Marschall S. Runge, MD, PhD

• Charles Addison and Elizabeth Ann Sanders Distinguished
• Professor of Medicine
• Professor and Chair, Department of Medicine
• Division of Cardiology
• University of North Carolina School of Medicine
• Chapel Hill, North Carolina

Pathogenicity of Erysipelothrix rhusiopathiae: virulence factors and protective immunity herbals a to z ayurslim 60 caps generic. Erysipelothrix rhusiopathiae-induced aortic valve endocarditis: case report and literature review 840 herbals discount ayurslim 60 caps buy on line. Erysipelothrix bacteremia without endocarditis: rare event or under-reported occurrence Evaluation of the Andromas matrix-assisted laser desorption ionization-time of flight mass spectrometry system for identification of aerobically growing Gram-positive bacilli herbals are us buy ayurslim american express. The poultry red mite herbals stores discount ayurslim 60 caps otc, Dermanyssus gallinae herbals definition ayurslim 60 caps order with mastercard, a potential vector of Erysipelothrix rhusiopathiae causing erysipelas in hens. Erysipelothrix rhusiopathiae bacteremia most probably acquired from freshwater aquarium fish handling. Persistent bacteremia with Erysipelothrix rhusiopathiae in a hospitalized patient. Cutaneous Erysipelothrix rhusiopathiae (erysipeloid) infection in an immunocompromised child. Characterization of pathogenic roles of two Erysipelothrix rhusiopathiae surface proteins. Genetic and antigenic diversity of the surface protective antigen proteins of Erysipelothrix rhusiopathiae. Erysipelothrix rhusiopathiae endocarditis: clinical features of an occupational disease. Erysipelothrix rhusiopathiae endocarditis: microbiologic, epidemiologic and clinical features of an occupational disease. Aortic valve endocarditis with paravalvular abscesses caused by Erysipelothrix rhusiopathiae. A case of multiple brain infarctions associated with Erysipelothrix rhusiopathiae endocarditis. Mitro-aortic infective endocarditis produced by Erysipelothrix rhusiopathiae: case report and review of the literature. Erysipelothrix rhusiopathiaeinduced aortic valve endocarditis: case report and literature review. Active infective endocarditis due to Erysipelothrix rhusiopathiae: zoonosis caused by vancomycin-resistant gram-positive rod. Erysipelothrix rhusiopathiae bloodstream infection ­ a 22-year experience at Mayo Clinic, Minnesota. Systemic Erysipelothrix rhusiopathiae infection not associated with endocarditis highlighting bacteriological diagnosis difficulties case report and literature review. Erysipelothrix rhusiopathiae bacteremia without endocarditis associated with psoas abscess: the first case report in Thailand. Erysipelothrix rhusiopathiae septicaemia with prolonged hypotension: a case report. Occupational injury in a fishmonger with a macular rash, hepatosplenomegaly and pancytopenia. Something fishy: an unusual Erysipelothrix rhusiopathiae infection in an immunocompromised individual. Septic arthritis caused by Erysipelothrix rhusiopathiae in a prosthetic knee joint. Septic arthritis caused by Erysipelothrix rhusiopathiae infection after arthroscopically assisted anterior cruciate ligament reconstruction. Animal-associated bacteria, Erysipelothrix rhusiopathiae, as the cause of infection in a total hip arthroplasty. Acute meningitis as an initial manifestation of Erysipelothrix rhusiopathiae endocarditis. Peritoneal dialysis­ related peritonitis with bacteraemia due to Erysipelothrix rhusiopathiae. Empyema in spinal canal in thoracic region, abscesses in paravertebral space, spondylitis: in clinical course of zoonosis Erysipelothrix rhusiopathiae. A case of Erysipelothrix rhusiopathiae causing bilateral endogenous endophthalmitis. Erysipelothrix rhusiopathiae: bacteriology, epidemiology and clinical manifestations of an occupational pathogen. Infectious tenosynovitis with bloodstream infection caused by Erysipelothrix rhusiopathiae, a case report on an occupational pathogen. First report of macrolide resistance gene erm (T) harbored by a novel small plasmid from Erysipelothrix rhusiopathiae. Human Erysipelothrix rhusiopathiae infection: unsolved issues and possible solutions. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated and Fastidious Bacteria. In vitro activity of daptomycin against clinical isolates of gram-positive bacteria. This chronic disease, first described by Whipple as "intestinal lipodystrophy," preferentially affects middle-aged white men, who may present with weight loss, arthralgia, diarrhea, and abdominal pain. In addition, individuals with isolated heart valve involvement or asymptomatic carriers may be observed. In 1907 Whipple found rod-shaped structures with silver stain in his original case but noted the following: "Whether this is the active agent in this peculiar pathological complex cannot be determined from the study of this single case but its distribution in the glands is very suggestive. The bacillus can be found typically in macrophages of the lamina propria of the small intestine and its lymphatic drainage but also has been observed in endothelial and epithelial cells, muscle cells, and various cells of the immune system, including polymorphonuclear leukocytes, plasma cells, mast cells, and intraepithelial lymphocytes. It has been suggested that bacteria multiply in the digestive lumen, become phagocytized, and then are degraded in macrophages. Genomic variants are associated with neither the geographic residence of the patients nor the organotropism of the agent. The bacillus is found typically in macrophages of the lamina propria of the small intestine. Large numbers of purple-stained macrophages in the lamina propria and lymphectasia can be seen. The bacterium was found in the stool of young children with gastroenteritis; in a study including 241 samples from children aged 2 to 4 years, T. In addition, the bacterium has been detected in sewage and is more prevalent in the fecal samples of healthy sewage workers (12%­26%) compared with the general population. The prevalence recently has been estimated at approximately 10 per 1 million people. Only rare occurrences have been reported in Hispanics, African Americans, Native Americans, and Asians. In the published literature the disease is approximately eight times more common in men than in women2,8; newer series find a relatively higher incidence in women (male-to-female ratio 3: 1). On the other hand, it may prevent a mucosal barrier defect by reducing local inflammation. Despite the more recent findings describing the subtle and persistent immune disturbance causing a disturbed phagocytosis and intracellular degradation of T. On gross inspection the duodenum and jejunum, which are the sites most frequently affected, often appear thickened and edematous. Based on these and similar observations in the draining mesenteric lymph nodes, G. Whipple assumed, in 1907, a disorder of fat metabolism and suggested the name intestinal