and urinary losses of unconjugated hormones in normal subjects and in patients treated long‐term with therapeutic doses of phenytoin have been measured.
Decreases in serum total hormone concentrations with increased free fractions and resultant significant increase in the concentration of free thyroxine but not triiodothyronine were apparent in phenytoin‐treated subjects. However, serum free hormone concentrations remained within the euthyroid range.
These changes in serum free hormone concentration were reflected by an increased urinary loss of unconjugated thyroxine, but normal excretion of unconjugated triiodothyronine.
Phenytoin in therapeutic doses displaces thyroxine and to a lesser extent, triiodothyronine from binding proteins in serum and thus increases peripheral clearance of thyroid hormones.
THE RADIOIMMUNOASSAY OF TRICYCLIC ANTIDEPRESSANTS
Authors: AHERNE G.W. , PIALL E.M. , MARKS V. 
Published: July 2012

An antiserum to nortriptyline has been produced in a sheep against a nortriptyline‐bovine serum albumin conjugate. The conjugate was prepared using the reagent N‐(4‐bromobutyl) phthalimide followed by a carbodiimide reaction to link the hapten to the carrier protein.
The antibodies produced were shown to be specific for the tricyclic group of drugs.
The sensitivity of the radioimmunoassay developed is currently limited by the lack of a high specific activity label. The possibilities of developing a radioimmunoassay for nortriptyline in plasma are discussed.
A THERAPEUTIC AUDIT AT AUTOPSY
Authors: WADE O.L. , TESH D.E. 
Published: July 2012

A survey of one hundred patients submitted to autopsy has been carried out to assess the contribution of investigational procedures, surgery and drug therapy to death.
In nineteen patients drug therapy, usually appropriate and necessary therapy, was thought to have contributed to death. In five patients failure to continue therapy properly contributed to death.
The survey was not representative either of patients dying in hospital or in the community, but it suggests that a larger and more comprehensive survey should be undertaken.
α‐ADRENOCEPTOR BLOCKING DRUGS IN ASTHMA
Authors: PATEL K.R. 
Published: July 2012

The effect of α‐adrenoceptor blocking drug, thymoxamine alone and in combination with isoprenaline, was studied on the specific airways conductance (SGaw) in ten patients with extrinsic asthma.
Thymoxamine when given together with isoprenaline produced significantly greater increase in SGaw as compared to improvement achieved with isoprenaline alone.
It is suggested that the potentiation of isoprenaline induced bronchodilatation by thymoxamine is mediated by increased cyclic AMP formation in the bronchial smooth muscle.
A COMPARISON OF THE EFFECT OF FRUSEMIDE AND BUMETANIDE ON THE DIURETIC RESPONSE AND FIBRINOLYTIC MECHANISM IN MAN
Authors: MACKIE P.H. , THOMSON M.R. , LEVINE D.F. , BRANCH R.A. 
Published: July 2012

A double‐blind, crossover trial has compared the diuretic response of ten normal male subjects to the oral administration of frusemide (40 mg) and bumetanide (1 mg).
Both drugs gave a similar profile, with acute onset and cessation of response, and a marked peak effect.
There was no significant difference between the times taken for each drug to produce its peak diuretic effect.
The peak rate of diuretic response, and the total response for six hours after drug ingestion, were significantly greater after bumetanide, with respect to urinary volume and sodium excretion. The peak rate of magnesium excretion was greater after bumetanide. There was no difference between the drugs with respect to potassium, calcium or creatinine excretion or the urinary Na/K ratio. Following peak diuresis, potassium excretion did not show a linear return to its control value.
At the time of peak diuresis, both drugs caused a significant reduction of euglobulin lysis time; levels of available plasmin were significantly lowered after frusemide, and levels of active plasmin were significantly raised after bumetanide. The significance of these findings in relation to the fibrinolytic mechanism is discussed.
Estimations of plasma viscosity, serum total protein and magnesium concentrations showed that maximal haemoconcentration occurred several hours after diuresis.
PHENELZINE IN URINE: ASSAY AND RELATION TO ACETYLATOR STATUS
Authors: CADDY B. , TILSTONE W.J. , JOHNSTONE E.C. 
Published: July 2012

Phenelzine cannot be extracted as such from biological fluids.
Formation of the acetonide derivative prior to extraction allows phenelzine to be extracted and assayed by gas chromatography at levels down to 0.5 μg/ml.
At this sensitivity the drug can be detected in urine but not in plasma, after therapeutic doses.
Persons typed as slow acetylators of sulphadimidine excreted approximately twice as much unmetabolized phenelzine in urine compared to fast acetylators.
INCREASED PLATELET AGGREGATION IN PATIENTS RECEIVING CHLORPROMAZINE: RESPONSES TO 5‐HYDROXYTRYPTAMINE, DOPAMINE AND N‐DIMETHYL DOPAMINE
Authors: BOULLIN D.J. , GRIMES R.P.J. 
Published: July 2012

