P REHOSPITAL U SE OF A NALGESIA FOR S USPECTED E XTREMITY F RACTURES

Introduction. Pain and its control have been studied extensively in the emergency department. Numerous studies indicate that inadequate treatment of pain is common, despite the availability of myriad analgesics. It has been suggested that oligoanesthesia is also a common practice in the prehospital setting. Objective. To assess the use of prehospital analgesia in patients with suspected extremity fracture. Methods. Emergency medical services (EMS) call reports were reviewed for all patients with suspected extremity fractures treated from June 1997 to July 1998 in a midwestern community with a population base of 223,000. Data collected included demographic information, mechanism of injury, medications given, and field treatment. Standing orders for administration of analgesia were available and permitted paramedics to give either morphine sulfate or nitrous oxide per protocol. Results. The EMS call reports were analyzed for 1,073 patients with suspected extremity fractures. The mean patient age was 47 years. Accidental injuries comprised 86.5% of those reviewed. Suspected leg fractures were most common (20%), followed by hips (18%), arms (11%), knees (10%), ankles (9%), shoulders (7.2%), hands (5.5%), and wrists (5.3%). Multiple trauma and assorted broken digits accounted for the remaining 14%. The most common mechanisms of injury were: fall (43%), motor vehicle collision (21%), and human assault (10%). Intravenous lines were placed in 9.4% of patients; 17% received ice packs; 16% received bandage/dressings; 25% received air splints; and 19% were fully immobilized. Analgesia was administered to 18 patients (1.8%): 16 patients received nitrous oxide and two received morphine. Conclusion. Administration of analgesics to prehospital patients with suspected fractures was rare. Prehospital identification and treatment of pain for patients with musculoskeletal trauma could be improved.     

Nonembolic Predictors of Stroke Risk in Coronary Artery Bypass Patients

The aim of this study was to identify and stratify the most important nonembolic risk factors for stroke after coronary bypass grafting. From June 1994 to June 1997 a series of 1532 patients (pts) underwent isolated myocardial revascularization on cardiopulmonary bypass (CPB). A retrospective chart review selected 1417 pts in whom the presence of aortic calcification or left ventricular mural thrombi was not detectable by echocardiogram, angiogram, and intraoperative records. Univariate and multivariate analyses were conducted to identify nonembolic variables independently correlated to postoperative stroke. A predictive model of stroke probability was then constructed by means of a mathematic method with the variables selected from logistic regression analyses. The global incidence of stroke was 1.8%. Univariate analysis revealed that, among 29 preoperative and operative variables, age, vasculopathy, emergency operation, previous cerebrovascular accident (CVA), CPB, and aortic cross-clamping times were factors strongly associated with postoperative stroke (p < 0.01). A first logistic regression analysis (LRA) selected as independent predicting variables (p < 0.05) age [odds ratio (OR) 1.07/year], vasculopathy (OR 4), previous CVA (OR 7.2), CPB time (OR 1/year), and emergency operation (OR 4.2). In a second stepwise LRA, age and CPB time were subdivided into cohorts as follows: age ≤ 65 years, > 65 but < 75 years, ≥ 75 years; CPB time ≤ 120 minutes, > 120 but < 180 minutes, ≥ 180 minutes. Both age ≥ 75 years (p= 0.024; OR 3.3) and CPB time ≥ 180 minutes (p= 0.002; OR 4.2), were found to be predictors of postoperative neurologic damage. Finally, a probability table of stroke risk was obtained with the logistic regression coefficients. A lower stroke probability (0.7%) was calculated in the absence of risk variables and a higher one in the presence of all of them (83.3%). Between these extremes, a total of 158 combinations of stroke probabilities were obtained. We concluded that previous CVA, vasculopathy, emergency operation, and age > 75 years are variously associated with a high risk of nonembolic stroke after myocardial revascularization. A duration of CPB longer than 3 hours strongly increases the probability of neurologic damage in the presence of the aforementioned variables.     

