docid: cvvjgkmw

title: The Use of Antiallergic and Antiasthmatic Drugs in Viral Infections of the Upper Respiratory Tract

text: Despite their frequency, upper respiratory tract infections (URTIs) constitute an area with few, if any, effective treatment remedies. Asthma and airway allergies share similar pathogenetic mechanisms to URTIs and it is not surprising, therefore, that agents used to treat allergic disorders have also been studied in URTIs. Their possible effects, limitations and hypothetical modes of action in URTIs are reviewed. In controlled clinical trials of satisfactory scientific standard, symptom reductions in both experimental rhinovirus infections and natural colds have occurred with topical anticholinergics, oral antihistamines and topical chromones. Future treatment alternatives for URTIs may include the intranasal anticholinergic ipratropium bromide, new nonsedating antihistamines and sodium cromoglycate (cromolyn sodium). The latter has a record of safety and an absence of adverse effects that would make it an attractive alternative for this common but not particularly serious condition in otherwise healthy individuals.


title: New concepts in viral gastroenteritis

text: The use of negative contrast electronmicroscopy of stool suspension in the investigation of the aetiology of childhood gastroenteritis has led to the recognition of a number of candidate viral agents. There is convincing evidence that rotavirus is the single most important cause of community acquired gastroenteritis, and is responsible for some nosocomial outbreaks. The epidemiology of rotavirus acquisition, differential clinical susceptibilities of young and older infants, pathogenesis of disease, mechanisms of immunity and breast milk protection, and the role of different viral serotypes are aspects as yet poorly understood; and attempts to propagate human rotavirus in tissue culture have met with only limited success. Moreover, the aetiologically unaccountable one third of cases of infantile diarrhoea, and the association of enteritis with up to six other virus-like particles add to the complexity of the problem. This review considers the available data from human and animal studies, and based on the experience of ourselves and others comments on the present state of knowledge and trends in continuing research.


Whose world? Which health? What security? The facts and fictions of global health security


title: Linkage and independence of AIDS and kaposi disease: The interaction of human immunodeficiency virus and some coagents

text: Through epidemiological considerations we conclude that full-blown AIDS may occur only if the index patient is infected by the human immunodeficiency virus (HIV) and, in addition, by some other infectious coagent. Since the dynamical behaviour of the spread of AIDS cases with manifestation of Kaposi's sarcoma differs fundamentally from that of the non-Kaposi cases, we conjecture that two independent coagents (together with HIV) are responsible for the outbreak of full-blown AIDS with or without manifestation of Kaposi's sarcoma, respectively. Our formal epidemiological considerations appear to be supported by recent microbiological findings.


Deutsche Gesellschaft für Pharmakologie und Toxikologie Abstracts of the 34th Spring Meeting 16–18 March 1993, Mainz


title: Comparison of the Laboratory Data Between Kawasaki Disease and Enterovirus After Intravenous Immunoglobulin Treatment

text: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology. The laboratory findings before and after intravenous immunoglobulin (IVIG) in KD have been discussed, but the characteristics of IVIG therapy still are unclear. This study aimed to compare laboratory data from patients with KD and enterovirus (EV) infection to evaluate the differences after IVIG therapy. The study enrolled 171 KD patients and 38 EV patients treated with a single dose of IVIG from 2003 to 2010. Laboratory data including total white blood cell counts (WBC) and hemoglobin (Hb), platelet, segment, lymphocyte, eosinophil, and monocyte levels were analyzed. Compared with the KD patients, the EV patients had higher Hb, lymphocyte, and monocyte levels and lower eosinophil levels before IVIG treatment (p < 0.05). After IVIG treatment, the KD patients had lower Hb and segment levels but higher platelet, lymphocyte, and eosinophil levels than the EV patients (p < 0.05). In the KD patients, the platelet, eosinophil, and monocyte levels increased after IVIG treatment, whereas Hb, WBC, and segment levels decreased significantly (p < 0.001). In the EV patients, eosinophil levels increased after IVIG treatment, whereas WBC and Hb levels decreased significantly (p < 0.05). The study results provide evidence that eosinophilia may be related to IVIG therapy in KD and EV patients. The KD patients had higher eosinophil levels both before and after IVIG therapy than the EV patients, which may have been due to the inflammatory mechanism of KD. The KD patients had higher platelet levels than the EV patients, suggesting that platelets are involved in the inflammatory response to KD.


title: Microbiological effects and quality control in laboratory rodents

text: Numerous viruses, mycoplasmas, bacteria and parasites have been associated with infectious diseases in laboratory animals. It is clear that pathogenic agents causing overt disease represent a serious hazard to research results in both short- as well as long-term studies. However, these organisms may contaminate colonies without causing any clinical or pathological symptom. This makes research less reliable because of the more subtle effects of the silent infections, especially in long-term studies as in aging research. The establishment of animal colonies that were free from these (micro-) organisms has increased substantially the value of animals used in biomedical research. Characterization of the health status and microbiological monitoring of the animals in experiments are particularly important. This paper reviews many of the major considerations in the efforts to maintain animals free of unwanted organisms, including quality and sources of animals, transportation and quarantine, maintenance during experimentation, microbiological characterization and monitoring of animals and environment. (Aging Clin. Exp. Res. 5: 317–323, 1993)


title: Extracorporeal membrane oxygenation in spina bifida and (H1N1)-induced acute respiratory distress syndrome

text: Acute respiratory distress syndrome (ARDS) is characterized as an acute hypoxemic and/or hypercapnic respiratory failure seen in critically ill patients and is still, although decreased over the past few years, associated with high mortality. Furthermore, ARDS may be a life-threatening complication of H1N1 pneumonia. We report on a 45-year-old spina bifida patient with confirmed H1N1 influenza virus infection causing acute respiratory failure, who was successfully weaned from 42-day veno-venous extracorporeal membrane oxygenation (vv-ECMO) treatment with an excellent outcome. Due to the physical constitution of spina bifida patients, we experienced challenges concerning cannula positioning and mechanical ventilation settings during weaning.


docid: cbelsymu

title: Current Recommendations for the Prevention and Treatment of Influenza in the Older Population

text: Influenza is a major cause of morbidity and mortality in the elderly. Influenza vaccine is recommended for people aged 65 years and older and those in long term care. Currently only 30% of high risk persons are vaccinated. Vaccination generally stimulates an adequate immune response, is well tolerated and is to be encouraged. Prophylactic amantadine 100 mg/day should be given for 2 weeks with influenza vaccine in the aged population when they have not been previously immunised. Broad application of these preventive measures would have a significant impact on reducing influenza prevalence in the elderly and other high risk groups.


title: Pediatric Hospitalizations Associated with 2009 Pandemic Influenza A (H1N1): An Experience from a Tertiary Care Center in North India

text: OBJECTIVES: To describe our experience in children hospitalized with the pandemic Influenza A (H1N1) from Northern India. METHODS: The retrospective case study was conducted at the Pediatric ward and Pediatric Intensive Care Unit (PICU) dedicated to the children (aged 18 years or younger) with influenza-like illness (ILI) with positive laboratory test results for pandemic H1N1 by reverse-transcriptase polymerase-chain-reaction assay. RESULTS: Between August 2009 and January 2010, a total of 100 children were hospitalized with suspected 2009 H1N1 influenza with Category “C” as described by the Government of India. Twenty five patients were positive for H1N1 and 9 for seasonal influenza A. The most common presentation (H1N1 positive) was with fever (100%), cough (100%), coryza (52%), respiratory distress (88%), vomiting (28%) and diarrhea (16%). One child presented with hypernatremic dehydration and seizures (Serum sodium 174 meq/l). Of the H1N1 positive hospitalized children, 7 (28%) had respiratory failure and required PICU admission, 4 (16%) required mechanical ventilation, and 3 (12%) died. The major radiological findings were bilateral pulmonary infiltrates and consolidation. All patients were treated with oral Oseltamivir suspension or capsule as per appropriate weigh band and supportive care as required. Two deaths were caused by refractory hypoxemia and one by refractory shock. CONCLUSIONS: The exact incidence of Pandemic 2009 H1N1 influenza on morbidity and mortality is difficult to calculate since only Category “C” patients were screened.