lipodystrophy. In addition, the intestinal lymphangiectasia and protein-losing enteropathy seem to be mainly secondary to the lymphatic blockage. In the course of short-term and self-limiting diarrheal disease, up to 75% of patients may excrete T. An increased proportion (12%­26%) of asymptomatic carriers were found in workers who have close contact with sewage. This manifestation occurs most frequently as culture-negative bacterial endocarditis, for instance, on degenerative valve lesions, leading to a slowly progressive valve damage. In some instances immunosuppressive therapy, such as tumor necrosis factor blocker therapy, is initiated in patients with unclear arthritis. This symptom may precede the diagnosis by a considerable length of time (mean, 8 years in one series, up to 30 years),33 and consists usually of chronic migratory, nondestructive, and seronegative joint disease involving predominantly the peripheral joints; in addition, it often is accompanied by myalgias. We found that weight loss was present in two-thirds of patients more than 4 years before diagnosis and was clinically relevant (often loss of 20% of initial weight). Skin hyperpigmentation, particularly affecting light-exposed skin, has been observed. Chronic, nonproductive cough, chest pain, and reversible pulmonary hypertension have been described. Less frequently, involvement of the genitourinary system and the endocrine system have been reported (see Table 210. Clinical symptoms depend on the stage of the disease and may include cardiac murmur and valve (often aortic or mitral) insufficiency, leading finally to valve replacement. In one large retrospective series, greater than 6% of all infective endocarditis cases were due to T. This involvement manifests most often as memory disorder, personality change, and dementia. Tissues for diagnostic sampling should be prepared in accordance with the symptoms of the patient. If only one diagnostic tool results in a positive finding, it should be confirmed by a second method. If alternative tests are not practicable with the samples available, additional tissue samples should be analyzed to avoid false-positive results. Organ-Specific Involvement Gastrointestinal tract Cardiac involvement Pulmonary involvement Central nervous system Ocular involvement a 95­100 55 50 20­30 10 Incidence ranges reported in the literature: references 2, 8, 33, 38, and 45. Various cranial nerve symptoms, such as hearing loss and blurred vision, have been reported. In some patients a specific, if not pathognomonic, oculomasticatory myorhythmia or myoclonus with ophthalmoplegia has been described. Magnification endoscopy may reveal edematous mucosa with blunted microvilli and yellow spots representing engorged lymphatic vessels. In unclear situations it is advisable that specialists usually should be consulted. Laboratory testing can reveal evidence of malabsorption and protein-losing enteropathy: reduced serum levels of -carotene, various vitamins (B12, D, K, and folic acid), albumin, cholesterol, and electrolytes; lymphocytopenia; elevated stool fat excretion; and reduced d-xylose absorption. Diarrhea and fever may disappear within 1 week of therapy, whereas arthropathy and other symptoms often are improved after 2 to 4 weeks. Clinical improvement usually is accompanied by a gradual reconstitution of the villous architecture of the small intestine and by a disappearance of the bacteria over several weeks. In contrast, the subtle defect in cellmediated immunity persists for years, if not indefinitely. This is followed by 1-year (continuous) treatment with oral cotrimoxazole (trimethoprim-sulfamethoxazole) twice daily. The results of the therapy trial show a very high rate of clinical remission, which might be due to better adherence of medication intake during controlled studies. Although most patients recover completely and long-lastingly after antibiotic therapy, on occasion, inflammation reappears (mostly as high and recurrent fevers) after initial improvement; this is often interpreted as refractory or recurrent disease. Although nonspecific focal lesions of the brain and 2584 ophthalmoplegia and other movement disorders respond better to antibiotic treatment, other more structural changes, such as granulomas, infarcts, abscesses, or atrophic changes, may lead to persistent symptoms or even to fatal courses. A possible alternative to long-term oral cotrimoxazole may be doxycycline (2 × 100 mg/day; in some cases minocycline has been used) in combination with hydroxychloroquine (600 mg/day), which enhances the in vitro activity of doxycycline by increasing the pH in the phagolysosomes of the macrophages. Relapsing disease may occur in some patients despite an adequate and prolonged antibiotic treatment, still after many years of remission, more than once, and remarkably even with different strains of T. We recommend, even in successfully treated patients in whom therapy has been discontinued, performing follow-up biopsies at increasingly longer intervals for at least 5 years after the establishment of diagnosis. If bacterial material persists after 1 year of treatment, therapy should be continued. Therapy probably can be stopped safely if the histology has been stationary for more than 2 years. A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii. Tropheryma whipplei twist: a human pathogenic Actinobacteria with a reduced genome. Tropheryma whipplei in the environment: survey of sewage plant influxes and sewage plant workers. Prevalence of asymptomatic Tropheryma whipplei carriage among humans and nonhuman primates. Whipple disease: intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. Systemic Tropheryma whipplei: clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Whipple disease a century after the initial description: increased recognition of unusual presentations, autoimmune comorbidities, and therapy effects. Gastrointestinal diagnosis of classical Whipple disease: clinical, endoscopic, and histopathologic features in 191 patients. The immune reconstitution inflammatory syndrome in Whipple disease: a cohort study. Meningococcemia: In 20% to 30% of cases, septicemia with shock is the dominant clinical finding, with sudden onset of fever, gastrointestinal symptoms, generalized malaise, weakness, cold extremities and skin pallor, leukocytosis or leukopenia, erythematous blanching, petechial or purpuric rash, headache and/or drowsiness, and hypotension. Meningitis: Meningitis is the most common presentation of invasive meningococcal disease and occurs in 40% to 65% of cases, reflecting the meningeal tropism of N. Findings include sudden-onset headache, fever, vomiting, myalgias, photophobia, irritability, decreased ability to concentrate, agitation, drowsiness and meningeal signs (neck stiffness, Kernig or Brudzinski sign), and cloudy cerebrospinal fluid. Rash: Skin lesions are present in 28% to 77% of patients with invasive meningococcal disease on admission.

