吉兰-巴雷综合征的研究进展

吉兰-巴雷综合征是一种由于感染等原因所致的自身免疫性多发性神经疾病,主要的感染菌为空肠弯曲杆菌。男性患者多于女性。目前临床较为支持的发病机制为分子模拟理论,临床最主要的两大分类是轴索型及脱髓鞘型。欧美等国家以脱髓鞘型为主,亚洲国家以轴索型为主。另外还有一些在吉兰-巴雷综合征中所占比例较低的临床特殊分型,如:Miller Fisher综合征和咽-颈-臂变异型。吉兰-巴雷综合征最有效的治疗方法为静滴丙种球蛋白与血浆置换,且这两种方法的有效性已有循证医学证据支持。激素治疗目前循证医学证据提示无效,基础支持疗法不可轻视。大部分吉兰-巴雷综合征患者为单相病程,仅极少部分患者可复发。Miller Fisher综合征临床预后较好,高龄、轴索型等预后较差。     

登革病毒疫苗研究现状与展望

登革病毒是属于黄病毒科的小型包膜病毒,在热带和亚热带地区通过蚊媒传播。其感染可引起临床症状轻微的登革热,甚至危及生命的登革出血热和登革休克综合征。登革病毒包含4种血清型,有效的登革病毒疫苗需对4种血清型的登革病毒均具有抗病毒保护作用。目前,尚未有针对登革病毒的特效药和成熟的疫苗产品。各类登革病毒疫苗均在研发中,其中一些已进入临床试验阶段。本文就登革病毒疫苗研究进展作一综述并对未来发展进行展望。     

Is there a gas (general adaptation syndrome) response to various types of environmental stress?

A hypothesis of existence of a general adaptation syndrome (GAS), in which different types of stress evoke similar coping mechanisms, resulting in adaptations, is tested for plants. As stress coping mechanisms, oxy-free radical scavengers and antioxidants, osmoregulation, the role of abscisic acid, jasmonates, nitric oxide, synthesis of heat shock proteins and phytochelatins as heavy metal detoxifiers are discussed. The authors would like to thank the Netherlands Organization for Scientific Research (NWO) which enabled their collaboration and the formulation of some of the concepts here presented.     

Hemodynamic monitoring in acute myocardial infarction.

The main cause of in-hospital death in patients with acute myocardial infarction is the "power failure syndrome". Hemodynamic monitoring provides precise and current data on the filling and output status of the left ventricle and, when indicated, the right ventricle. The information obtained is used to determine the hemodynamic status more precisely than is possible from conventional clinical assessment. It permits categorization of patients by hemodynamic status; the hemodynamic subset classification of Forrester, Diamond and Swan is a powerful tool in guiding therapy and establishing prognosis in individual patients. In addition to guiding the initiation of therapy, hemodynamic monitoring is useful in the continuing assessment of potent and complex treatment. This therapy is directed at resolving hemodynamic derangements without unfavourably altering the myocardial oxygen supply-demand relationship. Specific clinical indications for hemodynamic monitoring may include confusing or complicated clinical situations in which diagnostic problems exist, complicating mechanical derangements, severe congestive heart failure, cardiogenic shock and clinical research in acute myocardial infarction.     

Lemierre's Syndrome: Two Cases of Septicemia due to Fusobacterium necrophorum

Two cases of Lemierre's syndrome are reported. The first patient presented with septic shock, multiple pulmonary infiltrates and thrombophlebitis of the right internal jugular vein. The second patient had septicemia due toFusobacterium necrophorum and Peptostreptococcus micros with multiple pulmonary abscesses, cholestatic liver dysfunction and severe thrombocytopenia. Clinical course, radiological and laboratory findings and therapy are discussed.     

Renal gene transfer: nonviral approaches

Gene therapy has the potential to become an important modality for treating both hereditary and acquired renal diseases. Since renal diseases may involve different cell types in the kidney, it is critical to achieve efficient gene transfer specifically to each cell type. We reviewed the literature on nonviral gene transfer techniques, which are designed to target the kidney specifically. A variety of approaches have been developed to target glomeruli, tubules, renal vasculature, and interstitium with different degree of success. Besides using delivery systems based on liposomes, polycations, and viral fusion proteins, investigators have adopted newer approaches including electroporation and hydrodynamic-based gene transfer, and demonstrated that they are efficient and safe in animal models. Potential clinical applications and safety concerns of gene therapy for renal diseases are discussed.     

Stem cell therapy for COVID-19 and other respiratory diseases: Global trends of clinical trials

Respiratory diseases, including coronavirus disease 2019 and chronic obstructive pulmonary disease (COPD), are leading causes of global fatality. There are no effective and curative treatments, but supportive care only. Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses, as proved by accumulating preclinical studies. Stem cells consist of totipotent, pluripotent, multipotent, and unipotent cells with the potential to differentiate into cell types requested for repair. Mesenchymal stromal cells, endothelial progenitor cells, peripheral blood stem cells, and lung progenitor cells have been applied to clinical trials. To date, the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD, acute respiratory distress syndrome, bronchial dysplasia, idiopathic pulmonary fibrosis, pulmonary artery hypertension, and silicosis. Five routes and a series of doses have been tested for tolerance and advantages of different regimes. In this review, we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials. The future directions for both new clinical trials and preclinical studies are discussed.     

