Unilateral optic neuropathy following subdural hematoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Unilateral optic neuropathy is commonly due to a prechiasmatic affliction of the anterior visual pathway, while losses in visual hemifields result from the damage to brain hemispheres. Here we report the unusual case of a patient who suffered from acute optic neuropathy following hemispherical subdural hematoma. Although confirmed up to now only through necropsy studies, our case strongly suggests a local, microcirculatory deficit identified through magnetic resonance imaging <it>in vivo</it>.</p> <p>Case presentation</p> <p>A 70-year-old Caucasian German who developed a massive left hemispheric subdural hematoma under oral anticoagulation presented with acute, severe visual impairment on his left eye, which was noticed after surgical decompression. Neurologic and ophthalmologic examinations indicated sinistral optic neuropathy with visual acuity reduced nearly to amaurosis. Ocular pathology such as vitreous body hemorrhage, papilledema, and central retinal artery occlusion were excluded. An orbital lesion was ruled out by means of orbital magnetic resonance imaging. However, cerebral diffusion-weighted imaging and T2 maps of magnetic resonance imaging revealed a circumscribed ischemic lesion within the edematous, slightly herniated temporomesial lobe within the immediate vicinity of the affected optic nerve. Thus, the clinical course and morphologic magnetic resonance imaging findings suggest the occurrence of pressure-induced posterior ischemic optic neuropathy due to microcirculatory compromise.</p> <p>Conclusion</p> <p>Although lesions of the second cranial nerve following subdural hematoma have been reported individually, their pathogenesis was preferentially proposed from autopsy studies. Here we discuss a dual, pressure-induced and secondarily ischemic pathomechanism on the base of <it>in vivo </it>magnetic resonance imaging diagnostics which may remain unconsidered by computed tomography.</p

Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors

Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Processo clinical caritas: novos rumos para o cuidado de enfermagem transpessoal Proceso clinical caritas: nuevos rumbos para el cuidado de enfermería transpersonal Human caring processes: direction for nursing care

O objetivo deste artigo é fazer uma reflexão sobre o cuidado humano à luz da evolução teórica das concepções de Jean Watson, tendo em vista as suas novas proposições do que venha ser o homem e sua conexão com o cosmos e as possibilidades de cuidado ante o potencial existente dentro de cada um. Esta forma de cuidar propõe a reestruturação do homem para melhor vivenciar os diferentes momentos da vida, rompendo com os antigos paradigmas em relação ao cuidado de enfermagem. Demonstra as diferentes possibilidades para a prática da enfermagem, bem como os desdobramentos concernentes ao ensino e à pesquisa.<br>El objetivo de este artículo es hacer una reflexión sobre el cuidado humano a la luz de la evolución teórica de las concepciones de Jean Watson, teniendo en vista sus nuevas propuestas respecto a lo que es el hombre y su conexión con el cosmos y las posibilidades de cuidado ante el potencial existente dentro de cada uno. Esta forma de cuidar propone la reestructuración del hombre para vivenciar mejor los diferentes momentos de la vida, rompiendo con los antiguos paradigmas en relación al cuidado de enfermería. Demuestra las diferentes posibilidades para la práctica de la enfermería, así como también los desdoblamientos concernientes a la enseñanza y a la investigación.<br>This article discusses Jean Watson theoretical work on human caring processes, which acknowledges unity of life and men-universe connection. Caring encompasses the reorganization of the human being in order to live deeply the different moments of life, and the breaching of old paradigms in relation to nursing care. Watson's theoretical work suggests different possibilities for nursing practice, teaching, and research

O conhecimento político na atuação do enfermeiro El conocimiento político en la actuación del enfermero The political knowing in the acting of the nurse

O artigo tem por objetivo refletir acerca do conhecimento empírico, ético, estético e pessoal proposto por Carper e de um quinto padrão de conhecimento denominado sociopolítico segundo White. A Enfermagem, ao delimitar seu campo de atuação, necessita explicitar suas formas de conhecer, produzir e validar o conhecimento, para consolidar-se como disciplina e profissão que se organiza e expressa socialmente com identidade singular em um complexo campo de conhecimento. O padrão de conhecimento sociopolítico contribui para que o enfermeiro tenha uma visão abrangente, na qual se particulariza a responsabilidade e o compromisso como agente de mudança organizacional, social e política, investindo na inovação e sustentabilidade do processo de trabalho da enfermagem em defesa da saúde individual e coletiva.<br>El artículo tiene el objetivo de hacer una reflexión respecto al conocimiento empírico, ético, estético y personal propuesto por Carper y de un quinto patrón de conocimiento denominado socio político según White. La enfermería, al delimitar su campo de actuación necesita mostrar sus formas de conocer, producir y validar el conocimiento, para consolidarse como disciplina y profesión que se organiza y expresa socialmente con identidad particular en un complejo campo de conocimiento. El patrón de conocimiento socio político contribuye para que el enfermero tenga una visión global, en la cual se destaca la responsabilidad y el compromiso como agente de cambio orgánico, social y político invirtiendo en la innovación y mantenimiento del proceso de trabajo de enfermería en defensa de la salud individual y colectiva.<br>This article objectifies to reflect on empirical, ethical, esthetical and personal patterns of knowing proposed by Carper as well as a fifth one called sociopolitical pattern of knowing according to White. By delimiting its acting field, nursing needs to explicit its ways of knowing, producing and validating knowledge in order to consolidate as a discipline and profession which is organized and socially expressed with unique identity in a complex knowledge field. The sociopolitical pattern of knowing contributes for nurses to have a broad view, particularly the responsibility and commitment as agents of organizational, social and political change, investing on the innovation and sustainability of nursing work process in favor of individual and collective health