Multicentre, controlled, randomised and blinded field study comparing efficacy of suxibuzone and phenylbutazone in lame horses.

REASONS FOR PERFORMING STUDY: In horses, it has been demonstrated that suxibuzone (SBZ) has a lower gastric ulcerogenic effect than phenylbutazone (PBZ). However, no field trials have been reported comparing the efficacy of the drugs in alleviating lameness. OBJECTIVES: To compare the therapeutic effect of SBZ to that of PBZ when administered orally in lame horses. Acceptability of both products was also compared. METHODS: Lame horses (n = 155) were used in a multicentre, controlled, randomised and double-blinded clinical trial. Horses were treated orally with either SBZ or PBZ at equivalent therapeutic dosages. PBZ was given to 79 horses at a dose of 4.4 mg/kg bwt/12 h for 2 days, followed by 2.2 mg/kg bwt/12 h for 6 days. SBZ was given to 76 horses at 6.6 mg/kg bwt/12 h for 2 days, followed by 3.3 mg/kg bwt/ 12 h for 6 days. Efficacy of treatments was evaluated by clinicians in equine practices according to lameness progression throughout the study. Product ingestion was checked daily to evaluate product acceptability. RESULTS: Although SBZ showed a statistically significant tendency to have a better efficacy than PBZ (Odds ratio = 2.7; P = 0.016), significance dissipated once the analysis was adjusted for some imbalanced baseline covariates, confirming that they were actually related to the apparent advantage of SBZ over PBZ. Product acceptability was significantly higher in the SBZ group than in the PBZ group (96.1% vs. 77.2%; P = 0.001). CONCLUSIONS: SBZ and PBZ did not show significant differences in alleviating lameness in horses. However, SBZ had better product acceptability when administered orally with some food. POTENTIAL RELEVANCE: SBZ is a good therapeutic alternative to PBZ in horses since there is no significant difference in alleviating lameness between the 2 therapies.

An improved method to determine neuromuscular properties using force laws - From single muscle to applications in human movements.

We evaluate an improved method for individually determining neuromuscular properties in vivo. The method is based on Hill's equation used as a force law combined with Newton's equation of motion. To ensure the range of validity of Hill's equation, we first perform detailed investigations on in vitro single muscles. The force-velocity relation determined with the model coincides well with results obtained by standard methods (r=.99) above 20% of the isometric force. In addition, the model-predicted force curves during work loop contractions very well agree with measurements (mean difference: 2-3%). Subsequently, we deduce theoretically under which conditions it is possible to combine several muscles of the human body to model muscles. This leads to a model equation for human leg extension movements containing parameters for the muscle properties and for the activation. To numerically determine these invariant neuromuscular properties we devise an experimental method based on concentric and isometric leg extensions. With this method we determine individual muscle parameters from experiments such that the simulated curves agree well with experiments (r=.99). A reliability test with 12 participants revealed correlations r=.72-.91 for the neuromuscular parameters (p<.01). Predictions of similar movements under different conditions show mean errors of about 5%. In addition, we present applications in sports practise and theory.

Efficacy and safety of lesopitron in outpatients with generalized anxiety disorder.

OBJECTIVE: To compare the relative efficacy and safety of lesopitron 4-80 mg/d versus lorazepam 2-4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD). DESIGN: Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study. SETTING: Outpatient clinic. PATIENTS: One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup. METHODS: After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring. RESULTS: An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design. CONCLUSIONS: The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.

[Diltiazem compared with placebo in the prevention of myocardial ischemia during non-cardiac surgery]. / Diltiazem frente a placebo en la prevención de la isquemia miocárdica durante la cirugía no cardíaca.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of intravenous diltiazem to prevent myocardial ischemia during surgery on patients with ischemic heart disease undergoing non cardiac surgery under general anesthesia. PATIENTS AND METHOD: Sixty patients scheduled for elective non cardiac surgery under general anesthesia were randomly assigned to two groups to receive diltiazem or placebo under double blind conditions. After an intravenous dose of 0.15 mg/kg of diltiazem or an equivalent amount of placebo, an infusion of 3 micrograms/kg/min of diltiazem or placebo was begun and continued until three hours after surgery. Thirty minutes after starting the infusion, anesthesia was induced by 0.1 mg/kg diazepam, 3 micrograms/kg of fentanyl and 0.3 mg/kg of etomidate. Intubation followed administration of 0.6 mg/kg of atracurium. Anesthesia was maintained with N2O/O2 and halothane and was the same for both groups. DII and V5 leads were monitored on a Cardiowiss CM-8 ECG machine that allowed us to set the alarm when ST segment variations reached 1 mm above or below baseline. We analyzed the number, intensity and duration of ischemic episodes recorded, as well as hemodynamic variables and side effects. RESULTS: Data for 46 patients were valid. At least one ischemic episode was experienced by 15% of patients in the placebo group and 1 in the diltiazem group (p < 0.05). The episodes were related to increased systolic arterial pressure (p = 0.04). ST segment decreases were 1.1 to 3.6 mm (1.75 +/- 0.7) (mean +/- SD) and lasted between 1 and 45 minutes (11.62 +/- 13.26) (mean +/- SD). No significant side effects were observed. CONCLUSIONS: Intravenous diltiazem administered to patients with ischemic heart disease under general anesthesia for non cardiac surgery was effective in our study for preventing intraoperative ischemic episodes.

