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Biomedical subjects

E C Meyer

Publications and source records attributed to E C Meyer.

At least 37 records · Page 2Linked to original sources
PubMed1992

The absorption characteristics of six sustained-release theophylline preparations.

Dosing intervals for sustained-release theophylline preparations depend on the rate of formulation absorption, the rate of elimination by the patient, and clinically acceptable fluctuations in serum concentration. A comparative study of intersubject variation in fraction absorbed-time profiles, a process-independent method of comparing rates of absorption, was performed with 6 sustained-release preparations in 6 healthy male volunteers. The sulphasalazine/sulphapyridine method of assessing orocaecal transit time was implemented so that upper gastrointestinal and colonic absorption could be estimated. Time until 90% absorption varied from 4.43 hours to 7.46 hours and the mean percentages of theophylline remaining to be absorbed from the colon were limited to between 7.5% and 29.7% with the various formulations. There was a great intersubject variability in the rate of theophylline absorption and also considerable differences among the volunteers in their formulation-to-formulation absorption profiles. Promotional literature depicting mean or group data masks this variability in absorption profiles. Because host factors related to gastro-intestinal physiology impose highly variable theophylline absorption profiles on sustained-release formulations, it is technically impossible to formulate a suitable once-a-day product for the majority of patients.

Adult↗
PubMed1992

Properdin factor B and complement factor C4 allotypes in rheumatoid arthritis: results of a follow-up study.

The association between allotypes of properdin factor B (Bf), the fourth component of complement (C4A and C4B), and rheumatoid arthritis (RA), was investigated in a well-characterized cohort of RA patients who were followed from an early phase of the disease for a mean duration of 6 years. The frequencies of probable heterozygous C4AQ0 and of C4A3 were lower in RA patients compared to controls, irrespective of the presence of DR4 [relative risk (RR): 0.52 and 0.49, respectively, 95% confidence intervals (95% CI): 0.34-0.80 and 0.29-0.82]. The frequency of C4A4 was higher in RA patients compared to controls (RR: 1.86, 95% CI: 1.03-3.35), especially in DR4 positive RA patients compared to DR4 positive controls (RR: 2.58, 95% CI: 1.07-6.25), indicating a positive association of this allotype with RA additional to DR4. Bf and C4B allotypes were comparable in RA patients and controls. We did not find significant differences in Bf and C4 allotype frequencies in RA patients subdivided according to severity of the disease into a mild group and a progressive group. Because of inconsistent results in all studies on Bf and C4 allotypes, we conclude that C4 and Bf allotypes do not seem to have an important independent effect on determining disease susceptibility.

Adult↗
PubMed1992

The influence of codeine, propantheline and metoclopramide on small bowel transit and theophylline absorption from a sustained-release formulation.

1. The effects of the anticholinergic agent, propantheline, the opiate, codeine, and the prokinetic agent, metoclopramide, on oral-caecal transit time and on the absorption of theophylline from a sustained-release formulation were examined in six healthy male volunteers. 2. A cross-over randomised sequence design was followed, allowing at least 2 weeks interval between studies. On each occasion 500 mg theophylline in a sustained-release formulation was taken simultaneously with 2 g sulphasalazine at zero time. On three of the four occasions one of the following treatments was given concurrently at -0.5 h, +3.5 h, and +7.5 h: 30 mg codeine phosphate, 30 mg propantheline bromide, or 10 mg metoclopramide monohydrochloride. 3. The appearance of sulphapyridine in the plasma was used to assess oral-caecal transit time and the mean fraction absorbed-time profile of theophylline was calculated from serial serum theophylline concentration measurements using the Wagner-Nelson method. 4. Codeine increased the mean (s.d.) oral-caecal time (h) significantly (5.14 +/- 0.94) compared with the control value (3.78 +/- 0.34). Propantheline inhibited peristaltic contractions to such an extent that the oral-caecal transit time in five of the volunteers was between 9 and 25 h, while sulphapyridine appeared in the 9 h serum sample of the sixth. Metoclopramide did not significantly alter the oral-caecal transit time. 5. Despite the observed changes in oral-caecal transit time the rate and extent of theophylline absorption was similar with all regimens.

