title: Role of endothelial cell survival and death signals in angiogenesis

text: Angiogenesis, the process of new microvessel development, is encountered in a select number of physiological processes and is central to the pathogenesis of a wide variety of diseases. There is now convincing evidence that regulated patterns of endothelial cell survival and death, a process known as apoptosis, play a central role in the periodic remodeling of the vasculature, and in the timely evolution and regression of angiogenic responses. In this review we discuss the current evidence suggesting a role for inducers and inhibitors of angiogenesis as well as other mediators that modify endothelial cells functions in the survival and death of endothelial cells. We also discuss how dysregulation of apoptosis can lead to aberrant angiogenesis as demonstrated in the pathogenesis of retinopathy of prematurity and cancer.


Paradoxical worsening in tuberculosis during therapy in an HIV-infected patient


title: Renal polyamine excretion, tubular amino acid reabsorption and molecular genetics in cystinuria

text: Cystinuria is an autosomal recessive disorder of the tubular and intestinal resorption of cystine, ornithine, lysine and arginine leading to nephrolithiasis. Three cystinuria types can be distinguished by the mode of inheritance (true recessive or intermediate) and by the pattern of the intestinal amino acid transport. In the present study phenotypes were assessed by the urinary excretion of amino acids related to creatinine, the percentage tubular amino acid reabsorption and the urinary excretion of polyamines as a possible indicator of the intestinal transport defect. However, our thorough phenotyping did not reveal more than two cystinuria types. Genotypes were examined in linkage analyses and single-strand conformation polymorphism-based mutation identification. The SLC3A1 mutations M467T and T216M were disease causing in our homozygous patients of type I cystinuria. We can show the association of type I cystinuria with SLC3A1 and of non-type I cystinuria with a yet unidentified gene on chromosome 19q13.1. Our phenotype and genotype analyses provide evidence for only two types of cystinuria in the investigated patient cohort.


title: Selectin Antagonists: Therapeutic Potential in Asthma and COPD

text: Asthma and COPD are chronic inflammatory conditions that affect hundreds of millions of patients worldwide. New therapeutics are desperately needed, especially those that target the underlying causes and prevent disease progression. Although asthma and COPD have distinct etiologies, both are associated with reduced airflow caused by excess infiltration of inflammatory cells into healthy lung tissues. As selectin-mediated adhesion of leukocytes to the vascular endothelium is a key early event in the initiation of the inflammatory response, selectin inhibition is thought to be a good target for therapeutic intervention. Three known selectins are expressed in distinct subsets of cells: P-selectin is presented on the surface of activated platelets and endothelial cells, L-selectin is constitutively expressed on leukocytes, and E-selectin synthesis is upregulated in activated endothelial cells. They mediate cell-cell adhesion in the shear flow of the bloodstream via specialized interactions with clusters of oligosaccharides presented on cell surface glycopeptide ligands. The role of selectin-ligand interactions in the inflammatory response has been demonstrated in various animal models, prompting considerable attention from the pharmaceutical industry. Drug discovery efforts have yielded many different classes of selectin inhibitors, including soluble protein ligands, antibodies, oligosaccharides and small molecules. Although many selectin inhibitors have shown activity in preclinical models, clinical progress of selectin-directed therapies has been slow. Early approaches employed carbohydrate-based inhibitors to mimic the natural ligand sialyl Lewis X; however, these compounds proved challenging to develop. Cytel’s CY 1503, a complex oligosaccharide, progressed to phase II/III trials for reperfusion injury, but further development was halted when it failed to demonstrate clinical efficacy. Two protein-based selectin inhibitors have reached phase II development. These included Wyeth’s recombinant soluble P-selectin ligand, TSI (PSGL-1), which was discontinued after disappointing results in myocardial infarction trials and Protein Design Labs’ humanized anti-L-selectin monoclonal antibody, which is currently in development for trauma. Bimosiamose, discovered by Encysive Pharmaceutical and presently being developed by Revotar Biopharmaceuticals, is an 863 g/mol molecular weight dimer with minimal carbohydrate content and is, to date, the leading selectin inhibitor in clinical development. This compound has shown promise in a phase Ha ‘proof of concept’ trial in patients with asthma, reducing airway recruitment of eosinophils after intravenous administration. Further clinical development of an inhaled formulation is underway. Despite a significant need for new therapeutics, selectin inhibitors have not yet been explored for the treatment of COPD. Bimosiamose represents an important proof of principle, and hopefully continued success will spark renewed interest in selectin-directed therapeutics for respiratory diseases.


title: Effects of mechanical ventilation with different tidal volume on oxidative stress and antioxidant in lung

text: PURPOSE: The aim of this study was to investigate the changes in oxidative stress and antioxidants in lung tissue under different tidal volume ventilation conditions. METHODS: Forty-eight male Wistar rats were randomized into four groups, namely, group C, the control group, which was not ventilated, and groups C1, C2 and C3, the treatment groups, which were ventilated for 2 h with tidal volumes of 8, 30 and 42 ml/kg, respectively. The right middle lobe was assayed for malondialdehyde (MDA), the right posterior lobe was assayed using Western blotting for Nrf2, GCLm and SrX1 and the left lobe was assayed for Nrf2, GCLm and SrX1 mRNA. RESULTS: The MDA levels were increased in the three treatment groups, with MDA levels highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). The mRNA expression of Nrf2, GCLm and SrX1 was highest in group C3 and lowest in group 1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). A Western blot analysis showed that Nrf2, GCLm and SrX1 expression was highest in group C3 and lowest in group C1 (C3 > C2 > C1) (all P < 0.05). No significant difference was observed between group C1 and group C (P > 0.05). CONCLUSIONS: Oxidative stress and antioxidant enzyme levels in the lungs of rats were positively associated with the tidal volumes of mechanical ventilation, suggesting that higher tidal volumes cause more severe oxidative stress and increased antioxidant responses.


6th Congress of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung): Kiel, February 21–24, 1990


title: Persistence of human parvovirus B19 in tissues from adult individuals: a comparison with serostatus and its clinical utility

text: Human parvovirus B19 (PVB19) is linked to variety of diseases, including erythema infectiosum, transient aplastic crisis, fetal hydrops, cardiomyopathy and, recently, hepatitis and arthritis. Persistence of PVB19 in asymptomatic individuals has been reported in skin, synovium, myocardium and bone marrow. A higher level of PVB19 DNA has been observed in various tissues from cases of disease than in controls. Simultaneously, equal detection of PVB19 DNA has been shown in both cases and controls. Thus, it has become fundamental to study PVB19 DNA persistence in tissues that are unaffected by disease. This will help to better understand PVB19 DNA persistence in symptomatic and asymptomatic individuals and its possible pathogenic role in various diseases. A total of 70 adult autopsies were included and divided into seropositive (SP) and seronegative (SN) groups based on PVB19 IgG. Nested PCR for PVB19 DNA was carried out in myocardium, liver, kidney, and bone marrow. Of the 70 patients, 60 % belonged to the SP group and 40 % to the SN group. Seropositivity ranged from 50 % in the 12 to 20 year old group to 66.7 % in the 61 to 80 year old group. The viral genome was detected in 34.3 % of myocardium, 20 % of bone marrow, 10 % of kidney and 8.6 % of liver samples. There was no significant difference in the persistence rates between the SP and SN groups. The persistence of PVB19 DNA in various tissues ranged from 8.3 % to 36 % in the SP group and 10 % to 30 % in the SN group. The persistence of PVB19 DNA in all the tissues was low, and PVB19 serostatus had no influence on the persistence of PVB19 DNA.


title: Der potentielle Organspender – Evaluierung unter besonderer Berücksichtigung der Herzentnahme

text: Regarding limited availability of organ donors for heart transplantation, it is necessary to discuss optimal donor evaluation and donor management. In this manuscript general donor-related parameters as well as heart-specific parameters are discussed regarding international literature. In addition, "marginal" donors and in contrast "optimal" donors are defined. Donor management including optimal hemodynamic management and additional specific intensive care aspects are presented. Exact donor evaluation allows for matching the organ to the most suitable recipient and is therefore especially in the context of marginal donors a crucial step within transplantation process.


title: Studying neuroprotective effect of Atorvastatin as a small molecule drug on high glucose-induced neurotoxicity in undifferentiated PC12 cells: role of NADPH oxidase

text: Overproduction of reactive oxygen species (ROS) by NADPH oxidase (NOX) activation has been considered the essential mechanism induced by hyperglycemia in various tissues. However, there is no comprehensive study on the role of NOXs in high glucose (HG)-induced toxic effect in neural tissues. Recently, a therapeutic strategy in oxidative related pathologies has been introduced by blocking the undesirable actions of NOX enzymes by small molecules. The protective roles of Statins in ameliorating oxidative stress by NOX inhibition have been shown in some tissues except neural. We hypothesized then, that different NOXs may have role in HG-induced neural cell injury. Furthermore, we postulate that Atorvastatin as a small molecule may modulate this NOXs activity to protect neural cells. Undifferentiated PC12 cells were treated with HG (140 mM/24 h) in the presence and absence of Atorvastatin (1 μM/96 h). The cell viability was measured by MTT assay and the gene and protein expressions profile of NOX (1–4) were determined by RT-PCR and western blotting, respectively. Levels of ROS and malondialdehyde (MDA) were also evaluated. Gene and protein expression levels of NOX (1–4) and consequently ROS and MDA levels were elevated in HG-treated PC12 cells. Atorvastatin could significantly decrease HG-induced NOXs, ROS and MDA elevation and improve impaired cell viability. It can be concluded that HG could elevate NOXs activity, ROS and MDA levels in neural tissues and Atorvastatin as a small molecule NOX inhibitor drug may prevent and delay diabetic complications, particularly neuropathy.


