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PubMed1987

Relative efficacy of maintenance therapy with theophylline, inhaled albuterol, and the combination for chronic asthma.

The relative benefit of maintenance therapy with theophylline, inhaled albuterol, and the combination was examined in 18 adolescents and adults with chronic asthma during a 3-month, randomized, double-blind, crossover trial. Theophylline and combination regimens were associated with significantly fewer days with symptoms (52% and 55%) than albuterol (72%). The greater frequency of symptoms during the albuterol regimen was increasingly apparent more than 4 hours after albuterol doses and was greatest between 4 and 8 A.M. Albuterol transiently inhibited histamine-induced bronchospasm to a much greater degree than did theophylline, and combining the drugs produced at least an additive effect. The effect of albuterol was completely absent by 4 hours, however, whereas that of theophylline persisted. Thus, in spite of greater acute effects on the airways, the transient duration of effect from inhaled albuterol appears to limit its usefulness as maintenance therapy, especially for patients with nocturnal symptoms.

Adolescent↗
PubMed1992

Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations.

The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control.

Adult↗
PubMed2003

Effect of chronic bilateral subthalamic nucleus (STN) stimulation on postural control in Parkinson's disease.

Postural instability is one of the most incapacitating factors in Parkinson's disease (PD). The underlying deficits and the effects of treatment are still not well understood. The aims of the present study were: (i) to identify abnormalities of postural control in PD patients during unperturbed stance and externally perturbed stance (anterior-posterior tilts of the support surface and of the visual scene); (ii) to assess the effects of L-dopa medication and subthalamic nucleus (STN) stimulation on posture control; and (iii) to characterize potential differential or additive effects of both treatments. Eight PD patients under chronic STN stimulation were investigated and compared with 10 normal controls. The assessment was performed in a crossover design (+/- STN stimulation, +/- L-dopa). During unperturbed stance, we recorded measures of spontaneous sway in terms of displacement, velocity and frequency of the centre of pressure (COP), lower body (LB) and upper body (UB) excursions. In addition, inter-segmental UB-LB coupling was investigated as a measure of axial stiffness. All these measures were abnormally large in patients OFF treatment. Under L-dopa treatment, the velocity, frequency and coupling measures were reduced, whereas sway amplitude increased. Very similar effects were obtained under STN stimulation, and these effects became more pronounced in the combined treatment condition. In these data, reduction of inter-segmental coupling correlated with increase in sway amplitude. The finding suggests that axial stiffness reduction under treatment revealed a treatment- resistant deficit in the sensorimotor postural control loop. However, these two effects did not correlate with the motor subscores of the unified Parkinson's disease rating scale (UPDRS), which indicates that they are of minor functional relevance for posture control. A frequency peak in the COP excursions at 0.7-1.1 Hz, which we take to indicate a resonance behaviour of the postural control loop, became reduced under therapy. The reduction of this peak did correlate with most improvements in the UPDRS under therapy. Support surface tilt revealed that an UB righting on the LB segment, which is present in normal controls, is missing in the patients. The postural responses to visual tilt were abnormally large in patients, independent of whether the support was stable or slightly moving, while the control subjects clearly profited from a stable support. This finding suggests that PD patients lack the ability of normal subjects to use sensory or cognitive information when suppressing the destabilizing effect of visual tilt. These abnormal tilt reactions of the patients were resistant to treatment with L-dopa, STN stimulation and a combination of the two. Overall, the effects of STN stimulation on posture control essentially paralleled those of L-dopa during both unperturbed and externally perturbed stance.

Activities of Daily Living↗
PubMedDate not supplied

The location of a mutator factor in a strain of Drosophila melanogaster by assaying male recombination.

In a set of "mutation accumulation lines," of Drosophila melanogaster that had originated from two different wild-caught lethal-carrying second chromosomes (Yamaguchi and Mukai 1974; Mukai and Cockerham 1977; Voelker, Schaffer and Mukai 1980) a correlation exists between high rates of reverse mutation at two visible loci and the ability to induce male recombination (Scobie and Schaffer 1982). The second and third chromosomes were extracted from the lines demonstrating these phenomena and tested for independent ability to induce male recombination. When the wild chromosome being tested was of male origin extracted second chromosome lines were found to induce moderate to high levels of male recombination and reduced transmission frequency of the wild chromosome (the k value). The recombinants recovered in these crosses also demonstrated a high level of double-crossover recombination without the recovery of the reciprocal double-recombinant types. In addition, identifiable portions of extracted second chromosomes of male origin have been placed on very similar, marked genetic backgrounds and tested for their ability to induce male recombination. Results of this procedure have identified two regions of the second chromosome that induce male recombination and reduce k values. These results are consistent with the hypothesis that there exist two mutator factors and the second chromosome, each associated with a "mutation accumulation line" with an unstable locus.

