The influence of hand posture on corticospinal excitability during motor imagery: a transcranial magnetic stimulation study

In order to study the interaction between proprioceptive information and motor imagery, we herein investigate how compatible and incompatible postural signals influence corticospinal excitability during the mental simulation of hand movements. Subjects were asked to imagine themselves joining the tips of the thumb and the little finger while they maintained one of the two following hand postures: posture A (PA, compatible), little finger, index and thumb extended, the remaining fingers flexed; or posture B (PB, incompatible), index and thumb extended, other fingers flexed. All subjects rated the imagined finger opposition movements as easier to perform when the hand was kept in PA than in PB (P < 0.01) and the correlation between the duration of motor imagery and movement execution was also higher for PA than PB (P < 0.01). For each posture, motor evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) of the left motor cortex were recorded from the right opponens pollicis muscle during both motor imagery (MI) and rest (R) conditions. MEP area varied according to the hand posture: PA induced a higher increase in corticospinal excitability, when compared with PB. These results indicate that the actual limb posture affects the process of motor imagery. The source of this postural modulation effect is discussed.     

Recommendations for the use of new methods to assess the efficacy of disease-modifying drugs in the treatment of osteoarthritis

BACKGROUND: Recent innovations in the pharmaceutical drug discovery environment have generated new chemical entities with the potential to become disease modifying drugs for osteoarthritis (DMOAD's). Regulatory agencies acknowledge that such compounds may be granted a DMOAD indication, providing they demonstrate that they can slow down disease progression; progression would be calibrated by a surrogate for structural change, by measuring joint space narrowing (JSN) on plain X-rays with the caveat that this delayed JSN translate into a clinical benefit for the patient. Recently, new technology has been developed to detect a structural change of the OA joint earlier than conventional X-rays. OBJECTIVE: The Group for the Respect of Ethics and Excellence in Science (GREES) organized a working party to assess whether these new technologies may be used as surrogates to plain x-rays for assessment of DMOADs. METHODS: GREES includes academic scientists, members of regulatory authorities and representatives from the pharmaceutical industry. After an extensive search of the international literature, from 1980 to 2002, two experts meetings were organized to prepare a resource document for regulatory authorities. This document includes recommendations for a possible update of guidelines for the registration of new chemical entities in osteoarthritis. RESULTS: Magnetic resonance imaging (MRI) is now used to measure parameters of cartilage morphology and integrity in OA patients. While some data are encouraging, correlation between short-term changes in cartilage structure observed with MRI and long-term radiographic or clinical changes are needed. Hence, the GREES suggests that MRI maybe used as an outcome in phase II studies, but that further data is needed before accepting MRI as a primary end-point in phase III clinical trials. Biochemical markers of bone and cartilage remodelling are being tested to predict OA and measure disease progression. Recently published data are promising but validation as surrogate end-points for OA disease progression requires additional study. The GREES suggests that biochemical markers remain limited to 'proof of concept' studies or as secondary end-points in phase II and III clinical trials. However, the GREES emphasizes the importance of acquiring additional information on biochemical markers in order to help better understand the mode of action of drugs to be used in OA. Regulatory agencies consider that evidence of improvement in clinical outcomes is critical for approval of DMOAD. Time to total joint replacement surgery is probably the most relevant clinical end-point for the evaluation of efficacy of a DMOAD. However, at this time, time to surgery can not be used in clinical trials because of bias by non disease-related factors like patient willingness for surgery or economic factors. At this stage, it appears that DMOAD should demonstrate a significant difference compared to placebo. Benefit should be measured by 3 co-primary end-points: JSN, pain and function. Secondary end-points should include the percentage of patients who are 'responder' (or 'failure'). The definition of a 'failure' patient would be someone with progression of JSN>0.5mm over a period of 2-3 years or who has a significant worsening in pain and/or function, based on validated cut-off values. The definition of the clinically relevant cut-off points for pain and function must be based on data evaluating the natural history of the disease (epidemiological cohorts or placebo groups from long-term studies). These cut-offs points should reflect a high propensity, for an individual patient, to later require joint replacement. CONCLUSION: GREES has outlined a set of guidelines for the development of a DMOAD for OA. Although these guidelines are subject to change as new information becomes available, the information above is based on the present knowledge in the field with the addition of expert opinion.     

Immediate Extubation after Aortic Valve Surgery Using High Thoracic Epidural Anesthesia

Abstract Purpose: Fast-track anesthesia has gained widespread use in cardiac centers around the world. No study has focused on immediate extubation after aortic valve surgery. This study examines the feasibility and hemodynamic stability of immediate extubation after simple or combined aortic valve surgery using thoracic epidural anesthesia. Methods: Thirty patients undergoing aortic valve surgery with an ejection fraction of more than 30% were included in this prospective audit. After insertion of a high thoracic epidural catheter, induction with fentanyl 2 to 4 microg/kg, administration of propofol 1 to 2 mg/kg, and endotracheal intubation facilitated by rocuronium, anesthesia was maintained with sevoflurane titrated according to bispectral index (target, 50). Perioperative analgesia was provided by high thoracic epidural analgesia (TEA) (bupivacaine 0.125% 6-14 mL/h). Hemodynamic data were compared by Friedman test. P <.05 was considered to show a significant difference. Data are presented as median (25th-75th percentile). Results: Patients underwent simple aortic valve surgery (n = 17) or combined aortic valve surgery (n = 13) with additional coronary artery bypass grafting (n = 8), replacement of the ascending aorta (Bentall procedure) (n = 4), and repair of open foramen ovale (n = 1). All 30 patients were extubated within 15 minutes after surgery at 36.5 degrees C (36.4 degrees C-36.6 degrees C). There was no need for reintubation. Pain scores were low immediately after surgery and 6, 24, and 48 hours after surgery at 0 (0-3.5), 0 (0-2), 0 (0-2), and 0 (0-2), respectively. During and up to 6 hours after surgery, there was no significant hemodynamic change due to TEA. Fifteen of 30 patients needed temporary pacemaker activation. There were no complications related to TEA. Conclusions: Immediate extubation is feasible after aortic valve surgery with high thoracic epidural analgesia and maintenance of hemodynamic stability throughout surgery. Immediate extubation after aortic valve surgery is a promising new path in cardiac anesthesia.     