The OptiMARK clinical development program: summary of safety data

PURPOSE: To describe and summarize the safety data from the OptiMARK clinical development program. MATERIALS AND METHODS: In the 18 clinical studies comprising the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to healthy adult volunteers, patients with hepatic or renal impairment, and patients with confirmed or highly suspected central nervous system (CNS), liver, breast, vascular, bone, or soft tissue pathologies. A total of 2038 injections of OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety assessments were performed at appropriate intervals during all Phase 1, 2, and 3 studies. RESULTS: Of the 1684 subjects exposed to a study drug or placebo in the clinical development program, 646 subjects experienced 1293 adverse events. Thirty-one percent of the OptiMARK injections were associated with an adverse event. In comparison, 35% of Magnevist injections and 48% of placebo injections were associated with at least one adverse event. CONCLUSIONS: OptiMARK was safe and well-tolerated with a safety profile similar to that of Magnevist.     

l‐DOPA‐induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron‐microglia‐astrocyte interactions play a major role in the plasticity of neuronal response to l ‐DOPA in post‐synaptic neurons, we focused this review on our recent results of l ‐DOPA‐induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l ‐DOPA‐induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine‐denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l ‐DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l ‐DOPA treatment.     

Generation of GFAP::GFP astrocyte reporter lines from human adult fibroblast‐derived iPS cells using zinc‐finger nuclease technology

Astrocytes are instrumental to major brain functions, including metabolic support, extracellular ion regulation, the shaping of excitatory signaling events and maintenance of synaptic glutamate homeostasis. Astrocyte dysfunction contributes to numerous developmental, psychiatric and neurodegenerative disorders. The generation of adult human fibroblast‐derived induced pluripotent stem cells (iPSCs) has provided novel opportunities to study mechanisms of astrocyte dysfunction in human‐derived cells. To overcome the difficulties of cell type heterogeneity during the differentiation process from iPSCs to astroglial cells (iPS astrocytes), we generated homogenous populations of iPS astrocytes using zinc‐finger nuclease (ZFN) technology. Enhanced green fluorescent protein (eGFP) driven by the astrocyte‐specific glial fibrillary acidic protein (GFAP) promoter was inserted into the safe harbor adeno‐associated virus integration site 1 (AAVS1) locus in disease and control‐derived iPSCs. Astrocyte populations were enriched using Fluorescence Activated Cell Sorting (FACS) and after enrichment more than 99% of iPS astrocytes expressed mature astrocyte markers including GFAP, S100β, NFIA and ALDH1L1. In addition, mature pure GFP‐iPS astrocytes exhibited a well‐described functional astrocytic activity in vitro characterized by neuron‐dependent regulation of glutamate transporters to regulate extracellular glutamate concentrations. Engraftment of GFP‐iPS astrocytes into rat spinal cord grey matter confirmed in vivo cell survival and continued astrocytic maturation. In conclusion, the generation of GFAP::GFP‐iPS astrocytes provides a powerful in vitro and in vivo tool for studying astrocyte biology and astrocyte‐driven disease pathogenesis and therapy. GLIA 2016;64:63–75     

The monobloc hydrogel breast implant,experiences and ideas

This study is focused on the properties of the monobloc hydrogel (MH) breast implant, which has been around for more than 30 years, and to see how it behaves with regard to health complaints as sometimes seen in some patients who had received silicone gel (SG) breast implants. Patients responded to a questionnaire examining their experience with breast implants. Three groups were included. First, the control group (n = 34) of women without breast implants. Second, a C group of women (n = 42) who began and remained on the MH implant. Third, the B group of women who had their silicone gel implant replaced by the MH implant. In the B1 subgroup (n = 22), a capsulectomy was also performed. In the B2 subgroup (n = 13), the replacement was carried out without a capsulectomy. The C group behaved very much like the control group. The women of the B group experienced an improvement of their complaints and the improvement was even better after a capsulectomy. The only difference between the MH and SG implants is the content of the implant. The satisfaction of women with MH implants is generally high and not or hardly associated with health complaints. In women with SG implants and health complaints, these complaints can be relieved by replacement of the implants by MH implants.