Only 1% to 3% of the patients with positive culture results met the serologic criteria neem himalaya herbals 60 kapsuliu purchase ayurslim with mastercard, and approximately 70% with positive culture results for C herbs pool ayurslim 60 caps purchase visa. Ample evidence exists for a huge diversity and wide distribution of chlamydiae in nature verdure herbals generic ayurslim 60 caps buy on line, and humans are exposed to that diversity of species herbals side effects cheap ayurslim master card. As an example herbals uk discount 60 caps ayurslim amex, the recovery of a novel environmental Chlamydia strain from activated sludge with cocultivation with an Acanthamoeba sp. Acquisition of infection via droplet aerosol was described during a laboratory accident. Several serologic surveys have documented rising chlamydial antibody prevalence rates, beginning in school-age children and reaching 30% to 45% by adolescence. A recent study reported the presence of 14 respiratory viruses and atypical bacteria (M. The most frequent respiratory viruses detected were respiratory syncytial virus subtype A (n = 35), influenza virus (n = 21), and parainfluenza virus (n = 10). Initial reports emphasized mild atypical pneumonia clinically resembling that associated with M. Chlamydia pneumoniae was found in 73% of samples from patients with pneumonia but also in 36% of samples from patients with upper respiratory disease without pneumonia, all of whom recovered without therapy. Chlamydia pneumoniae can be a serious pathogen even in the absence of underlying disease; it was isolated from the respiratory tract and the pleural fluid of a previously healthy adolescent boy with severe pneumonia complicated by respiratory failure and pleural effusions. Chlamydia pneumoniae was responsible for 6 of 31 episodes (19%) of acute chest syndrome in children with sickle cell disease in New York. Most published pneumonia treatment studies, including all recent studies, have used serology alone for diagnosis of C. Results of several multicenter treatment studies that used culture showed 70% to 86% efficacy of treatment with erythromycin, clarithromycin, azithromycin, levofloxacin, and moxifloxacin in eradicating C. Persistence did not appear to be the result of the development of antibiotic resistance because the minimal inhibitory concentrations of the isolates obtained after treatment did not change. For children, the following regimens can be used: erythromycin suspension, 50 mg/kg/day for 10 to 14 days; clarithromycin suspension, 15 mg/kg/day for 10 days; or azithromycin suspension, 10 mg/kg once on the first day, followed by 5 mg/kg once daily for 4 days. Treatment of asthma exacerbations frequently includes systemic steroids, which have been shown to enhance the in vitro infectivity of C. Study design has been complicated by the fact that macrolides, quinolones, and tetracyclines all have immunomodulatory activity independent of their antimicrobial activity. Several uncontrolled studies showed beneficial effects of antibiotics on patients with asthma with proven or presumed C. A placebo-controlled 6-week trial of roxithromycin in patients with asthma who were seropositive for C. A double-blind, randomized, placebo-controlled study of telithromycin in patients with acute exacerbations of asthma found reduction of asthma symptoms among those treated with the active drug; however, the study could not adequately assess the effect of infection because only 1 of 278 enrolled patients was positive for C. From a clinical standpoint, chlamydiae may be the persistent infection par excellence, capable of persisting in the host for months to years, often without causing obvious illness. From a microbiologic standpoint, persistence also refers to long-term intracellular infection that can be detected with antigen, microscopy, or nucleic acid­based amplification methods. The controversy about definition of infection and diagnostic tests contributes to the difficulty in interpretation and comparison of studies. The field is further complicated by differences in study populations in regard to asthma phenotype and the presence of acute symptoms. The wide range of positivity illustrates the sometimes contradictory findings regarding an association between C. In 1991, Hahn and colleagues75 reported an association between serologic evidence of acute C. Studies that have shown an association or lack of association between the presence of antibodies (IgG, IgM, and IgA) and higher antibody titers (IgG) against C. Positivity rate during 3-month (October to December) longitudinal study (at least one positive sample obtained on repeat sampling). This, in turn, makes determination of the efficacy of any therapeutic intervention difficult. Inflammation of the vessel wall plays an essential role in the initiation and progression of atherosclerosis, erosion, fissure, and eventual rupture of the atheromatous plaques. Infectious agents, including cytomegalovirus, human herpesviruses, enteroviruses, Helicobacter pylori, bacteria involved with periodontal disease, and C. In 2002, Boman and Hammerschlag42 reviewed 14 seroepidemiologic studies published from 1992 to 2000 and found a great deal of heterogeneity among these studies in terms of the serologic tests used and the criteria for seropositivity. In some studies, an IgG or IgA titer of 1: 64 or more was used as an indicator of chronic infection; in others, the same criteria were used as indicators of past infection. The remaining studies used a variety of other methods, including genus-specific enzyme immunoassays and whole-cell immunofluorescence. Earlier case-control studies that showed an association were generally small and based on single serum samples, which does not take into account that antibody titers fluctuate over time. The positivity rate in the clinical specimens ranged from 0% to 60%, and three laboratories identified C. The samples were divided and sent to two different laboratories, where they were tested for C. Only two samples from the younger­than­20-yearold group were positive in one of the laboratories but negative in the second. None of the samples for the more­than­60-year-old group was positive in either laboratory. Results of the initial seroepidemiologic and organism detection studies led to several preliminary studies that investigated the efficacy of antibiotic treatment directed at C. The results of these preliminary studies suggested an effect but the studies were underpowered and raised questions about the antibiotic regimens used and methods of identification of patients with C. The major assumption of many of the seroepidemiologic studies of the association of C. However, earlier studies of patients with respiratory