Animals↗
PubMed1995

Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes.

We have constructed novel DNA substrates (one inverted and three direct repeats) based on the same 0.6-kb repeat sequence to study deletions and inversions in Saccharomyces cerevisiae. Spontaneous deletions occur six to eight times more frequently than inversions, irrespective of the distance between the repeats. This difference can be explained by the observation that deletion events can be mediated by a recombination mechanism that can initiate within the intervening sequence of the repeats. Spontaneous and double-strand break (DSB)-induced deletions occur as RAD52-dependent and RAD52-independent events. Those deletion events initiated through a DSB in the unique intervening sequence require the Rad1/Rad10 endonuclease only if the break is distantly located from the flanking DNA repeats. We propose that deletions can occur as three types of recombination events: the conservative RAD52-dependent reciprocal exchange and the nonconservative events, one-ended invasion crossover, and single-strand annealing (SSA). We suggest that one-ended invasion is RAD52 dependent, whereas SSA is RAD52 independent. Whereas deletions, like inversions, occur through reciprocal exchange, deletions can also occur through SSA or one-ended invasion. We propose that the contribution of reciprocal exchange and one-ended invasion crossover vs. SSA events to overall spontaneous deletions is a feature specific for each repeat system, determined by the initiation event and the availability of the Rad52 protein. We discuss the role of the Rad1/Rad10 endonuclease on the initial steps of one-ended invasion crossover and SSA as a function of the location of the initiation event relative to the repeats. We also show that the frequency of recombination between repeats is the same independent of their location (whether on circular plasmids, linear minichromosomes, or natural chromosomes) and have similar RAD52 dependence.

Chromosome Inversion↗
PubMed2002

Dynamic structure of He-Ne mixtures by molecular dynamics simulation: from hydrodynamic to fast and slow sound modes.

Molecular dynamics (MD) results for the dynamic structure of a He(0.77)Ne(0.23) gas mixture at two densities (15.8 and 36.1 nm(-3)) show a clear crossover from hydrodynamic modes to distinct excitations for the two species. The higher density dispension curve neatly shows high- and low-frequency branches setting on with a rather localized transition. The lower density results agree very well with existing neutron scattering data and, in particular, display hydrodynamic behavior up to k approximately 2 nm(-1), in contrast with the conclusions of previous simulation studies. A smooth transition to fast sound is shown to take place for 2<k/nm(-1)<5, where the present MD data fill the existing gap in the experimental results.

Journal Article↗
PubMedDate not supplied

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Adolescent↗
PubMed2001

Triggering myocardial infarction by marijuana.

BACKGROUND: Marijuana use in the age group prone to coronary artery disease is higher than it was in the past. Smoking marijuana is known to have hemodynamic consequences, including a dose-dependent increase in heart rate, supine hypertension, and postural hypotension; however, whether it can trigger the onset of myocardial infarction is unknown. METHODS AND RESULTS: In the Determinants of Myocardial Infarction Onset Study, we interviewed 3882 patients (1258 women) with acute myocardial infarction an average of 4 days after infarction onset. We used the case-crossover study design to compare the reported use of marijuana in the hour preceding symptoms of myocardial infarction onset to its expected frequency using self-matched control data. Of the 3882 patients, 124 (3.2%) reported smoking marijuana in the prior year, 37 within 24 hours and 9 within 1 hour of myocardial infarction symptoms. Compared with nonusers, marijuana users were more likely to be men (94% versus 67%, P<0.001), current cigarette smokers (68% versus 32%, P<0.001), and obese (43% versus 32%, P=0.008). They were less likely to have a history of angina (12% versus 25%, P<0.001) or hypertension (30% versus 44%, P=0.002). The risk of myocardial infarction onset was elevated 4.8 times over baseline (95% confidence interval, 2.4 to 9.5) in the 60 minutes after marijuana use. The elevated risk rapidly decreased thereafter. CONCLUSIONS: Smoking marijuana is a rare trigger of acute myocardial infarction. Understanding the mechanism through which marijuana causes infarction may provide insight into the triggering of myocardial infarction by this and other, more common stressors.