Unusual small supernumerary marker chromosome (sSMC) 9 in a Klinefelter patient

Small supernumerary marker chromosomes (sSMC) are small additional chromosomes characterizable for their origin only by molecular cytogenetic approaches. sSMC have been reported previously in four types of syndromes associated with chromosomal imbalances: in approximately 150 cases with Turner syndrome, 26 cases with Down syndrome and only one case each with Klinefelter syndrome and "Triple-X"-syndrome. Here we report the second case with an sSMC detected in addition to a Klinefelter karyotype. Molecular cytogenetics applying centromere-specific multicolor FISH (cenM-FISH) and a specific subcentromere-specific (subcenM-FISH) probe set characterized the sSMC as a dic(9)(:p12-->q11.1::q11.1--> p11.1:). The reported patient was described with hypogonadism, gynaecomastia plus a bronchial carcinoma. The patient's clinical features are discussed in connection with other Klinefelter cases and possible consequences of presence of the sSMC(9). Furthermore, a suggestion is made for the mode of sSMC-formation in this case.     

Hantavirus infections and their prevention.

Hantaviruses are rodent-borne bunyaviruses which cause haemorrhagic fever with renal syndrome and Hantavirus pulmonary syndrome in humans. This review covers the host interactions of the viruses, including the rodent reservoirs, the clinical outcome of human infections as well as the pathogenesis and laboratory diagnosis of infections. The current stage in prophylaxis and therapy of hantaviral diseases is described and different approaches in vaccine development are discussed.     

Flavonoids protect mice from two types of lethal shock induced by endotoxin

The protective effect of flavonoids on two types of lethal endotoxic shock was studied. A lethal endotoxic shock was induced by administration of lipopolysaccharide (LPS) into D-galactosamine (D-GalN)-sensitized mice and another one was done by administration of a high dose of LPS into normal mice. Pretreatment with a series of flavonoids protected mice from two types of endotoxin lethality. Flavonoid pretreatment reduced the serum tumor necrosis factor-alpha (TNF-alpha) level in mice injected with D-GalN and LPS, but not in mice injected with a high dose of LPS. TNF-alpha-induced lethal shock in D-GalN-sensitized mice was also protected by pretreatment with flavonoids, suggesting that flavonoids augmented the resistance to TNF-alpha lethality. On the other hand, flavonoids reduced the plasma level of lipid peroxides in mice injected with a high dose of LPS, but not in D-GalN-sensitized mice. Taken together, these results indicated that flavonoids might protect mice from two types of endotoxin lethality. The protective mechanism of flavonoids in each endotoxin lethality is discussed.     

PITUITARY TUMOR, QT PROLONGATION AND VENTRICULAR ARRHYTHMIA

Various types of nervous system diseases have been associated with QT prolongation and ventricular arrhythmias. This report describes a young woman with a pituitary tumor, who had QT prolongation and recurrent syncope secondary to ventricular fibrillation. Effective therapy with digoxin and propranolol are described, and pathophysiology of the syndrome is discussed.     

The surgical management of Melkersson-Rosenthal syndrome.

A triad of facial palsy, orofacial edema, and furrowed tongue constitutes an uncommon condition known as Melkersson-Rosenthal syndrome (MRS). We report on 14 patients with Melkersson-Rosenthal syndrome. Two patients had facial palsy, 12 had orofacial edema, and 1 patient had a furrowed tongue. Nine patients were treated medically. Intralesional steroid therapy had a 75 percent recurrence rate. Systemic steroid therapy resulted in remission in two of three patients. Surgical excision and reconstruction were carried out in five patients with chronic lip or eyelid edema. This provided relief in all cases. The etiology, clinical presentation, and histologic features are discussed. Three illustrative cases are presented. An algorithm is provided that guides the surgeon with regard to both the medical and surgical treatment of the patient with Melkersson-Rosenthal syndrome.     

Toxic shock syndrome after suction lipectomy

We present a case of toxic shock syndrome with necrotizing fasciitis after suction lipectomy. The patient underwent aesthetic suction lipectomy of the abdomen, buttocks, and thighs during an office procedure by a cosmetic surgeon. On postoperative day 2, the patient was referred to the emergency department of our hospital because of pain. On admission, the patient was in toxic shock. She required intensive medical treatment for about 1 month, along with psychiatric help to adapt after the illness. Although toxic shock syndrome is a rare postoperative complication, every plastic surgeon should be acquainted with it. A combination of early recognition, diagnosis, and aggressive supportive therapy is the only successful treatment.     