Platelet aggregation responses to 5‐HT, dopamine, N‐dimethyl dopamine and adenosine diphosphate were compared in normal subjects and patients treated with chlorpromazine (CPZ) for longer than 6 months.
We confirmed our previous finding that 5‐HT induced aggregation is enhanced in CPZ treated patients.
Increased aggregation responses were also observed with dopamine and N‐dimethyl dopamine.
Quantitative comparisons of aggregation rates and total changes in optical density of platelet rich plasma relative to adenosine diphosphate showed significant increases with 5‐HT, dopamine and N‐dimethyl dopamine.
Implication of dopaminergic mechanisms in the central effects of phenothiazines suggests that changes in dopamine induced aggregation responses may be useful in attempting correlations of clinical and pharmacological effects.
THE EFFECT OF FRUSEMIDE, MEXILETINE, (+)‐PROPRANOLOL AND THREE BENZODIAZEPINE DRUGS ON INTERICTAL SPIKE DISCHARGES IN THE ELECTROENCEPHALOGRAMS OF EPILEPTIC PATIENTS
Authors: AHMAD S. , PERUCCA E. , RICHENS A. 
Published: July 2012

The effects of single intravenous doses of diazepam, clonazepam, lorazepam, frusemide, mexiletine and (+)‐propranolol on the frequency of electroencephalographic (EEG) interictal spike discharges were assessed in three double‐blind placebo‐controlled trials in fourteen epileptic patients.
Diazepam (5 mg) produced a significant mean decrease of spike discharges to about one third of the control frequency. The effect developed rapidly and persisted for the duration of the study (up to 25 min after injection). A larger dose (10 mg) failed to produce a further reduction in the frequency of the spike discharges.
Clonazepam (0.5 mg), frusemide (40 mg) and lorazepam (2 mg) appeared to be as effective as diazepam in reducing spike discharges, although the effect of the latter drug seemed to develop with some delay.
Mexiletine (100 mg) and (+)‐propranolol (50 mg) did not reduce paroxysmal EEG discharges, their effects being not significantly different from that of saline.
EEG spike counting after intravenous administration of single test‐doses appeared to be both a simple and promising technique for the rapid preliminary evaluation of the clinical efficacy of new anti‐epileptic drugs.
EFFECT OF URINARY pH AND NICOTINE EXCRETION RATE ON PLASMA NICOTINE DURING CIGARETTE SMOKING AND CHEWING NICOTINE GUM
Authors: FEYERABEND C. , RUSSELL M.A.H. 
Published: July 2012

Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH.
Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum.
Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow.
Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.
DEGREE OF TOLERANCE AND THE RELATIONSHIP BETWEEN PLASMA MORPHINE CONCENTRATION AND PUPIL DIAMETER FOLLOWING INTRAVENOUS HEROIN IN MAN
Authors: TRESS KATHLEEN H. , EL‐SOBKY A.A. , AHERNE WYNNE , PIALL EVELYN 
Published: July 2012

After doses of heroin to tolerant (heroin‐dependent) persons and non‐tolerant (non‐dependent) persons, pupil diameter varies with the degree of physical dependence and the plasma concentration of the drug.
The linear regression slopes of pupil diameter on plasma drug concentration correlate with daily prescription of opiates. That is, the greater the degree of physical dependence the higher the plasma drug concentration that is required for a given degree of miosis.
It is suggested that these observations might provide the basis of a test to estimate the drug requirements of drug dependent patients attending treatment clinics.
PHARMACOKINETICS OF SUSTAINED RELEASE ASPIRIN
Authors: BROOKS P.M. , ROBERTS M.S. , PATEL B. 
Published: July 2012

Salivary salicylate concentrations were used to study the pharmacokinetics of a sustained release aspirin (SRA) in normal volunteers.
The effect of fasting, food and metoclopramide were studied.
Metoclopramide hastens absorption while a heavy meal delays absorption of SRA.
The mean urinary recovery of aspirin in all the trials was 608 mg and the different treatments did not significantly alter urinary recovery.
PHARMACOKINETICS AND METABOLISM OF TEMAZEPAM IN MAN AND SEVERAL ANIMAL SPECIES
Authors: SCHWARZ H.J. 
Published: July 2012