title: New Cancer Therapies: Implications for the Perioperative Period

text: PURPOSE OF REVIEW: Cancer is on the rise. Standing on verge of exciting discoveries, research is being translated into therapies that are being widely administered to patients. Providing a hope for cure, where none existed before. This new body of knowledge has come from a better understanding of cancer genetics, molecular and sub molecular behavior, and understanding of cancer-generated cellular environments. These have led to development of immunotherapy and its many sub-genres, improvement and introduction of new radiation technologies, and decreasing toxicities of existing chemotherapies. RECENT FINDINGS: The purpose of this review is to have a summary look at this huge landscape of cancer therapy. Specially looking at toxicities that an anesthesiologist should be familiar with while providing perioperative care for these patients, complications like tumor lysis syndrome, cytokine release syndromes, Kounis syndrome, myocarditis, encephalopathies, and pituitary failure need to be kept in mind. SUMMARY: One should be knowledgeable about these therapies and approach these patients with a high index of suspicion. Anesthesiologists will need to refine preoperative assessment with appropriate testing and intraoperative and postoperative management in collaboration with oncologists, while involving the expertise of internists, cardiologist, and endocrinologists in helping assess and manage these patients in the perioperative period.


title: Increased serum catalase activity in rats subjected to thermal skin injury

text: We found that: rats subjected to thermal skin injury (burn) had increased serum hydrogen peroxide (H(2)O(2)) scavenging activity, serum catalase activity, erythrocyte (RBC) fragility, and edematous lung injury (lung leak) when compared to sham-treated rats. Serum H(2)O(2) scavenging activity was inhibited by addition of sodium azide, a catalase inhibitor. Treatment of rats with the oxygen radical scavenger, dimethylthiourea (DMTU), decreased RBC fragility and lung leak but did not alter increased H(2)O(2) scavenging or catalase activity of serum from rats subjected to skin burn. We conclude that increased serum catalase activity is a consequence of thermal skin injury and that increased serum catalase activity may be a mechanism that modulates H(2)O(2)-dependcnt processes following skin burn.


title: Leptospirosis-associated catastrophic respiratory failure supported by extracorporeal membrane oxygenation

text: A previously healthy, 39-year-old obese farmer, arrived hypotensive and tachycardic, with fever, myalgia, headache, abdominal pain, diarrhea, and progressive dyspnea. Ten days before symptoms onset, he was in direct contact with mice and working in a contaminated drain. Patient laboratory showed acute kidney injury and thrombocytopenia. Chest X-ray exhibited bilateral diffuse interstitial infiltrates. First-line empirical antibiotics were started and influenza discarded. Patient evolved with severe respiratory failure, associated with hemoptysis, and rapidly severe hemodynamic compromise. Despite neuromuscular blockade and prone positioning, respiratory failure increased. Accordingly, veno-venous ECMO was initiated, with bilateral femoral extraction and jugular return. After ECMO connection, there was no significant improvement in oxygenation, and low pre-membrane saturations and low arterial PaO(2) of the membrane showed that we were out of the limits of the rated flow. Thus, a second membrane oxygenator was installed in parallel. Afterward, oxygenation improved, with subsequent perfusion enhancement. Regarding etiology, due to high suspicion index, Leptospira serology was performed, coming back positive and meropenem was maintained. The patient ultimately recovered and experience excellent outcome. The clinical relevance of the case is the scared evidence of leptospirosis-associated severe respiratory failure treated with ECMO. This experience emphasizes the importance of an optimal support, which requires enough membrane surface and flow for an obese, highly hyperdynamic patient, during this reversible disease. A high index of suspicion is needed for an adequate diagnosis of leptospirosis to implement the correct treatment, particularly in the association of respiratory failure, pulmonary hemorrhage, and an epidemiological-related context.


title: Plasma Surfactant Protein-B Is Elevated in Infants with Respiratory Syncytial Virus-Induced Bronchiolitis

text: Respiratory syncytial virus (RSV) is the most frequent cause of bronchiolitis. However the pathophysiology of bronchiolitis is unclear. Leukocytes, especially neutrophils, may play an important role in the pathogenesis of bronchiolitis. Whereas we have previously shown that neutrophils augment epithelial leakage and detachment in RSV infection in vitro, it is unknown whether epithelial damage occurs in vivo in infants with RSV bronchiolitis. We hypothesized that respiratory epithelial damage occurs in infants with RSV bronchiolitis and that surfactant proteins leak into the circulation. The plasma concentrations of surfactant protein-A and surfactant protein-B in infants with RSV bronchiolitis were measured by ELISA. Plasma immunoreactive surfactant protein-B in infants with RSV bronchiolitis was markedly higher than that in matching controls. Our study suggests that alveolocapillary permeability is increased in infants with RSV bronchiolitis in vivo and that surfactant protein-B may be a sensitive marker for lung injury in such infants.


title: The role of bronchoalveolar lavage in the diagnosis of bacterial pneumonia

text: Bronchoalveolar lavage (BAL) has become an invaluable diagnostic tool with important clinical implications in both opportunistic infections and the pulmonary pathology of immunologic disease. Until recently, the use of BAL was limited primarily to two areas: the study of interstitial lung diseases and the diagnosis of lung infections by opportunistic microorganisms in severely immunocompromised patients with lung infiltrates. Over the past decade, the use of BAL has been expanded to include the conventional diagnosis of bacterial pneumonia in non-immunocompromised patients. In the past, different clinical studies proposed using BAL to quantify cultures in the sample obtained as a means of increasing the tool's effectiveness. Recent developments have led to a number of newer applications of BAL, such as bronchoscopic BAL, non-bronchoscopic BAL and protected BAL. The most important use of BAL in the non-immunocompromised patient is the diagnosis of pneumonia in the mechanically ventilated patient.


title: Aktueller Stand der Lungentransplantation: Pulmonale und nichtpulmonale Komplikationen

text: Lung transplantation is an established therapeutic option for selected patients with various end stage pulmonary diseases which prolongs survival and improves quality of life. A multitude of pulmonary and non-pulmonary complications can lead to significant morbidity thus impairing short and long-term survival. Early recognition and fast treatment of these complications are fundamental measures to prevent secondary destructive incidents. This article reviews the most frequent complications arising after lung transplantation.


title: Is a single set of negative blood cultures sufficient to ensure clearance of bloodstream infection in patients with Staphylococcus aureus bacteremia? The skip phenomenon

text: BACKGROUND: The most recent version of the Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus infections states that a single set of negative blood cultures is sufficient to demonstrate clearance of bacteremia. However, S. aureus might exhibit fluctuating blood culture positivity, labeled as “the skip phenomenon”. Our objectives were to determine the prevalence of the skip phenomenon in a cohort of hospitalized patients with S. aureus bacteremia and to determine the associated clinical variables. METHODS: We conducted a nested case–control study, using a previous cohort of 757 adult inpatients between July 2006 and June 2011 with ≥ 3 days of S. aureus bacteremia. Each case of S. aureus bacteremia with the skip phenomenon was matched to 2 to 4 controls based on age, gender, and duration of bacteremia. The association of clinical characteristics with the skip phenomenon was analyzed via conditional logistic regression. RESULTS: Of the 757 patients in the cohort, 29 (4%) had the skip phenomenon. 26 (90%) patients in the cases group were male. The median age was 69.4 years (interquartile range [IQR] 58.7 to 80.3). Although an attempt to match for the duration of bacteremia was done, there was a statistically longer duration in patients with cases as compared to that in controls (median [IQR], 10 [7–12] days, vs 8 [6–10] days; P = 0.015). Accordingly, duration of bacteremia was adjusted for in regression models. Notably, 26 (90%) patients in the case group were receiving chronic immunosuppressive therapy, as compared to 69 (79%) patients in the control group (P = 0.427). CONCLUSION: Our findings prompt consideration of a practice chance to obtain serial negative blood cultures to ensure clearance of bacteremia among patients with S. aureus bacteremia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-019-01339-w) contains supplementary material, which is available to authorized users.