title: Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide for Primary Immune Deficiency Disorders in Children: Challenges and Outcome from a Tertiary Care Center in South India

text: Haploidentical stem cell transplantation (haplo SCT) has emerged as an acceptable alternative to matched family donor transplantation for children diagnosed to have primary immune deficiency disorders (PIDs). We present data over 4 years on the challenges and efficacy of unmanipulated T cell replete haplo SCTs with post-transplant cyclophosphamide (PTCy) in children diagnosed to have PIDs. We performed a retrospective study in the pediatric blood and marrow transplantation unit where all children less than 18 years of age diagnosed to have PIDs and who underwent haplo SCT with PTCy from January 2014 to February 2018 were included in the study. Of the 16 transplants included in the study, 5 children were diagnosed to have Wiskott-Aldrich syndrome, 3 with congenital hemophagocytic lymphohistiocytosis, 2 each with Griscelli syndrome and Mendelian susceptibility to mycobacterial diseases, and one each with Chediak-Higashi syndrome, ORAI 1 mutation immune deficiency, severe combined immune deficiency, and Hyper IgM syndrome. The source of stem cells was PBSC in 62.5% and bone marrow in 32.5%. Engraftment by day 16–21 post hematopoietic stem cell transplantation was achieved in 75% transplants with 91% of these remaining in sustained complete chimerism. Acute skin and gut graft versus host disease of grade 2–3 were noted in 50% transplants and cytomegalovirus (CMV) reactivation in 43.7% transplants. One child with congenital HLH succumbed to refractory CMV, adenovirus, and BK virus infection. Cytokine release syndrome (CRS) was noted in 75% transplants with 2 children succumbing to the illness. Tocilizumab was successfully used early in one child. Overall mortality was found to be 37.5% with overall survival of 62.5% with a median follow-up of 23.3 months. In resource limited settings, PTCy has the potential to provide a cost-effective advantage in terms of accessibility of this curative procedure among children with PIDs.


title: Severe pneumococcal community-acquired pneumonia admitted to medical Tunisian ICU

text: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP). There are no available data about this disease in Tunisian intensive care patients. The objective of this study is to describe the clinical and microbiological features of pneumococcal CAP and determine the prognostic factors. This is a retrospective cohort study of all pneumococcal CAP cases hospitalized in the medical intensive care unit (ICU) of Hospital A. Mami of Ariana (Tunisia) between January 1999 and August 2008. Included were 132 patients (mean age, 49.5 years; 82.6% males); 30 patients had received antimicrobial treatment before hospital admission. The mean of the Simplified Acute Physiology Score II was 32.9. All patients had an acute respiratory failure; 34 patients (25.8%) had pneumococcal bacteremic CAP. Among the isolated strains, 125 antimicrobial susceptibility tests were performed. The use of the new Clinical and Laboratory Standards Institute breakpoints for susceptibility when testing penicillin against S. pneumoniae showed that all isolated strains were susceptible to penicillin. The mortality rate was 25%. The need of mechanical ventilation at admission [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.67–6.94; P = 0.001), Sepsis-related Organ Failure Assessment (SOFA) score at admission ≥4 (OR, 3.1; 95% CI, 1.56–6.13; P = 0.001), and serum creatinine at admission ≥102 μmol/l (OR, 1.8; 95% CI, 1.02–3.17; P = 0.043) were independent factors related to ICU mortality. In conclusion, pneumococcal CAP requiring hospitalization in the ICU is associated with high mortality. All isolated stains were susceptible to penicillin.


ECDC's Growing Responsibilities in Defending Europe Against Infectious Diseases


title: Diarrhea in newborn cynomolgus monkeys infected with human rotavirus

text: Of six newborn cynomolgus monkeys (Macaca fascicularis) naturally delivered and normally nursed five developed diarrhea after oral administration of human rotavirus. Virus excretion was observed in the stool of four animals. This virus was transmitted to four out of six other monkeys causing diarrhea in only one animal.


FatalPasteurella multocida infection in a systemic lupus erythematosus patient


title: An Approach to the Management of High Risk Asthmatic Patients

text: This review briefly outlines an approach to the management of high risk asthmatic patients. This approach involves: (i) identification of such high risk patients; (ii) investigation of precipitating factors contributing to severe attacks; and (iii) the introduction of a management strategy based on a simple system of self-assessment and self-treatment.


title: Antimicrobial Agents are Societal Drugs: How Should This Influence Prescribing?

text: This paper is concerned with how those who prescribe antimicrobials should consider the wider repercussions of their actions. It is accepted that in an ecological system, pressure will cause evolution; this is also the case with antimicrobials, the result being the development of resistance and the therapeutic failure of drugs. To an extent, this can be ameliorated through advances by the pharmaceutical industry, but that should not stop us from critically appraising our use and modifying our behavior to slow this process down. Up to 50% of prescribing in human medicine and 80% in veterinary medicine and farming has been considered questionable. The Alliance for the Prudent Use of Antimicrobials (APUA) was approached by the WHO to review the situation. Their recommendations include decreasing the prescribing of antibacterials for nonbacterial infections. In the UK, there has been an initiative called ‘the path of least resistance’. This encourages general practitioners to avoid prescribing or reduce the duration of prescriptions for conditions such as upper respiratory tract infections and uncomplicated urinary tract infections; this approach has been successful. Another recommendation is to reduce the prescribing of broad-spectrum antibacterials. In UK hospitals, the problems identified with the inappropriate use of antibacterials are insufficient training in infectious disease, difficulty in selecting empirical antibacterial therapy, poor use of available microbiological information, the fear of litigation and the fact that the majority of antibacterials are prescribed by the least experienced doctors. With close liaison between the laboratories and clinicians, and the development of local protocols, this can be addressed. Another recommendation is to tighten the use of antibacterial prophylaxis and to improve patient compliance. Through a combination of improved education for doctors and patients, and improved communication skills, these problems can be addressed. A further recommendation is to encourage teaching methods that modify prescribing habits. It has been shown that workshops have led to a significant reduction in the prescribing of broad-spectrum antibacterials in the community. Auditing the prescribing of antibacterials has also been recommended. Surveillance systems around the world monitor trends in resistance: the European Antimicrobial Resistance Surveillance Progamme (EARSS) monitors antibacterial resistance; the WHO and the International Union Against Tuberculosis and Lung Disease collaborate to monitor tuberculosis; the WHO and the International AIDS Society monitor HIV. In the third world, a bigger problem than resistance is whether drugs are even effective, as they are often spoiled by climactic conditions, and poor quality generics and counterfeit drugs are common. Also, patients may not be able to complete a course for financial reasons. Facts about Antimicrobial resistance in Animals (and agriculture) and Impact on Resistance (FAAIR) was commissioned by APUA. They conclude that the nonhuman use of antibacterials can lead to the development of antibacterial resistance in human pathogens. The European commission banned the use of antibacterials as growth promoters in 1999. In the Western world, we should improve our diagnosis of sepsis, access local guidelines and consider withholding treatment pending investigations, decide if treatment can be stopped earlier and treat the patient not the result. Many developing countries need improved access to more antimicrobials, preferably in the controlled environment of appropriate medical advice.


Exercise and Upper Respiratory Tract Infections: Is There a Relationship?


title: Use of permissive hypercapnia in the ventilation of infants with respiratory syncytial virus infection

text: We wished to retrospectively evaluate the effects of permissive hypercapnia (PHY) on barotrauma, mortality and length of stay when applied to ventilated infants with respiratory syncytial virus (RSV) bronchiolitis. Nineteen control infants with RSV induced respiratory failure were treated with conventional ventilation (April 1991–January 1994), after which time PHY was adopted as unit policy. A further 28 infants were then treated with PHY (January 1994–April 1996). Demographic and physiological data were collected from admission, and outcome variables including length of stay, barotrauma and mortality were recorded. The PHY group showed a significantly higher mean pCO(2) (7.6 vs 5.2 kPa), a lower mean pH (7.34 vs 7.40), and a reduction in maximal peak inspiratory pressures (25 vs 30 cmH(2)O). Mortality, barotrauma, use of neuromuscular blockade and nosocomial infection did not differ between groups. There was a trend towards increased length of ventilation in the PHY group (median 7 vs 5 days). Conclusion Based on this retrospective data we can show no benefit for the use of permissive hypercapnia as a ventilatory strategy in this patient group. A prospective randomised controlled trial is warranted to accurately assess the outcome variables and cost implications of this strategy.


title: Viral Illnesses and Sports Performance

text: Viruses are ubiquitous and cause numerous infections in humans. These may vary from asymptomatic infection to severe debilitating illness. Viruses enter the host cells to replicate, using host synthetic mechanisms, and, thus, are resistant to conventional antibiotics. The human body responds to viral infection by synthesising specific antibody which can be used to aid diagnosis. Infectious mononucleosis (glandular fever) commonly affects the 15 to 30 years age group. It may produce severe debility which may last a month or more. Coxsackie virus infection can produce symptoms of the common cold but may also invade heart muscle and produce myocarditis, a potentially serious disease. Other viruses also produce a wide spectrum of disease. Recent evidence has shown that people undergoing severe mental or physical stress may have reduced immunity to viral infections. There are risks associated with strenuous physical activity during the acute phase of viral infection, and there are reports of sudden death and serious complications occurring in previously fit young adults who undertake vigorous exercise when in the acute phase of a viral illness. Abnormalities of skeletal muscle have been demonstrated in patients with viral infection and this may explain the loss of performance experienced by athletes after upper respiratory tract infection. As a general rule, for all but mild common colds, it is advised that the athlete avoids hard training for the first month after infection.


