Intravenous immunoglobulins in refractory childhood-onset epilepsy: effects on seizure frequency, EEG activity, and cerebrospinal fluid cytokine profile

PURPOSE: Several studies have reported favorable effects of intravenous immunoglobulins (IVIG) in refractory epilepsy. Evidence substantiating an immunomodulatory action is scarce. In an open-label study, we prospectively investigated the effect of IVIG on clinical, EEG and serum/CSF immunological parameters in patients with refractory childhood-onset epilepsy. METHODS: Thirteen patients (median age 6.9 years; range 1.6-25.8) with refractory seizures despite 3-4 antiepileptic drug regimens were given IVIG (Sandoglobulin, ZLB-Behring, add-on, 4 x 400 mg/kg/3 weeks). Seizure frequency, 24-h video-EEG, and CSF/serum immunological parameters and cytokine profiles (IL-6/IL-8/IL-12/IL-10) were documented before and after completion of the course. RESULTS: Seizure frequency was reduced by > or = 50% in four, and by 25%-50% in three patients. In contrast, variation in automatically recorded spike counts (1-h-wake and -sleep) did not correlate with clinical improvement. Serum immunological parameters showed variable deviations in eight patients (e.g., IgG(2) deficiency) and CSF immunoblotting showed oligoclonal bands in two patients. Blood-brain barrier permeability was normal in 12 patients. IL-6 and IL-8 were clearly detectable in CSF of all patients; the levels were significantly higher than those in plasma but remained unaffected by IVIG treatment. CONCLUSIONS: Despite unchanged EEG spike counts, substantial reductions in seizure frequency occurred in 7 of 13 patients, suggesting that IVIG hinder progression of central epileptic activity into clinical seizures. Intrathecal presence of IL-8 and IL-6 was documented in all patients, but was unaffected by IVIG, suggesting that their production is directly related to electrical seizure activity and that IVIG may act through interference with immune pathways downstream to IL-6 and IL-8.     

Lateral epicondylitis in tennis: update on aetiology, biomechanics and treatment

Lateral epicondylitis (tennis elbow) is the most frequent type of myotendinosis and can be responsible for substantial pain and loss of function of the affected limb. Tennis biomechanics, player characteristics and equipment are important in preventing the condition. This article presents an overview of the current knowledge on lateral epicondylitis, and focuses on treatment strategies. Conservative and surgical treatment options are discussed, and recent techniques are outlined.     

A simple method to estimate cardiac function during routine multi-row detector CT exams

Cardiac dysfunction may be suggested at computed tomography (CT) exams by the presence of morphological abnormalities such as cardiac enlargement and thickening of the pulmonary interlobular septa. However, these morphological signs are non specific. We evaluated whether right-to-left cardiac transit time of contrast during single-level timing scans could predict the cardiac output and ejection fraction. In a consecutive group of 100 patients referred for body CT, a preliminary single-level study was used to measure the right-to-left ventricular transit time of intravenously injected contrast medium. In all these patients, the cardiac index (cardiac output corrected for body surface area, CI) and ejection fraction (EF) were calculated using cardiac magnetic resonance imaging (CMR). Data of the first half (50 patients, group A) were used to establish a method and concept to predict the cardiac index and ejection fraction with CT. The method was validated in the next half (50 patients, group B) by comparing the predicted CT results with those obtained with CMR. There was a good correlation of the observed CI with CMR and observed transit time on CT in group B (P < 0.05; R² 0.70 ). Functional CT estimates of CI and EF in group B correlated well with the CMR results for CI and EF (P < 0.05; R² 0.66 for CI and P < 0.05; R² 0.49 for EF). The presence of a right-to-left ventricular transit time of more than 10.5 s indicated cardiac dysfunction with a specificity and positive predictive value of 100%. Right-to-left transit time obtained during routine body CT exams can provide valuable physiological information on global cardiac function.     