Making pregnancy safer for patients with lupus

Systemic lupus erythematosus is a hormone-dependent disorder predominantly affecting young women in whom changes in hormonal activity affect the course of the disease. More specifically, pregnancy is associated in 50 to 60% of cases with a clinical flare manifesting as renal or hematological symptoms, usually during the second or third trimester but occasionally in the postpartal period. Patients should be strongly advised to start a pregnancy only if their disease has been stable for at least 6 months, and they should be informed of the few contraindications. Severe flares are uncommon (10%) and the risk of maternal death is now 2 to 3%. The risk of the fetus remains high, however. Thus, fetal loss is common, particularly in patients with a lupus anticoagulant, renal failure, or arterial hypertension. Preterm birth occurs in 25% to 50% of cases and intrauterine growth retardation in 30%. Neonatal lupus with or without congenital heart block is exceedingly rare, being seen in the 1% of SLE women who have anti-SSA (Ro) and/or SSB (La) antibodies. To ensure a favorable outcome for both the mother and the child, the pregnancy should be planned, started during a period of disease stability, monitored closely (physical examination, laboratory tests, and Doppler ultrasound), and treated as needed (with antimalarial therapy throughout the pregnancy). Even with these precautions, however, preterm birth remains common.     

Foot orthotics decrease pain but do not improve gait in rheumatoid arthritis patients

OBJECTIVES: Prescribing foot orthotics in rheumatoid arthritis patients with symptomatic forefoot involvement is a standard practice. However, limited research has been reported regarding gait and pain improvement with the use of foot orthotics. PATIENTS AND METHODS: Sixteen patients (13 F, 3 M; mean age: 52 +/- 12 years) with metatarsalgia due to rheumatoid arthritis were included in this prospective, randomized with crossover study, and received foot orthotics. At 1 month follow-up, space and time gait variables with and without foot orthotics were assessed by Bessou's locometer; pain was assessed by visual analogue scale (VAS). RESULTS: Pain levels significantly decreased (P = 0.008) by wearing foot orthotics. Despite a significant step length increase (P = 0.05) with orthotics, there was no significant improvement of stride length, cadence, or walking speed which was the main assessment criterion. CONCLUSIONS: Wearing foot orthotics improves pain, but not sufficiently to improve gait in rheumatoid arthritis patients with metatarsalgia. Foot orthotics improved comfort levels because of a decrease in pain, but was not sufficient to correct gait.     

Acute pseudoseptic arthritis after intraarticular sodium hyaluronan

A 70-year-old woman with a history of knee osteoarthritis was admitted for acute arthritis 9 days after a second intraarticular injection of sodium hyaluronan (Ostenil). The joint fluid was purulent, with no crystals, and laboratory tests showed marked inflammation, leading to antibiotic treatment for suspected septic arthritis. Incapacitating symptoms persisted, prompting surgical lavage of the knee, which failed to relieve the severe pain. The persistent symptoms and negative results of joint fluid and blood cultures led to discontinuation of the antibiotic therapy after 10 days. Antiinflammatory therapy relieved the symptoms, and the patient was discharged home 1 month after her admission. Nevertheless, the pain persisted, requiring rehabilitation therapy of the knee. Aseptic arthritis induced by repeated sodium hyaluronan injection is the most likely diagnosis. Physicians should be aware of this extremely severe complication.     

A novel NPHS2 gene mutation in Turkish children with familial steroid-resistant nephrotic syndrome

We report in this paper two siblings aged 8 and 17 months who were clinically diagnosed with familial steroid-resistant nephrotic syndrome (SRNS). By mutation screening of the NPHS2 gene, a homozygous missense mutation, P118L, was detected in both children. This study is the first systematic investigation of NPHS2 gene mutations in Turkish children with familial SRNS. If this mutation is a hot spot of mutation in the Turkish population, screening this novel mutation in Turkish children with SRNS may be of great clinical use to prevent unnecessary treatment modalities, provide accurate genetic counselling and predict the prognosis of the disease.     

Associations between parental and child attachment representations

In the present article on intergenerational transmission of attachment representations, we use mothers' and fathers' Adult Attachment Interview classifications to predict a 3-year-old's responses to the Attachment Story Completion Task (ASCT). We present a Q-sort coding procedure for the ASCT, which was developed for children as young as three. The Q-sort yields scores on four attachment dimensions (security, deactivation, hyperactivation, and disorganization). One-way ANOVAs revealed significant mother-child associations for each dimension, although results for the hyperactivation and disorganization dimensions were significant only according to contrast tests. Conversely, no father-child association was found, regardless of the dimension considered. Findings are discussed in terms of the respective part played by each parent in their children's emotional development.