Absorption, excretion and detoxification of temazepam were investigated in man, mouse, rat and dog. Considerable interspecies variation was apparent with respect to excretion and metabolite patterns in blood and urine. Animal species were exposed to equal or greater concentrations of all the metabolites occurring in man.
Pharmacokinetics of temazepam in man were investigated in a single dose study at two dose levels, and in a multiple dose study. The results of both studies were analyzed and interpreted with the help of compartmental models. Values were obtained for excretion pattern (0‐∞), half lives (1.95, 0.5, 10.0 and 1.9 h), amounts in all compartments, and for steady‐state conditions.
The bioavailability of the hard gelatin capsule dosage form was compared with that of a suspension serving as the ideal dosage form, and found to be acceptable.
EFFECTS OF TEMAZEPAM, FLURAZEPAM ANDQUINALBARBITONE ON SLEEP: PSYCHOMOTOR AND COGNITIVE FUNCTION
Authors: ROTH T. , PICCIONE P. , SALIS P. , KRAMER M. , KAFFEMAN M. 
Published: July 2012

The effect of temazepam 15 and 30 mg, flurazepam 15 and 30 mg, quinalbarbitone 100 and 200 mg and placebo were studied in 14 healthy male volunteers according to a Latin‐square design. At 14‐d intervals subjects received capsules 30 min before bedtime on 2 consecutive nights and were evaluated for objective sleep characteristics, for morning estimates of sleep characteristics, and for cognitive and psychomotive performance and subjective state at 3.5, 10.0 and 22.5 h after ingestion.
Changes in sleep induction and sleep maintenance were observed with temazepam 30 mg and flurazepam 30 mg. REM sleep was suppressed by quinalbarbitone, and by flurazepam 30 mg.
Flurazepam 30 mg had the greater effect on cognitive performance, whereas quinalbarbitone 20 mg had the greater effect on psychomotive performance. Subjective assessments of alertness were most affected by flurazepam, and by quinalbarbitone 200 mg.
The results suggest that temazepam produces less residual effects and is shorter acting than quinalbarbitone and flurazepam.
DOUBLE‐BLIND EVALUATION OF THE EFFICACY AND SAFETY OF TEMAZEPAM IN OUTPATIENTS WITH INSOMNIA
Authors: FILLINGIM J.M. 
Published: July 2012

The efficacy and safety of temazepam 30 mg, compared with glutethimide 500 mg and placebo, were evaluated in double‐blind conditions in a 4‐day study in 75 outpatients with a history of insomnia.
Temazepam and glutethimide were rated by the patients as effective and significantly superior to placebo for general quality of sleep, time requiredto fall asleep, frequency of nocturnal and early morning awakenings, and duration of sleep.
Residual effects reported for temazepam and glutethimide immediately after awakening and during the day were similar to or less than those reported for placebo.
Pharmacokinetics, beta‐adrenoceptor blockade and anti‐hypertensive action of labetalol during chronic oral treatment
Authors: Sanders GL , Davies GM , Rawlins MD 
Published: July 2012

Br J Clin Pharmacol 1980 Aug;10(2):121‐61 beta‐Adrenoceptor blockade, plasma labetalol concentrations and anti‐ hypertensive actions were investigated at 2 hourly intervals during the interdose period of chronic oral therapy in six hypertensive patients. 2 beta‐adrenoceptor blockade varied during the inter‐dose period and was maximal 2 and 4 h after the oral dose (P > 0.05). 3 Systolic pressure rose during the interdose period (P > 0.05). A significant correlation was found between the degree of beta‐adrenoceptor blockade and the change in systolic pressure at 2 h after the oral dose. 4 Efficacy of labetalol as a beta‐adrenoceptor antagonist and anti‐ hypertensive drug was assessed 2 h after an oral dose during chronic eight hourly dosage in sixteen hypertensive patients. Pharmacokinetics of labetalol were studied in the same patients. 5 Peak plasma labetalol concentration occurred 2 h after the oral dose and subsequently the plasma concentration declined monoexponentially. 6 The steady state concentration (CSS) of labetalol was correlated significantly with the daily oral dose in mg kg‐1, the mid point labetalol concentration (Cmax+Cmin) divided by 2 and the isoprenaline dose ratio‐1 at 2 h after the oral dose. 7 No correlation was found between the antihypertensive effect and the CSS ng ml‐1 labetalol or between the isoprenaline dose ratio‐1 and the CSS labetalol ng ml‐1.
LOW, SINGLE DAILY DOSES OF GUANFACINE IN THE AMBULATORY TREATMENT OF HYPERTENSION
Authors: JERIE P. 
Published: July 2012

