Effects of benfluorex on fatty acid and glucose metabolism in isolated rat hepatocytes: from metabolic fluxes to gene expression

The effects of benfluorex and two of its metabolites (S 422-1 and S 1475-1) on fatty acid and glucose metabolic fluxes and specific gene expression were studied in hepatocytes isolated from 24-h fasted rats. Both benfluorex and S 422-1 (0.1 or 1 mmol/l) reduced beta-oxidation rates and ketogenesis, whereas S 1475-1 had no effect. At the same concentration, benfluorex and S 422-1 were more efficient in reducing gluconeogenesis from lactate/pyruvate than S 1475-1. Benfluorex inhibited gluconeogenesis at the level of pyruvate carboxylase (45% fall in acetyl-CoA concentration) and of glyceraldehyde-3-phosphate dehydrogenase (decrease in ATP/ADP and NAD(+)/NADH ratios). Accordingly, neither benfluorex nor S 422-1 inhibited gluconeogenesis from dihydroxyacetone, but both stimulated gluconeogenesis from glycerol. In hepatocytes cultured in the presence of benfluorex or S 422-1 (10 or 100 micromol/l), the expression of genes encoding enzymes of fatty acid oxidation (carnitine palmitoyltransferase [CPT] I), ketogenesis (hydroxymethylglutaryl-CoA synthase), and gluconeogenesis (glucose-6-phosphatase, PEPCK) was decreased, whereas mRNAs encoding glucokinase and pyruvate kinase were increased. By contrast, Glut-2, acyl-CoA synthetase, and CPT II gene expression was not affected by benfluorex or S 422-1. In conclusion, this work suggests that benfluorex mainly via S 422-1 reduces gluconeogenesis by affecting gene expression and metabolic status of hepatocytes.     

Music decreases sedative requirements during spinal anesthesia

Ambulatory surgery can create significant anxiety. This prospective study measured whether music can influence anxiety and perioperative sedative requirements in outpatients undergoing surgery with spinal anesthesia. We also evaluated the correlation between two anxiety measures, the State-Trait Anxiety Inventory test (STAI) and the 0- to 10-cm visual analog scale (VAS 0-10), with 0 meaning complete relaxation and 10 the worst feeling of anxiety possible. Fifty unpremedicated patients were randomly assigned to listen to music of their choice via headset during the perioperative period (Group I) or to have no music (Group II). All participants used patient-controlled IV midazolam sedation and underwent repeated evaluations of their anxiety level with the STAI and the VAS 0-10. Midazolam requirements during surgery (Group I, 0.6 +/- 0.7 versus Group II, 1.3 +/- 1.1 mg; P < 0.05) and for the whole perioperative period (Group I, 1.2 +/- 1.3 versus Group II, 2.5 +/- 2.0 mg; P < 0.05) were smaller in patients listening to music. Anxiety levels, measured with STAI or VAS 0-10, were similar in both groups. The Spearman's coefficient values between STAI and VAS 0-10 ranged from 0.532 to 0.687. We conclude that patients listening to music require less midazolam to achieve a similar degree of relaxation as controls and that measures of anxiety obtained from the STAI and the VAS 0-10 are positively, but only moderately, correlated. IMPLICATIONS: It is possible to decrease sedative requirements during surgery under spinal anesthesia by allowing patients to listen to music to reduce their anxiety.     

Correlation between groin pain and cup design of hip-resurfacing implants: a prospective study

Purpose

Cup design has been incriminated as the source of groin pain after hip resurfacing but has not been well described; thus, it was assessed in a prospective study looking at three implant types.

Methods

A group-match was done between three groups of hip resurfacing devices according to age, sex, body mass index, activity level, osteoarthritis aetiology and pre-operative scores.

Results

The global groin pain rate was 5.7 % at six months and 2.7 % at last follow-up. Groin pain rate was significantly different between the three groups (p = 0.004) and had a strong influence on the subjective results (p = 0.04). No groin pain emerged between six months and last follow-up. No clinical differences were noted in Harris hip score and Merle d’Aubigné-Postel score at last follow-up. However, the Oxford hip score and Devane activity score were significantly lower for cups with macrostructures.

Conclusion

The low groin pain rate in this prospective cohort was probably secondary to the specific surgical technique used and seems to be correlated with cup design. Macrostructures on the external part of the cup could be significantly harmful.     

Submandibular puncture of the facial vein: An original route for endovascular therapy of cavernous sinus dural fistulas

Introduction

Carotid cavernous sinus fistulas are a potentially severe pathology. Their basic standard treatment is an occlusion of the CCF performed by retrograde venous catheterization via the inferior petrous sinus. When the inferior petrous sinuses are occluded, other alternative venous routes are possible with various subsequent difficulties and risks. We report an original and safe method for endovascular treatment using submandibular puncture of the facial vein.

