Long-Lasting Cerebral Vasospasm,Microthrombosis, Apoptosis and Paravascular Alterations Associated with Neurological Deficits in a Mouse Model of Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality and morbidity. Long-term cognitive and sensorimotor deficits are serious complications following SAH but still not well explained and described in mouse preclinical models. The aim of our study is to characterize a well-mastered SAH murine model and to establish developing pathological mechanisms leading to cognitive and motor deficits, allowing identification of specific targets involved in these long-term troubles. We hereby demonstrate that the double blood injection model of SAH induced long-lasting large cerebral artery vasospasm (CVS), microthrombosis formation and cerebral brain damage including defect in potential paravascular diffusion. These neurobiological alterations appear to be associated with sensorimotor and cognitive dysfunctions mainly detected 10 days after the bleeding episode. In conclusion, this characterized model of SAH in mice, stressing prolonged neurobiological pathological mechanisms and associated sensitivomotor deficits, will constitute a validated preclinical model to better decipher the link between CVS, long-term cerebral apoptosis and cognitive disorders occurring during SAH and to allow investigating novel therapeutic approaches in transgenic mice.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy—Part IV: Selection and Management of Patients

Most serious hemorrhages that occur during long-term anticoagulant drug therapy are due either to poor patient selection or to poor management of the patient, or both.In each patient being considered for treatment, the risk of bleeding must be evaluated and classified as high, moderate or low.The clinician must especially assess the risk of intracranial hemorrhage in hypertensive patients, and must screen all patients for potential sources of gastrointestinal bleeding. There is ample time for such investigations, since initiating long-term anticoagulant therapy is not an emergency procedure.The desired level of prothrombin activity must be adjusted to the risks determined for each individual patient. There is no single “therapeutic range” applicable to all patients with their varying hemorrhagenic risks.Proper management includes sufficient laboratory testing to maintain the desired prothrombin level, and continued vigilance to detect signs of early bleeding.Preventable hemorrhage cannot be cited as evidence against the value of anticoagulant drug therapy.     

Optimal Drug Regimen and Combined Drug Therapy and Its Efficacy in the Treatment of COVID-19: A Within-Host Modeling Study

Acta Biotheoretica - Nonlocal reaction–diffusion equations describe various biological and biomedical applications. Their mathematical properties are essentially different in comparison with...     

SARS-CoV-2与SARS-CoV:病原学、流行病学、临床与病理

2019年12月在武汉暴发了由SARS-CoV-2感染引起的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19),并迅速扩散至全国.SARS-CoV-2和SARS冠状病毒(SARS-CoV)都属于套式病毒目、冠状病毒科、冠状病毒属中的SARS相关冠状病毒种,本文总结了两者在来源、病毒结构、流行病学、临床表现和病理学特征等方面的差异,以期更全面认识SARS-CoV和SARS-CoV-2,为COVID-19的防治研究提供帮助.     

Pathology: Cervical Pathology—The Bethesda System and the `Atypical Squamous Cells of Undetermined Significance' Controversy

The Council on Scientific Affairs of the California Medical Association presents the following epitomes of progress in pathology. Each item, in the judgment of a knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and clinical importance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of progress in medicine, whether in their own field of special interest or another.The epitomes included here were selected by the Advisory Panel to the Section on Pathology of the California Medical Association, and the summaries were prepared under the direction of Yutaka Kikkawa, MD, and the panel.     

波生坦治疗特发性肺动脉高压的疗效与安全性观察

目的:探讨波生坦治疗特发性肺动脉高压(IPAH)的疗效与安全性。方法:16例IPAH患者予波生坦口服治疗20周,比较治疗前后患者心功能、6分钟步行距离(6MWD)、肺动脉压力以及血常规、肝肾功能变化。结果:患者心功能由治疗前Ⅲ级13例、Ⅳ级3例变为Ⅱ级14例、Ⅲ级2例。6MWD较治疗前明显延长(P<0.01),肺动脉收缩压、肺动脉平均压及肺动脉舒张压均较治疗前显著降低(P<0.01),患者血常规、肝肾功能较治疗前无明显变化。结论:口服波生坦治疗IPAH可明显改善患者的临床症状与血流动力学指标,安全性好。     

The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis

Background

Inconsistent results have been reported for hyperbaric oxygen therapy (HBO) for acute stroke. We conducted a systematic review and meta-analysis to evaluate the benefit of HBO in animal studies of middle cerebral artery occlusion (MCAO).