Assessment of isometric contractions performed with maximal subjective effort: corresponding results for EEG changes and force measurements.

In order to find a parameter or parameters that can be attributed to movements performed with maximal subjective effort, EEG recordings and force measurements were taken in connection with isometric muscle contractions performed with 80% of the subjective maximal force (IMC80) or with maximal subjective effort (IMC100). Criteria based on EEG recordings and force measurements have been considered as indicators for maximal subjective effort in a given movement. The following criteria were selected: A. If the mean spectral theta amplitude across the parieto-occipital area decreases from IMC80 to IMC100 then the isometric contraction is taken to be performed with maximal effort; B. If the obtained force values can be fitted to a switch function and if the achieved forces are only a predetermined percentage lower than the maximal force value obtained over all trials then this isometric contraction is accepted to be performed with maximal effort. 18 out of 24 cases fulfill the EEG criterion whereas the criterion for force measurements is fulfilled in 16 out of 24 trials. The comparison between the results obtained by means of the EEG criterion and by means of criterion for force measurement shows that the results are in agreement in 22 out of 24 cases (p < .001). The high correspondence of the assessments allows us to suspect that both criteria specify the same phenomenon, namely the performance of a motor task with maximal subjective effort.

Theta power decreases in preparation for voluntary isometric contractions performed with maximal subjective effort.

In order to find EEG parameters that can be attributed to movements performed with maximal subjective effort, EEG recordings and force measurements were realized in connection with isometric contractions (IMC). IMC were performed with submaximal and maximal subjective effort. Mean spectral power density within the theta band was found as an indicator for maximal subjective effort. The theta power across the parieto-occipital area decreases from rest through movements performed with submaximal force to movements performed with maximal effort. It is argued that this theta decrease possibly reflects a down-regulation of the posterior attention system in order to minimize the influences of external stimuli during the preparation for voluntary IMC performed with maximal subjective effort.

Regional distribution of glycogen, glucose and phosphorylated sugars in rat brain after intoxicating doses of ethanol.

Ethanol and anaesthetics increase glycogen levels in the brain. However, no data have been reported about the effect of ethanol on glycogen and glucose metabolism in specific brain regions. We have studied the concentrations of glycogen, glucose, glucose 6-P, glucose 1,6-P2 and fructose 2,6-P2 and the activities of glycogen synthase, glycogen phosphorylase and glycogen phosphorylase kinase in seven brain regions of starved rats following treatment with a single dose or several doses of ethanol. Our results show that: (1) the effect of ethanol on glucose metabolism depends on whether it is given in one single dose or in a series of doses; (2) glycogen concentration increases after a single dose of ethanol but not after long exposure; (3) glucose, glucose 6-P in some areas, and the bisphosphorylated sugar, fructose 2,6-P2 significantly increase after prolonged exposure to ethanol; and (4) the enzymatic activities of glycogen metabolism are not modified after a long exposure to ethanol. In summary, these data show that ethanol may modify the use of glycogen, glucose and derivatives in brain. Moreover, the changes produced depend on the pattern of ethanol intake and the brain area considered.

Subcostal incision versus midline laparotomy in gallstone surgery: a prospective and randomized trial.

We report the results of a prospective and randomized trial designed to study the incidence of abdominal and pulmonary complications in gallstone surgery comparing subcostal (SI) with midline incision. The need for postoperative analgesia was lower in the SI group. There was no difference in the degree of hypoxaemia in the first two postoperative days, but there was less impairment of pulmonary function in terms of vital capacity and forced expiratory volume in 1 s (P less than 0.0001) in the SI group. SI patients also had a lower incidence of pulmonary or abdominal complications but the difference was not significant. Finally, we found a reduced hospital stay for the SI patients (P less than 0.01), probably related to a reduced postoperative analgesic requirement and an improved pulmonary function. We conclude that subcostal incision is a better approach for biliary tract surgery and should be used whenever possible.