infection often found a poor correlation between serology and isolation of the organism from the respiratory tract. The antibiotic regimen used by Gupta and colleagues102 was never studied for treatment of C. A meta-analysis of 11 randomized trials, which enrolled a total of 19,217 patients, was published in 2005. Three studies used roxithromycin for 30 days to 6 weeks; one used clarithromycin, 500 mg/day for 85 days; and one used gatifloxacin 400 mg/day for 10 days/month for 2 years. The results of two of six of the earlier small studies (150 patients in each arm) favored antibiotic treatment, but all of the remaining five large studies favored placebo for all end points, including total mortality; subsequent myocardial events, including infarction; and unstable angina. The results of subsequent studies from a number of other groups were conflicting, some finding C. Interlaboratory reliability of microimmunofluorescence test for measurement of Chlamydia pneumoniae-specific immunoglobulin A and G antibody titers. Involvement of Chlamydia pneumoniae in atherosclerosis: more evidence for lack of evidence. Conserved indels in essential proteins that are distinctive characteristics of Chlamydiales and provide novel means for their identification. Prevalence of asymptomatic nasopharyngeal carriage of Chlamydia pneumoniae in subjectively healthy adults: assessment by polymerase chain reaction-enzyme immunoassay and culture. Acute respiratory infection due to Chlamydia pneumoniae: current status of diagnostic methods. The association of Chlamydia pneumoniae infection and reactive airway disease in children. Effect of prolonged treatment with azithromycin, clarithromycin and levofloxacin on Chlamydia pneumoniae in a continuous infection model. Role of persistent infection in the control and severity of asthma: focus on Chlamydia pneumoniae. Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the mouse. Collaborative multi-disciplinary workshop report: interface of lipid metabolism, atherosclerosis and Chlamydia infection. Detection of circulating Chlamydophila pneumoniae in patients with coronary artery disease and healthy control subjects. Effects of antibiotic therapy on outcomes of patients with coronary artery disease. Azithromycin for secondary prevention of coronary artery disease: a meta-analysis. Is Chlamydia pneumoniae found in spinal fluid samples from multiple sclerosis patients Isolation and antimicrobial susceptibilities of chlamydial isolates from western barred bandicoots. In vitro models of acute and long-term continuous infection of human respiratory epithelial cells with Chlamydophila pneumoniae have opposing effects on host cell apoptosis. Multicenter evaluation of the ePlex Respiratory Pathogen panel for the detection of viral and bacterial respiratory tract pathogens in nasopharyngeal swabs. Age-related interference with Chlamydia pneumoniae microimmunofluoresence serology due to circulating rheumatoid factor. Immunohistostaining assays for detection of Chlamydia pneumoniae in atherosclerotic arteries indicate cross-reactions with nonchlamydial plaque constituents. Detection of Chlamydia pneumoniae by polymerase chain reaction-enzyme immunoassay in an immunocompromised population. Diagnosis of Chlamydia pneumoniae infection in patients with community-acquired pneumonia by polymerase chain reaction enzyme immunoassay. In-house nucleic acid amplification assays in research: how much quality control is needed before one can rely upon the results Chlamydia pneumoniae and atherosclerosis: a critical assessment of diagnostic methods and the relevance to treatment studies. Comparison of five commercial serological tests for the detection of anti-Chlamydia trachomatis antibody. Incidence of respiratory pathogens in persons hospitalized with pneumonia in two provinces in Thailand. Etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods. Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China. Persistent infection with Chlamydia pneumoniae following acute respiratory illness. The etiology of community-acquired pneumonia among hospitalized patients during a Chlamydia pneumoniae epidemic in Finland. Molecular etiological profile of atypical bacterial pathogens, viruses and coinfections among infants and children with community acquired pneumonia admitted to a national hospital in Lima, Peru. Isolation of Chlamydia pneumoniae from the lungs of patients infected with the human immunodeficiency virus. Genetic and culture-based approaches for detecting macrolide resistance in Chlamydia pneumoniae. Serine-to-asparagine substitution in the GyrA gene leads to quinolone resistance in moxifloxacin-exposed Chlamydia pneumoniae. Detection of anti-Chlamydia pneumoniae IgE in children with reactive airway disease. The effect of hydrocortisone succinate on the growth of Chlamydia pneumoniae in vitro. Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae. Minocycline treatment results in reduced oral steroid requirements in adult asthma. Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research. A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. Chlamydia pneumoniae in peripheral blood mononuclear cells from individuals younger than 20 years and older than 60 years. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Infectious agents and multiple sclerosis: are Chlamydia pneumoniae and human herpes virus 6 involved Is Chlamydia pneumoniae present in the cerebral spinal fluid of multiple sclerosis patients D Mycoplasma Diseases 183 Definition Mycoplasma pneumoniae and Atypical Pneumonia Robert S. The onset tended to be slower than that of the lobar pneumonia of civil life; the course more prolonged. Crisis was relatively rare; physical signs were slow of development and of patchy distribution and scattered in several lobes. The term "primary atypical pneumonia" was given to these cases; the prefix "primary" indicated that no causative agent could be determined. Since then, as diagnostic microbiology and virology advanced, it was recognized that, in addition to Mycoplasma pneumoniae, multiple etiologic agents can produce the atypical pneumonia syndrome, including influenza virus, adenovirus, respiratory syncytial virus, cytomegalovirus, Chlamydia spp. Additional agents will surely be recognized in the course of time, and the prefix "primary" is now mostly of historical interest. Atypical pneumonia is best regarded as a syndrome to be contrasted with the classic symptom complex of "typical" or lobar pneumonia, as exemplified by pneumococcal pneumonia. In these original experiments sputum and homogenized lung tissue from autopsied patients with primary atypical pneumonia were inoculated into cotton rats, where they produced pneumonitis.