title: Invasive Group A Streptococcal Disease: Epidemiology, Pathogenesis and Management

text: Invasive group A streptococcal infections are uncommon, although serious, infections with high case fatality rates. Periodic resurgences in invasive group A streptococcal infections in industrialized countries have been reported from the 1980s onwards, with current estimates of incidence in these countries of approximately 3–4 per 100000 population. Infants, pregnant women and the elderly are at increased risk of invasive group A streptococcal infection. The group A streptococcus has an array of virulence factors that underpin its invasive capacity and, in approximately 10% of cases, super-antigen toxins produced by the bacteria stimulate a large proportion of T cells, leading to streptococcal toxic shock syndrome. Given the rapid clinical progression, effective management of invasive group A streptococcal infections hinges on early recognition of the disease and prompt initiation of supportive care (often intensive care) together with antibacterial therapy. In cases of toxic shock syndrome, it is often difficult to distinguish between streptococcal and staphylococcal infection before cultures become available and so antibacterial choice must include coverage of both of these organisms. In addition, clindamycin is an important adjunctive antibacterial because of its anti-toxin effects and excellent tissue penetration. Early institution of intravenous immunoglobulin therapy should be considered in cases of toxic shock syndrome and severe invasive infection, including necrotizing fasciitis. Early surgical debridement of necrotic tissue is also an important part of management in cases of necrotizing fasciitis.


title: Recent Progress in Anti-Influenza Chemotherapy

text: Influenza virus infections in high risk individuals, such as infants, the elderly, and patients with cardiopulmonary disorders or immunocompromised states, cause severe manifestations which often result in fatalities. The emergence of a new antigen type of influenza A virus (H5N1) in Hong Kong during 1997 and 1998 threatened a possible pandemic of a new influenza infection. The investigation for anti-influenza chemotherapies has progressed in the last decade whereas clinical trials of new compounds have been limited to amantadine, rimantadine and ribavirin. Fusion inhibitors which directly inhibit conformational change of haemagglutinin (HA), protease inhibitors which inhibit cleavage of HA to HA1 and HA2, RNA transcription inhibitors which inhibit cap formation of mRNA and antisense oligonucleotides targeted at mRNA of PB2 (a part of viral RNA polymerase) have been reported, in their development phases. Recently, 2 neuraminidase (NA) inhibitors, zanamivir and oseltamivir (GS 4104), were used in clinical trials for the treatment of patients with influenza. Both agents showed promising results. A polyoxometalate, PM-523, inhibits fusion between the virus envelope and cell membrane and inhibits the penetration of the virus into cells. This compound has shown potent anti-influenza activity and synergistic inhibitory activity in combination with ribavirin or zanamivir in vitro and in vivo. Resistant strains for zanamivir, oseltamivir or PM-523 have been isolated. The analysis of mutation points of these strains have contributed to the investigation of the antiviral mechanisms of action of these compounds and the mechanism of resistance of the mutants to these compounds.


title: Global dynamics for a class of discrete SEIRS epidemic models with general nonlinear incidence

text: In this paper, a class of discrete SEIRS epidemic models with general nonlinear incidence is investigated. Particularly, a discrete SEIRS epidemic model with standard incidence is also considered. The positivity and boundedness of solutions with positive initial conditions are obtained. It is shown that if the basic reproduction number [Formula: see text] , then disease-free equilibrium is globally attractive, and if [Formula: see text] , then the disease is permanent. When the model degenerates into SEIR model, it is proved that if [Formula: see text] , then the model has a unique endemic equilibrium, which is globally attractive. Furthermore, the numerical examples verify an important open problem that when [Formula: see text] , the endemic equilibrium of general SEIRS models is also globally attractive.


title: The Use of Interferon-α in Virus Infections

text: The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-α (IFNα) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future. In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFNα have been identified. There are also 3 slightly different verrions of the same single subtype, IFNα-2, made by recombinant DNA procedures in bacteria. IFNα preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFNα-2 than after IFN derived from human cells. Given intranasally, IFTα can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible. IFNα has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments. IFNα and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFNα are effective against Kaposi’s sarcoma in some AIDS patients. In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFNα gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFNα. In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFNα administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.


title: A bivalent vaccine confers immunogenicity and protection against Shigella flexneri and enterotoxigenic Escherichia coli infections in mice

text: Vaccine studies for Shigella flexneri and enterotoxigenic Escherichia coli have been impaired by the lack of optimal animal models. We used two murine models to show that a S. flexneri 2a bivalent vaccine (CVD 1208S-122) expressing enterotoxigenic Escherichia coli colonization factor antigen-I (CFA/I) and the binding subunits A2 and B of heat labile-enterotoxin (LTb) is immunogenic and protects against weight loss and diarrhea. These findings document the immunogenicity and pre-clinical efficacy effects of CVD 1208S-122 vaccine and suggest that further work can help elucidate relevant immune responses and ultimately its clinical efficacy in humans.


title: The Application of Internet-Based Sources for Public Health Surveillance (Infoveillance): Systematic Review

text: BACKGROUND: Public health surveillance is based on the continuous and systematic collection, analysis, and interpretation of data. This informs the development of early warning systems to monitor epidemics and documents the impact of intervention measures. The introduction of digital data sources, and specifically sources available on the internet, has impacted the field of public health surveillance. New opportunities enabled by the underlying availability and scale of internet-based sources (IBSs) have paved the way for novel approaches for disease surveillance, exploration of health communities, and the study of epidemic dynamics. This field and approach is also known as infodemiology or infoveillance. OBJECTIVE: This review aimed to assess research findings regarding the application of IBSs for public health surveillance (infodemiology or infoveillance). To achieve this, we have presented a comprehensive systematic literature review with a focus on these sources and their limitations, the diseases targeted, and commonly applied methods. METHODS: A systematic literature review was conducted targeting publications between 2012 and 2018 that leveraged IBSs for public health surveillance, outbreak forecasting, disease characterization, diagnosis prediction, content analysis, and health-topic identification. The search results were filtered according to previously defined inclusion and exclusion criteria. RESULTS: Spanning a total of 162 publications, we determined infectious diseases to be the preferred case study (108/162, 66.7%). Of the eight categories of IBSs (search queries, social media, news, discussion forums, websites, web encyclopedia, and online obituaries), search queries and social media were applied in 95.1% (154/162) of the reviewed publications. We also identified limitations in representativeness and biased user age groups, as well as high susceptibility to media events by search queries, social media, and web encyclopedias. CONCLUSIONS: IBSs are a valuable proxy to study illnesses affecting the general population; however, it is important to characterize which diseases are best suited for the available sources; the literature shows that the level of engagement among online platforms can be a potential indicator. There is a necessity to understand the population’s online behavior; in addition, the exploration of health information dissemination and its content is significantly unexplored. With this information, we can understand how the population communicates about illnesses online and, in the process, benefit public health.


title: Histologische Klassifikation interstitieller Lungenerkrankungen

text: The 2002 ATS/ERS consensus classification of idiopathic interstitial pneumonias standardizes definitions and criteria for classification and diagnosis of idiopathic interstitial pneumonias and replaces previous classifications. Based on clinico-radiologic-pathologic criteria seven entities were defined: idiopathic pulmonary fibrosis, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia and lymphoid interstitial pneumonia. The following paper includes a brief overview of the histopathological diagnosis of these entities as compared to other diffuse interstitial pulmonary diseases and pulmonary manifestations of collagenvascular diseases.


title: Cellular events in alveolitis and the evolution of pulmonary fibrosis

text: “Alveolitis”, as opposed to “pneumonia”sensu striction, is a term used to denote diffuse inflammatory changes of the pulmonary parenchyma, excluding those that result from local bacterial, fungal or other extracellular microbial growth. The various types of alveolitis are classified according to their histological characteristics and range from “luminal phagocytic” or “mural lymphoplasmacellular” and “exudative” to “fibrosing” alveolitis. In this overview, various exogenous and endogenous causes of different types of alveolitis, and the cellular events in their pathogenesis are briefly discussed to illustrate the complex mechanisms involved. Particular emphasis is placed on the possible transition from diffuse exudative to fibrosing alveolitis. It appears that pulmonary fibrosis, which is usually patchy rather than truly diffuse, does not have a uniform pathogenesis. Besides the possibility of a certain degree of a diffuse fibrosis three major pathways are evident: (1) granulation tissue budding into alveolar lumina (luminal fibrosis) (2) exudate incorporation into alveolar walls (mural fibrosis) and — at least equally important-(3) so-called collapse (atelectatic) induration (obliterative-interseptal fibrosis), a process that has largely been neglected so far.


