Diffuse analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers

We investigated the analgesic effects of unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) or dorsolateral prefrontal cortex (DLPFC) in two models of experimental pain in healthy volunteers. Two studies were carried out in parallel in two groups of 26 paid healthy volunteers. The effects of active or sham rTMS (frequency, 10 Hz; intensity, 80% resting motor threshold) applied to the right M1 or DLPFC were compared in a double-blind randomized cross-over design. In the first series of experiments, we analyzed the effects of rTMS on thermal (heat and cold) detection and pain thresholds measured on both hands and the left foot, by standardized quantitative sensory testing methods. In the second series of experiments, we measured the effects of M1 or DLPFC rTMS on the threshold and recruitment curves of the RIII nociceptive reflex evoked by ipsilateral electrical stimulation of the sural nerve and recorded on the biceps femoris of both lower limbs. In both studies, measurements were taken before and up to 60 min after the end of rTMS. Active rTMS of both M1 and DLPFC significantly increased the thermal pain thresholds, measured for both hands and the left foot, this effect being most marked for cold pain. These effects, which lasted at least 1 h after rTMS, were selective because they were not associated with changes in non-painful thermal sensations. By contrast, the second study showed that rTMS of M1 or DLPFC had no significant effect on the threshold or recruitment curve of the nociceptive flexion RIII reflex. Our findings demonstrate that unilateral rTMS of M1 or DLPFC induces diffuse and selective analgesic effects in healthy volunteers. The lack of effect on the RIII reflex suggests that such analgesic effects may not depend on the activation of descending inhibitory systems. (C) 2009 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.

TRANSFER OF A FASCICLE FROM THE POSTERIOR CORD TO THE SUPRASCAPULAR NERVE AFTER INJURY OF THE UPPER ROOTS OF THE BRACHIAL PLEXUS: TECHNICAL CASE REPORT

OBJECTIVE: A new nerve transfer technique using a healthy fascicle of the posterior cord for suprascapular nerve reconstruction is presented. This technique was used in a patient with posttraumatic brachial plexopathy resulting in upper trunk injury with proximal root stumps that were unavailable for grafting associated with multiple nerve dysfunction. CLINICAL PRESENTATION: A 45-year-old man sustained a right brachial plexus injury after a bicycle accident. Clinical evaluation and electromyography indicated upper trunk involvement. Trapezius muscle function and triceps strength were normal on physical examination. INTERVENTION: The patient underwent a combined supra- and infraclavicular approach to the brachial plexus. A neuroma-in-continuity of the upper trunk and fibrotic C5 and C6 roots were identified. Electrical stimulation of the phrenic and spinal accessory nerves produced no response. The suprascapular nerve was dissected from the upper trunk, transected, and rerouted to the infraclavicular fossa. A healthy fascicle of the posterior cord to the triceps muscle was transferred to the suprascapular nerve. At the time of the 1-year follow-up evaluation, arm abduction against gravity and external rotation reached 40 and 34 degrees, respectively. CONCLUSION: The posterior cord can be used as a source of donor fascicle to the suprascapular nerve after its infraclavicular relocation. This new intraplexal nerve transfer could be applied in patients with isolated injury of the upper trunk and concomitant lesion of the extraplexal nerve donors usually used for reinnervation of the suprascapular nerve.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Ranolazine Exerts Potent Effects on Atrial Electrical Properties and Abbreviates Atrial Fibrillation Duration in the Intact Porcine Heart

Introduction: In vitro studies and ambulatory ECG recordings from the MERLIN TIMI-36 clinical trial suggest that the novel antianginal agent ranolazine may have the potential to suppress atrial arrhythmias. However, there are no reports of effects of ranolazine on atrial electrophysiologic properties in large intact animals. Methods and Results: In 12 closed-chest anesthetized pigs, effects of intravenous ranolazine (similar to 9 mu M plasma concentration) on multisite atrial effective refractory period (ERP), conduction time (CT), and duration and inducibility of atrial fibrillation (AF) initiated by intrapericardial acetylcholine were investigated. Ranolazine increased ERP by a median of 45 ms (interquartile range 29-50 ms; P < 0.05, n = 6) in right and left atria compared to control at pacing cycle length (PCL) of 400 ms. However, ERP increased by only 28 (24-34) ms in right ventricle (P < 0.01, n = 6). Ranolazine increased atrial CT from 89 (71-109) ms to 98 (86-121) ms (P = 0.04, n = 6) at PCL of 400 ms. Ranolazine decreased AF duration from 894 (811-1220) seconds to 621 (549-761) seconds (P = 0.03, n = 6). AF was reinducible in 1 of 6 animals after termination with ranolazine compared with all 6 animals during control period (P = 0.07). Dominant frequency (DF) of AF was reduced by ranolazine in left atrium from 11.7 (10.7-20.5) Hz to 7.6 (2.9-8.8) Hz (P = 0.02, n = 6). Conclusions: Ranolazine, at therapeutic doses, increased atrial ERP to greater extent than ventricular ERP and prolonged atrial CT in a frequency-dependent manner in the porcine heart. AF duration and DF were also reduced by ranolazine. Potential role of ranolazine in AF management merits further investigation. (J Cardiovasc Electrophysiol, Vol. 20, pp. 796-802, July 2009).