The development of an antigen capture polymerase chain reaction assay to detect and type human enteroviruses top 10 herbs order ayurslim 60 caps visa. Neonatal enterovirus infection: virology ayur xaqti herbals purchase ayurslim 60 caps free shipping, serology herbals shoppes cheap ayurslim express, and effects of intravenous immune globulin herbs pool cheap ayurslim 60 caps buy line. Three-dimensional structure-activity relationships for antiviral agents that interact with picornavirus capsids jiva herbals order 60 caps ayurslim overnight delivery. Conformational change in floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors. Risk factors for hand, foot, and mouth disease and herpangina and the preventive effect of hand-washing. An unidentified, filtrable agent isolated from the feces of children with paralysis. A virus from patients diagnosed as non-paralytic poliomyelitis or aseptic meningitis. Characteristics of poliomyelitis and other enteric viruses recovered in tissue culture from healthy American children. Complete nucleotide sequence of wild-type hepatitis A virus: comparison with different strains of hepatitis A and other picornaviruses. Therapy Microbiology · the polioviruses are members of the genus Enterovirus, family Picornaviridae. Supportive measures to ensure airway patency, adequate respiratory effort, and clearance of secretions are the mainstay of treatment for severe cases of paralysis. Prevention Epidemiology Diagnosis · Wild-type poliovirus type 2 no longer circulates worldwide and was declared eradicated in 2015. Serotype 1 remains endemic in three countries (Afghanistan, Nigeria, and Pakistan). In 2017, · Polioviruses can be isolated from throat secretions and from feces and rarely from the cerebrospinal fluid. In preparation for the global eradication of the polioviruses, a worldwide switch to bivalent oral polio vaccine containing poliovirus types 1 and 3 occurred in 2016. Public health measures, such as provision of potable water and proper sewage disposal, play major roles in the community-wide control of the polioviruses. The name of the disease (polios, "gray"; myelos, "marrow" or "spinal cord"), now commonly shortened to polio, is descriptive of the pathologic lesions that involve neurons in the gray matter, especially in the anterior horns of the spinal cord. However, as of 2017,1 the goal of worldwide poliomyelitis eradication has not yet been achieved, having been hampered by unforeseen scientific challenges, geopolitical unrest, and social disruption, among other factors. It depicts the priest Rom with an atrophic lower extremity and foot held in a talipes equinus position. Charles Caverly wrote the first description of epidemic poliomyelitis in the United States, an outbreak of 132 cases near Rutland, Vermont, in 1894. Accompanying the increased incidence was a shift in the peak-affected age group from 2220 infants to school-aged children and young adults. Both the appearance of epidemic disease and the rising age incidence have been attributed to rising standards of hygiene, which delayed the age of infection beyond infancy and loss of maternal antibody, thus creating a pool of susceptible people large enough to permit the spread of epidemic disease. Scientific progress remained somewhat limited until the landmark discovery in 1949 by Enders, Weller, and Robbins8 that poliovirus could be propagated in vitro in cultures of human embryonic cells of nonneural origin. This discovery facilitated experimental investigation of the pathogenesis of the disease in primates and the development of vaccines. Bodian and associates9 first recognized the three distinct serotypes of poliovirus. By 1952, Bodian10 and Horstmann11 had independently discovered that viremia occurred early in infection, which explained the systemic phase of the illness. The last case of endemic wild-type poliomyelitis occurred in 1979, indicating complete cessation of transmission of naturally occurring polioviruses. As of the end of 2017, worldwide, endemic circulation of polioviruses had been controlled by all countries with the exception of Pakistan, Afghanistan, and Nigeria. At this point, the course of poliomyelitis deviates from that of other enteroviral diseases in the ability of polioviruses to infect neurons in the gray matter of the brain and spinal cord. Neuronal destruction is accompanied by inflammatory lesions consisting of polymorphonuclear leukocytes, lymphocytes, and macrophages that are distributed throughout the gray matter of the anterior horns of the spinal cord and the motor nuclei of the pons and medulla. The dorsal root ganglia are commonly involved pathologically, but this does not result in sensory deficits. Polioviruses can be isolated from the spinal cord for only the first few days after the onset of paralysis, but the inflammatory lesions may persist for months. Chapter 171 Poliovirus Polioviruses are prototypic members of the genus Enterovirus15 (see Chapter 171). Three poliovirus serotypes exist, and infection with each confers serotype-specific, lifelong immunity to disease but little or no immunity to infection or disease caused by heterologous serotypes. For all three serotypes, analogous nucleotide substitutions in the 5-noncoding region are associated with reduced neurovirulence. Usual estimates of the ratio of unapparent to clinically recognized polio infection, which vary by serotype, range from 60: 1 to 1000: 1. After implantation at a mucosal site and replication in the gut, or less frequently the throat and adjacent lymphoid tissues, polioviruses disseminate to susceptible reticuloendothelial tissues via a minor viremia. In asymptomatic infections, the virus is contained at this point and elicits the formation of type-specific antibodies. This graphic representation shows the presence of virus and antibodies in relation to the development and persistence of the infection. At least 95% of infections are asymptomatic or unapparent and can be recognized only by the isolation of poliovirus from feces or oropharynx or by a rise in antibody titer. Abortive poliomyelitis, which occurs in 4% to 8% of infections, is characterized by a 2- to 3-day period of fever, which may be accompanied by headache, sore throat, listlessness, anorexia, vomiting, or abdominal pain. Because the neurologic examination findings are normal, abortive poliomyelitis cannot be distinguished from other viral infections and can be clinically suspected only during an epidemic. Nonparalytic poliomyelitis differs from abortive poliomyelitis by the presence of signs of meningeal irritation. The systemic manifestations of nonparalytic poliomyelitis are generally more severe than in abortive poliomyelitis. A biphasic course with minor and major illnesses is observed in approximately one-third of children with paralytic poliomyelitis. The minor illness, coinciding with viremia, corresponds to the symptoms of abortive poliomyelitis and lasts 1 to 3 days. Adults usually experience a single phase of illness, with a prolonged prodrome of symptoms preceding the gradual onset of paralysis. The meningismus and muscle pain are present for 1 to 2 days before frank weakness and paralysis ensue. The severity of the disease varies from weakness of a single portion of one muscle to complete quadriplegia. The paralysis is flaccid; deep tendon reflexes are initially