title: Findings in children severely infected with a novel influenza A virus of swine origin: pulmonary imaging

text: BACKGROUND: This article reviews the chest radiography of children with severe infection caused by a novel influenza A (H1N1) virus of swine origin (S-OIV). We analyzed the role of their pulmonary images in predicting the severity and diagnosis of the disease. METHODS: Among 97 patients with confirmed novel H1N1 infection, 42 patients treated with mechanical ventilation formed group 1, and the remaining 55 patients constituted group 2. The initial and subsequent radiograhic findings in groups 1 and 2 were compared with respect to the pattern, distribution, and extent of the abnormality. RESULTS: In group 1, 24 patients presented with three or more lung zone diseases, whereas only 5 patients in group 2 demonstrated these findings (P<0.001). A pneumomediastinum or pneumothorax was observed in 24/42 patients in group 1 and in 18/55 patients in group 2 (P=0.019). Twelve patients in group 1 and 5 in group 2 developed a ground-glass opacity cyst with a honeycomb appearance (P=0.007). CONCLUSIONS: The most common radiographic and computed tomography findings in children who were severely infected with S-OIV included unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. Children with bilateral involvement or with greater opacity on the chest radiographs were more likely to worsen and require the mechanical ventilation.


title: KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia

text: Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor–patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/leu.2008.365) contains supplementary material, which is available to authorized users.


title: Eosinophilie bei pulmonalen Infektionen

text: Eosinophilia can be caused by a variety of diseases including allergies, autoimmune diseases, vasculitides, dermatoses, malignancies and drug-induced side effects as well as parasitic and non-parasitic infections. In patients returning from the tropics parasitic infections are the most frequent cause of eosinophilia. The extent of eosinophilia can provide information about the type of pathogen. The diagnostic approach to eosinophilia in travelers returning from the tropics primarily includes three stool examinations for worm eggs and, if necessary, serological tests for helminths. Additionally, a chest x‑ray, an ultrasound of the abdomen and an electrocardiogram (ECG) provide information about organ involvement. Recently, specialized laboratories use molecular techniques (multiplex PCR) to detect worm eggs and intestinal parasites in the stool, which provide a significantly higher sensitivity than traditional stool examination techniques. Cryptococcosis, endemic systemic mycoses (coccidioidomycosis, very rarely histoplasmosis) and invasive mould infections (Aspergillus fumigatus, Mucor spp.) are non-parasitic causes of eosinophilia in blood and bronchoalveolar lavage (BAL).


title: Measles-induced respiratory distress, air-leak and ARDS

text: Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006–2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.


title: Interstitielle Lungenerkrankungen

text: Interstitial pneumonia is a rare disease, posing a diagnostic challenge to pneumologists, pediatricians, radiologists and pathologists. Only by the combined efforts of the European Respiratory Society (ERS) and the American Thoracic Society (ATS) has has been possible to standardize the formerly different European and Northern American nomenclature of interstitial lung diseases (alveolitis versus interstitial pneumonia) in adults and to clearly and unambiguously define the diagnostic criteria. The ATS/ERS classification of 2002 comprises seven entities: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), cryptogenic organizing pneumonia (COP), lymphocyte interstitial pneumonia (LIP), and acute interstitial pneumonia (AIP). Using the ATS/ERS classification of interstitial pulmonary diseases in premature infants, infants and children is problematic, since UIP, RB-ILD and AIP do not occur at this age. Although infants with severe respiratory insufficiency may sometimes show morphological features similar to DIP or NSIP, this entity should rather be classified as chronic pneumonitis of infancy (CPI) because of differences in etiology, pathogenesis and prognostic outcome.


docid: iacifhko

title: Bronchoalveolar lavage

text: The technique of BAL performed through the fiberoptic bronchoscope has, in two decades, provided clinicians and researchers with the ability to safely sample the inflammatory-immune cell milieu of the human lung. Standardized BAL and processing of the lavage constituents provides assistance in determining the optimal care of patients with a variety of lung diseases, and renders diagnosis in selected cases. It has become indispensable in the diagnosis of pulmonary infiltrates in immunocompromised patients, and plays an important role in improving clinical management. Finally, it continues to yield an ever increasing amount of data for the researchers studying the mechanisms and pathogenesis of lung disease. It is likely that BAL will become an even more valuable tool with increasing relevance to the practice of chest medicine in the 1990s.


title: Novel Ethanol-in-Fluorocarbon Microemulsions for Topical Genetic Immunization

text: Purpose. Traditionally, vaccines have been administered by needle injection. Topical immunization through the intact skin with either protein- or DNA-based vaccines has attracted much attention recently. We sought to enhance the immune responses induced by DNA-based vaccines after topical application by developing novel ethanol-in-fluorocarbon (E/F) microemulsion systems to aid in the delivery of plasmid DNA (pDNA). Methods. Ten different fluorosurfactants were selected or synthesized and screened by pseudo-phase-diagram construction for their ability to form E/F microemulsions. Plasmid DNA was successfully incorporated into E/F microemulsions using several different fluorosurfactants and perfluorooctyl bromide as the continuous fluorocarbon phase. For several reasons, Zonyl® FSN-100 (an ethoxylated nonionic fluorosurfactant) was selected for further studies. In vivo studies were performed in mice to assess pDNA expression in skin and immunologic responses after topical application of this system using a luciferase-encoding plasmid (CMV-luciferase) and a CMV-β-galactosidase-encoding plasmid, respectively. Results. Plasmid DNA incorporated into E/F microemulsion using FSN-100 as the surfactant was found to be stable. After topical application of this E/F microemulsion system, significant enhancements in luciferase expression and antibody and T-helper type-1 biased immune responses were observed relative to those of “naked” pDNA in saline or ethanol. For example, with the E/F microemulsion system, the specific serum IgG and IgA titers were increased by 45-fold and over 1000-fold, respectively. Conclusion. A novel fluorocarbon-based microemulsion system for potential DNA vaccine delivery was developed.


title: Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance

text: Carbon monoxide (CO), a gaseous second messenger, arises in biological systems during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. HO exists as constitutive (HO-2, HO-3) and inducible isoforms (HO-1), the latter which responds to regulation by multiple stress-stimuli. HO-1 confers protection in vitro and in vivo against oxidative cellular stress. Although the redox active compounds that are generated from HO activity (i.e. iron, biliverdin-IXα, and bilirubin-IXα) potentially modulate oxidative stress resistance, increasing evidence points to cytoprotective roles for CO. Though not reactive, CO regulates vascular processes such as vessel tone, smooth muscle proliferation, and platelet aggregation, and possibly functions as a neurotransmitter. The latter effects of CO depend on the activation of guanylate cyclase activity by direct binding to the heme moiety of the enzyme, stimulating the production of cyclic 3′:5′-guanosine monophosphate. CO potentially interacts with other intracellular hemoprotein targets, though little is known about the functional significance of such interactions. Recent progress indicates that CO exerts novel anti-inflammatory and anti-apoptotic effects dependent on the modulation of the p38 mitogen activated protein kinase (MAPK)-signaling pathway. By virtue of these effects, CO confers protection in oxidative lung injury models, and likely plays a role in HO-1 mediated tissue protection.


title: Severe combined immune deficiency presenting with cyclic hematopoiesis

text: At age 2 months a male infant presented with a cyclic clinical syndrome every 14–21 days that included pharyngeal aphthous ulcers, high fever, lymphadenopathy, pallor, and malaise. Serial blood studies indicated cycling of all blood cell elements, compatible with a diagnosis of cyclic hematopoiesis (CH). He also manifested a progressively severe immune deficiency, not described before in human CH. When first studied at age 5 months, he was hypogammaglobulinaemic with normal B lymphocyte numbers. By 6.5 months, he was agammaglobulinaemic. At age 8 months, he developed severe pneumocystis carinii pneumonia, and studies showed a state of severe combined immune deficiency. The patient received a bone marrow transplant from his HLA-identical sister with no preconditioning therapy. Subsequently, normal immune function developed and the cyclic hematopoiesis resolved. The majority of lymphocytes is of donor origin. Persistence of erythrocytes and neutrophils of recipient origin suggests that the hematopoietic stem cells were not abnormal. We speculate that this patient had a primary deficiency of a differentiation factor affecting maturation of lymphoid and myeloid progenitor cells.


docid: zdwzkaoo

title: Detection of acute inhalation injury in fire victims by means of technetium-99m DTPA radioaerosol inhalation lung scintigraphy

text: Mortality and morbidity in fire victims are largely a function of injury due to heat and smoke. While the degree and area of burn together constitute a reliable numerical measure of cutaneous injury due to heat, as yet no satisfactory measure of inhalation injury has been developed. In this study, we employed technetium-99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal controls and 17 survivors from a fire accident were enrolled in the study. All patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum).(99m)Tc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects, using a commercial lung aerosol delivery unit. The degree of lung damage was presented as the clearance rate (k; %/min) calculated from the time-activity curve over the right lungs. In addition, the distribution pattern of the radioactivity in the lungs was evaluated and classified into two groups: homogeneous distribution and inhomogeneous distribution. A plain chest radiograph (CxR) and pulmonary function test (PFT) were performed in the same group of patients. The results showed that 6/17 (35.3%) opatients had inhomogeneous distribution of radioactivity in their inhalation scans, and 11/17 (64,7%) had homogeneous scans. Five of the six patients with inhomogeneous scans were admitted for further management, and all patients with homogeneous scans were discharged from the emergency department and needed no further intensive care. The clearance rates of the right lung were 0.73%±0.13%/min from normal controls and 1.54%±0.58%/min for fire victims. The difference was significant, with aP value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects were below 0.9%/min) 14 (82.4%) patients had abnormal clearance rates of(99m)Tc-DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and three (17.6%) had abnormal PFTs. We conclude that (1) conventional CxR and PFT are not good modalities for evaluating inhalation injury in fire victims because of their low sensitivity, and (2)(99m)Tc-DTPA radioaerosol inhalation scintigraphy can provide an objective evaluation of inhalation injury during a fire accident and may be useful in therapeutic decision-making and disease monitoring.