Adult↗
PubMed1992

Maternal self-esteem: from theory to clinical practice in a special care nursery.

Maternal self-esteem is examined from theoretical and clinical perspectives. The construct of maternal self-esteem is described, and infant and maternal factors affecting it are delineated. These factors include infant health, maternal perception of infant health, and newborn characteristics. Particular emphasis is placed on maternal perception of the infant's health and behavior. The preterm infant within the context of the special care nursery is used as a clinical illustration, thus bridging the gap from theory to clinical practice. General unit guidelines and clinical intervention strategies, for all disciplines, are suggested to enhance the maternal self-esteem of preterm mothers.

Female↗
PubMed1991

The effect of verapamil on cardiac sympathetic function.

We have used systolic time intervals (STI) to measure inotrophy and chronotropy as indirect measures of the actions of noradrenaline, in order to ascertain whether the depletion of cardiac noradrenaline stores which has been shown to occur in laboratory rats after chronic verapamil treatment could be demonstrated in healthy volunteers. Placebo, verapamil, or atenolol were given by slow intravenous injection to 8 healthy volunteers and QS2I, LVETI, and PEP/LVET were measured. Verapamil pretreatment resulted in a positive inotropic state. Intravenous verapamil after oral pretreatment caused accentuated negative inotropic and chronotropic responses as compared with acute verapamil without pretreatment. We postulate that the observed initial inotropic effect may be in part due to an increase in the amount of noradrenaline available to the myocardium intrasynaptically, and that the accentuated negative response after intravenous or oral verapamil may result from a decrease in cardiac noradrenaline storage.

Adult↗
PubMed1991

Atropine and verapamil interactions in healthy volunteers.

The calcium antagonist falipamil, a chemical congener of verapamil, has anticholinergic properties. It was decided to study the interaction of verapamil with the anticholinergic drugs, atropine and pirenzepine, using healthy male volunteers. After atropine alone a significant tachycardia developed at 2 min and remained significant up to 90 min. Verapamil pretreatment followed by atropine administration resulted in a significantly greater tachycardia. Pirenzepine alone caused a bradycardic response which was accentuated after verapamil pretreatment. It is postulated that short term verapamil administration is accompanied by reflex activation of the sympathetic nervous system which does not manifest with a tachycardia owing to combined influence of verapamil and vagus on the sino-atrial node. Reduction of vagal tone with atropine treatment results in sympathetic overriding of the sino-atrial suppression, thus causing an additive tachycardia. The clinical use of atropine for prolonged verapamil-induced atrio-ventricular conduction is supported by these results.

Adult↗
PubMed1991

Effects of enhancement and antagonism of 5-hydroxytryptamine activity on metoclopramide-induced aldosterone secretion in man.

This study examines the contribution of the serotonergic system to metoclopramide-induced aldosterone secretion. Six normal male volunteers, at 13 h, 9 h, and 2 h before the i.v. bolus of 10 mg metoclopramide, received the following pre-treatments in a single-blind cross-over randomized sequence: fluoxetine 20 mg, metergoline 6 mg, pizotifen 0.5 mg, or methysergide 2 mg. One regimen consisted of metoclopramide alone. Pizotifen and fluoxetine pre-treatment increased metoclopramide-induced aldosterone secretion significantly after 15 min, for the duration in the case of fluoxetine, and up to 90 min with pizotifen. The increase with metergoline was never significant, while methysergide had a negligible influence. Serotonin is postulated to play an intermediary role in acetylcholine-facilitated aldosterone release. The mechanism of fluoxetine-mediated serotonin increase is a re-uptake inhibition and that of pizotifen is suggested to be the elimination of an auto-inhibitory mechanism.

Acetylcholine↗
PubMed1991

The influence of co-administered organic acids on the kinetics and dynamics of frusemide.