Adult↗
PubMed2006

A sex-linked allele, autosomal modifiers and temperature-dependence appear to regulate melanism in male mosquitofish (Gambusia holbrooki).

About 1% of male mosquitofish (Gambusia holbrooki) express melanic (mottled-black) body coloration, which differs dramatically from the wild-type, silvery-gray coloration. Here, I report on the genetic inheritance pattern of melanic coloration, which indicates Y-linkage, and at least one autosomal modifier. Phenotypic expression of melanism is also affected by temperature. Expression is constitutive (temperature insensitive) in some populations, inducible (temperature sensitive) in others. Constitutive and inducible expression occur among geographically proximal populations. However, males from any single population demonstrate the same constitutive or inducible expression pattern as one another. The F1 males from inter-population crosses demonstrate temperature-related expression patterns like their sires'. As well, the sex ratio of melanic males' progeny differs among populations. Here, inter-population crosses demonstrate a sex-ratio bias in the same direction as intra-population crosses of the sire population. About 20% of the male progeny of melanic sires express the wild-type phenotype. These silver F1 males sire only silver offspring, suggestive of loss of the melanin gene in F1 males from crossover between sex chromosomes, or control by additional modifiers, or involvement of additional factors. In nature, melanic males persist at very low frequencies. The data collected here on heritability indicate that genetic factors contribute to the rarity of melanic male mosquitofish.

Animals↗
PubMed1995

Effects of guaifenesin on nasal mucociliary clearance and ciliary beat frequency in healthy volunteers.

STUDY OBJECTIVE: Mucociliary clearance is an important host defense function of the upper respiratory tract that requires the coordinated beating of cilia and results in the transport of mucus to the oropharynx. Guaifenesin is a commonly prescribed drug that is reported to improve the clearance of respiratory secretions. We hypothesized that guaifenesin increases nasal mucociliary clearance related to increases in ciliary beat frequency (CBF) and that a direct relationship exists between nasal CBF and nasal mucociliary clearance. DESIGN: Double-blind placebo-controlled crossover study. PARTICIPANTS: Ten healthy volunteers with a previous history of sinus disease. INTERVENTIONS: Subjects received guaifenesin or placebo on days 1 to 7 or days 14 to 21. MEASUREMENTS AND RESULTS: In vivo saccharine transit time (STT) was measured by noting the time in minutes required for the subject to taste a saccharin particle placed on the inferior turbinate of the naris. The CBF was determined by video microscopy on ten separate groups of beating ciliated nasal mucosal cells obtained by brushing immediately after each STT determination. We found that there was no significant change between the guaifenesin-or placebo-treated groups from baseline values of STT (p = 0.94) or CBF (p = 0.46). Regression analysis demonstrated no relationship between STT and CBF for repeated measures within subjects (mean r2 = 0.18; mean p = 0.66) and between STT and CBF when all paired measurements were combined across subjects (r2 = 0.47; p = 0.46). CONCLUSION: We conclude that guaifenesin exerts no measurable effect on in vivo nasal mucociliary clearance or ex vivo nasal ciliary motility in healthy volunteers with previous sinus disease. In addition, there appears to be no relationship between nasal STT measured in vivo and CBF measured ex vivo. The lack of correlation is most likely due to variations in CBF related to sampling artifacts introduced by the nasal brushing process.

Cilia↗
PubMed1989

The effects of epanolol on quality of life.

The concept of quality of life is used to determine clinically relevant aspects of subjective symptoms and well-being, and refined psychometric instruments are now being developed to assess changes in well-being during pharmacological therapy. In order to evaluate general well-being, subjective symptoms and common side effects during cardiovascular therapy, workers at this hospital have designed a quality of life questionnaire. This consists of a generic section for the evaluation of 3 global aspects of well-being (hedonic tone, activity and relaxation) and a specific symptoms section for assessing 21 common side effects of cardiovascular drugs. The test is based on visual analogue scales. This questionnaire was used in a Swedish subsample (n = 211) of the epanolol versus metoprolol study in patients with stable angina pectoris (VISA 1). In this double-blind crossover study, there were no significant differences between epanolol and metoprolol as regards general well-being with this sample size. The frequency of some specific symptoms (fatigue, sleep disturbances, vivid dreams and cold digits) was somewhat lower during epanolol treatment, but the differences did not attain statistical significance.

