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Effects of acute treatment with tamsulosin versus alfuzosin on ejaculatory function in normal volunteers.

PURPOSE: The frequency of ejaculatory dysfunction in men varies among the alpha-blockers used in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. We assessed the effect of acute administration of tamsulosin, alfuzosin and placebo on ejaculate volume and sperm concentration in post-ejaculate urine, and addressed the mechanism of action of tamsulosin and alfuzosin on ejaculation. MATERIALS AND METHODS: Using a randomized, 3-way crossover design, the effects of 5 days of treatment with 0.8 mg tamsulosin daily, 10 mg alfuzosin daily and placebo on ejaculation in healthy adult men were compared. The primary end points of the study were ejaculate volume and sperm concentration in post-ejaculate urine on each treatment. To aid in clinical interpretation of primary efficacy end points, each primary end point was transformed into a binary outcome, that is subjects with a greater than 20% decrease in ejaculate volume and subjects with a greater than 20% increase in sperm concentration in post-ejaculate urine. RESULTS: In healthy volunteers who completed the study (48), tamsulosin resulted in significantly decreased ejaculate volume (-2.4 +/- 0.17 ml) compared to alfuzosin (+0.3 +/- 0.18 ml, p < 0.0001 vs tamsulosin) or placebo (+0.4 +/- 0.18 ml, p < 0.0001 vs tamsulosin, p = nonsignificant vs alfuzosin). Among completers the incidence of more than 20% decreased ejaculate volume was significantly greater with tamsulosin (89.6%) compared to alfuzosin (20.8%, p < 0.0001 vs tamsulosin) or placebo (12.5%, p < 0.0001 vs tamsulosin, p = nonsignificant vs alfuzosin). While on tamsulosin 35.4% of 48 completers had complete lack of ejaculation (anejaculation) and no subjects experienced anejaculation while on alfuzosin or placebo. CONCLUSIONS: On 0.8 mg tamsulosin daily ejaculatory function in subjects was marked by decreased ejaculate volume in almost 90% of subjects and anejaculation in approximately 35% of participants. These ejaculatory disorders with tamsulosin were not attributed to retrograde ejaculation. In contrast, anejaculation was not observed in any subjects in the alfuzosin or placebo groups.

Adrenergic alpha-Antagonists↗

Recombination between a resident plasmid and the chromosome following irradiation of the radioresistant bacterium Deinococcus radiodurans.

Interplasmidic and intrachromosomal recombination in Deinococcus radiodurans has been studied recently and has been found to occur at high frequency following exposure to ionizing radiation. In the current work, we document plasmid-chromosome recombination following exposure of D. radiodurans to 1.75 Mrad (17.5 kGy) 60Co, when the plasmid is present in the cell at the time of irradiation. Recombination is assayed using both physical and allelic polymorphisms of homologous genes in the plasmid and chromosome. Recombination was found to be largely, but not entirely, recA-dependent. Crossovers occur frequently, and a significant fraction of these are non-reciprocal.

Bacterial Proteins↗

Effect of right atrial overdrive pacing in the prevention of symptomatic paroxysmal atrial fibrillation: a multicenter randomized study, the PAF-PACE study.

The aim of this study was to assess if right atrial overdrive pacing can suppress symptomatic episodes of paroxysmal atrial fibrillation (PAF) in patients without bradyarrhythmias. Forty-two patients with frequent and symptomatic PAF without other pacing indication had a pacemaker implanted after a 4-week run-in period, during which the frequency of symptomatic PAF episodes and the mean heart rate were objectively documented. Depending on the mean heart rate recorded during run-in, the pacemaker was programmed in random order to right atrial AAI pacing at 10-19 beats/min > mean heart rate (medium overdrive [MO]), at 20-29 beats/min > mean heart rate (high overdrive [HO]) and to no pacing (OAO mode) for 4-12 weeks each using a crossover design. In the 35 patients who completed the protocol, the number of symptomatic episodes of PAF (>30-second duration) per week was significantly lower during MO pacing (median 0.88, P = 0.001, n = 35) and during HO pacing (median 0.75, P = 0.002, n = 20) than during OAO (median 2.02 and 2.04, respectively). There was no difference between MO and HO pacing in the 20 patients paced at both rates (0.97 vs 0.75, P = 0.33). Seven patients did not complete the protocol due to persistent atrial fibrillation (n = 4), angina pectoris requiring surgery (n = 1), and unwillingness to continue the study due to improvement (n = 1) or worsening (n = 1) of symptoms during the study periods. Right atrial overdrive pacing can reduce the number of symptomatic PAF episodes in patients with frequent and drug refractory PAF but without bradyarrhythmias.