1. This study examines the effects of pretreatment with probenecid with and without pyrazinamide on the elimination kinetics and diuretic action of frusemide. 2. Six normal male volunteers received 40 mg frusemide i.v. on three occasions; i.e. once on its own and twice after pretreatment with 2 g probenecid with and without 3 g pyrazinamide. Both these latter drugs were administered orally 3 h before frusemide administration thereby attempting optimal suppression of proximal tubular secretion. Urinary losses were replaced i.v. with isovolumetric amounts of normal saline while insensible losses were compensated for by taking tap water orally. 3. The mean cumulative urinary frusemide excretion was significantly and similarly decreased by pretreatment with probenecid (34.9%) and probenecid plus pyrazinamide (33.6%), but the mean total volume of diuresis and the mean cumulative urinary sodium excretion did not differ significantly between treatments over the 5 h period. 4. The diuretic efficiency of frusemide was significantly increased with probenecid pretreatment during the first 90 min period after frusemide administration. Furthermore, in the first 30 min after administration the percent sodium fractional excretion was higher after pretreatment with probenecid even though the mean frusemide excretion rate was more than three times with frusemide alone than with probenecid-frusemide (374.4 micrograms min-1 vs 119.1 micrograms min-1). Pretreatment with probenecid results in a higher concentration on the peritubular or blood side of the tubules and these results lead us to question the unconditional acceptance of a luminal site of action for the loop diuretics. Alternatively, probenecid may act in some other way to increase the effects of frusemide.

Adult↗
PubMed1991

Monotherapy of stable angina pectoris with bopindolol in comparison with diltiazem.

The efficiency of bopindolol (B) in the treatment of moderate stable angina pectoris was compared with that of diltiazem (D) by clinical evaluation and exercise tolerance. Following washout of previous treatment, patients were randomly assigned to either medication: 16 to D and 15 to B. The initial dose of B was 1 mg once daily, increased after 4 weeks to 2 mg once daily; the respective doses of D were 120 and 240 mg, given in 4 divided doses. Therapy resulted in an average decrease of 22 pain episodes and 256 min of pain time per month in the B group, whereas the respective reductions in the D group were 1.65 episodes and 129 min. Improvement in the exercise test indices following 8 weeks of treatment was more marked in the B group than in the D group. The average double product at peak exercise decreased markedly in the B group and more moderately in the D group. Thus, 2 mg B given once daily effectively blocked B receptors and relieved angina more efficiently than 240 mg D given in 4 divided doses.

Adrenergic beta-Antagonists↗
PubMed1990

Fraction of theophylline in sustained-release formulation which is absorbed from the large bowel.

In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in the blood provides an approximation of the oral--caecal transit time. The mean fraction absorbed--time profile was calculated from serial serum concentration measurements of theophylline by a modification of the Wagner-Nelson equation. The mean cumulative fraction of the dose absorbed following administration of the plain tablets was maximal at 3 h i.e. approximately 3 h ahead of the mean oral-caecal transit time, which was 5.9 h. Thus complete absorption occurred in the small intestine. With the sustained--release formulation, approximately only half of the dose was absorbed at the time the medication reached the large bowel i.e. at about 5.4 h. Absorption continued and at least 38% of the administered dose was additionally absorbed over the next 25 h. A reliable lengthened dosage interval is therefore possible with this particular sustained--release formulation.

Adult↗
PubMed1990

Inotropic effects of ranitidine.

The purpose of this controlled study was to study the effect of cimetidine and ranitidine on the myocardium of 8 healthy male volunteers using systolic time intervals. Ranitidine caused a significant decrease in the QS2I, as from 40 min indicating a positive inotropic effect. There were no significant changes in heart-rate or blood-pressure. It is postulated that ranitidine, differing structurally from cimetidine, may have a higher affinity for H2-presynaptic receptors at the sympathetic myocardial junction resulting in an increase in noradrenaline and an increased inotropic effect.

Adult↗
PubMed1990

Circulating met-enkephalin in trained athletes during rest, exhaustive treadmill exercise and marathon running.

Twelve trained male athletes were subjected to a progressive intensity treadmill exercise test to total exhaustion and at a later date took part in the Comrades Marathon. Blood was taken in order to determine whether plasma met-enkephalin levels increase in an exercise-intensity dependent manner. The mean concentrations in f mol/ml were as follows: post-exercise levels (266) were significantly higher than basal levels (172), and the post-marathon levels (378) rose significantly above the post-exercise levels. The magnitude of the responses is thus correlated with the amount of work performed and would suggest that this opioid peptide is involved in physiological actions that perhaps extend beyond the pharmacological actions of opiate drugs.