Methods

A systematic search of the literature published prior to September 2015 was performed using Embase, Medline (OvidSP), Web of Science and PubMed. Keywords included “hyperoxia” OR “hyperbaric oxygen” OR “HBO” AND “isch(a)emia” OR “focal cerebral ischemia” OR “stroke” OR “infarct” OR “middle cerebral artery occlusion (MCAO).” The primary endpoints were the infarct size and/or neurological outcome score evaluated after HBO treatment in MCAO. Heterogeneity was analyzed using Cochrane Library’s RevMan 5.3.5.

Results

Fifty-one studies that met the inclusion criteria were identified among the 1198 studies examined. When compared with control group data, HBO therapy resulted in infarct size reduction or improved neurological function (32% decrease in infarct size; 95% confidence interval (CI), range 28%–37%; p < 0.00001). Mortality was 18.4% in the HBO group and 26.7% in the control group (RR 0.72, 95% CI, 0.54–0.98; p = 0.03). Subgroup analysis showed that a maximal neuro-protective effect was reached when HBO was administered immediately after MCAO with an absolute atmospheric pressure (ATA) of 2.0 (50% decrease; 95% CI, 43% -57% decrease; p < 0.0001) and more than 6 hours HBO treatment (53% decrease; 95% CI, 41% -64% decrease; p = 0.0005).

Conclusions

HBO had a neuro-protective effect and improved survival in animal models of MCAO, especially in animals given more than 6 hours of HBO and when given immediately after MCAO with 2.0 ATA.     

Childhood Psychosis or Mental Retardation: A Diagnostic Dilemma: II. Pediatric and Neurological Aspects

A pediatric and neurological study of 62 retarded psychotic children revealed more family psychopathology, complications of pregnancy, and serious postnatal illness than in a control group. Motor development and speech development were slow in psychotic children, but obstetrical complications at the time of birth were not significantly more frequent than in controls. Abnormal physical findings in psychotic children were mainly congenital anomalies. Neurological deficits included mental retardation, speech defects, strabismus, and other non-localizing signs. EEG tracings were abnormal in 27 of 51 psychotic patients. At least 46 of the 62 psychotic children studied had evidence of organic brain disease.Although an inadequate family background may be associated with the development of psychosis, a severe disturbance of temporal and frontal lobe function may produce psychotic symptoms with or without familial predisposition.     

Hemorrhage During Long-Term Anticoagulant Drug Therapy — Part III: The Relationship of Minor to Serious Bleeding

In a study of reports of 805 instances of spontaneous bleeding occurring among 2,189 patients receiving long-term anticoagulant drug therapy, 124 episodes were considered serious and 681 minor. There was no significant correlation of minor bleeding and serious bleeding.Minor bleeding unassociated with excessive reduction of coagulability or an underlying organic lesion could not be considered, according to this evidence, an indication for discontinuance of anticoagulant drug therapy.In apparently minor internal bleeding, however, hidden underlying organic lesions must be excluded. If gross hematuria occurs, renal lesions must be excluded.Rectal bleeding must not be considered minor until gastrointestinal lesions have been excluded.     