Adrenergic beta-Antagonists↗
PubMed1991

What is the dose-response relationship between exercise training and blood pressure?

Most studies of exercise and blood pressure have used a standard exercise programme with a single level of physical activity. To determine the nature of the dose-response relationship however it is necessary to examine several levels of activity, preferably in the same subjects. We have recently performed several randomised crossover studies comparing different levels of regular exercise. The intensity and duration of exercise bouts were constant throughout the studies, but their frequency was varied. Standard bouts consisted of 30 min of bicycling at 60%-70% of maximum work capacity. The exercise was performed either three-weekly or 7-weekly in randomised order and each level was maintained for one month. In sedentary normal subjects three bouts of exercise/week for a total of 90 min lowered blood pressure by 10/7 mmHg. With seven bouts, i.e. a total of 210 min exercise/week, blood pressure was only slightly lower than 3-week exercise and was 12/7 mmHg below sedentary values. Responses to measures of physical fitness including maximum oxygen consumption and work capacity were linearly related to the amount of exercise performed each week. Similar results were obtained in hypertensives. Another randomised study was performed amongst expeditioners to Antarctica where environmental conditions determined that they were sedentary in winter and active in summer. The addition of either 3-week or 7-week exercise in winter significantly lowered blood pressure. In summer when the background level of activity was higher, blood pressure with no added exercise was similar to exercising levels in winter. There was no further fall in blood pressure with either 3-week or 7-week additional exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Low level laser therapy in primary Raynaud's phenomenon--results of a placebo controlled, double blind intervention study.

OBJECTIVE: To assess the efficacy of low level laser therapy in patients with primary Raynaud's phenomenon and predict the success of laser therapy by clinical characteristics. METHODS: Forty-eight patients were included in a randomized placebo controlled, double blind crossover study. Laser and sham therapy each were applied 5 days a week for 3 weeks. Clinical symptoms, exposure to triggers, and frequency and intensity of attacks were recorded in diaries. Results of infrared thermography before onset and at the end of both irradiation sequences were evaluated. Primary endpoint was the average intensity of attacks; secondary endpoints were average number of attacks and thermography results. Age, sex, duration of symptoms, age at onset of symptoms, evoking conditions other than cold, maximum temperature drop after cold provocation, and rewarming time after cold provocation were tested as potential predictors. RESULTS: Number of attacks and their intensity were significantly reduced during laser therapy compared to sham treatment. Thermographic parameters did not reach statistical significance. In a stepwise multiple regression analysis, evoking conditions other than cold (stress, wetness as additional triggers), rewarming time, and temperature decrease after cold provocation were significant predictors of therapeutic efficacy. CONCLUSION: Low level laser therapy reduces frequency and severity of Raynaud attacks. The effect is most pronounced in patients with signs of decreased threshold for vasospasm and less effective in patients with delayed hyperemia.

Analysis of Variance↗
PubMed1991

Improved verbal learning after outpatient oral physostigmine therapy in patients with dementia of the Alzheimer type.

BACKGROUND: Previous investigators have reported improvements in verbal learning in outpatients suffering from dementia of the Alzheimer type (DAT) when they were treated daily with oral physostigmine for periods of days to months. Questions remain, however, regarding both the specificity of the induced cognitive changes and the time course of the biological activity of the drug when physostigmine was used to treat DAT patients. We examined both of these parameters in an outpatient, double-blind, placebo-controlled study that examined the effect of physostigmine on memory and other cognitive functions. METHOD: Eight DAT patients were treated for 3 weeks with oral physostigmine administered four times daily in a double-blind, crossover, placebo-controlled study. An auditory verbal learning test (AVLT) was administered to assess verbal learning. Digit span, word fluency, and frequency of intrusions served as controls for nonspecific changes in attention and verbal responsiveness. RESULTS: AVLT scores improved after drug administration compared with scores for baseline and placebo performances (p = .04). Other measures were unchanged. Improvement was unrelated to the time interval between memory testing and last ingested dose. CONCLUSIONS: These results indicate a longer period of biological activity for physostigmine than previously considered and extend previous reports of improved verbal learning after oral physostigmine treatment to a more convenient dosing schedule. These results suggest further that the improvements induced by physostigmine result specifically from enhancement of long-term memory processes.