title: Serum Surfactant Protein D (SP-D) is a Prognostic Marker of Poor Outcome in Patients with A/H1N1 Virus Infection

text: INTRODUCTION: Surfactant protein D (SP-D) plays an important role in the innate responses against pathogens and its production is altered in lung disorders. METHODS: We studied the circulating levels of SP-D in 37 patients with acute respiratory distress syndrome due to the A/H1N1 virus infection and in 40 healthy controls. Cox logistic regression models were constructed to explore the association of SP-D levels and risk of death. RESULTS: Mortality rate after a 28-day was 32.42 %. Significant higher levels of SP-D were detected in A/H1N1 patients with fatal outcome (p < 0.05). After adjusting for confounding variables, levels of SP-D ≥250 ng/mL were associated with increased the risk of death (HR = 8.27, 95 % CI 1.1–64.1, p = 0.043). CONCLUSIONS: Our results revealed that higher circulating levels of SP-D are associated with higher mortality risk in critically ill A/H1N1 patients. SP-D might be a predictive factor of poor outcomes in viral pneumonia.


title: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) with CD30-positive lymphocyte-predominant (LP) cells

text: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a distinct neoplasm within the spectrum of Hodgkin lymphomas with characteristic clinical, morphological, and immunohistochemical features. According to the WHO definition, lymph nodes involved by NLPHL should have a nodular or nodular and diffuse proliferation of scattered large neoplastic lymphocyte-predominant (LP) cells in a small cell background that reside in expanded follicular dendritic cell meshworks; the LP cells must also have a distinct immunophenotypic profile. The LP cells are monoclonal B cells that are typically CD20, BCL6, CD79a, and CD45 positive and are CD30 and CD15 negative. In contrast, the Reed-Sternberg cells of classical Hodgkin lymphoma (CHL) are typically positive for CD15 and CD30. However, in CHL, CD20 staining is variable, and CD15 staining may be absent in some cases. Thus, CD30 is often considered to be the most distinctive marker between CHL and NLPHL. In order to better assess CD30 staining in NLPHL, we reviewed 220 cases of NLPHL and found 21 cases that showed at least focal staining of the neoplastic cells for CD30. The CD30 staining was often faint, but occasionally strong, and typically was found only on a subset of the LP cells. We evaluated the clinicopathologic features of these cases to determine whether they showed differences from typical CD30-negative NLPHL and found no significant difference with respect to clinical presentation, histology, other immunophenotypic features or outcome. In summary, we conclude that CD30 expression by LP cells in NLPHL can be seen and should not lead to a misdiagnosis of CHL. The presence of CD30-positive LP cells is not associated with other features of CHL or unusually aggressive behavior.


title: Genetic polymorphisms of the lymphotoxin alpha gene are associated with increased risk for lethal infections during induction therapy for childhood acute leukemia: a case-control study

text: Specific mutations of the TNF-alpha (TNF-α) and Lymphotoxin-alpha (LT-α) genes are correlated to the outcome of patients during serious infections. This study aimed at correlating these polymorphisms to lethal infections during childhood acute lymphoblastic leukemia (ALL). A matched case-control study of 34 patients who died due to infections during ALL treatment and 68 ALL patients without lethal infections was performed. Genomic DNA was isolated from blood smears and specific fragments including the polymorphic site of each gene were amplified. In the total study population, 23/102 (22.5%) of the children carried at least two variant alleles (high-producer haplotype). The variant genotypes were equally distributed between cases and controls [relative risk (RR) 1.17 (CI 0.33–2.22, P = 0.752)]. With regard to infective organisms, no statistically significant differences could be detected between the groups for bacterial infections [RR 1.59 (CI 0.56–4.50), P 0.379]. Patients with a LT-α (10.5 kb/5.5 kb; 5.5 kb/5.5 kb) haplotype, however, seemed to have a significant higher risk of attracting a lethal infection during induction/consolidation chemotherapy (RR 2.98, CI 0.98–9.01, P = 0.05). These results support a role of specific genetic polymorphisms on lethal infections during induction chemotherapy of ALL treatment.


title: Dengue Shock Syndrome with Two Atypical Complications

text: The authors present 2 cases of dengue shock syndrome with unusual complications. In the first case, a 14-y-old boy with dengue shock syndrome who required aggressive fluid resuscitation, developed abdominal compartment syndrome (ACS). Patient developed severe shock, increased ventilator requirement and oliguria as a consequence of ACS. Patient responded well to abdominal paracentesis draining 2.7 l of fluid and made rapid recovery. In the second case, 8-y-old girl was treated for dengue shock syndrome, including mechanical ventilation for ARDS. In the second wk of illness, she developed severe neurological manifestations including frequent episodes of convulsions, hallucinations and altered sensorium. She was diagnosed to have acute demyelinating encephalomyelitis from CT brain findings. She responded well to pulse steroid therapy with complete neurological recovery.


Management of respiratory failure


title: Pulmonary technetium-99m diethylene triamine penta-acetic acid aerosol clearance as an index of lung injury

text: Although the clearance of an inhaled nebulised radioaerosol has long been employed as a measure of lung function, this test has not found favour in nuclear medicine units to the extent that might originally have been anticipated. In this review the theoretical basis of solute transfer is considered and the measurement of radioaerosol clearance discussed. Thereafter the various clinical applications of alveolar permeability measurement are outlined. Finally, possible reasons for the restricted clinical use of the diethylene triamine penta-acetic acid clearance technique are considered. It is concluded that the technique should provide a rapid screening evaluation of the HIV+ve patient presenting predominantly with chest symptoms.


title: -572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease

text: Single nucleotide polymorphisms (SNPs) of interleukin (IL)-6 are associated with the development of chronic renal disease (CRD). Their impact for sepsis in the field of CRD was investigated. One control cohort of 115 patients with CRD without infection and another case cohort of 198 patients with CRD and sepsis were enrolled. Genotyping at the −174 (rs1800795) and −572 positions of IL-6 (rs1800796) was done by restriction fragment length polymorphism. Circulating IL-6 was measured by an enzyme immunoassay. The GG genotype of rs1800796 was more frequent among cases (78.3 %) than controls (62.6 %). No difference in the genotype frequencies of rs1800795 between cases and controls were found. Odds ratio for sepsis was 2.07 (95%CI 1.24–3.44, p = 0.005) with the GG genotype of rs1800796, which was confirmed by logistic regression analysis taking into consideration the presence of chronic comorbidities. All-cause mortality until day 28 was similar between patients with the GG genotype and the GC/CC genotypes of rs1800796, but death caused from cardiovascular events not-related with infection was more frequent with the GG genotype (14.6 % vs 2.4 %, p = 0.031). Circulating IL-6 was greater among patients of the GC/CC genotypes of rs1800796 and multiple organ dysfunction (p = 0.013). The GG genotype of rs1800796 predisposes to sepsis in CRD and to 28-day mortality by sepsis-unrelated cardiovascular phenomena.


title: Respiratory infections: Community-acquired pneumonia and newer microbes

text: Respiratory infections, especially community-acquired forms of pneumonia (CAP), are challenging for clinicians because (1) a causative microorganism can only be found in about 50% of cases; (2) initial therapy, therefore, must be based on a probable or most likely etiology in the context of the patient's overall medical condition; and (3) new microbes or those considered previously as normal flora or less virulent forms seem responsible for some cases. It is important to be acquainted with new causes of infection which include Legionella species, Chlamydia pneumoniae, diphtheroids in certain instances (Corynebacterium pseudodiphtheriticum), and viruses such as the Hanta strains. Infections with Bordetella pertussis are increasing. However, the ever present and most common cause of CAP, Streptococcus pneumoniae, continues to present problems because of increasing antibiotic resistance, the high case fatality rate when bacteremia accompanies pneumonia, and the inability to give prophylactic immunization to all people with risk factors for this infection.


title: Prevention and management of oral infections in cancer patients

text: The successful prevention and management of oral infections and infections from the oral cavity in cancer patients are based on identification of risk patients, selection of patients for prophylactic measures, diagnosis of infection and implementation of directed or empiric antimicrobial therapy. Identification of patients at risk for infection is based on each patient's type of oral microbial colonization and the presence of latent viral infections. Systemic and local resistance to infection will be decisive, and in many patients the risk can be estimated from the expected myelosuppressive effect of anticancer treatment. Diagnosis of infection is often based on clinical findings together with the results of microbiological investigations. Biopsies could be useful, but can seldom be obtained. Blood samples are mandatory for isolation of microorganisms involved in systemic infections in myelosuppressed patients. Prevention of infection requires both local and systemic measures. Elimination of the risk of a breach in the first line of defence is urgent, and the maintenance of mucosal integrity is important. Monitoring microbial colonization is common, as is the institution of antiviral prophylaxis in patients with increased anti-HSV IgG (ELISA >10 000). Antifungal prophylaxis, to avoid colonization and superinfection, should be instituted in patients with low neutrophil counts. Gastrointestinal prophylaxis with quinolones is also commonly used in these patient groups. Treatment of oral infections in cancer patients should include systemic antimicrobial agents in most cases. Special attention should be directed to oral infections in neutropenic (<0.5×l0(9)/l) patients in whom oral microorganisms are the leading cause of bacteraemia. Invasive fungal infections of the oral cavity can be associated with systemic fungal infection and are indications for the use of liposomal amphotericin B.