急性脑出血患者颈动脉斑块与血清hs CRP 及HbAlc的相关性研究

目的:探究急性脑出血患者颈动脉斑块与血清超敏C反应蛋白(hs-CRP)及糖化血红蛋白(Hb Alc)的相关性。方法:随机选取我院2013年5月至2015年1月脑科收治的急性脑出血患者84例,根据颈动脉粥样硬化标准将所有患者分为单纯脑出血组(n=25)、轻度粥样硬化组(n=34)和重度粥样硬化组(n=25)三组,另选取同期我院健康体检者50人(对照组)。对比分析四组颈总动脉膜厚度(IMT)空腹血糖(FPG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、hs-CRP与Hb Alc水平,分析急性脑出血患者颈动脉斑块的危险因素。结果:四组的IMT、TC、TG、HDL、LDL、hs-CRP和Hb Alc水平差异均具有统计学意义(P0.05),其中hs-CRP和Hb Alc水平在单纯脑出血组轻度粥样硬化组重度粥样硬化组(P0.05);IMT与hs-CRP和Hb Alc均呈现正相关(r=0.388、0.420,P0.05);IMT、hs-CRP和Hb Alc均为颈动脉粥样硬化的危险因素(OR=3.065、1.978、1.647,P0.05)。结论:急性脑出血患者体内hs-CRP及Hb Alc水平是颈动脉斑块形成的危险因素。     

Orofacial Dyskinesia: Clinical Features,Mechanisms and Drug Therapy

Orofacial or tardive dyskinesias are involuntary repetitive movements of the mouth and face. In most cases, they occur in older psychotic patients who are in institutions and in whom long-term treatment with antipsychotic drugs of the phenothiazine and butyrophenone groups is being carried out. These dyskinesias are frequent in occurrence and characteristically are irreversible. Several biochemical mechanisms have been proposed as causes, including hypersensitivity or partially deneverated brain dopamine receptors and low affinity of the offending drugs for brain muscarinic cholinergic receptors. Clinical therapy has been attempted primarily with drugs that antagonize dopamine receptors or deplete brain dopamine. The benefits of drug treatment have been variable and lack of consistent improvement has been discouraging. Early recognition of dyskinesia should be attempted, and the dose reduced or the drug omitted at the first sign.     

微创穿刺引流联合开颅血肿清除术对高血压脑出血合并脑疝患者神经功能、炎症反应及脑部血流的影响

摘要 目的：探讨开颅血肿清除术联合微创穿刺引流对高血压脑出血（HICH）合并脑疝患者神经功能、炎症反应及脑部血流的影响。方法：回顾性选择2014年4月~2019年11月期间我院收治的HICH合并脑疝患者80例,按照手术方式的不同分为A组（n=38,行开颅血肿清除术）和B组（n=42,行微创穿刺引流联合开颅血肿清除术）,对比两组疗效、神经功能、炎症反应、脑部血流及预后情况。结果：B组的总有效率为92.86%（39/42）,高于A组的76.32%（29/38）,差异有统计学意义（P<0.05）。两组术后7 d血清神经元特异性烯醇化酶（NSE）、S100β蛋白水平以及术后3个月美国国立卫生研究院卒中量表（NIHSS）评分均较术前降低,且B组低于A组（P<0.05）。两组术后7 d血清白介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、超敏-C反应蛋白（hs-CRP）均较术前降低,且B组低于A组（P<0.05）。两组术后1个月、术后3个月大脑中动脉平均流速（Vm）均较术前增加,且B组高于A组（P<0.05）;两组术后1个月、术后3个月大脑中动脉搏动指数（PI）较术前降低,且B组低于A组（P<0.05）。两组预后良好率无差异（P>0.05）。结论：与开颅血肿清除术相比,开颅血肿清除术联合微创穿刺引流治疗HICH合并脑疝患者可有效恢复患者脑部血流速度,降低炎症反应,有利于患者神经功能的恢复。     