title: Left ventricular hypertrophy and renin-angiotensin system blockade

text: The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis. The main causal mechanism is the increase in blood pressure, which leads to increased left ventricular wall stress; however, aldosterone release from the adrenals and (more controversially) the direct action of angiotensin II on the cardiomyocytes also play a role. Large clinical trials evaluating the blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated an ability to prevent progression and induce regression of left ventricular mass, thereby reducing the significant and independent cardiovascular risk conferred by LVH. Regression of left ventricular mass is also achieved by other medication classes, but the RAS blockers have an additional beneficial effect for the same blood pressure reduction, for which the mechanism is not entirely clear. Studies comparing the efficacy of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers to achieve LVH regression have not demonstrated any clear benefit of one class over the other.


title: Protein modeling and molecular dynamics simulation of the two novel surfactant proteins SP-G and SP-H

text: Surfactant proteins are well known from the human lung where they are responsible for the stability and flexibility of the pulmonary surfactant system. They are able to influence the surface tension of the gas–liquid interface specifically by directly interacting with single lipids. This work describes the generation of reliable protein structure models to support the experimental characterization of two novel putative surfactant proteins called SP-G and SP-H. The obtained protein models were complemented by predicted posttranslational modifications and placed in a lipid model system mimicking the pulmonary surface. Molecular dynamics simulations of these protein-lipid systems showed the stability of the protein models and the formation of interactions between protein surface and lipid head groups on an atomic scale. Thereby, interaction interface and strength seem to be dependent on orientation and posttranslational modification of the protein. The here presented modeling was fundamental for experimental localization studies and the simulations showed that SP-G and SP-H are theoretically able to interact with lipid systems and thus are members of the surfactant protein family. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-014-2513-0) contains supplementary material, which is available to authorized users.


title: NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury

text: The innate immune response is important in paraquat-induced acute lung injury, but the exact pathways involved are not elucidated. The objectives of this study were to determine the specific role of the NLRP3 inflammasome in the process. Acute lung injury was induced by administering paraquat (PQ) intraperitoneally. NLRP3 inflammasome including NLRP3, ASC, and caspase-1 mRNA and protein expression in lung tissue and IL-1β and IL-18 levels in BALF were detected at 4, 8, 24, and 72 h after PQ administration in rats. Moreover, rats were pretreated with 10, 30, and 50 mg/kg NLRP3 inflammasome blocker glybenclamide, respectively, 1 h before PQ exposure. At 72 h after PQ administration, lung histopathology changes, NLRP3, ASC, and caspase-1 protein expression, as well as secretion of cytokines including IL-1β and IL-18 in BALF were investigated. The NLRP3 inflammasome including NLRP3, ASC, caspase-1 expression, and cytokines IL-1β and IL-18 levels in PQ poisoning rats were significantly higher than that in the control group. NLRP3 inflammasome blocker glybenclamide pretreatment attenuated lung edema, inhibited the NLRP3, ASC, and caspase-1 activation, and reduced IL-1β and IL-18 levels in BALF. In the in vitro experiments, IL-1β and IL-18 secreted from RAW264.7 mouse macrophages treated with paraquat were attenuated by glybenclamide. In conclusion, paraquat can induce IL-1β/IL-18 secretion via NLRP3-ASC-caspase-1 pathway, and the NLRP3 inflammasome is essential for paraquat-induced acute lung injury.


title: Long-Term Maintenance of the Functional Changes Induced by Influenza A Virus and/or LPS in Human Endothelial ECV-304 Cell Sublines

text: Influenza A virus and secondary bacterial infection may have remote effects in the form of cardiovascular complications or fibrosis in different organs. However, the mechanisms governing the development of complications remain poorly studied. The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The pattern of changes depended on the type of the agent (agents) to which the cells were exposed. The differences in migratory activity (which was at its maximum 4 h after wounding) between the cell sublines at the sixth passage correlated with the differences in their proliferation activity at the first passage (proliferation data were obtained previously). In particular, an increase in migration and proliferation was observed in the sublines exposed to low virus doses (ECV-1ID), as well as exposed to LPS (ECV-LPS), while the suppression of migration and proliferation was observed in the subline exposed to high virus doses (ECV-1000ID). In the ECV-1ID, ECV-LPS, and most notably in ECV-1ID + LPS sublines, we detected an increase in the expression of mRNA for cytokines TNFα and TGFβ, which, however, didn’t lead to the induction of apoptosis. We have also demonstrated an increase in cell permeability in the analyzed sublines, which was indicated by a decrease in the expression of the mRNAs for the genes encoding occludin and ZO-1, the tight junctions proteins . This paper also reports an evaluation of the effects of the antiviral preparations rimantadine and alpisarin on the functional state of cell sublines. As a result, it has been demonstrated that these drugs may be able to prevent the development of the pathological changes caused by influenza A virus and/or LPS in endothelial cells. The results obtained in the present work may be of use when studying the mechanisms of development of the influenza A virus and secondary bacterial infection complications.


title: Arzneimittelinduzierte Lungenerkrankungen

text: It is well-known that more than 350 drugs can cause unwanted effects in the lungs, bronchi, and neighboring structures of the thorax with a corresponding spectrum of pathological changes. Cardinal symptoms are often new onset of dyspnea on exertion and a cough that is usually dry. Further diagnostic work-up includes comprehensive pulmonary function testing with determination of diffusing capacity, high-resolution computed tomography, and bronchoscopy with bronchoalveolar lavage. There is no specific pathological alteration for a defined drug. In case of doubt the potentially pneumotoxic drug should be discontinued. An attempt should be made to treat severely compromised lung function with systemic corticosteroids.


title: Low C-reactive protein values at admission predict mortality in patients with severe community-acquired pneumonia caused by Streptococcus pneumoniae that require intensive care management

text: PURPOSE: To identify risk factors associated with mortality in patients with severe community-acquired pneumonia (CAP) caused by S. pneumoniae who require intensive care unit (ICU) management, and to assess the prognostic values of these risk factors at the time of admission. METHODS: Retrospective analysis of all consecutive patients with CAP caused by S. pneumoniae who were admitted to the 32-bed medico-surgical ICU of a community and referral university hospital between 2002 and 2011. Univariate and multivariate analyses were performed on variables available at admission. RESULTS: Among the 77 adult patients with severe CAP caused by S. pneumoniae who required ICU management, 12 patients died (observed mortality rate 15.6 %). Univariate analysis indicated that septic shock and low C-reactive protein (CRP) values at admission were associated with an increased risk of death. In a multivariate model, after adjustment for age and gender, septic shock [odds ratio (OR), confidence interval 95 %; 4.96, 1.11–22.25; p = 0.036], and CRP (OR 0.99, 0.98–0.99 p = 0.034) remained significantly associated with death. Finally, we assessed the discriminative ability of CRP to predict mortality by computing its receiver operating characteristic curve. The CRP value cut-off for the best sensitivity and specificity was 169.5 mg/L to predict hospital mortality with an area under the curve of 0.72 (0.55–0.89). CONCLUSIONS: The mortality of patients with S. pneumoniae CAP requiring ICU management was much lower than predicted by severity scores. The presence of septic shock and a CRP value at admission <169.5 mg/L predicted a fatal outcome.


title: Intestinal Transplantation in Children: A Review of Immunotherapy Regimens

text: This review summarizes the outcomes and known adverse effects of current immunosuppression strategies in use in pediatric intestinal transplantation. Intestinal transplantation has evolved from an experimental therapy to a highly successful treatment for children with intestinal failure who have complications with total parenteral nutrition. Because of continued success with intestinal transplantation over the past decade, the focus of clinicians and researchers is shifting from short-term patient survival to optimizing long-term outcomes. Current 5-year patient and graft survival rates after intestinal transplantation are 58% and 40%, respectively, in the US; single centers have reported nearly 80% patient and 60% graft survival rates at 5 years. The immunosuppression strategy in intestinal transplantation includes a tacrolimus-based regimen, usually in conjunction with an antibody induction therapy such as rabbit-antithymocyte globulin, interleukin-2 receptor antagonists, or alemtuzumab. The use of these immunosuppressive regimens, along with improved medical and surgical care, has contributed significantly toward improved outcomes. Optimization of post-transplant immunosuppression strategies to reduce adverse effects while minimizing acute and chronic graft rejection is a strong clinical and research focus.