Anti-Arrhythmia Agents↗

Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial.

OBJECTIVE: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate. DESIGN: Prospective, randomized, crossover, single-blind study. SETTING: Clinical research center in a federal, nonuniversity hospital. SUBJECTS: Healthy volunteers. INTERVENTIONS: Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms. CONCLUSIONS: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.

Adult↗

Oxcarbazepine (GP 47.680): a possible alternative to carbamazepine?

A double-blind randomized crossover design trial of carbamazepine (CBZ) and oxcarbazepine (OCBZ) was performed with 48 in-patients with epilepsy. All were stabilized on polytherapy including CBZ and had at least two seizures per week. CBZ was replaced by the trial medication. Each trial period started with a titration, followed by a 12-week steady state. Concomitant medications were kept constant during the trial. The criteria for assessment were seizure fit frequency and severity; tolerability; hematology and blood chemistry; plasma levels of antiepileptic drugs; EEG; cardiovascular parameters; and treatment preference. The following differences regarding OCBZ were detected: 9% reduction of the total number of seizures, with a significant reduction of tonic-clonic (20%) and tonic (31%) seizures; increased alertness and concentration ability in five patients; an allergic skin reaction with CBZ that completely disappeared in two patients while receiving OCBZ; an increase of valproate and phenytoin plasma levels in a number of patients, probably caused by reduced enzyme induction; a slight but significant reduction of serum Na, not causing clinical symptoms; less seizures than in the CBZ period in 25 patients (52%); and a preference for OCBZ in 23 patients (48%). We consider OCBZ at least as effective as CBZ with a slightly better tolerability. In severe cases, the wider therapeutic window might improve seizure control.

Adolescent↗

Effect of the quaternary ammonium compound trospium chloride on 24 hour jejunal motility in healthy subjects.

This study aimed to record 24 hour jejunal motility in healthy ambulant subjects and to analyse changes in motility caused by the oral administration of an anticholinergic agent, the quaternary ammonium compound, trospium chloride. In a placebo-controlled, double blind crossover trial, 24 hour jejunal motility was recorded in 12 healthy volunteers, aged 25 (21-30) years, using a digital data logger connected to two strain-gauge transducers mounted 20 cm apart in a flexible nasojejunal catheter. A computer program was developed to determine contraction parameters. Trospium chloride (15 mg orally thrice daily) prolonged the duration of irregular contractile activity after meals (p < 0.02) and reduced its contraction frequency and amplitude (p < 0.001). In the fasting state, the cycle length of the migrating motor complex was prolonged (p < 0.01) by an extended phase I (p < 0.025). Phase III was shortened (p < 0.005) and showed a slower aboral migration velocity (p < 0.005). Clustered contractions were less frequent during postprandial and fasting periods (p < 0.01). Runs of clustered contractions were completely absent with trospium chloride. Digital manometry was useful for long term recordings of jejunal motility and enabled the motor effects of an anticholinergic agent to be characterised in ambulant subjects.

Adult↗

Homeologous recombination in Solanum lycopersicoides introgression lines of cultivated tomato.

A library of "introgression lines" containing Solanum lycopersicoides chromosome segments in the genetic background of cultivated tomato (Lycopersicon esculentum) was used to study factors affecting homeologous recombination. Recombination rates were estimated in progeny of 43 heterozygous introgressions and whole-chromosome substitution lines, together representing 11 of the 12 tomato chromosomes. Recombination within homeologous segments was reduced to as little as 0-10% of expected frequencies. Relative recombination rates were positively correlated with the length of introgressed segments on the tomato map. The highest recombination (up to 40-50% of normal) was observed in long introgressions or substitution lines. Double-introgression lines containing two homeologous segments on opposite chromosome arms were synthesized to increase their combined length. Recombination was higher in the double than in the single segment lines, despite a preference for crossovers in the region of homology between segments. A greater increase in homeologous recombination was obtained by crossing the S. lycopersicoides introgression lines to L. pennellii--a phylogenetically intermediate species--or to L. esculentum lines containing single L. pennellii segments on the same chromosome. Recombination rates were highest in regions of overlap between S. lycopersicoides and L. pennellii segments. The potential application of these results to breeding with introgression lines is discussed.