小骨窗与大骨瓣开颅血肿清除术治疗高血压脑出血的疗效分析

目的:探讨小骨窗开颅血肿清除术与大骨瓣开颅血肿清除术治疗高血压脑出血的疗效。方法:选取120例高血压脑出血患者,分为两组,对照组(60例)给予大骨瓣开颅血肿清除术,观察组(60例)给予小骨窗开颅血肿清除术。观察并记录患者围手术期指标,术前术后6个月神经功能缺损情况,术后6个月生活能力及随访12个月期间并发症、死亡例数情况,对比两种手术方法治疗高血压脑出血的疗效。结果:经小骨窗开颅血肿清除术治疗,观察组患者手术时间,术中输血量,住院时间均明显短于或少于采用大骨瓣开颅术治疗的对照组患者(P0.05),但两组患者在血肿清除率上相比,差异没有统计学意义(P0.05)。术前两组NIHSS评分相比,差异没有统计学意义(P0.05)。术后6个月,两组NIHSS评分均明显降低,且观察组分值更低(P0.05),术后6个月,观察组ADL评分为17.24±3.52,对照组ADL评分为22.73±5.67,观察组ADL评分明显低于对照组(P0.05)。随访期间,两组死亡率相比较,差异没有统计学意义(P0.05);并发症发生率方面相比较,观察组更低(P0.05)。结论:小骨窗开颅血肿清除术对高血压脑出血具有较好的治疗效果,手术创伤小,神经功能影响小,能提高患者生活能力,术后并发症较少,值得临床推广使用。     

Chinese Herbal Therapy and Western Drug Use,Belief and Adherence for Hypertension Management in the Rural Areas of Heilongjiang Province,China

Background

Traditional Chinese medicine (TCM) including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China.

Methodology and Principal Findings

This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users). When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy.

Conclusions and Significance

Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.     

Promise and Deceit: Pharmakos,Drug Replacement Therapy,and the Perils of Experience

The problem of lying as a feature of medication compliance has been well documented in anthropological and clinical literatures. Yet the role of the lie—its destabilizing effects on the continuity of drug treatment and therapy, as a technology of drug misuse, or as a way to understand the neuro-chemical processes of treatment (pharmacotherapy “tricking” or lying to the brain)—has been less considered, particularly in the context of opioid replacement therapy. The following paper is set against the backdrop of a three-year study of adolescents receiving a relatively new drug (buprenorphine) for the treatment of opiate dependency inside and outside of highly monitored treatment environments in the United States. Lies give order not only to the experience of addiction but also to the experience of therapy as well. In order to better understand this ordering of experience, the paper puts the widely discussed conceptual duality of the pharmakon (healing and poison) in conversation with a perilously overlooked subject in the critical study of pharmacotherapy, namely the pharmakos or the personification of sacrifice. The paper demonstrates how the patient-subject comes to represent therapeutic promise by allowing for the possibility of (and often performing) deceit.     

Effects of High-Pressure Oxygen Therapy on Brain Tissue Water Content and AQP4 Expression in Rabbits with Cerebral Hemorrhage

To investigate the effects of different atmosphere absolutes (ATA) of high-pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4) expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits were selected and randomly divided into normal group (n = 30), control group (n = 30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was divided into group A, B, C and D with 30 rabbits in each group. The groups received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits in each group were killed at first, third and fifth day to detect the brain tissue water content and change of AQP4 expression. In cerebral hemorrhage group, brain tissue water content and AQP4 expression after model establishment were first increased, then decreased and reached the maximum on third day (p < 0.05). Brain tissue water content and AQP4 expression in control group and cerebral hemorrhage group were significantly higher than normal group at different time points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in group C were significantly lower than in group A, group B, group D and control group (p < 0.05). In control group, AQP4-positive cells significantly increased after model establishment, which reached maximum on third day, and positive cells in group C were significantly less than in group A, group B and group D. We also found that AQP4 expression were positively correlated with brain tissue water content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4 expression along with increased brain tissue water content. In conclusion, HPO can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage to suppress the progression of brain edema and promote repairing of injured tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for ATA selection of HPO in treating cerebral hemorrhage.     

Efficacy of Deferoxamine in Animal Models of Intracerebral Hemorrhage: A Systematic Review and Stratified Meta-Analysis

Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2–4 h after ICH at a dose of 10–50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.