title: Liposomen-mediierter Gentransfer — die zukünftige Therapieform bei Sepsis und intraabdomineller Infektion?

text: Background: It is now generally accepted that over-production of pro-inflammatory cytokines (TNF-α, IL-1β) produced by inflammatory cells contributes to the pathological consequences of septic shock. Neutralizing this exaggerated immune response by monoclonal antibodies (anti-TNF-α), receptor antagonists (IL-1rα) and anti-inflammatory cytokines (IL-10) did not result in a better outcome in septic patients. Firstly, this is due to the short biological half-lives of these natural antagonists or inhibitors of pro-inflammatory cytokines. Secondly, exaggerated pro-inflammatory cytokine production may contribute to pathology in one body compartment while, simultaneously, the same mediators may have beneficial effects in another compartment. Thus, systemic administration of cytokine inhibitors at levels sufficient to neutralize exaggerated cytokine production in one organ may also block the presumably beneficial aspects of cytokine production in another. Methods: Our own results of animal experiments of the liposome mediated gene transfer are presented. Results: Liposome mediated gene transfer seems to be a promising low-risk alternative to systemic anti-inflammatory therapies as it ensures the local delivery of high doses of cytokine inhibitors and antagonists over a prolonged period of time. Conclusions: The pathophysiological mechanism of sepsis and septic shock are well established. The concept of local intervention or compartimental blockade of overwhelming mediator production by gene transfer will be a new challenge in the future.


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title: Übersicht Über neue ernährungswissenschaftliche Publikationen


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title: Management of complications in surgery of the colon

text: BACKGROUND: General surgeons are frequently confronted with colorectal diseases in their daily practice, whereby colorectal cancer is the second most common malignant tumour, with almost 5000 new cases every year in Austria. The incidence of benign colon disorders requiring surgery (e.g. colon polyps, sigmoid diverticulitis) is also increasing. The first aim in colon surgery should be to avoid complications and if they occur to treat them properly. METHODS: We basically distinguish between general and special complications. As general complications, prevention of malnutrition and support of the immune system should receive special attention. As the number of elderly patients increases, so does the risk not only of thrombembolic complications but also of critical cardiocirculatory situations, and renal and hepatic failure. Special complications depend either on the type of surgery (laparoscopic assisted, conventional open surgery) or the techniques employed (stapled, hand sutured). Handling of the tissue also plays a major role (e.g. dry versus wet pads). RESULTS: Shortening of the postoperative stay decreases both hospital costs and the incidence of infections, meaning that minimally invasive surgery and postoperative "fast track nutrition" should be promoted. Emergency operations should be avoided (e.g. bridging through colonic stents), as morbidity and mortality are clearly increased in comparison to (semi-) elective operations. During the operation itself, new equipment and techniques (such as Ultracision(®), Ligasure(®)) as well as a well coordinated team help to reduce complications and duration of surgery. CONCLUSIONS: To avoid is better than to repair. If complications do occur, appropriate surgical and intensive – care measures should be taken immediately.


Ultrastructural characterization of avian influenza A (H7N9) virus infecting humans in China


title: Infections and immunological hazards of allogeneic bone transplantation

text: Allogeneic transplantation of human cancellous and cortical bone is a controversially discussed concept in trauma and orthopaedic surgery. Biological and immunological arguments support transplantation of autologous material whenever this is technically possible. On the other hand, synthetic alloplastic materials for bone substitution are available free of immunological and hygienic hazards. In this context the value of allogeneic bone grafts is discussed, especially considering the problem of AIDS. If autologous corticospongious bone is to be used its supply is limited. On the other hand, alloplastic synthetic artificial bone does not meet all the requirements demanded for substitution of large osseous defects up to now. The problems of geometric and mechanical stability of these alloplastic materials still remain. Therefore, no alternative to allografting of large, stable, corticospongious fragments exists in some cases. Bone transplantation is performed without vital indication in nearly every case. Thus an optimum of hygienic security has to be claimed for recipients of allogeneic bone. The “Munich model” for bone transplantation is presented and discussed.


title: What treating Ebola means for pandemic influenza

text: Almost all new treatments being developed for the next influenza pandemic target the virus. During the Ebola crisis in West Africa, patients were treated with an inexpensive generic statin/angiotensin receptor blocker combination that appeared to greatly improve survival. These drugs target the host response, not the virus, and probably reverse endothelial dysfunction. Scientists and health officials have shown little interest in this idea. Yet, during the early months of the next pandemic, vaccines will be unavailable and treatment options will be limited. Physicians should be prepared to undertake clinical trials of widely available generic drugs to determine whether they improve survival in patients with seasonal influenza, other emerging virus diseases, and other forms of acute critical illness. Public health officials should give these studies their strong support. If successful, they will suggest a ‘bottom up’ approach to patient care that could be implemented worldwide on the first pandemic day.


title: Non-atopic IgE and eosinophil cationic protein after allogeneic hematopoietic stem cell transplantation in children

text: Allogeneic hematopoietic stem cell transplantation (HSCT) in childhood is associated with severe pulmonary complications, but the pathophysiologic mechanisms remain unclear. Our aim was to evaluate the association of total and specific IgE, eosinophil cationic protein (ECP) and eosinophilia in HSCT recipients with pulmonary complications. We prospectively measured total and specific serum IgE, eosinophils, and ECP before and 28, 100, and 180 days after HSCT. We included 30 children (age 2–17 years) undergoing HSCT. Nine patients had a history of previous atopy without being associated with pulmonary complications after HSCT until day +360. Specific IgE levels showed a decline after HSCT, associated with the absence of allergy symptoms, suggesting a reduction of atopy. Elevated total serum IgE levels occurred in seven patients on day +28 after HSCT. This elevation did not coincide with allergy symptoms. ECP showed no correlation with total allergy symptoms, eosinophilia, IgE levels, or pulmonary complications. There was a significant correlation (p = 0.0367) between ECP levels on day +28 and concurrent acute graft-versus-host disease (GvHD). Non-atopic serum ECP and IgE levels are elevated on day +28 after HSCT in children, with ECP showing a potential relation to acute GvHD.


title: Characteristics of pulmonary complications in non-Hodgkin’s lymphoma patients treated with rituximab-containing chemotherapy and impact on survival

text: Patients with non-Hodgkin’s lymphoma (NHL) receiving rituximab-containing chemotherapy are at risk of developing respiratory complications, but comprehensive information on these complications and their impact on survival is lacking. We performed a retrospective cohort analysis on 123 NHL patients who received rituximab-containing chemotherapy between 2009 and 2016 in order to describe the incidence, etiologies and effect on survival of respiratory complications defined by new or worsening respiratory symptoms requiring diagnostic work-up or hospitalization. Thirty patients (24%) developed respiratory complications during a follow-up time of 825 (555–1338) days after chemotherapy. They had a higher prevalence of congestive heart failure and lung or pleural involvement at diagnosis as compared to patients who did not develop complications. Overall, 58 episodes of pulmonary complications were observed after median (interquartile) times from the first and last rituximab doses of 205 (75–580) days and 27 (14–163) days respectively. Infectious etiologies accounted for 75% of the respiratory complications, followed by heart failure exacerbation, lymphomatous involvement, and ARDS. Two Pneumocystis jirovecii pneumonias were observed, and no complication was ascribed to rituximab toxicity. Respiratory complications required ICU admission in 19 cases (33%) and invasive mechanical ventilation in 14 cases (24%). Using a time-dependent Cox regression analysis, we observed that the occurrence of respiratory complications was associated with a 170% increase in death hazard (hazard ratio 2.65, 95% CI 1.60–4.40, p = 0.001). In conclusion, respiratory complications in NHL patients receiving chemotherapy are relatively frequent, severe, and mostly infectious and are associated with increased mortality.


docid: oanejpbw

title: Fatal Outcome of a Hyperinfection Syndrome despite Successful Eradication of Strongyloides with Subcutaneous Ivermectin

text: We report the case of a 77–year–old man who developed a Strongyloides hyperinfection syndrome following immunosuppressive therapy more than 60 years after he moved away from an area endemic for Strongyloides stercoralis. Successful eradication of the nematode was achieved with an off label subcutaneous formulation of ivermectin. However, the patient subsequently died from acute respiratory distress syndrome (ARDS). Despite a high wormload in the stool and sputum of the patient and delayed infection control measures in the hospital, testing of the medical staff revealed a very low risk of Strongyloides transmission among healthcare workers.