Progress for dengue virus diseases. Towards the NS2B-NS3pro inhibition for a therapeutic-based approach

Transmitted by the Aedes aegypti mosquito, the dengue virus is the etiological agent of dengue fever, dengue hemorrhagic fever and dengue shock syndrome, and, as such, is a significant factor in the high death rate found in most tropical and subtropical areas of the world. Dengue diseases are not only a health burden to developing countries, but pose an emerging problem worldwide. The immunopathological mechanisms appear to include a complex series of immune responses. A rapid increase in the levels of cytokines and chemical mediators during dengue disease plays a key role in inducing plasma leakage, shock and hemorrhagic manifestations. Currently, there are no vaccines available against dengue virus, although several tetravalent live-attenuated dengue vaccines are in clinical phases I or II, and prevention through vaccination has become a major priority on the agendas of the World Health Organization and of national ministries of health and military organizations. An alternative to vaccines is found in therapeutic-based approaches. Understanding the molecular mechanisms of viral replication has led to the development of potential drugs, and new molecular viral targets for therapy are emerging. The NS3 protease domain of the NS3 protein is responsible for processing the viral polyprotein and its inhibition is one of the principal aims of pharmacological therapy. This review is an overview of the progress made against dengue virus; in particular, it examines the unique properties--structural and functional--of the NS3 protease for the treatment of dengue virus infections by the inhibition of viral polyprotein processing.     

Induction of a Stress Protein in Developing Cell Cultures of the Rat Cerebellum

Abstract: We examined the ability of developing cere-bellar cell cultures to synthesize a 71,000 MW stress protein (SP71) in response to heat shock and Cd²⁺ treatment. The induction of SP71 synthesis appeared to be dependent on both the age of the culture and the stressor used. Heat shock induced SP71 synthesis in freshly prepared cells and in cell cultures at each age examined, whereas Cd²⁺ was effective only in cultures at 7 days of age and older. These findings are discussed with reference to the development of various cell types in these cultures.     

Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1)

Streptococcal pyrogenic exotoxin A (SpeA1) is a bacterial superantigen associated with scarlet fever and streptococcal toxic shock syndrome (STSS). SpeA1 is found in both monomeric and dimeric forms, and previous work suggested that the dimer results from an intermolecular disulfide bond between the cysteines at positions 90 of each monomer. Here, we present the crystal structure of the dimeric form of SpeA1. The toxin crystallizes in the orthorhombic space group P212121, with two dimers in the crystallographic asymmetric unit. The final structure has a crystallographic R-factor of 21.52% for 7248 protein atoms, 136 water molecules, and 4 zinc atoms (one zinc atom per molecule). The implications of SpeA1 dimer on MHC class II and T-cell receptor recognition are discussed.     

Pyridoxalated hemoglobin polyoxyethylene: a nitric oxide scavenger with antioxidant activity for the treatment of nitric oxide-induced shock

Hemoglobins modified for therapeutic use as either hemoglobin-based oxygen carriers or scavengers of nitric oxide are currently being evaluated in clinical trials. One such product, pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), is a human-derived and chemically modified hemoglobin that has yielded promising results in Phase II clinical trials, and is entering a pivotal Phase III clinical trial for the treatment of shock associated with systemic inflammatory response syndrome (SIRS). Shock associated with SIRS is a NO-induced shock. PHP, a new mechanism-based therapy, has been demonstrated in clinical trials to have the expected hemodynamic activity of raising blood pressure and reducing catecholamine use, consistent with its mechanism of action as a NO scavenger. PHP is conjugated with polyoxyethylene, which results in a surface-decorated molecule with enhanced circulation time and stability as well as in attachment of soluble red blood cell enzymes, including catalase and superoxide dismutase. PHP thus contains an antioxidant profile similar to the intact red blood cell and is therefore resistant to both initial oxidative modification by oxidants such as hydrogen peroxide and subsequent ferrylhemoglobin formation. These studies suggest both that the redox activity of modified hemoglobins can be attenuated and that modified hemoglobins containing endogenous antioxidants, such as PHP, may have reduced pro-oxidant potential. These antioxidant properties, in addition to the NO-scavenging properties, may allow the use of PHP in other indications in which excess NO, superoxide, or hydrogen peroxide is involved, including ischemia-reperfusion injury and hemorrhagic shock.     

系统理论指导下辩证思维模式与抗休克决策

休克是由于有效循环血量不足引发的微循环障碍而表现一系列症候群,作为一种系统性疾病,病因十分复杂多样,诊疗过程中的临床决策应全面而富有针对性,并充分考虑到救治措施的协调一致和互相配合。系统论主张整体大于部分之和强调的就是措施之间的整体化效果,充分考虑到患者个体间差异,辩证分析不同类型休克、不同个体间不同表现,在系统理论指导下的富有针对性措施间协调一致的决策模式才是较为完整的休克救治临床决策模式。