title: Systemic Administration of FC-77 Dampens Ischemia–Reperfusion-Induced Acute Lung Injury in Rats

text: Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia–reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-α and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-κB activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-κB activation and attenuation of subsequent inflammatory response.


title: Time interval between the onset of type A influenza and consultation at the outpatient clinic in a community hospital: 1999–2000 epidemic

text: We investigated the proportion of patients with laboratory-confirmed type A influenza who visited an outpatient clinic and who were suitable for receiving treatment with anti-influenza viral agents. Between December 1999 and March 2000, in a community hospital, 40 patients were diagnosed as having type A influenza by specific antigen detection (n = 39) and reverse transcriptase-polymerase chain reaction (n = 1). These patients with laboratory-confirmed type A influenza were enrolled in the study. We investigated the time interval between the onset of illness and visit to the outpatient clinic at the community hospital. The results indicated that 57.5% of the patients with type A influenza visited the hospital within 1 day of the onset of illness, and 77.5% visited the hospital within 2 days. The body temperature (mean ± SD) during the initial consultation was 38.9 ± 0.8°C (n = 40). Seventeen of the 40 patients (42.5%) were hospitalized. In conclusion, in the majority of patients, the time from onset of symptoms to consultation was appropriate for treatment with anti-influenza viral agents. A rapid antigen-detection assay, such as Directigen Flu A, is useful for early diagnosis and allows for early treatment with anti-influenza viral agents.


15th European Workshop for Rheumatology Research: Erlangen/Bamberg, March 16–19, 1995


title: Bonded-communities in HantaVirus research: a research collaboration network (RCN) analysis

text: Hantavirus, one of the deadliest viruses known to humans, hospitalizes tens of thousands of people each year in Asia, Europe and the Americas. Transmitted by infected rodents and their excreta, Hantavirus are identified as etiologic agents of two main types of diseases—Hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, the latter having a fatality rate of above 40 %. Although considerable research for over two decades has been going on in this area, bibliometric studies to gauge the state of research of this field have been rare. An analysis of 2631 articles, extracted from WoS databases on Hantavirus between 1980 and 2014, indicated a progressive increase (R (2) = 0.93) in the number of papers over the years, with the majority of papers being published in the USA and Europe. About 95 % papers were co-authored and the most common arrangement was 4–6 authors per paper. Co-authorship has seen a steady increase (R (2) = 0.57) over the years. We apply research collaboration network analysis to investigate the best-connected authors in the field. The author-based networks have 49 components (connected clump of nodes) with 7373 vertices (authors) and 49,747 edges (co-author associations) between them. The giant component (the largest component) is healthy, occupying 84.19 % or 6208 vertices with 47,117 edges between them. By using edge-weight threshold, we drill down into the network to reveal bonded communities. We find three communities’ hotspots—one, led by researchers at University of Helsinki, Finland; a second, led by the Centers of Disease Control and Prevention, USA; and a third, led by Hokkaido University, Japan. Significant correlation was found between author’s structural position in the network and research performance, thus further supporting a well-studied phenomenon that centrality effects research productivity. However, it was the PageRank centrality that out-performed degree and betweenness centrality in its strength of correlation with research performance.


Renal insufficiency on presentation of bird flu infection: is it correlated to outcome?


title: Hemorrhagic Cystitis and Possible Neurologic Disease from BK Virus Infection in a Patient with AIDS

text: BK virus (BKV)-associated hemorrhagic cystitis occurs in bone marrow transplant recipients but is rare among other immunosuppressed patients. We present a rare case of BKVassociated hemorrhagic cystitis in a 48-year-old man with AIDS and previously diagnosed progressive multifocal leukoencephalopathy.


title: Biology of Secretory Phospholipase A(2)

text: INTRODUCTION: The secretory phospholipase A(2) (sPLA(2)) family provides a seemingly endless array of potential biological functions that is only beginning to be appreciated. In humans, this family comprises 9 different members that vary in their tissue distribution, hydrolytic activity, and phospholipid substrate specificity. Through their lipase activity, these enzymes trigger various cell-signaling events to regulate cellular functions, directly kill bacteria, or modulate inflammatory responses. In addition, some sPLA(2)’s are high affinity ligands for cellular receptors. OBJECTIVE: This review merely scratches the surface of some of the actions of sPLA(2)s in innate immunity, inflammation, and atherosclerosis. The goal is to provide an overview of recent findings involving sPLA(2)s and to point to potential pathophysiologic mechanisms that may become targets for therapy.


title: Clinical Pharmacological and Therapeutic Considerations in General Intensive Care: A Review

text: The application of clinical pharmacological concepts and therapeutic standards in intensive care settings presents particularly difficult problems due to the lack of adequately controlled background information and the highly variable and rapidly evolving clinical conditions where drugs must be administered and their impact evaluated. In this review, an attempt has been made to discuss the available knowledge within the framework of a problem-oriented approach, which appears to provide a more clinically useful insight than a drug-centred review. Following a brief discussion of the scanty data and the most interesting models to which reference can be made from a pharmacokinetic point of view (the burn patient being taken as an example), the review concentrates on the main general intervention strategies in intensive care patients. These are based mainly on non-pharmacological measures (correction of fluid and electrolyte balance, total parenteral nutrition, enterai nutrition, oxygenation and ventilatory management) and are discussed with respect to the specific challenge they present in various clinical conditions and organ failure situations. In addition, 4 major selected clinical conditions where general management criteria and careful use of prophylactic and therapeutic drug treatments must interact to cope with the variety of presentations and problems are reviewed. These include: acute cerebral damage; anti-infective prophylaxis and therapy; cardiovascular emergencies; and problems of haemostasis. Each problem is analysed in such a way as to frame the pharmacological intervention in its broader context of the underlying (established or hypothesised) pathophysiology, with special attention being paid to those methodological issues which allow an appreciation of the degree of reliability of the data and the recommendations which appear to be practiced (often haphazardly) in intensive care units. The thorough review of the published literature provided (up to mid-1986) clearly shows that in this field the quality of randomised controlled and epidemiological studies is rather unsatisfactory. It would be highly beneficial to research and to clinical care if larger multicentric protocols and prospective epidemiological comparative investigations could be carried out to investigate more timely and adequately the variables which determine drug action, and the final outcome in the many subgroups of patients which must be considered in a proper stratification of intensive care unit populations.


Septic shock—an update


docid: zmdbpxzc

title: Anabolic androgenic steroid induced necrotising myopathy

text: We describe the case of a 23-year-old gentleman who developed a severe generalised necrotising myopathy. Initially presenting with features of a virus-induced polymyositis, both symptomatic and biochemical improvements were initially achieved with glucocorticoid-based immunosuppression. Subsequently he represented with evidence of severe generalised rhabdomyolysis (creatinine kinase peaking at 210,000 U/L). Rendered anuric from the myogloburic assault, he required intensive care support from the development of multi-organ failure. Subsequent investigations failed to demonstrate an infective, inflammatory, metabolic or inherited aetiology. Muscle biopsy demonstrated severe generalised necrotising myopathy in the notable absence of inflammation. Confidential discussion with the patient and relatives confirmed a suspicion of anabolic androgenic steroid (AAS) abuse. There is limited literature as to the toxic effect of AAS compounds on muscle tissue, and these tend to focus on localised disease. Indeed, AAS have consistently been shown in animal models to produce a generalised myotrophic state. Apart from the social uses of such compounds, the scope for their supervised use in various medical conditions has been established since the 1960s.


title: Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection

text: BACKGROUND: Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection. METHODS: Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24–48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range. RESULTS: Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63–0.94)]. Kaplan–Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2–29.1, p = 0.007). CONCLUSIONS: This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.


title: PWP2, a member of the WD-repeat family of proteins, is an essentialSaccharomyces cerevisiae gene involved in cell separation

text: WD-repeat proteins contain four to eight copies of a conserved motif that usually ends with a tryptophan-aspartate (WD) dipeptide. TheSaccharomyces cerevisiae PWP2 gene, identified by sequencing of chromosome III, is predicted to contain eight so-called WD-repeats, flanked by nonhomologous extensions. This gene is expressed as a 3.2-kb mRNA in all cell types and encodes a protein of 104 kDa. ThePWP2 gene is essential for growth because spores carrying thepwp2Δ1::HIS3 disruption germinate before arresting growth with one or two large buds. The growth defect ofpwp2Δ1::HIS3 cells was rescued by expression ofPWP2 or epitope-taggedHA-PWP2 using the galactose-inducibleGAL1 promoter. In the absence of galactose, depletion of Pwp2p resulted in multibudded cells with defects in bud site selection, cytokinesis, and hydrolysis of the septal junction between mother and daughter cells. In cell fractionation studies, HA-Pwp2p was localized in the particulate component of cell lysates, from which it would be solubulized by high salt and alkaline buffer but not by nonionic detergents or urea. Indirect immunofluorescence microscopy indicated that HA-Pwp2p was clustered at multiple points in the cytoplasm. These results suggest that Pwp2p exists in a proteinaceous complex, possibly associated with the cytoskeleton, where it functions in control of cell growth and separation.