title: Review of 17 Cases of Pneumonia Caused by Streptococcus pyogenes

text: Streptococcus pyogenes is an uncommon cause of community-acquired pneumonia and there have been few recent specific accounts of the condition. To describe the current nature of this disease in the UK, data was gathered on patients with clinical pneumonia from whom Streptococcus pyogenes was cultured principally from blood or other relevant normally sterile sites. In the Harrogate and Northallerton districts of North Yorkshire, pneumonia accounted for nine (20%) cases and a quarter of all deaths in a complete sequence of 45 patients with Streptococcus pyogenes bacteraemia detected during the 16-year-period 1981–1996. An analysis is presented of those cases together with eight recent cases from counties York, Durham and Isle of Wight during 1995–1997. Of the total 17 cases, nine occurred in women and eight in men; the age range was 30–92 years. The organism was isolated from blood culture in 15 (88%) patients. Eight (47%) patients died, five within 1 day of hospitalisation. Fourteen (82%) cases occurred in the winter months October to March, including all the fatal cases and all eight in which a clinical 'viral' prodrome was observed. Predisposing medical or surgical conditions were present in 65% of the patients. Major complications included septicaemia, pleural reaction, shock, pulmonary cavitation, osteomyelitis and metastatic abscesses. Seven serotypes of Streptococcus pyogenes were encountered, with M-type 1 predominating (the cause in 60% of cases). All infections were community acquired; two small clusters of fatal pneumonia were seen.


docid: ymcrbzha

title: Long-Term Results After Adult Ex Situ Split Liver Transplantation Since Its Introduction in 1987

text: BACKGROUND: Split liver transplantation is still discussed controversially. Utilization of split liver grafts has been declining since a change of allocation rules for the second graft abolished incentives for German centres to perform ex situ splits. We therefore analysed our long-term experiences with the first ex situ split liver transplant series worldwide. METHODS: A total of 131 consecutive adult ex situ split liver transplants (01.12.1987–31.12.2010) were analysed retrospectively. RESULTS: Thirty-day mortality rates and 1- and 3-year patient survival rates were 13, 76.3, and 66.4 %, respectively. One- and three-year graft survival rates were 63.4 and 54.2 %, respectively. The observed 10-year survival rate was 40.6 %. Continuous improvement of survival from era 1 to 3 was observed (each era: 8 years), indicating a learning curve over 24 years of experience. Patient and graft survival were not influenced by different combinations of transplanted segments or types of biliary reconstruction (p > 0.05; Cox regression). Patients transplanted for primary sclerosing cholangitis had better survival (p = 0.021; log-rank), whereas all other indications including acute liver failure (13.6 %), acute and chronic graft failure (9.1 %) had no significant influence on survival (p > 0.05; log-rank). Biliary complications (27.4 %) had no significant influence on patient or graft survival (p > 0.05; log-rank). Hepatic artery thrombosis (13.2 %) had a significant influence on graft survival but not on patient survival (p = 0.002, >0.05, respectively; log-rank). CONCLUSIONS: Split liver transplantation can be used safely and appears to be an underutilized resource that may benefit from liberal allocation of the second graft.


35. Gemeinsame Jahrestagung der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin und der Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin : 25.–28. Juni 2003, Braunschweig


Infection by H1N1 flu virus revealing T-cell acute lymphoid leukaemia: about two cases


title: Changes in the coagulation-fibrinolysis balance of endothelial cells and mononuclear phagocytes: role in disseminated intravascular coagulation associated with infectious diseases

text: Over the last few years, evidence has accumulated that the pathogenetic mechanism of disseminated intravascular coagulation encountered in patients with infectious diseases is extraordinarily complex and involves multiple interactions between the microorganism itself and/or a number of mediators, both microorganism derived and host manufactured, and multifunctional cellular systems, namely endothelial cells and mononuclear phagocytes. In particular, infectious agents and mediators shift the coagulation-fibrinolysis equilibrium of these cells towards fibrin formation and accumalation, via enhancement of procoagulant and fibrinolytic capacities. New insights into the pathogenetic mechanism may have important implications for the management of infected patients with disseminated intravascular coagulation.


title: Identification of complement-related host genetic risk factors associated with influenza A(H1N1)pdm09 outcome: challenges ahead

text: Influenza remains an important threat for human health, despite the extensive study of influenza viruses and the production of effective vaccines. In contrast to virus genetics determinants, host genetic factors with clinical impact remained unexplored until recently. The association between three single nucleotide polymorphisms (SNPs) and influenza outcome in a European population was investigated in the present study. All samples were collected during the influenza A(H1N1)pdm09 post-pandemic period 2010–11 and a sufficient number of severe and fatal cases was included. Host genomic DNA was isolated from pharyngeal samples of 110 patients from northern Greece with severe (n = 59) or mild (n = 51) influenza A(H1N1)pdm09 disease, at baseline, and the genotype of CD55 rs2564978, C1QBP rs3786054 and FCGR2A rs1801274 SNPs was investigated. Our findings suggest a relationship between the two complement-related SNPs, namely, the rare TT genotype of CD55 and the rare AA genotype of C1QBP with increased death risk. No significant differences were observed for FCGR2A genotypes neither with fatality nor disease severity. Additional large-scale genetic association studies are necessary for the identification of reliable host genetic risk factors associated with influenza A(H1N1)pdm09 outcome. Prophylactic intervention of additional high-risk populations, according to their genetic profile, will be a key achievement for the fight against influenza viruses.


title: Post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia: role of follow-up CT

text: PURPOSE: Our aim was to evaluate the evolution of 20 patients with H1N1 pneumonia, focusing our attention on patients with severe clinical and radiological findings who developed post-acute respiratory distress syndrome (post-ARDS) pulmonary fibrosis. MATERIALS AND METHODS: Twenty adult patients (nine women and 11 men; mean age 43.5±16.4 years) with a diagnosis of H1N1 infection confirmed by pharyngeal swab came to our attention from September to November 2009 and were followed up until September 2010. All patients were hospitalised in consideration of the severity of clinical findings, and all underwent chest X-ray. Twelve of them underwent at least one computed tomography (CT) scan of the chest. RESULTS: In 75% of cases (15/20), there was complete resolution of the clinical and radiological findings. Twenty-five percent of patients (5/20) developed acute respiratory distress syndrome (ARDS), which progressed to predominantly peripheral pulmonary fibrosis in 10% (2/20; one died and one had late-onset pulmonary fibrosis, documented on day 68). Moreover, in one patient with a CT diagnosis of pulmonary fibrosis, we observed progressive regression of radiological findings over 4 months of follow-up. CONCLUSIONS: In patients with H1N1 pneumonia, post-ARDS pulmonary fibrosis is not a rare complication. Therefore, a CT scan should be performed in all patients with severe clinical findings. Our study demonstrated that in these patients, fibrosis could present a different spatial distribution and a different temporal trend, with delayed late onset; moreover, in one case, the signs of interstitial lung disease partially regressed over time. Therefore, CT should be considered not only in the diagnostic stage, but also during the follow-up.


title: Current concepts in ablative procedures for primary benign liver lesions: a step forward to minimize the invasiveness of treatment when deemed necessary

text: With increased use of medical imaging, the incidental detection of benign solid liver tumors has become more frequent. Facing with benign disease, the indications for surgery are still object of discussion in light of the stable natural course of most lesions and obvious drawbacks of any surgical intervention; therefore, in most situations, a conservative approach is recommended, and surgery is mainly reserved for those cases with persistent or worsening symptoms, or who are at risk for complications as malignant transformation. The advent of ablative techniques has widened the range of treatment options available to these patients, presenting as a valid alternative to resection in terms of safety and efficacy in selected cases, particularly in patients who are considered poor surgical candidates and with smaller lesions. This review outlines the role of percutaneous ablative methods for benign solid liver tumors that are encountered in adults, providing a per histology analysis of the existing evidence. The up-to-date strategies for management of the most common benign solid tumors are recapitulated.


docid: exkrhhop

title: Polygalasaponin F treats mice with pneumonia induced by influenza virus

text: BACKGROUND: Influenza is an acute viral respiratory illness that causes high morbidity and mortality globally. Therapeutic actions are limited to vaccines and a few anti-viral drugs. Polygala (P.) japonica herba is rich in Polygalasaponin F (PSF, C(53)H(86)O(23)), used for acute bronchitis, pharyngitis, pneumonia, amygdalitis, and respiratory tract infections treatment in China. Hypercytokinemia is often correlated with severe pneumonia caused by several influenza viruses. PSF was reported to have anti-inflammatory effects and its mechanism is associated with the nuclear factor (NF)-κB signaling pathway. The action of PSF to alleviate pulmonary inflammation caused by influenza A virus (IAV) infection requires careful assessment. In the present study, we evaluated the effect and mechanism of PSF on mice with pneumonia caused by influenza H1N1 (A/FM/1/47). METHODS: Mice were infected intranasally with fifteen 50% mouse lethal challenge doses (MLD(50)) of influenza virus. BALB/c mice were treated with PSF or oseltamivir (oral administration) for 2 h post-infection and received concomitant treatment for 5 days after infection. On day 6 post-infection, 10 mice per group were killed to collect related samples, measure body weight and lung wet weight, and detect the viral load, cytokine, prostaglandins, pathological changes, and cell pathway protein expression in the lungs. In addition, the survival experiments were carried out to investigate the survival of mice. The expression profile of cell pathway proteins was detected and analyzed using a broad pathway antibody array and confirmed the findings from the array by western blotting. RESULTS: Polygalasaponin F and oseltamivir can protect against influenza viral infection in mice. PSF and oseltamivir significantly relieved the signs and symptoms, reduced body weight loss, and improved the survival rate of H1N1-infected mice. Moreover, PSF efficiently decreased the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-4, interferon (IFN)-γ, thromboxane A(2) (TXA(2)), and prostaglandin E(2) (PGE(2)) in lung tissues of mice infected with influenza virus (p < 0.05–0.01). Oseltamivir had a similar effect to lung cytokine of PSF, but did not decrease the levels of TXA(2) and PGE(2). There was a twofold or greater increase in four cell pathway protein, namely NF-κB p65 (2.68-fold), I-kappa-B-alpha (IκBα) (2.56-fold), and MAPK/ERK kinase 1 (MEK1) (7.15-fold) assessed in the array induced by influenza virus. Western blotting showed that the expression of these proteins was significantly decreased in lung after influenza virus challenge in PSF and oseltamivir-treated mice (p < 0.05–0.01). CONCLUSION: Polygalasaponin F appears to be able to augment protection against IAV infection in mice via attenuation of pulmonary inflammatory responses. Its effect on IAV-induced pulmonary inflammation was associated with suppression of Raf/MEK/ERK and NF-κB expressions.