Pharmacoeconomic impact of adverse events of long-term opioid treatment for the management of persistent pain

Opioids are the most powerful analgesic drugs currently available and consequently form an essential part of the treatment options for malignant and non-malignant chronic pain. However, the benefits of these medications can be offset by gastrointestinal adverse events such as nausea, vomiting and constipation, as well as adverse events affecting the CNS. These occur relatively frequently in patients receiving long-term opioids for pain relief and are a cause of additional patient suffering and reduced work and social functioning, measured as reductions in quality-of-life outcomes. Consequently, adverse events are often the cause of treatment non-compliance or discontinuation (non-persistence). A literature search was conducted using BIOSIS Previews, EMBASE, Cochrane Collaboration and MEDLINE databases to identify references with specific relevance to the measurement of health outcomes related to adverse events of long-term opioid treatment of chronic pain. The results of this search highlighted that clinical interventions required to manage adverse events associated with opioids, and to provide alternative methods of pain control, both incur direct costs. These are largely driven by the cost of medical consults and drug supplies. Indirect costs are generated from work absences and reduced social functioning. Estimated preference ratings, providing an insight into the trade-off between effective pain control and adverse events, have shown that utility decrements associated with an increase in adverse-event severity were similar in size to those caused by a shift from well controlled to poorly controlled pain. Given the rising prevalence of chronic pain conditions (affecting one in five adult Europeans), the direct and indirect costs incurred from the management of adverse events with long-term opioids are likely to be multiplied, contributing to the socioeconomic burden of chronic pain. For this reason, the adverse-event profile of opioid-based analgesics should be improved to achieve more efficient long-term pain control.     

The future of induced pluripotent stem cells for cardiac therapy and drug development

The field of stem cell research was revolutionized with the advent of induced pluripotent stem cells. By reprogramming somatic cells to pluripotent stem cells, most ethical concerns associated with the use of embryonic stem cells are overcome, such that many hopes from the stem cell field now seem a step closer to reality. Several methods and cell sources have been described to create induced pluripotent stem cells and we discuss their characteristics in terms of feasibility and efficiency. From these cells, cardiac progenitors and cardiomyocytes can be derived by several protocols and most recent advances as well as remaining limitations are being discussed. However, in the short time period this technology has been around, evidence emerges that induced pluripotent stem cells may be more prone to genetic defects and maintain an epigenetic memory and thus may not be entirely the same as embryonic stem cells. Despite the lack of a complete fundamental understanding of stem cell biology, and even more of ways how to coax them into defined cell types, the technology is quickly adopted by industry. This paper gives an overview of the current applications of induced pluripotent stem cells in cardiovascular drug development and highlights active areas of research towards functional repair of the damaged heart. Adult stem cells have already been taken to clinical trials and we discuss these results in light of potential and hurdles to be taken to move induced pluripotent stem cells to the clinic.     

Prosthetic component relationship of the reverse Delta III total shoulder prosthesis in the transverse plane of the body

The Delta III (DePuy International Ltd, Leeds, UK) reverse total shoulder prosthesis has provided a successful functional outcome in cuff tear arthropathy (CTA); however, internal and external rotation remain compromised. Positioning of the prosthetic components in the transverse plane has theoretically been suggested to affect rotation. Twenty-seven patients who received a Delta III reversed total shoulder prosthesis for CTA were analyzed (mean follow-up, 43 months) using standard radiographs and computed tomography. The position of the prosthetic components and the possible influence of scapular rotation was analyzed using a uniform spatial reference system using axes in reference to the sagittal or coronal plane. We assessed impingement of the humeral component on the glenoid neck in neutral and internal rotation. An increase in the anterior divergence of the glenoid and humeral prosthetic components correlates with an increase in radiologically measured internal rotation (r = 0.932, P < .001). The uniformity of the reference system used seems to allow accurate positioning of the components intraoperatively and can be useful for analysis of the prosthetic component relationship postoperatively.