Clinical cases

We report 4 cases of patients with severe unilateral carotid cavernous sinus fistula associated with the occlusion of both inferior petrous sinuses. A submandibular surgical puncture of the ipsilateral inferior facial vein permitted the catheterization of the fistula. Complete occlusion of carotid cavernous sinus fistula was obtained by using a combination of microcoils and Onyx™.

Discussion

When inferior petrous sinuses are occluded, endovascular treatment of carotid cavernous sinus fistulas is more difficult. After reviewing the other treatment options reported in the literature and their respective advantages and adverse effects, we describe an original technique based on the surgical puncture of the ipsilateral facial vein. The occlusion of the fistula is then obtained by using a combination of microcoils and Onyx™.

Conclusion

When the inferior petrous sinuses are occluded, an endovascular treatment for a carotid cavernous sinus fistula can be performed using an original and secure method. This method relies on a simple surgical puncture of the facial vein in the submandibular region, which then permits a retrograde catheterization of the carotid cavernous sinus fistula with no significant risk.     

A difficult airway is not more prevalent in patients suffering from spasmodic torticollis: a case series

PURPOSE: We designed this retrospective study to assess the frequency of difficult airway and difficult intubation in patients with spasmodic torticollis and compare it to that of the general population. METHODS: After Institutional Review Board approval, data were collected from the charts of all the patients with spasmodic torticollis who underwent selective peripheral denervation at our institution between 1988 and 2001. The intubation grade was determined using the Cormack and Lehane laryngoscopic classification. The best laryngeal view was recorded. RESULTS: Data from 342 patients were available for analysis. Fourteen patients had a difficult airway. In two patients, intubation was difficult with three attempts at laryngoscopy in one patient and use of fibreoptic bronchoscopy in the other. Twelve (3.5%) patients presented with laryngoscopic grades of III or IV. The combined prevalence of laryngoscopic view grade III and IV and difficult intubation was 4.4%. CONCLUSIONS: This study assesses the frequency of difficult intubation in patients suffering from spasmodic torticollis. When compared to the general population, these patients do not appear to have a higher frequency of difficult airway or difficult intubation.     

Tramadol added to 1.5% mepivacaine for axillary brachial plexus block improves postoperative analgesia dose-dependently

Adjuncts to local anesthetics for peripheral plexus blockade may enhance the quality and duration of anesthesia and postoperative analgesia. The analgesic, tramadol, has a unique mechanism of action that suggests efficacy as such an adjunct. It displays a central analgesic and peripheral local anesthetic effect. We designed a prospective, randomized, controlled and double-blind clinical trial to assess the effect of tramadol added to brachial plexus anesthesia. One-hundred patients scheduled for carpal tunnel release surgery under brachial plexus anesthesia were randomized into four groups. All patients received 1.5% mepivacaine 40 mL plus a study solution containing either isotonic sodium chloride (Group P, n = 17), tramadol 40 mg (Group T(40), n = 22), tramadol 100 mg (Group T(100), n = 20) or tramadol 200 mg (Group T(200), n = 20). We evaluated the time of onset of anesthesia, duration of sensory and motor blockade, duration and quality of postoperative analgesia, and occurrence of adverse effects. Onset and duration of sensory and motor blocks were not different among groups. The number of patients requesting analgesia in the postoperative period was significantly less in the 3 tramadol groups compared with the placebo group (P = 0.02); this was also noted with the placebo and T(40) groups compared with the T(200) group. No statistical significance was demonstrated between the placebo and the T(40) group or the T(100) group and the T(200) group. Furthermore, there was a significant trend effect among groups applying the Cochran-Armitage tendency test (P = 0.003), suggesting a dose-dependent decrease for additional postoperative analgesia requirements when tramadol was added. Side effects did not differ among groups, although they were more frequently recorded in the T groups. Our study suggests that tramadol added to 1.5% mepivacaine for brachial plexus block enhances in a dose-dependent manner the duration of analgesia with acceptable side effects. However, the safety of tramadol has to be investigated before allowing its use in clinical practice. IMPLICATIONS: Tramadol's unique mechanism of action suggests efficacy as a local anesthetic adjunct for peripheral plexus blockade. Our study demonstrates that tramadol, added to mepivacaine for brachial plexus anesthesia, extends the duration and improves the quality of postoperative analgesia in a dose dependent fashion with acceptable side effects.