Centromere↗

Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes.

OBJECTIVE: To examine the influence of caffeine on the frequency and perception of hypoglycemia in "free-living" patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 34 patients with type 1 diabetes were recruited for a prospective randomized placebo-controlled double-blind study. After a lead-in phase and while adhering to a low-caffeine diet, subjects were randomized to capsules containing either 200 mg caffeine or matched placebo with crossover at 3 months. Hypoglycemic episodes were monitored throughout with capillary blood glucose readings and a symptom questionnaire. During the study, measurements of blood pressure, middle cerebral artery blood velocity (a surrogate measure of cerebral blood flow), cognitive function (via a four-choice reaction time test), HbAlc levels, and lipid profiles were taken at the beginning and end of each phase. RESULTS: Throughout the study, no changes were evident regarding glycemic control or lipid profile. The number of symptomatic episodes was greater with caffeine (1.3 vs. 0.9 episodes/week; P < 0.03) and was associated with more intense warning symptoms (29 vs. 26 total symptom score; P < 0.05). For women, caffeine ingestion caused a modest pressor response (115 vs. 110 mmHg; P < 0.01). Four-choice reaction time improved slightly with caffeine supplementation (P < 0.05). CONCLUSIONS: Ingestion of modest amounts of caffeine enhances the intensity of hypoglycemia warning symptoms in patients with type 1 diabetes without altering the prevailing standard of glycemic control or increasing the incidence of severe hypoglycemic episodes.

Adult↗

Efficacy of transdermal clonidine for headache prophylaxis and reduction of narcotic use in migraine patients. A randomized crossover trial.

Thirty patients completed a double-blind, randomized crossover study utilizing transdermal clonidine and an identical-appearing placebo. Crossover occurred at 6 weeks, with a total study time of 12 weeks. Subjects were asked to record daily in a special diary (1) the presence or absence of headache, (2) duration of headache, (3) severity of headache, and (4) use of pain medication for headache relief. The severity of the headaches was rated from 1 (very mild) to 5 (very severe). Although the subjects reported a decrease in frequency, duration, and intensity of headaches while using the medicated patch, these differences did not reach statistical significance. Nineteen patients subjectively preferred the medicated patch, while five preferred the placebo (P less than .01). During use of the medicated patch, a significant reduction (P = .039) occurred in use of class II narcotics. Three doses of these substances were used by the patients when treated with clonidine, while 34 doses were taken during placebo use. These findings suggest that clonidine might have a role in reduction of parenteral narcotic use in acute pain syndromes.

Administration, Cutaneous↗

Oral tocainide versus disopyramide: a double-blind, randomized, crossover study of outpatients with stable ventricular premature beats.

Oral tocainide and disopyramide were compared in a double-blind, crossover trial in 10 outpatients with stable ventricular premature beats (VPBs). Efficacy was assessed by suppression of VPB activity and reduction of VPB grade during an exercise test and an 18-h Holter recording. An estimate of variance of VPB activity was obtained from two separate placebo periods, and a 95% confidence limit for VPB suppression was calculated. During Holter recording, both drugs produced a significant reduction in VPB frequency and grade (p less than 0.05). During the exercise challenge, tocainide produced a reduction in VPB frequency and grade, but this did not reach statistical significance; VPB frequency was unaltered by disopyramide, but VPB grade was significantly reduced (p less than 0.01).

Adult↗

Hemodynamic effects of different modes of mechanical ventilation in acute cardiac and pulmonary failure: an experimental study.