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n = 9, 1 mg/day) or placebo (n = 9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59 +/- 2 vs. 71 +/- 2 beats/min, P < 0.01). In both groups, exercise produced significant decreases in systolic BP (145 +/- 3 vs. 154 +/- 3 mmHg, P = 0.01), diastolic BP (71 +/- 3 vs. 75 +/- 2 mmHg, P = 0.04), mean BP (89 +/- 2 vs. 93 +/- 2 mmHg, P = 0.02), MSNA (29 +/- 2 vs. 35 +/- 1 bursts/min, P < 0.01), and FVR (33 +/- 4 vs. 55 +/- 10 units, P = 0.01), whereas it increased FBF (2.7 +/- 0.4 vs. 1.6 +/- 0.2 ml (.) min(-1) (.) 100 ml(-1), P = 0.02) and did not change HR (64 +/- 2 vs. 65 +/- 2 beats/min, P = 0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.

Studies of RET gene expression and acetylcholinesterase activity in a series of sporadic Hirschsprung`s disease

The purpose is to present the studies of RET gene expression and acetylcholinesterase activity in 23 patients operated for Hirschsprung`s disease (HD). The patients underwent either transanal endorectal pull-through or Duhamell`s procedure. Full-thickness intestinal samples from the three different segments (ganglionic, intermediate and aganglionic) were collected. Each tissue sample was divided in two portions, one for AChE histochemical staining and the other for examination of RET mRNA expression level. All patients had an uneventful postoperative recovery. In all patients, the AChE stainings demonstrated the absence of activity in the ganglionic area, the marked increase of positive fibers in the aganglionic area, and little increase of positive fibers in the intermediate area. In the ganglionic and intermediate areas, all patients (100%) showed significant RET gene expression. In the aganglionic area, 18 patients (78.3%) did not present gene expression and the other five patients (21.7%) presented gene expression that was similar to the ganglionic and intermediate areas. The results reinforce the conclusion that the method of AChE staining is effective for the diagnosis of intestinal aganglionosis and confirm the knowledge that genes beyond RET may be implicated in the genesis of sporadic cases of HD.

Quantitative parameters of facial motor evoked potential during vestibular schwannoma surgery predict postoperative facial nerve function

Background Facial motor evoked potential (FMEP) amplitude ratio reduction at the end of the surgery has been identified as a good predictor for postoperative facial nerve outcome. We sought to investigate variations in FMEP amplitude and waveform morphology during vestibular schwannoma (VS) resection and to correlate these measures with postoperative facial function immediately after surgery and at the last follow-up. Methods Intraoperative orbicularis oculi and oris muscles FMEP data from 35 patients undergoing surgery for VS resection were collected, then analysed by surgical stage: initial, dural opening, tumour dissection (TuDis), tumour resection (TuRes) and final. Findings Immediately after surgery, postoperative facial function correlated significantly with the FMEP amplitude ratio during TuDis, TuRes and final stages in both the orbicularis oculi (p = 0.003, 0.055 and 0.028, respectively) and oris muscles (p = 0.002, 0.104 and 0.014, respectively). At the last follow-up, however, facial function correlated significantly with the FMEP amplitude ratio only during the TuDis (p = 0.005) and final (p = 0.102) stages for the orbicularis oris muscle. At both time points, postoperative facial paresis correlated significantly with FMEP waveform deterioration in orbicularis oculi during the final stage (immediate, p = 0.023; follow-up, p = 0.116) and in orbicularis oris during the TuDis, TuRes and final stages (immediate, p = 0.071, 0.000 and 0.001, respectively; follow-up, p = 0.015, 0.001 and 0.01, respectively). Conclusions FMEP amplitude ratio and waveform morphology during VS resection seem to represent independent quantitative parameters that can be used to predict postoperative facial function. Event-to-baseline FMEP monitoring is quite useful to dictate when intraoperative changes in surgical strategy are warranted to reduce the chances of facial nerve injury.