Administration, Oral↗
PubMed1989

Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats.

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.

Administration, Oral↗
PubMed1990

Diuretic therapy and ventricular arrhythmias in persons 65 years of age and older.

Comparatively high doses of thiazide diuretics have been implicated as a possible cause of ventricular arrhythmias. With the advent of lower recommended dosages, the effect of hydrochlorothiazide 50 mg daily alone and in combination with the potassium-sparing drug, amiloride 5 mg, on the frequency and severity of ventricular arrhythmias was examined in 37 elderly patients. The mean age was 81 +/- 2 years. The study used a randomized, double-blind, crossover design with 3 treatment phases: hydrochlorothiazide, hydrochlorothiazide + amiloride and placebo. A 24-hour Holter monitor recording and serum potassium measurement were obtained at the end of each treatment. Mean serum potassium was significantly (p less than 0.001) reduced with hydrochlorothiazide (3.5 +/- 1 mEq/liter) compared with placebo (4.1 +/- 0.1) and hydrochlorothiazide + amiloride (4.1 +/- 0.1). Serious ventricular arrhythmias occurred in 13 of 37 patients receiving hydrochlorothiazide compared with 15 of 37 receiving placebo and 9 of 37 receiving hydrochlorothiazide + amiloride. Patients who exhibited ventricular ectopy during the placebo phase tended to have an increase in the number of ventricular premature complexes receiving hydrochlorothiazide, although the difference was not statistically significant. There was a significant (p = 0.045) difference in the hourly ventricular premature complex frequency for hydrochlorothiazide compared with hydrochlorothiazide + amiloride. Patients with hypokalemia did not exhibit greater ventricular ectopic activity than those with a normal serum potassium, and concurrent digoxin therapy did not affect arrhythmia occurrence. Hydrochlorothiazide, 50 mg daily, did not affect the frequency or severity of ventricular ectopic activity in this elderly population.

Aged↗
PubMed2001

Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial.

OBJECTIVE: To determine the effect of injections of botulinum toxin on simple motor tics. BACKGROUND: Case series with unblinded assessments have reported improvement in tic frequency and associated urge with botulinum toxin. METHODS: Patients with suitable simple motor tics were randomized to receive botulinum toxin and placebo in a double blind, crossover design. All outcomes compared week 2 to baseline measurements. The primary outcome measure was the number of treated tics per minute on a videotape segment. Secondary outcome measures were number of untreated tics per minute, the Shapiro Tourette Syndrome Severity Scale score, a numerical assessment of the urge to perform the treated tic (0 to 4), the premonitory sensation associated with the treated tic (0 to 4), and the patient's global impression of change. RESULTS: Eighteen patients completed the study. The median relative change in treated tics per minute with botulinum toxin was -0.39 (or a 39% reduction) versus 0.058 (or a 5.8% increase) with placebo (net effect -0.37, p = 0.0007). The average change in urge scores (score range 0 to 4) was -0.46 in the treatment phase and +0.49 in the placebo phase (net effect 0.94, p = 0.02). Other secondary outcome measures were not significantly different between the two groups. CONCLUSION: Botulinum toxin reduced treated tic frequency and the urge associated with the treated tic. Despite these changes, patients did not report an overall benefit from the treatment. Careful consideration of the contribution of the target tic to the patient's disability is needed before making treatment decisions.

Adolescent↗
PubMed1998

Mebeverine decreases mass movements and stool frequency in lactulose-induced diarrhoea.

BACKGROUND: In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine's mode of action in man. AIM: To examine mebeverine's effect on transit though the gut during lactulose-induced diarrhoea. METHODS: Nine healthy volunteers undertook a two-way randomized crossover study. Diarrhoea was induced using lactulose pre-treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric-coated capsules containing radiolabelled 8.4 mm tablets and 180-250 microM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards. RESULTS: Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75-2.75) to 1.5 (IQR 1.25-2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2-2) to 1 (1-2), and the number of retrograde movements from 1 (0-2) to 0 (0-0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9-3.2) to 2.8 (2.6-4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8-2.0) h to 1.0 (0.52-1.32) h, P=0.02). CONCLUSION: Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.

Adolescent↗