hyperactive and then become absent. The most characteristic feature of the paralysis is its asymmetrical distribution, which affects some muscle groups while sparing others. Proximal muscles of the extremities tend to be more involved than distal muscles, the legs are more commonly involved than the arms, and the large muscle groups of the hand are at greater risk than the small ones. Any combination of limbs may be paralyzed, but the most common pattern is involvement of one leg, followed by one arm, or both legs and both arms. Sensory loss in poliomyelitis is very rare,39 and its occurrence should strongly suggest some other diagnosis. The most important complication of paralytic poliomyelitis is respiratory compromise caused by paralysis of the respiratory muscles, including the diaphragm and intercostal muscles, by airway obstruction from involvement of the cranial nerve nuclei, or by lesions of the medullary respiratory center. Gastrointestinal events such as hemorrhage, paralytic ileus, and gastric dilatation may complicate acute paralysis. Several preexisting factors and provocative events are known to influence the risk of poliovirus infection and, after infection with poliovirus, the risk of developing paralysis. Before puberty, poliovirus infections occur equally in boys and girls, although paralysis is more common in boys. Among adults, women are at greater risk of infection but are not necessarily at greater risk of paralysis. Strenuous exercise increases both incidence and severity of paralytic poliomyelitis. Sporadic cases of acute motor neuron disease that is indistinguishable from poliomyelitis may be caused by other enteroviruses, especially enteroviruses A-71 and D-68 (see Chapter 172) or West Nile virus infection58 (see Chapter 153). Few other diseases are confused with paralytic poliomyelitis, except Guillain-Barré syndrome, which, unlike poliomyelitis, produces symmetrical, bilateral ascending paralysis, with loss of sensation that in most cases may progress over a period of 1 to 2 weeks. In acute poliomyelitis, pleocytosis and a minimally elevated protein concentration are present, whereas in Guillain-Barré syndrome the protein level is elevated with absent or minimal pleocytosis (the albuminocytologic dissociation). The frequency of the bulbar form of the disease has varied in different epidemics from 5% to 35% of paralytic cases. The ninth and tenth cranial nerves are most commonly involved, and pharyngeal paralysis with pooling of secretions often is the only obvious sign. Involvement of the circulatory and respiratory centers of the medulla represents the most serious form of bulbar poliomyelitis. In contrast to spinal paralytic polio, there may be spastic paralysis, indicating the presence of upper motor neuron involvement. The illness is not clinically distinguishable from other forms of viral encephalitis. Polioviruses usually can be isolated from throat secretions in the first week of illness and from feces, often for several weeks. In all cases, this is accomplished by genomic sequencing, available only in public health reference laboratories. In the absence of a viral isolate, the diagnosis of poliovirus infection can be established serologically by testing paired acute and convalescent sera for neutralizing antibodies to each of the three poliovirus serotypes. Serologic tests cannot distinguish between wild-type virus and vaccine virus infection. Muscle paralysis usually progresses or extends for only 1 to 3 days after its onset but occasionally for as long as 1 week. Complete recovery is less likely when acute paralysis is severe and when patients require mechanical ventilation. An estimate of the eventual outcome can be made after 1 month, when most reversible damage has disappeared. Recovery from pharyngeal paralysis usually is evident by 10 days and is eventually complete. Bulbar poliomyelitis is rarely responsible for permanent sequelae in surviving patients. Available mortality figures date from the era of epidemic poliomyelitis, a period when critical care medicine was less advanced than it is today. The reported overall mortality for acute paralytic poliomyelitis during this period was approximately 5% to 10%. Physical therapy should be initiated once the progression of paralysis has ceased. Paralysis of the respiratory muscles necessitates mechanical ventilation before hypoxia develops, generally when the vital capacity falls to less than 50%. Pooling of secretions in the pharynx in mild bulbar poliomyelitis, if unaccompanied by spinal respiratory paralysis, can be managed with postural drainage and suction. Management of the long-term physical and psychiatric sequelae of paralytic poliomyelitis is beyond the scope of this text. Progression of new symptoms is gradual, and affected persons are seldom severely disabled. Population-based studies have suggested that the syndrome affects 20% to 85% of previously paralyzed patients. Although the cause is unknown, the leading theory is that late progression of muscle weakness is a result of physiologic attrition of motor units innervating muscles and muscle groups already less innervated as a result of earlier acute poliomyelitis. Studies conducted in the United States demonstrate that neutralizing antibodies are detectable to all three types in 99% of recipients after two doses and in 100% after the third dose. Based on information derived from high-income countries, circulating antibody persists for decades and possibly for life. After a primary immunizing series of three or four doses, neutralizing antibodies are a usually found in all individuals at 5 years after immunization. Detectable serum antibody to all three types persists in 84% to 98% of vaccinees 5 years after primary immunization,101 and reexposure to vaccine viruses likely contributes to the maintenance of antibody levels in the population. However, data obtained during a type 1 poliovirus outbreak in Taiwan demonstrated estimated efficacy of 82%, 96%, and 98% for one, two, and three or more doses, respectively. The importance of this "backdoor" method of protecting the community is uncertain. A study of Moroccan children found that seroprevalence rates for poliovirus types 1 to 3 were significantly lower among malnourished children. For this Use of Poliomyelitis Vaccines in the Developing World Chapter 171 Poliovirus Even after the introduction of polio vaccines, poliomyelitis was regarded as an epidemic disease of wealthier nations and was ignored in developing countries. However, surveys regarding lameness in schoolchildren in the 1960s and 1970s in more than 20 nations revealed lower limb paralysis prevalence rates of 2 to 11 per 1000 population, figures that reflect poliomyelitis incidence rates that equal or exceed those of the peak epidemic years in the United States. In 1983, an international conference held in Bellagio, Italy, soon after smallpox eradication, articulated the feasibility of worldwide poliomyelitis eradication,150 and in 1988 the World Health Assembly set a goal of global eradication of poliomyelitis by the year 2000. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissue. Progress in the development of poliovirus antiviral agents and their essential role in reducing risks that threaten eradication. Serologic response to oral polio vaccine and enhanced-potency inactivated polio vaccines.