OBJECTIVE: To determine the hemodynamic effects of four different modes of mechanical ventilation in an animal model of acute cardiac and pulmonary failure. DESIGN: Prospective, randomized, crossover design. SETTING: University research laboratory. SUBJECTS: Twelve piglets weighing 10 to 16 kg. INTERVENTIONS: The experimental protocol consisted of three stable 30-min periods: when ventricular and pulmonary functions were normal (control), after the induction of acute cardiac failure by the administration of a beta-adrenergic receptor blocker, and after pulmonary failure induced by repeated lung lavage. Modes of mechanical ventilation included controlled mechanical ventilation, high-frequency oscillation, synchronized high-frequency jet ventilation, and external negative pressure oscillation combined with pressure support ventilation. Each mode of respiratory support was randomly and sequentially applied to each animal with the assessment of cardiopulmonary function at the end of each period. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring included electrocardiogram, right atrial, left ventricular end-diastolic, pulmonary arterial, intrathoracic aortic, arterial, esophageal, and transpulmonary pressures and arterial and mixed venous oxygen saturation measurements. In addition, cardiac output using the thermodilution technique was measured intermittently. Whereas in the control period cardiac index was significantly (p < .05) higher during synchronized high-frequency jet ventilation (193 +/- 19.3 mL/kg/min) than during controlled mechanical ventilation (151 +/- 12.1 mL/kg/min) and high-frequency oscillation (151 +/- 18.1 mL/kg/min), there was no significant hemodynamic difference between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. In the pulmonary failure period, transpulmonary pressure was significantly higher during high-frequency oscillation (7.1 +/- 1.6 mm Hg) than during controlled mechanical ventilation (5.6 +/- 0.6 mm Hg), high-frequency ventilation (4.1 +/- 0.4 mm Hg), and external negative pressure oscillation combined with pressure support ventilation (5.3 +/- 0.5 mm Hg). CONCLUSIONS: Synchronized high-frequency ventilation improves cardiac performance in control conditions. No hemodynamic difference is present between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. External negative pressure oscillation combined with pressure support ventilation has moderate hemodynamic advantages over controlled mechanical ventilation and high-frequency oscillation in different clinical settings, but it also results in a deterioration of pulmonary gas exchange during the pulmonary failure period.

Animals↗

A reliability study of potential risk factors for acute traumatic occupational hand injuries.

BACKGROUND: A reliability study of transient workplace exposures was conducted within a case-crossover study of acute traumatic occupational hand injuries. Exposures examined included features of work equipment (unusual performance of equipment or materials, glove use), work practices (performing an uncommon work task, using an unusual work method), and worker-related factors (being rushed, distracted, ill, or working overtime). METHODS: Interviewers administered a follow-up questionnaire about exposure up to 4 days after the initial interview. The reliability of the usual frequency of exposure in the past month, exposure reported at the time of the injury, and the degree to which subjects had confidence in the accuracy of their memory for exposure was assessed. RESULTS: The test-retest reliability for the estimated number of hours of exposure during the past month was high for six of the eight potential risk factors (intraclass correlation coefficients (ICC) ranging from 0.84-0.99). ICC for the frequency per month and minutes per exposure, used to calculate the estimated number of hours per month, ranged from 0.12-0.99 and 0.49-0.99, respectively. Agreement of reported exposure at the time of the injury, evaluated using the kappa statistic, ranged from substantial agreement to perfect agreement (0.65-1.0). However, for some factors, there was little or no reported exposure. Most subjects (74-100%) reported being "very confident" or "certain" in their memory for each exposure. CONCLUSIONS: These findings suggest that the frequency and duration of unusual transient workplace exposures can be reliably recalled by subjects interviewed by telephone within 4 days of an injury.

Accidents, Occupational↗

A model system for increased meiotic nondisjunction in older oocytes.

For at least 5% of all clinically recognized human pregnancies, meiotic segregation errors give rise to zygotes with the wrong number of chromosomes. Although most aneuploid fetuses perish in utero, trisomy in liveborns is the leading cause of mental retardation. A large percentage of human trisomies originate from segregation errors during female meiosis I; such errors increase in frequency with maternal age. Despite the clinical importance of age-dependent nondisjunction in humans, the underlying mechanisms remain largely unexplained. Efforts to recapitulate age-dependent nondisjunction in a mammalian experimental system have so far been unsuccessful. Here we provide evidence that Drosophila is an excellent model organism for investigating how oocyte aging contributes to meiotic nondisjunction. As in human oocytes, nonexchange homologs and bivalents with a single distal crossover in Drosophila oocytes are most susceptible to spontaneous nondisjunction during meiosis I. We show that in a sensitized genetic background in which sister chromatid cohesion is compromised, nonrecombinant X chromosomes become vulnerable to meiotic nondisjunction as Drosophila oocytes age. Our data indicate that the backup pathway that normally ensures proper segregation of achiasmate chromosomes deteriorates as Drosophila oocytes age and provide an intriguing paradigm for certain classes of age-dependent meiotic nondisjunction in humans.