title: Interstitial lung diseases—can pathologists arrive at an etiology-based diagnosis? A critical update

text: Interstitial lung diseases (ILD) encompass a group of diseases with a wide range of etiologies and a variety of tissue reactions within the lung. In many instances, a careful evaluation of the tissue reactions will result in a specific diagnosis or at least in a narrow range of differentials, which will assist the clinician to arrive at a definite diagnosis, when combining our interpretation with the clinical presentation of the patient and high-resolution computed tomography. In this review, we will exclude granulomatous pneumonias as well as vascular diseases (primary arterial pulmonary hypertension and vasculitis); however, pulmonary hypertension as a complication of interstitial processes will be mentioned. Few entities of pneumoconiosis presenting as an interstitial process will be included, whereas those with granulomatous reactions will be excluded. Drug reactions will be touched on within interstitial pneumonias, but will not be a major focus. In contrast to the present-day preferred descriptive pattern recognition, it is the author’s strong belief that pathologists should always try to dig out the etiology from a tissue specimen and not being satisfied with just a pattern description. It is the difference of sorting tissue reactions into boxes by their main pattern, without recognizing minor or minute reactions, which sometimes will guide one to the correct etiology-oriented interpretation. In the author’s personal perspective, tissue reactions can even be sorted by their timeliness, and therefore, ordered by the time of appearance, providing an insight into the pathogenesis and course of a disease. Also, underlying immune mechanisms will be discussed briefly as far as they are essential to understand the disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00428-012-1305-0) contains supplementary material, which is available to authorized users.


title: Skeletal muscle targeting in vivo electroporation-mediated HGF gene therapy of bleomycin-induced pulmonary fibrosis in mice

text: Lung fibrosis is a common feature of interstitial lung diseases, and apoptosis and fibrinogenesis play critical roles in its formation and progression. Hepatocyte growth factor (HGF) is one of the ideal therapeutic agents for prevention of lung fibrosis because of its antiapoptotic and fibrinolytic effects. The aim of this study is to establish nonviral HGF gene therapy of bleomycin-induced lung fibrosis avoiding the viral vector-related side effects. C57BL/6 mice were injected with 3.0 mg/kg body weight of bleomycin intratracheally. Following bleomycin injection, 50 μl of pUC-HGF (1 mg/ml) was injected into each of the quadriceps muscle. Immediately after plasmid injection, in vivo electroporation was performed with pulse generator. Skeletal muscle-targeting electroporation induced transgene expression on day 1 and persisted for 4 weeks, and human HGF was also detected in the lung. In mice transferred with HGF, pathological score (1.0±0.3 vs 3.2±0.6), TUNEL-positive cell index (4.5±1.1 vs 14.2±3.1), and hydroxyproline content (9.0±1.3 vs 14.4±5.1 μmol/g) were significantly reduced compared with the control. Furthermore, survival rate of HGF mice was significantly improved compared with the control. Our data indicate that HGF gene therapy with a single skeletal muscle-targeting electroporation has a therapeutic potential for bleomycin-induced lung fibrosis and this strategy can be applied as a practical gene therapy protocol for various organs.


title: Fungal infections of the lung

text: Fungi, both endemic and opportunistic, continue to be recognized as increasingly frequent pulmonary pathogens. Better appreciation of their epidemiology and clinical course, as well as clarification of the roles of the newer triazoles and lipid formulations of amphotericin B in treatment, have occurred within the past few years. Both endemic and opportunistic fungal pulmonary pathogens are reviewed, with emphasis on recent therapeutic advances.


title: Treatment and Prophylaxis of Pneumocystis carinii Pneumonia in AIDS Patients

text: Pneumocystis carinii pneumonia (PCP) is seen in people with a defect in cell-mediated immunity. Today the most common cause for this is the Acquired Immunodeficiency Syndrome (AIDS). There have been some remarkable advances recently in the development of new drug regimens to combat this otherwise fatal infection. Although cotripoxazole (trimethoprim-sulfamethoxazole) is still the drug of first choice it cannot be tolerated by a significant proportion of patients, and therapies such as pentamidine (pentamidine-isethionate) [intravenous or nebulised], dapsone-trimethoprim, eflornithine (DFMO; difluoromethylornithine), trimetrexate, and clindamycin-primaquine are finding therapeutic niches. The major advantage in these other agents is not improved efficacy but different toxicity profiles, enabling therapy to be most appropriately tailored to individual patients’ conditions. Although the majority of patients should now survive an attack of PCP, relapses will occur if prophylaxis is not used: There is also the capacity to predict accurately which patients are at risk for this pneumonia and prevent it through the use of chemoprophylaxis. These advances in the treatment and prevention of PCP, together with anti-retro viral therapy, mean that this is an area of AIDS management that has resulted in improved long term survival.


title: Treatment of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine

text: Objective: To explore treatments of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine (ICWM), in order to elevate the curing rate as well as to lower the death rate.Methods: Based on conventional ways of Western medical treatments of 18 cases of severe post-kidney-transplant lung infection, such as putting the patients in single individual ward, antibiotics to prevent infection, respiratory machines, blood filtration, nutritional support, steroids, and maintaining electrolytes balance, we applied integrated Chinese medicinal treatments, like altering conventional prescription “pneumonia III”, and conducted clinical observation of effectiveness, and indexes including white blood cell (WBC), neutrophilic granulocyte, blood urea nitrogen (BUN), blood creatinine (Cr), etc.Results: Of the 18 cases studied, 7 were already cured, 8 proved the treatment effective, 3 died. All clinical indexes had statistically significant changes compared with those of before treatment (P<0.01).Conclusion: ICWM can increase curing rate and lower death rate.


title: Clinical and epidemiological characteristics of 2009 pandemic influenza A in hospitalized pediatric patients of the Saurashtra region, India

text: BACKGROUND: The first case of 2009 pandemic influenza A or H1N1 virus infection in India was reported in May 2009 and in the Saurashtra region in August 2009. We describe the two waves clinicoepidemiological characteristics of children who were hospitalized with 2009 influenza A infection in the Saurashtra region. METHODS: From September 2009 to February 2011, we treated 117 children infected with 2009 influenza A virus who were admitted in different hospitals in Rajkot city. Real-time reverse transcriptase polymerase chain reaction (RT-PCR) test was used to confirm infection, and the clinico-epidemiological features of the disease were closely monitored. RESULTS: In the 117 patients, with a median age of 2 years, 59.8% were male. The median time from onset of the disease to influenza A diagnosis was 5 days, and that from onset of the disease to hospitalization was 7 days. The admitted patients took oseltamivir, but only 11.1% of them took it within 2 days after onset of the disease. More than one fourth (29.1%) of the admitted patients died. The most common symptoms of the patients were cough (98.3%), fever (94.0%), sore throat and shortness of breathing. Pneumonia was detected by chest radiography in 80.2% of the patients. CONCLUSIONS: In children with infection-related illness, the survival rate was about 71% after oseltamivir treatment. The median time for virus detection with real-time RT-PCR is 5 days. Early diagnosis and treatment may reduce the severity of the disease.