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Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial wiseways herbals best purchase for ayurslim. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised herbals for hot flashes buy cheap ayurslim 60 caps, double-blind herbals dictionary generic ayurslim 60 caps on line, placebo-controlled wtf herbals cheap ayurslim 60 caps buy on line, phase 1 trial herbals medicine purchase ayurslim 60 caps online. Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia Ankara-vectored Ebola vaccines: a randomized clinical trial. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. Critical care for multiple organ failure secondary to Ebola virus disease in the United States. Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone. A "Trojan horse" bispecific-antibody strategy for broad protection against Ebolaviruses. Antibodies from a human survivor define sites of vulnerability for broad protection against Ebolaviruses. A Two-Antibody Pan-Ebolavirus cocktail confers broad therapeutic protection in ferrets and nonhuman primates. Orthomyxoviridae 165 Definition Influenza Viruses, Including Avian Influenza and Swine Influenza John J. They cause epidemic acute respiratory disease characterized by fever, cough, and systemic symptoms. Three types (A, B, and C) are recognized, with many subtypes within the type A viruses. Microbiology · Influenza viruses are readily isolated in eggs or mammalian cell culture at 33°C. They undergo constant antigenic evolution, referred to as antigenic drift or shift, which allows them to reinfect individuals who have had previous infections. Prevention Diagnosis Epidemiology · Influenza viruses are transmitted by the respiratory route and cause large epidemics, which generally occur during the winter in temperate climates. In addition to infecting humans, influenza A viruses infect a wide variety of animals, particularly migratory waterfowl. New influenza A virus subtypes sporadically emerge in humans to cause widespread disease, or pandemics. Rapid detection of virus in respiratory secretions also can be accomplished through antigen detection or molecular techniques such as polymerase chain reaction assay. Therapy · Influenza vaccines are effective in the prevention of influenza illness, although improved vaccines are needed. Two unique features of influenza are the epidemic nature of the disease and the mortality that results in part from its pulmonary complications. Influenza virus has been causing recurrent epidemics of febrile respiratory disease every 1 to 3 years for at least the past 400 years. Although the disease is not associated with a characteristic manifestation such as rash, the high attack rate, the explosive nature of the epidemic, and the frequency of cough allow the identification of past epidemics. For example, Hirsch tabulated 299 outbreaks occurring at an average interval of 2. Finally, antiviral agents in two classes have been approved for prevention and treatment of influenza. There are significant differences in genetic organization, structure, host range, epidemiology, and clinical characteristics among the three influenza virus types (Table 165. However, all three viruses share certain features, including the presence of a host-cell­derived envelope, envelope glycoproteins of critical importance in virus entry and egress from cells, and a segmented genome of negative-sense. The standard nomenclature for influenza viruses includes the influenza type, place of initial isolation, strain designation, and year of isolation. Amantadine and rimantadine are not considered for use because of widespread resistance in influenza A/H3N2 and A/H1N1 viruses currently circulating. The preferred site for infants and young children is the anterolateral aspect of the thigh. Specific guidance regarding site and needle length for intramuscular administration may be found in the Advisory Committee on Immunization Practices General Recommendations on Immunization. They can be removed from the intact virion by sodium dodecyl sulfate, by bromelain, or by chymotrypsin. A third integral membrane protein, the M2 protein, is also present in small amounts on the viral envelope. This protein provides structure to the virion and is important for virus assembly. However, since 2001, two antigenically distinct lineages of influenza B viruses, termed the "Victoria" lineage and the "Yamagata" lineage, have cocirculated in humans. At the same time, the third envelope protein, the M2 protein, acts as an ion channel allowing H+ ions to enter the virion from the endosome. This in turn allows the viral gene segments to leave the virion and enter the cytoplasm, a process known as uncoating. The polymerase proteins also play a role in disruption of host cell protein synthesis. Because the genome of influenza virus is segmented, segments can be exchanged between viruses infecting the same cell, a process referred to as reassortment. Genetic reassortment plays an important role in the generation of pandemic influenza A viruses, and has also been taken advantage of for the construction of attenuated live influenza vaccines. Because not all influenza-related deaths manifest as pneumonia, the pneumonia and influenza mortality statistics probably underestimate the true impact of influenza on the population. As many as 51,000 deaths annually in the United States can be attributed to influenza. It has been estimated that a typical case of influenza, on average, is associated with 5 to 6 days of restricted activity, 3 to 4 days of bed disability, and about 3 days lost from work or school. In order to estimate the mortality burden of influenza, observed pneumonia- and influenza-related deaths during periods of influenza epidemic activity are compared with an expected seasonal baseline derived from a time-series regression model, and the excess mortality attributable to influenza is calculated. A historical tabulation of levels of excess pneumonia and influenza deaths attributable to influenza epidemics22 is shown in Table 165. Influenza-related death rates in nursing home residents with comorbid conditions are as high as 2. Rates of influenza-related hospitalizations are particularly high in healthy children younger than 2 years, in whom rates approach those of older children with high-risk conditions. An epidemic is an outbreak of influenza confined to one location, such as a city, town, or country. The epidemic began abruptly, reached a sharp peak in 2 to 3 weeks, and lasted 5 to 6 weeks. These reports were subsequently followed by increased hospital admissions for patients with pneumonia, exacerbation of chronic obstructive pulmonary disease, croup, and congestive heart failure, and finally by increased school and industrial absenteeism. During epidemics, attack rates in unvaccinated populations are estimated to be 10% to 20%, but rates as high as 40% to 50% have been reported. In temperate climates in either hemisphere, epidemics occur almost exclusively in the winter months (generally November to April in the Northern Hemisphere and May to September in the Southern Hemisphere). Seasonal periodicity is also observed in tropical climates, with increased activity during periods of low absolute humidity, although influenza can occur throughout the year and seasonal fluctuations are not as marked. Attack rates and hospitalizations occur at both extremes of age, but mortality occurs