Low dose treatment with guanfacine was tested in three open‐field national studies (Belgium, France, West Germany) under general practice conditions.
Of 11,270 patients originally selected, 4,627 were evaluated after 6 weeks, 1,234 after 8 weeks and 3,504 after 12 weeks of treatment. The patients studied suffered from various forms of hypertension, classified from mild to severe. The patients' ages ranged from 16 to 93 years (mean 60 ± 12), the male/female ratio being 45: 55.
With daily doses of 1 mg and 2 mg, 85–92% of the patients were adequately controlled; in 58–70% the blood pressure was normalised. The mean reduction of both systolic and diastolic blood pressure was 16%. The heart rate did not show any significant change.
The most common side effects were dryness of the mouth (14–22% of all patients treated), drowsiness (in 5–9%), tiredness (in 3–12%) and dizziness (4–9.4%).
The results indicate that 1–2 mg guanfacine given once daily control BP in more than 80% of patients with mild to moderate hypertension when given as monotherapy and in moderate to severe hypertension when given in combination with a diuretic.
Guanfacine can be used safely in hypertensive patients with heart failure, renal failure, diabetes mellitus or coronary heart disease.
CLINICAL ASPECTS OF BLOOD PRESSURE CRISIS DUE TO WITHDRAWAL OF CENTRALLY ACTING ANTIHYPERTENSIVE DRUGS
Authors: HANSSON L. 
Published: July 2012

Sudden cessation of antihypertensive therapy, in particular centrally acting drugs such as clonidine, may cause a withdrawal syndrome characterised by a rapid increase in blood pressure, headaches, tremor, restlessness and nausea.
The withdrawal syndrome is associated with a marked increase in sympathetic activity, as indicated by the increased levels of urinary and plasma catecholamines.
The clonidine withdrawal syndrome is reproducible.
The crisis can be managed acutely either by reinstituting the drug which has been withdrawn or by giving α‐ and β‐adrenoceptor blocking drugs, either separately or in the form of labetalol.
The withdrawal syndrome can now be reproduced in animal models, but in spite of extensive studies, the exact underlying mechanism remains to be elucidated.
THE INFLUENCE OF GUANFACINE ON BLOOD PRESSURE AND LUNG FUNCTION IN HYPERTENSIVE PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE
Authors: WEVER A.M.J. , VAN BRUMMELEN P. 
Published: July 2012

The effects of guanfacine, given once daily in dosages of 0.5‐3 mg, on blood pressure and lung function were investigated in a placebo controlled single‐blind trial in 10 patients with hypertension and chronic obstructive lung disease.
Six of the 10 patients also received a thiazide diuretic in an unchanged dose throughout the study.
Guanfacine lowered diastolic blood pressure to less than 95 mm Hg in 9/10 patients.
Lung function was not influenced by guanfacine.
A dry mouth was the most frequent side effect.
Morbidity and mortality in ageing HIV‐infected haemophilia patients
Authors: van de Putte D. E. Fransen , Fischer K. , Roosendaal G. , Hoepelman A. I. M. , Mauser‐Bunschoten E. P. 
Published: July 2012

SummaryOver 25 years of follow‐up is now available for HIV‐infected haemophilia patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV‐positive haemophilia patients who were treated at the Van Creveldkliniek since 1980 and compared with data from 152 HIV‐negative patients with severe haemophilia and the general age‐matched male population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS‐related in 71%. Development of AIDS and AIDS‐related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV‐positive haemophilia patients on HAART than in HIV‐negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV‐positive haemophilia patients on HAART appear to have an increased risk of spontaneous intracranial bleeding.
The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium
Authors: Karlinsey Joyce E. , Bang Iel‐Soo , Becker Lynne A. , Frawley Elaine R. , Porwollik Steffen , Robbins Hannah F. , Thomas Vinai Chittezham , Urbano Rodolfo , McClelland Michael , Fang Ferric C. 
Published: July 2012

SummaryNitric oxide (NO·) is an important mediator of innate immunity. The facultative intracellular pathogen Salmonella has evolved mechanisms to detoxify and evade the antimicrobial actions of host‐derived NO· produced during infection. Expression of the NO·‐detoxifying flavohaemoglobin Hmp is controlled by the NO·‐sensing transcriptional repressor NsrR and is required for Salmonella virulence. In this study we show that NsrR responds to very low NO· concentrations, suggesting that it plays a primary role in the nitrosative stress response. Additionally, we have defined the NsrR regulon in Salmonella enterica sv. Typhimurium 14028s using transcriptional microarray, qRT‐PCR and in silico methods. A novel NsrR‐regulated gene designated STM1808 has been identified, along with hmp, hcp‐hcr, yeaR‐yoaG, ygbA and ytfE. STM1808 and ygbA are important for S. Typhimurium growth during nitrosative stress, and the hcp‐hcr locus plays a supportive role in NO· detoxification. ICP‐MS analysis of purified STM1808 suggests that it is a zinc metalloprotein, with histidine residues H32 and H82 required for NO· resistance and zinc binding. Moreover, STM1808 and ytfE promote Salmonella growth during systemic infection of mice. Collectively, these findings demonstrate that NsrR‐regulated genes in addition to hmp are important for NO· detoxification, nitrosative stress resistance and Salmonella virulence.