title: A Green Tea-Derived Polyphenol, Epigallocatechin-3-Gallate, Inhibits IκB Kinase Activation and IL-8 Gene Expression in Respiratory Epithelium

text: Interleukin-8 (IL-8) is a principle neutrophil chemoattractant and activator in humans. There is interest in developing novel pharmacological inhibitors of IL-8 gene expression as a means for modulating inflammation in disease states such as acute lung injury. Herein we determined the effects of epigallocatechin-3-gallate (EGCG), a green tea-derived polyphenol, on tumor necrosis factor-α (TNF-α)-mediated expression of the IL-8 gene in A549 cells. EGCG inhibited TNF-α-mediated IL-8 gene expression in a dose response manner, as measured by ELISA and Northern blot analysis. This effect appears to primarily involve inhibition of IL-8 transcription because EGCG inhibited TNF-α-mediated activation of the IL-8 promoter in cells transiently transfected with an IL-8 promoter-luciferase reporter plasmid. In addition, EGCG inhibited TNF-α-mediated activation of IκB kinase and subsequent activation of the IκBα/NF-κB pathway. We conclude that EGCG is a potent inhibitor of IL-8 gene expression in vitro. The proximal mechanism of this effect involves, in part, inhibition of IκB kinase activation.


title: Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction

text: How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p < 0.0001). This increase was independently associated with progression into acute respiratory distress syndrome (ARDS) as shown after logistic regression analysis (odds ratio 2.91, p: 0.002). Changes of circulating cytokines do not mediate worsening of the critically ill patients. Instead endocan and Ang2 are increased and this may be interpreted as a key-playing role in the pathogenesis of ARDS and septic shock. Any increase of endocan is a surrogate of worsening of the clinical course.


title: High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases

text: T-cell depletion of the marrow graft using counterflow centrifugal elutriation reduces the risk of graft-versus-host disease (GVHD). However, because of high rates of graft failure and relapse, elutriation alone has not improved survival. We have carried out a phase II clinical trial in 54 pediatric patients to determine if CD34+ selection to rescue pluripotent stem cells from the small lymphocyte fraction improves engraftment. The processed grafts contained a mean of 5.5 × 10(7) cells/kg IBW, 4.7 × 10(6) CD34+ cells/kg IBW, and 6.3 × 10(5) CD3+cells/kg IBW. Patients achieved an ANC >500 at a median of 16 days and platelet count >20 000 at a median of 28 days. The incidence of clinically significant GVHD was 19%. In total, 10 patients enrolled in this study experienced graft failure, with eight of the 14 patients transplanted for nonmalignant indications failing to engraft stably. Graft failure was statistically significantly associated with nonmalignant diagnosis (P<0.001), but was not associated with CMV seropositivity, donor gender, or cell counts of the allograft. We conclude that although time to engraftment is similar to that seen with unmanipulated grafts, graft failure remains a significant problem in patients with hereditary, nonmalignant diseases. Future efforts will seek to preserve the benefits of elutriation with CD34+ selection by increasing immune ablation of the preparative regimen and/or increasing posttransplant immune suppression.


title: CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs

text: The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(−/−) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2015.84) contains supplementary material, which is available to authorized users.


title: Association Between Angiopoietin-2 and Enterovirus 71 Induced Pulmonary Edema

text: OBJECTIVE: To characterize pulmonary edema (PE) fluid induced by enterovirus 71 (EV71) infection, elucidate the relationship between angiopoietin-2 (Ang-2) and PE, and explore the pathogenesis of PE. METHODS: Clinical data were collected from critical infants with EV71 infection. The infants were grouped into PE, non-PE, and control groups. The control group included infants in the preoperative period of elective inguinal hernia surgery. Biochemical changes in PE fluid were evaluated, and Ang-2 levels in serum and PE fluid were measured. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with serum from the control and PE groups and human recombinant Ang-2 or serum from the PE group and human recombinant Ang-1, and changes in the intercellular junctions were recorded via immunofluorescence. RESULTS: Of the 161 infants with critical EV71 infection admitted to the hospital, 39 had PE. PE fluid was collected from 18 of these infants. The PE fluid-to-serum (P/S) ratio of total protein was 0.9 ± 0.2, and all P/S ratios of albumin were 1.0 ± 0.3. The Ang-2 level was higher in the non-PE group (333.2 ± 79.7 pg/ml) than in the control group (199.9 ± 26.7 pg/ml), although without statistical significance (P = 0.115). The Ang-2 level in the PE group (2819.2 ± 908.7 pg/ml) was higher than those in both the non-PE and the control groups (both, P < 0.001). Serum samples from the PE group had damaged cell junctions of confluent HPMEC monolayers that were reversed by Ang-1. CONCLUSIONS: The PE fluid of infants with EV71-induced PE was protein-rich, and elevated Ang-2 expression was associated with PE. The mechanism through which PE develops may be related to Ang-2-induced cell junction damage.


docid: wxparyeg

title: Emerging influenza virus: A global threat

text: Since 1918, influenza virus has been one of the major causes of morbidity and mortality, especially among young children. Though the commonly circulating strain of the virus is not virulent enough to cause mortality, the ability of the virus genome to mutate at a very high rate may lead to the emergence of a highly virulent strain that may become the cause of the next pandemic. Apart from the influenza virus strain circulating in humans (H1N1 and H3N2), the avian influenza H5N1 H7 and H9 virus strains have also been reported to have caused human infections, H5N1 H7 and H9 have shown their ability to cross the species barrier from birds to humans and further replicate in humans. This review addresses the biological and epidemiological aspects of influenza virus and efforts to have a control on the virus globally.


title: Endotoxin in the conscious piglet: Its effects on some general and gastrointestinal myoelectrical parameters

text: The effect of an intravenous bolus injection of endotoxin, 0.1, 1 or 10 μg/kg, on rectal temperature, clinical appearance, haematological parameters, and on gastrointestinal electrical activity was examined in 11 conscious piglets of 4–5 weeks of age, with implanted electrodes in the antrum pylori, duodenum, jejunum and ileum. All doses resulted in a significant and dose-dependent increase in rectal temperature, in pronounced clinical signs and in distinct changes in haematological values. These included shivering, depression, respiratory distress, a leukopenia (0.1 μg/kg) or a leukocytosis (1 μg/kg) with a shift to the left, an accelerated sedimentation rate and a decreased packed cell volume. Doses of 1 and 10 μg/kg induced a transient inhibition of gastroduodenal electrical activity. These results suggest that, in the piglet, endotoxin primarily manifests general clinical signs and that the gastrointestinal effects coincide with these.


title: Candidemia in immunocompromised and immunocompetent critically ill patients: a prospective comparative study

text: The purpose of this study was to compare the risk factors, clinical manifestations, and outcome of candidemia in immunocompromised (IC) and nonimmunocompromised (NIC) critically ill patients. Data were collected prospectively over a 2-year period (02/2000–01/2002) from patients in a 25-bed, medical–surgical intensive care unit (ICU). Eligible for participation in this study were patients who developed candidemia during their ICU stay. Patients under antifungal therapy and with a confirmed systemic fungal infection prior to the diagnosis of candidemia were excluded. Cultures of blood, urine, and stool were performed for all patients in the study, and all patients underwent endoscopy/biopsy of the esophagus for detection of Candida. Smears and/or scrapings of oropharyngeal and esophageal lesions were examined for hyphae and/or pseudohyphae and were also cultured for yeasts. During the study period, 1,627 patients were hospitalized in the ICU, 57% for primary medical reasons and 43% for surgical reasons. After application of the study’s inclusion and exclusion criteria, 24 patients with candidemia (9 IC and 15 NIC) were analyzed. Total parenteral nutrition was more common in IC than in NIC patients (9/9 [100%] vs 8/15 [53%], p = 0.02). Oropharyngeal candidiasis was detected in 5 of 9 (55.5%) IC patients and in 1 of 15 (6.5%) NIC patients (p = 0.015). Esophageal candidiasis was also more common in IC than in NIC patients (4/9 [44%] vs 0/15 [0%], p = 0.012). Among the 9 IC patients, all except 2 died, resulting in a crude mortality of 78%; among the 15 NIC patients, 9 died, resulting in a crude mortality of 60% (p > 0.05). Autopsy was performed in two IC and in six NIC patients, with disseminated candidiasis found in one IC patient. Oropharyngeal and esophageal candidiasis are frequent in IC patients with candidemia. In contrast, this coexistence is rare in NIC critically ill patients with Candida bloodstream infections. A high mortality was noted in both IC and NIC critically ill patients with candidemia.


docid: kbstdktc

title: Interstitielle Lungenerkrankungen: Was muss der Hausarzt wissen?