largely in those older than 65 years. Age distribution of patients with medically attended illnesses caused by sequential variants of influenza A/H1N1: comparison to age-specific infection rates, 1978­1989. Larger particles or droplets will typically fall to the ground within 3 meters of the infected person and would be expected to infect individuals in direct contact. Finally, viral particles could land on surfaces, where influenza viruses remain infectious and could infect others through indirect contact. There is substantial evidence for all three modes of transmission in experimental studies and epidemiologic observations, but the relative roles of each mode of transmission are uncertain and remain controversial, with obvious implications for infection control practices and for potential interventions to mitigate pandemics. The most often cited such outbreak occurred in a commercial airliner that was delayed for approximately 4½ hours with a poorly functioning ventilation system. The risk of transmission of influenza A from the index case to other passengers was related to the amount of time passengers spent on the aircraft, and not on their seating proximity to the index case. Because most of the passengers did not have direct contact with the index case, airborne transmission appears to be likely. In this study,66 subjects who received short-term prophylaxis with inhaled zanamivir were protected compared with placebo recipients, but recipients of zanamivir administered by nasal spray were not. In addition, the combination of nasal and inhaled zanamivir was no better than inhaled zanamivir alone. In most of these outbreaks, there were alternative explanations for the observations that could at least partially explain the epidemic behavior without requiring aerosol transmission,67 and the real role of aerosol transmission remains controversial. If aerosol transmission plays a dominant role in influenza, then health care workers would need to wear filtering face masks, and patients would require negative pressure isolation, to prevent nosocomial transmission of influenza. This has prompted several studies that have attempted to evaluate the role of face masks in infection prevention in hospitals. In one large randomized trial, nursing staff who were randomly assigned to wear N95 respirators had the same rate of influenza as staff assigned to wear simple surgical masks while caring for patients with influenza. In contrast, hand hygiene and simple surgical masks were reported to be modestly effective in the prevention of influenza transmission in households,69 suggesting that in this setting, droplet spread was the predominant modality. Industrial absenteeism is determined by the percentage with respiratory complaints. Possibly for this reason, the effects of weather variability may be greater in young children. However, this is not always the case, and in some seasons two different lineages or strains within a single subtype or two different influenza A subtypes (H1N1 and H3N2) or concomitant outbreaks of influenza A and B have occurred. In some years, the end of the influenza epidemic season is characterized by cases due to a new strain. These limited outbreaks, which have been referred % Respiratory 2149 Pandemic Influenza Pandemics are typically associated with the emergence of an antigenically variant influenza virus toward which the population has little or no prior immunity. In addition to higher attack rates overall with substantially greater disease impact, pandemics are typically associated with a different age distribution of cases, with greater impact in younger persons and relative sparing of the elderly. The reasons for this are unclear, although in some pandemics older segments of the population may have been exposed to antigenically related viruses in childhood, sometimes referred to as "antigenic recycling. Many pandemics are characterized by multiple waves of activity during the pandemic period, such as the H1N1 pandemic, with an initial wave in the spring followed by a more severe wave of cases in the early fall in much of the United States. The intervals between pandemics are quite variable and unpredictable, but it is likely that pandemics of influenza will continue to occur in the future. Alteration of the antigen structure of the virus leads to infection with variants to which little or no resistance is present in the population at risk. The phenomenon of antigenic variation helps explain why influenza continues to be a major epidemic disease of humans. Although there is generally a very tight correlation between genetic changes and antigenic distance78 the antigenic significance of any individual mutation can be more difficult to assess. These major antigenic changes are referred to as antigenic shifts, and result in viruses toward which the population has little or no prior immunity and is therefore highly susceptible. After one or more waves of pandemic influenza, the proportion of immune individuals in the population increases. Subsequent epidemics of seasonal epidemics due to strains of influenza A/HxNx that exhibit antigenic drift occur, with selection of new variants. After an unpredictable period of circulation of antigenic variants of the HxNx virus, a new virus, HyNy, will emerge, and the process repeats itself. In addition, serologic studies have suggested that H3 subtype viruses circulated before 1918. In 1977, viruses of the H1N1 subtype were reintroduced through an unknown mechanism. These viruses are genetically identical to the H1N1 viruses that were circulating in 1950. In 2009, a new variant of H1N1 viruses, referred to as pH1N1, emerged from pigs and replaced the previous H1N1 viruses. The origin of new pandemic strains has been the subject of intense interest and study, for obvious reasons. The most plausible explanation for their origin takes into account three features of this phenomenon: that the virus has a segmented genome, that pandemics occur only with influenza A viruses, and that influenza A viruses, but not other influenza viruses, maintain a large reservoir of genetic diversity, primarily in birds. Chapter 165 Influenza Viruses, Including Avian Influenza and Swine Influenza Antigenic Drift Incidence of clinically manifest influenza Mean level of population antibody vs. A/ HxNx and A/HyNy represent influenza viruses with completely different hemagglutinins and neuraminidases. Because the nature of influenza epidemics prior to 1918 is known only by serologic means, those boxes are shaded tan. Below the time line are the ages of individuals in 2004 who were alive during the various epidemic periods of earlier influenza subtypes. For example, individuals currently living who are between the ages of 47 and 86 probably experienced their first influenza A infection as an H1N1 virus. Individuals who are 36 years of age or younger have never been infected with H2N2 viruses. In these birds influenza A causes mild illness or may be shed asymptomatically at high levels and for long duration in the feces. These birds may transmit influenza to other animals, including domestic poultry, horses, swine, and marine mammals, which may in turn transmit these viruses to humans. Comparisons of sequence data from animal and human influenza viruses isolates has suggested that the 1918 virus was introduced into humans from such an animal population.

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