title: Trends in Treatment of Scheuermann Kyphosis: A Study of 1,070 Cases From 2003 to 2012

text: STUDY DESIGN: Retrospective review of KID Inpatient Database (KID) from 2003, 2006, 2009, and 2012. OBJECTIVES: The aim of this study was to evaluate the impact of advances in spinal surgery on patient outcomes in the treatment of Scheuermann kyphosis (SK). SUMMARY OF BACKGROUND DATA: SK is one of the most common causes of back pain in adolescents. Trends in diagnoses and surgical treatment and approach to SK have not been well described. METHODS: SK patients aged 0–20 years in KID were identified by ICD-9 code 732.0. KID-supplied year- and hospital-trend weights were used to establish prevalence. Patient demographics, surgical details, and outcomes were analyzed with analysis of variance. RESULTS: A total of 1,070 SK patients were identified (33.2% female), with increasing incidence of SK diagnosed from 2003 to 2012 (3.6–7.5 per 100,000, p < .001). The average age of operative patients was 16.1±2.0 years and did not change (16.27–16.06 years, p = .905). The surgical rate has not changed over time (72.8%–72.8%, p = .909). Overall, 96.3% of operative patients underwent fusion, with 82.2% of cases spanning ⩾4 levels; in addition, 8.6% underwent an anterior-only surgery, 74.6% posterior-only, and 13.6% combined approach. From 2003 to 2012, rates of posterior-only surgeries increased (62.4%–84.4%, p < .001) whereas the rate of combined-approach surgeries decreased (37.6%–8.8%, p < .001). Overall complication rates for SK surgeries have decreased (2003: 20.9%; 2012: 11.9%, p = .029). Concurrently, the rate of ⩾4-level fusions has increased (43.5%–89.6%, p < .001), as well as the use of Smith-Peterson (7.8%–23.6%, p < .001) and three-column osteotomies (0.0%–2.7%, p = .011). In subanalysis comparing posterior to combined approaches, complication rates were significantly different (posterior: 9.88%, combined: 19.46%, p = .005). Patients undergoing a combined approach have a longer length of stay (LOS) than patients undergoing a posterior-only approach (7.8 vs. 5.6 days, p < .001). CONCLUSIONS: Despite unchanged demographics and operative rates in SK, there has been a shift from combined to isolated posterior approaches, with a concurrent increase in levels treated. A combined approach was associated with increased complication rates, LOS, and total charges compared to isolated approaches. Awareness of these inherent differences is important for surgical decision making and patient education. LEVELS OF EVIDENCE: Level III.


title: Immunity following intranasal administration of an inactivated, freeze-dried A/England/42/72 vaccine

text: A group of 23 student volunteers were each inoculated intranasally with 400 IU of inactivated, freeze-dried A/England/42/72 vaccine. Only one volunteer showed a four-fold rise in serum HI antibody following immunization, and the mean increase in serum HI antibody (gmt) for all volunteers did not increase two-fold. Thirteen of the volunteers developed detectable levels of nasal wash neutralizing antibody after immunization; local antibody was most commonly found in volunteers who also produced a detectable but less than four-fold rise in serum antibody titre, and who produced nasal washings with relatively high concentrations of protein and secretory IgA. Four weeks after immunization, the vaccinees and a matched group of control subjects were inoculated with attenuated A/England/42/72 (MRC-7) virus. Evidence of infection was found in 14 of 23 (61 per cent) of control subjects and in seven of 23 (30 per cent) of immunized volunteers. This result showed a significant protection (P=0.04) against challenge virus infection for volunteers given intranasal vaccine.


An untreatable dyspnoea: more defendants under investigation


title: Analysis of early infectious complications in pediatric patients undergoing bone marrow transplantation

text: The purpose of the present study was to analyze the characteristics of infectious complications occurring during the first 100 days after bone marrow transplantation (BMT) in a cohort of 123 pediatric patients with hematological malignancies (n=73), solid tumors (n=32) and nonmalignant disorders (n=18). Fifty-eight patients received allogeneic grafts, and 65 patients an autologous transplant. Fever developed in 107 (87%) children; 82% of infectious complications occurred during the neutropenic period. Documented infection developed in 33 (31%) patients, while 74 (69%) patients had possible infection (i.e. fever of unknown origin). The incidence of bacteremia was 21%, and gram-positive cocci were the predominant pathogens; non-bacteremic microbiologically documented infection developed in 6% of patients; clinically evident infection developed in 4% of subjects. The incidence of primary febrile episodes was not significantly different between autologous and allogeneic BMT (86% vs 88%); nor did the median number of days to the onset of fever (5 days in both groups) or the median duration of fever (5 days in both groups) differ. In contrast, the frequency of secondary febrile episodes was significantly higher (P=0.0001) in allogeneic BMT recipients (40%) than in autologous recipients (15%). The mortality rate due to infections was 2/36 (5%) for matched sibling donor BMT, and 1/13 (8%) for matched unrelated donor BMT. No deaths occurred in the 65 patients who were autografted. Invasive fungal infections accounted for 2 of the 3 infectious deaths. In conclusion, the majority of children undergoing BMT experienced at least one infectious episode; allogeneic BMT recipients were at high risk of developing secondary febrile episodes, but the overall mortality rate due to infection in the first 100 days after transplantation was low.


Abstracts of the 50th Anniversary ESPN Meeting, Glasgow, September 2017


docid: ykfvbypo

title: The role of apoptotic cell death in cardiovascular disease

text: BACKGROUND: Programmed cell death, or apoptesis, is a distinct, managed form of cell death. It is fundamentally different from necrosis. It is a genetically controlled, energy-dependent method of cellular deletion without inflammation. In the cardiovascular system, apoptosis occurs as a primary and secondary event in disease pathogenesis. This review addresses our current understanding of the initiation, propagation and significance of apoptosis in the cardiovascular system, as well as assessing therapeutic potentials arising therefrom. METHODS: A Medline search was performed and relevant publications reviewed. Further articles were obtained from the references of these publications. RESULTS AND CONCLUSIONS: Apoptotic cell death is a key element in the pathogenesis and progression of ischaemia-reperfusion (IR) injury, cardiac failure, myocardial infarction, atherosclerosis, endothelial dysfunction and the clinical syndromes which these situations produce. Our increased understanding of the role of apoptosis in the pathogenesis of cardiovascular disease offers potential to develop new therapeutic strategies.


title: Paracrine and Intracrine Angiotensin 1-7/Mas Receptor Axis in the Substantia Nigra of Rodents, Monkeys, and Humans

text: In addition to the classical hormonal (tissue-to-tissue) renin-angiotensin system (RAS), there are a paracrine (cell-to-cell) and an intracrine (intracellular/nuclear) RAS. A local paracrine brain RAS has been associated with several brain disorders, including Parkinson’s disease (PD). Classically, angiotensin II (Ang II) is the main RAS effector peptide and acts through two major receptors: Ang II type 1 and 2 (AT1 and AT2) receptors. It has been shown that enhanced activation of the Ang II/AT1 axis exacerbates dopaminergic cell death. Several new components of the RAS have more recently been discovered. However, the role of new Ang 1-7/Mas receptor RAS component was not investigated in the brain and particularly in the dopaminergic system. In the present study, we observed Mas receptor labeling in dopaminergic neurons and glial cells in rat mesencephalic primary cultures; substantia nigra of rats, monkeys, and humans; and human induced pluripotent stem (iPS) cells derived from healthy controls and sporadic PD patients. The present data support a neuroprotective role of the Ang 1-7/Mas receptor axis in the dopaminergic system. We observed that this axis is downregulated with aging, which may contribute to the aging-related vulnerability to neurodegeneration. We have also identified an intracellular Ang 1-7/Mas axis that modulates mitochondrial and nuclear levels of superoxide. The present data suggest that nuclear RAS receptors regulate the adequate balance between the detrimental and the protective arms of the cell RAS. The results further support that the brain RAS should be taken into account for the design of new therapeutic strategies for PD.


title: Treatment of Complications from Immune Checkpoint Inhibition in Patients with Lung Cancer

text: Immune checkpoint inhibitors have revolutionized the management of advanced NSCLC. With the intention of generating an anti-tumor immune response, ICIs can also lead to inflammatory side effects involving a wide variety of organs in the body, termed immune-related adverse events. Although no prospective clinical trial exists to guide recommendations for optimal and more specific immunosuppressive treatments rather than corticosteroids, further studies may lead to a more mechanistic-based approach towards these toxicities in the future. In relation to current practice, we recommend adherence to the recent published guidelines which emphasize the importance of early recognition and administration of temporary immunosuppressive therapy with corticosteroids in most cases, depending on the organ system involved, and the severity of toxicity. Recognition of these toxicities is increasingly important as the use of these agents expand within different indications for patients with lung cancers, and to other tumor types.


title: Prognostic Factors for Pulmonary Metastasectomy in Hepatocellular Carcinoma

text: PURPOSE: To identify the prognostic factors for pulmonary metastasectomy (PM-ectomy) in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We conducted a retrospective review of patients with pulmonary metastases (PM) from HCC who had undergone curative PM-ectomy at National Taiwan University Hospital between 1990 and 2004. Univariate (log-rank) and multivariate (Cox’s model) analyses of survival were used to identify the significant prognostic factors. RESULTS: In total, 34 patients were eligible for curative PM-ectomy. The overall survival rates (Kaplan-Meier) after PM-ectomy were 65.2% and 27.5% at 2 and 5 years, respectively. High alpha-fetoprotein level, positive hepatic resection margin, and short disease-free interval (DFI) were unfavorable factors for overall survival from univariate analysis, however, only DFI (P = 0.028) was identified as an independently prognostic factor by multivariate analysis. Bilateral distribution and more PMs were unfavorable factors for PM-free survival from univariate analysis, with only PM number identified as an independent prognostic factor by multivariate analysis (P = 0.017). CONCLUSION: Patients with longer DFIs and fewer PMs can benefit from PM-ectomy in HCC.