Animals↗

Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers.

AIMS: Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries. This tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine (DMT), and beta-carboline alkaloids with MAO-inhibiting properties. In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self-assessment instruments. In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography (q-EEG), a noninvasive method measuring drug-induced variations in brain electrical activity. METHODS: Two doses (one low and one high) of encapsulated freeze-dried ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg(-1) body weight, were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen-lead recordings were undertaken from baseline to 8 h after administration. Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS). RESULTS: Ayahuasca induced a pattern of psychoactive effects which resulted in significant dose-dependent increases in all subscales of the HRS, and in significant and dose-dependent modifications of brain electrical activity. Absolute power decreased in all frequency bands, most prominently in the theta band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for total power and theta power, respectively. Relative power decreased in the delta (-1.20+/-1.31% after 120 min at P3) and theta (-3.30+/-2.59% after 120 min at P3) bands, and increased in the beta band, most prominently in the faster beta-3 (1.00+/-0.88% after 90 min at P3) and beta-4 (0.30+/-0.24% after 90 min at P3) subbands. Finally, an increase was also seen for the centroid of the total activity and its deviation. EEG modifications began as early as 15-30 min, reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4-6 h after administration. CONCLUSIONS: The central effects of ayahuasca could be objectively measured by means of q-EEG, showing a time pattern which closely paralleled that of previously reported subjective effects. The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs. The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system.

Adult↗

Migraine can be induced by sildenafil without changes in middle cerebral artery diameter.

Migraine is considered a neurovascular disease involving dilatation of cerebral arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial arteries and migraine, but NO has several mechanisms of action in addition to its cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. We included 12 patients with migraine without aura in this double-blind, placebo-controlled crossover study, in which placebo or sildenafil 100 mg was administered orally on two separate days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by transcranial Doppler ultrasonography and regional cerebral blood flow in the territory of the middle cerebral artery (rCBF(mca)) was measured using SPECT (single photon emission computed tomography) and xenon 133 inhalation. Radial and temporal artery diameters were studied using high-frequency ultrasonography. Headache response, tenderness of pericranial muscles, blood pressure and heart rate were measured repeatedly. We found that migraine attack was induced by sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P = 0.01). V(mca) (P = 0.1) and rCBF(mca) (P = 0.93) remained unchanged after sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and diastolic blood pressures were unchanged but heart rate increased from a mean of 62 +/- 2 to 74 +/- 3 beats/min (P = 0.01) after sildenafil. Our results demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we show for the first time that this occurs without initial dilatation of the middle cerebral artery. We propose that triggering mechanisms may reside within the perivascular sensory nerve terminals or the brainstem. However, other sites of action may also be possible and future studies are needed to elucidate this. In the clinical use of sildenafil, patients who have migraine should be informed about the risk of migraine attacks.

3',5'-Cyclic-GMP Phosphodiesterases↗

Facilitation of internal jugular venous cannulation using an audio-guided Doppler ultrasound vascular access device: results from a prospective, dual-center, randomized, crossover clinical study.

OBJECTIVE: To determine the utility of an audio-guided Doppler ultrasound device in improving success and decreasing complications in cannulation of the internal jugular vein in high-risk patients. DESIGN: Prospective, randomized, crossover clinical study. SETTING: Two major university medical centers in critical care environments. PATIENTS: Seventy-six consecutive, consenting adult patients with preexisting obesity or coagulopathy requiring central venous access. INTERVENTIONS: Subjects enrolled in the study were randomized to receive either the traditional "blind" (control) technique or the ultrasonic technique. A maximum of three cannulation attempts were allowed before crossover to three attempts with the alternative technique. All cannulations were attempted via the internal jugular vein through a high/central approach. RESULTS: Patient and operator characteristics were similar between groups. The initial use of an audio-guided ultrasound device was associated with increased success of cannulation (84.4% vs. 61.4%; p < .05) and decreased need to crossover to the alternative technique. Success on the first needle pass was more likely with the ultrasound technique (56.3% vs. 29.5%; p < .05). Significant complications were greater with the control technique (carotid artery puncture 16.3% vs. 2.0% [p < .02]; any significant complication 26.5% vs. 6.1% [p < .01]). CONCLUSIONS: The use of an audio-guided Doppler ultrasound vascular access device was associated with increased success of cannulation and a decreased frequency of significant complications in a population of high-risk patients with obesity or coagulopathy.