text: Kurzatmigkeit, Atemnot, trockener Husten — bei diesen Symptomen sollten Sie auch eine interstitielle Lungenerkrankung in Betracht ziehen und abklären. Dies gilt insbesondere, wenn bei der Auskultation beidseitig basal Knisterrasseln zu hören ist.


title: Therapeutic uses of recombinant complement protein inhibitors

text: In conclusion, it is apparent that researchers are poised at the threshold of developing inhibitors of complement activation from the molecules in the RCA family. By creating soluble forms of these protective proteins for in vivo administration, or by making transgenic animals expressing these proteins or their derivatives, it may be possible to inhibit complement-mediated pathology stemming from autoimmune disease, reperfusion injuries, and physical trauma. This technology combined with current attempts to protect allografts from cellular rejection with monoclonal antibodies against members of the integrin family of adhesion molecules [52] makes it possible that the excessive mortality due to the severe shortage of human donor organs could be overcome by the use of xenografts.


title: Seasonal Human Influenza: Treatment Options

text: Seasonal influenza can be a self-limiting illness in healthy individuals but is associated with short-term morbidity and economic burden. Influenza can cause significant morbidity and mortality in young children, the elderly, pregnant and post-partum women, patients with co-morbidities and the immunocompromised. Neuraminidase inhibitors (NAIs) are the treatment of choice for influenza due to widespread resistance to the adamantanes. NAIs are efficacious for the treatment of influenza in ambulatory patients with mild illness, when initiated within 48 h of symptom onset. Early treatment with NAIs has been shown to reduce otitis media in children, and lower respiratory tract complications, resulting in antibiotic therapy, in adults. Evidence on the efficacy of NAIs for the prevention of influenza-related complications in at-risk populations, based on reviews of data from randomised trials is inconclusive. However, observational studies suggest that in hospitalised patients early treatment with NAIs has been associated with reduced mortality. NAIs should be initiated as soon as possible in patients at high-risk of influenza-related complications, with suspected or proven influenza, hospitalised patients and patients with severe or progressive disease. NAIs can be considered in previously healthy patients when therapy can be initiated within 48 h of symptom onset. In previously healthy patients, the therapeutic efficacy of oseltamivir is time-dependent, with maximal benefit observed when therapy is initiated within 48 h of symptom onset. However, several observational studies suggest therapeutic benefit beyond 48 h, in hospitalised patients, severe disease, and patients at high risk of complications, including pregnant women. NAIs should be considered in patients at high risk of influenza-related complications who present late. Further studies are needed to define the optimal timing of NAIs. Oseltamivir-resistant virus has been widely reported but is predominantly an issue in H1N1 seasonal influenza. Zanamivir-resistant influenza virus is rare, and inhaled or intravenous (IV) zanamivir is the treatment of choice in proven or suspected oseltamivir-resistant virus. Intubated patients with severe influenza can be treated with oseltamivir (suspension) administered via nasogastric tube. The commercial dry powder formulation of zanamivir should not be administered, via nebulisation, as it has been associated with ventilator malfunction and mortality. In intubated patients, when there are concerns about gastric absorption, IV zanamivir should be obtained under Emergency Investigational New Drug access schemes. Currently available evidence does not support the use of high-dose or extended-duration oseltamivir in patients with severe influenza, but does require further investigation. Extracorporeal membrane oxygenation has not been shown to be superior to conventional management in patients with influenza-associated acute respiratory distress syndrome and should be considered as salvage therapy. Corticosteriods should not be used in the treatment of severe influenza as this has been associated with increased risk of mortality and bacterial superinfection.


title: Development of oncolytic virotherapy: from genetic modification to combination therapy

text: Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.


docid: dyxjpqfe

title: Score to identify the severity of adult patients with influenza A (H1N1) 2009 virus infection at hospital admission

text: The objective of this paper was to develop a prognostic index for severe complications among hospitalized patients with influenza A (H1N1) 2009 virus infection. We conducted a prospective observational cohort study of 618 inpatients with 2009 H1N1 virus infection admitted to 36 Spanish hospitals between July 2009 and February 2010. Risk factors evaluated included host-related factors and clinical data at admission. We developed a composite index of severe in-hospital complications (SIHC), which included: mortality, mechanical ventilation, septic shock, acute respiratory distress syndrome, and requirement for resuscitation maneuvers. Six factors were independently associated with SIHC: age >45 years, male sex, number of comorbidities, pneumonia, dyspnea, and confusion. From the β parameter obtained in the multivariate model, a weight was assigned to each factor to compute the individual influenza risk score. The score shows an area under the receiver operating characteristic (ROC) curve of 0.77. The SIHC rate was 1.9 % in the low-risk group, 10.3 % in the intermediate-risk group, and 29.6 % in the high-risk group. The odds ratio for complications was 21.8 for the high-risk group compared with the low-risk group. This easy-to-score influenza A (H1N1) 2009 virus infection risk index accurately stratifies patients hospitalized for H1N1 virus infection into low-, intermediate-, and high-risk groups for SIHC.


title: Free radicals, oxidative stress, and antioxidants in human health and disease

text: Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body. Free-radical mechanisms have been implicated in the pathology of several human diseases, including cancer, atherosclerosis, malaria, and rheumatoid arthritis and neurodegenerative diseases. For example, the superoxide radical (O(2)(·−)) and hydrogen peroxide (H(2)O(2)) are known to be generated in the brain and nervous system in vivo, and several areas of the human brain are rich in iron, which appears to be easily mobilizable in a form that can stimulate free-radical reactions. Antioxidant defenses to remove O(2)(·−) and H(2)O(2) exist. Superoxide dismutases (SOD) remove O(2)(·−) by greatly accelerating its conversion to H(2)O(2). Catalases in peroxisomes convert H(2)O(2) into water and O(2) and help to dispose of H(2)O(2) generated by the action of the oxidase enzymes that are located in these organelles. Other important H(2)O(2)-removing enzymes in human cells are the glutathione peroxidases. When produced in excess, ROS can cause tissue injury. However, tissue injury can itself cause ROS generation (e.g., by causing activation of phagocytes or releasing transition metal ions from damaged cells), which may (or may not, depending on the situation) contribute to a worsening of the injury. Assessment of oxidative damage to biomolecules by means of emerging technologies based on products of oxidative damage to DNA (e.g., 8-hydroxydeoxyguanosine), lipids (e.g., isoprostanes), and proteins (altered amino acids) would not only advance our understanding of the underlying mechanisms but also facilitate supplementation and intervention studies designed and conducted to test antioxidant efficacy in human health and disease.


title: Influenza A/pandemic 2009/H1N1 in the setting of allogeneic hematopoietic cell transplantation: a potentially catastrophic problem in a vulnerable population

text: We describe Influenza A/pandemic 2009/H1N1 in two allogeneic hematopoietic cell transplantation recipients. The main presentation in both cases consisted of flu-like symptoms manifesting as, fever, arthralgias and myalgias. The virus was isolated in one case from a throat swab and in another case following a bronchoalveolar lavage. Both patients received oseltamivir at a dose of 75 mg orally twice day. The dose of oseltamivir was increased to 150 mg twice per day due to the lack of improvement or progression of symptoms. In one case, clinical symptoms resolved without sequelae. In the second case, pulmonary symptomatology continued to deteriorate, despite aggressive polymicrobial treatment, requiring mechanical ventilation and ultimately the patient died from respiratory failure. These cases highlight the potentially serious effect of the ongoing Influenza A/pandemic 2009/H1N1 pandemic in this very vulnerable population and the urgent need to establish emergency preparedness strategies by oncology and bone marrow transplantation staff to face this serious healthcare challenge.


Abstracts of the 36th annual meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforchung) Heidelburg, 9–12 February 1992


title: Saturated Five-Membered Thiazolidines and Their Derivatives: From Synthesis to Biological Applications

text: In past decades, interdisciplinary research has been of great interest for scholars. Thiazolidine motifs behave as a bridge between organic synthesis and medicinal chemistry and compel researchers to explore new drug candidates. Thiazolidine motifs are very intriguing heterocyclic five-membered moieties present in diverse natural and bioactive compounds having sulfur at the first position and nitrogen at the third position. The presence of sulfur enhances their pharmacological properties, and, therefore, they are used as vehicles in the synthesis of valuable organic combinations. They show varied biological properties viz. anticancer, anticonvulsant, antimicrobial, anti-inflammatory, neuroprotective, antioxidant activity and so on. This diversity in the biological response makes it a highly prized moiety. Based on literature studies, various synthetic approaches like multicomponent reaction, click reaction, nano-catalysis and green chemistry have been employed to improve their selectivity, purity, product yield and pharmacokinetic activity. In this review article, we have summarized systematic approaches for the synthesis of thiazolidine and its derivatives, along with their pharmacological activity, including advantages of green synthesis, atom economy, cleaner reaction profile and catalyst recovery which will help scientists to probe and stimulate the study of these scaffolds.