Adult↗
PubMed1990

The effect of neostigmine on metoclopramide-induced aldosterone secretion after the administration of muscarinic antagonists in man.

In this study the effects of neostigmine on metoclopramide-induced aldosterone secretion were examined in the presence of a relatively selective M1-antagonist, pirenzepine and of a non-selective muscarinic antagonist, atropine. Six normal male volunteers received metoclopramide, 10 mg i.v. on three different occasions, each study day being preceded by a day in which the intake of sodium and potassium was limited. The dosing was either metoclopramide alone or combined with either neostigmine and pirenzepine or with neostigmine and atropine. Serum aldosterone increased significantly with all three regimens. The highest levels were attained with the metoclopramide/neostigmine/pirenzepine regimen and those were significantly higher than those after metoclopramide alone and also, from 45 min onwards, from those after the metoclopramide/neostigmine/atropine regimen. The results of this investigation suggest that the metoclopramide-induced aldosterone secretion in humans is augmented by an accumulation of acetylcholine at the nerve-zona glomerulosa junctions and that the receptors mediating aldosterone secretion are of the M2-subclass of muscarinic receptors.

Adult↗
PubMed1990

The effect of autonomic blockers on heart rate: a comparison between two ethnic groups.

The influence of autonomic blockers on the heart rate of ten Bushmen and eight White volunteers was studied. There were significant differences in heart rate response to atropine alone between the White's and Bushmen. However, after prior beta-adrenoceptor blockade, these differences were no longer significant. It is postulated that a varying pharmacogenetic sensitivity to autonomic blockers may result from inequality of vagal or sympathetic tone.

Adrenergic beta-Antagonists↗
PubMed1990

Vitamin E and benign breast disease.

Vitamin E has been used in the treatment of benign breast disease for 25 years. To evaluate the efficacy of treatment by means of mammography as the objective and sensitive parameter, 105 women were randomly selected and entered into a double-blind, placebo-controlled crossover trial. All patients had mammographic evidence of benign breast disease. They received 600 mg of placebo and alpha-tocopherol acetate in 3-month treatment phases. Breast examinations and mammography were done, after each treatment, at approximately the same phase of the patients menstrual cycle. No significant subjective or objective effects after treatment were observed. We conclude that alpha-tocopherol is not beneficial in the treatment of benign breast disease. We would warn against the use of alpha-tocopherol for misdirected treatment of undiagnosed overt disease because such treatment may delay the diagnosis of breast cancer.

Adult↗
PubMed1990

The mean cumulative fraction absorbed-time profiles of paracetamol as an index of gastric emptying.

The purpose of this study was to measure gastric emptying by using the cumulative fraction absorbed-time profiles of paracetamol. To evaluate the validity of the method as an index of gastric emptying, six healthy male volunteers were entered into an ethically approved trial using different regimens of cholinergic enhancing (i.e. metoclopramide and neostigmine) and blocking agents (i.e. atropine and pirenzepine) and the results were compared with the bioavailability (i.e. Cmax, Tmax, AUC) parameters of paracetamol as an index of gastric emptying. The cumulative fractional absorption of paracetamol appears to be a valuable index for the measurement of gastric emptying.

Acetaminophen↗
PubMed1989

Effect of neostigmine on metoclopramide-induced aldosterone secretion in man.

This study examines the role of a neostigmine-induced increase in acetylcholine on the aldosterone stimulating effect of metoclopramide. Six normal male volunteers received the following three treatments in a cross-over randomized sequence: neostigmine, 0.5 mg s.c.; metoclopramide 10 mg i.v.; and neostigmine 0.5 mg s.c., followed by metoclopramide 10 mg i.v. Metoclopramide increased serum aldosterone significantly to 161% of basal level at 15 min. With neostigmine aldosterone levels peaked (129%) significantly at 30 min. In the presence of neostigmine, however, the metoclopramide-induced aldosterone response was blunted significantly. These results would suggest that presynaptic autoreceptors depresses the continued output of acetylcholine, thereby blunting the aldosterone responses to metoclopramide significantly.

Adult↗