Catheterization, Central Venous↗

Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects.

1. The effects of two reversible, predominantly monoamine oxidase-A (MAO-A) inhibitors, moclobemide (150 mg three times daily) and toloxatone (400-200-400 mg day-1) on monoamine metabolites and psychometric performance were compared in a double-blind placebo controlled crossover study in 12 healthy subjects. 2. After 7 days of moclobemide/toloxatone/placebo administration subjects were hospitalized for 24 h on day 8. Blood samples were drawn every 2 h for determination of plasma noradrenaline (NA), 3,4-dihydroxyphenylglycol (DHPG), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA). Urine was collected for measurements of normetanephrine and 3-methoxytyramine excretion. Psychometric performance (short- and long-term memory, critical flicker fusion frequency, choice reaction time) and subjective feelings were assessed before each drug intake (in the morning, at noon, in the evening). 3. Compared with placebo, both reversible monoamine oxidase inhibitors decreased the plasma concentration of DHPG and HVA. The overall fall in DHPG (AUC from 0 to 24 h) was 44% during moclobemide and 12% during toloxatone (P less than 0.001) and the overall decrease in HVA was 38% and 20% (P less than 0.005) on moclobemide and toloxatone, respectively. 4. Before the next drug intake, MAO-A inhibition, as judged by the decrease of plasma DHPG concentration, was significantly different from placebo with moclobemide but not with toloxatone. 5. Moclobemide, but not toloxatone, exerted a moderate, but significant inhibition of the deamination of 5-hydroxytryptamine (5-HT) as judged by the fall in plasma 5-HIAA concentration. Neither drug influenced plasma NA concentration. 6. A significant rise in urinary excretion of normetanephrine was observed on moclobemide and to a lesser extent on toloxatone. The urinary excretion of 3-methoxytyramine was significantly raised by moclobemide but not by toloxatone. 7. Neither moclobemide nor toloxatone altered memory function, vigilance, subjective feelings or sleep characteristics of the subjects.

Adult↗

Electroacupuncture for tension-type headache on distal acupoints only: a randomized, controlled, crossover trial.

OBJECTIVE: To investigate the efficacy of electroacupuncture, applied to distal acupoints only, for tension-type headache. BACKGROUND: Electroacupuncture is commonly used for tension-type headache, but when applied to distal acupoints only, evidence of its efficacy is lacking. DESIGN: A randomized, single-blinded, sham-controlled, crossover clinical trial. Methods.-The trial had 5 stages: baseline (2 weeks), phases I and II (each 4 weeks), washout period (2 weeks), and follow-up (3 months after phase II). Forty patients were randomly assigned to either group A or group B. Group A received real electroacupuncture during phase I, then sham electroacupuncture in phase II. Group B received the treatments in reverse order. Outcome measures were headache frequency and duration, pain intensity using a visual analog scale, mechanical pain threshold, headache disability, and sickness impact. Data were analyzed by univariate 2-way analysis of variance. RESULTS: Thirty-seven patients completed the trial. There were no significant differences between the 2 groups at baseline. At the end of phase I, group A, but not group B, demonstrated significant improvement in mean (standard error of the mean [SEM]) headache frequency (3.0 per month [0.3] versus 12.0 per month [1.7]), duration (13.3 hours [3.5] versus 32.0 hours [6.2]), pain intensity (32.8 mm [4.1] versus 47.5 mm [2.7]), pain threshold (right side, 2.9 kg/second [0.1] versus 0.9 kg/second [0.1]; left side, 2.4 kg/second [0.1] versus 1.1 kg/second [0.1]), headache disability score (6.0 [1.0] versus 16.3 [1.6]), and sickness impact score (288.7 [48.0] versus 687.1 [77.2]). For each parameter, significant differences also were demonstrated for both groups between baseline and phase II, and baseline and follow-up. There were no significant differences between the groups at the end of follow-up (P >.05). CONCLUSION: Electroacupuncture to distal points alone is effective for short-term symptomatic relief of tension-type headache.

Acupuncture Points↗