Abstracts of the European Association of Nuclear Medicine Congress 23–26 August 1992 Lisboa, Portugal


docid: vhlshqbc

title: Generation of outbred Ace2 knockout mice by RNA transfection of TALENs displaying colitis reminiscent pathophysiology and inflammation

text: The angiotensin I converting enzyme 2 (ACE2) is a key factor in the maintenance of intestinal homeostasis. Dysregulation of homeostasis can lead to inflammation of the colon (colitis), which can cause life-threatening enfeeblement or even cancer. Animal models are valuable surrogates in deciphering the pathology behind such human conditions and for screening of putative therapeutic targets or treatment paradigms. However, development of disease models can be time-consuming and technical demanding, which might hamper their application-value. In this study, we genetically disrupted the mouse Ace2 gene by direct injection of in vitro transcribed mRNA coding for transcription activator-like effector nucleases (TALENs) into the cytoplasm of outbred Kunming mouse zygotes. Consequently, somatic mutations were induced with an efficiency of 57 %, of which 39 % were frameshift mutations. Moreover, all modifications were stably transferred during germline transmission. In Ace2-knockout male mice (Ace2 (−/y)), we observed severe chemical induced colitis, characterized by considerable weight loss, diarrhea and a shortened colon length. Histologically, Ace2 mutations resulted in the infiltration of leukocytes and the overt damage of the intestinal mucosal barrier. In addition, we detected an increased expression of inflammatory cytokines in the colon tissue of Ace2 (−/y) mice. Collectively, the data indicate that high targeting efficiency and heritability can be achieved in an outbred mouse model by zygote injection of TALEN mRNA. Furthermore, the generated Ace2 (−/y) mice display phenotypic traits reminiscent of colitis and we anticipate that such mice can be of value in studies of the intestinal microbiome or fecal transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-014-9855-3) contains supplementary material, which is available to authorized users.


Revised list of acronyms


docid: jrhmvxzf

title: Pulmonary complications of babesiosis: case report and literature review

text: Reported here is a rare case of babesiosis with pulmonary complications followed by a review of the literature. Babesiosis presents clinically as a malaria-like illness with fever, chills, headache, fatigue with lymphopenia, atypical lymphocytes, mildly or transiently elevated serum transaminases, thrombocytopenia, and increased lactate dehydrogenase (LDH) levels. The diagnosis of babesiosis is based on identification of Babesia spp. on a peripheral blood smear. Babesiosis is usually mild in normal hosts, but it may be severe or even fatal in asplenic patients. Pulmonary manifestations are rare in babesiosis, but non-cardiogenic pulmonary edema (NCPE) is the most frequent manifestation. NCPE in babesiosis does not appear to be related to the degree of parasitemia or splenic function and its onset may be early or late. NCPE usually resolves rapidly with supportive treatment; it is rarely fatal. Clinicians should suspect NCPE in patients with babesiosis who acutely develop shortness of breath and have chest radiograph findings compatible with acute pulmonary edema without cardiomegaly or pleural effusions.


title: The effects of intraoperative cryoprecipitate transfusion on acute renal failure following orthotropic liver transplantation

text: PURPOSE: The definition of risk factors associated with acute renal failure (ARF) following orthotropic liver transplantation (OLT) is still controversial. Cryoprecipitate, which can supply fibrinogen and other coagulation factors, is widely used in OLT. However, the effects of intraoperative cryoprecipitate transfusion on ARF following OLT remain unclear. METHODS: In a series of 389 adult patients who received grafts from deceased donors and underwent their first OLT, the clinical correlation between intraoperative cryoprecipitate transfusion and ARF following OLT was retrospectively studied after adjusting for potential confounders. The distribution of ARF and the causes of death within the first year after OLT were also compared separately in patients with and without cryoprecipitate transfusion. RESULTS: The incidence of ARF in patients with cryoprecipitate transfusion was significantly higher than in patients without cryoprecipitate transfusion (15.9 vs. 7.8 %, p = 0.012). A nonlinear relationship between intraoperative cryoprecipitate transfusion and ARF following OLT was observed. The risk of ARF increased with the cryoprecipitate transfusion level up to the turning point (16 U) (adjusted OR 1.1, 95 % CI 1.1–1.2; p < 0.001). When the cryoprecipitate level exceeded 16 U, the level of cryoprecipitate transfusion was not associated with the risk of ARF (OR 0.95, 95 % CI 0.85–1.1; p = 0.319). Deaths within the first year after the operation occurred more frequently in cases with cryoprecipitate transfusion (22.9 vs. 14.2 %, p = 0.029). CONCLUSIONS: These findings suggested that intraoperative cryoprecipitate transfusion is associated with ARF following OLT. Cryoprecipitate transfusion during OLT should be performed carefully until more convincing evidence has been found.


title: Off-label use of rituximab in systemic lupus erythematosus: a systematic review

text: Considerable interest in the efficacy of rituximab (a monoclonal CD20 antibody) in patients with systemic lupus erythematosus (SLE) has been generated due to its unique mode of action, culminating in a series of randomized and open trials, and case reports. However, this use is off-license and two significant RCTs have reported negative findings, reopening the debate on clinical benefit. This review of the available data suggests that rituximab induces B-cell depletion in 95% of patients, and a significant reduction in disease activity is achieved with a relatively good safety profile in patients with SLE.


docid: ywzpwlrb

title: Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals

text: We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.


The need for an organized ECMO-based respiratory program in Japan


title: Levels of IL-8 and myeloperoxidase in the lungs of pneumonia patients

text: Interleukin-8 (IL-8) is considered as the major polymorphonuclear neutrophils (PMNs) chemoattractant cytokine in lung diseases such as asthma and adult respiratory distress syndrome (ARDS). However, controversial results were obtained regarding the involvement of IL-8 in the pathogenesis of pneumonia. This study examines the role of IL-8 in the recruitment and activation of PMNs in the lung of pneumonia patients. The interesting aspect of this study is that it is a site- specific analysis of the infected and uninfected lungs of the same patient. The level of IL-8 mRNA, protein and myeloperoxidase present in the cells of the bronchioalveolar lavages (BALs) taken from the areas of known pneumonic consolidations on chest X-ray (infected lung) are compared with the BALs obtained from areas of no obvious infiltrate (non-infected lung). The results obtained from the infected and non-infected lungs of pneumonic patients were further compared with that of a control group of non-smoking patients. The level of IL-8 mRNA and protein were determined by RT-PCR and ELISA respectively. There was a significant increase in the level of IL-8 mRNA in the infected lung as compared to its level in the non-infected lung (p < 0.001). In correlation with the increase in mRNA, IL-8 protein concentrations in BAL fluids from the infected lung were 6 fold higher than those taken from the non-infected lung (p < 0.0001). This pattern was also consistent with MPO activity in the BALs (4.5 fold more MPO activity in the infected lung as compared to that of the non-infected lung), indicating that IL-8 is directly implicated in neutrophil accumulation that follows acute respiratory infection. The results of the present study, therefore, indicate the involvement of IL-8 in the pathogenesis of pneumonia.


title: Lipid Mediators in Inflammatory Disorders

text: During the past few decades, intensive collaborative research in the fields of chronic and acute inflammatory disorders has resulted in a better understanding of the pathophysiology and diagnosis of these diseases. Modern therapeutic approaches are still not satisfactory and shock, sepsis and multiple organ failure remain the great challenge in intensive care medicine. However, the treatment of inflammatory diseases like rheumatoid arthritis, ulcerative colitis or psoriasis also represents an unresolved problem. Many factors contribute to the complex course of inflammatory reactions. Microbiological, immunological and toxic agents can initiate the inflammatory response by activating a variety of humoral and cellular mediators. In the early phase of inflammation, excessive amounts of interleukins and lipid-mediators are released and play a crucial role in the pathogenesis of organ dysfunction. Arachidonic acid (AA), the mother substance of the pro-inflammatory eicosanoids, is released from membrane phospholipids in the course of inflammatory activation and is metabolised to prostaglandins and leukotrienes. Various strategies have been evaluated to control the excessive production of lipid mediators on different levels of biochemical pathways, such as inhibition of phospholipase A(2), the trigger enzyme for release of AA, blockade of cyclooxygenase and lipoxygenase pathways and the development of receptor antagonists against platelet activating factor and leukotrienes. Some of these agents exert protective effects in different inflammatory disorders such as septic organ failure, rheumatoid arthritis or asthma, whereas others fail to do so. Encouraging results have been obtained by dietary supplementation with long chain ω-3 fatty acids like eicosapentaenoic acid (EPA). In states of inflammation, EPA is released to compete with AA for enzymatic metabolism inducing the production of less inflammatory and chemotactic derivatives.


docid: jgystlhn

title: Cardiovascular genomics: A current overview of in vivo and in vitro studies

text: The cardiovascular system is the first system that is developed in the embryo. The cardiovascular development is a complex process involving the coordination, differentiation, and interaction of distinct cell lineages to form the heart and the diverse array of arteries, veins, and capillaries required to supply oxygen and nutrients to all tissues. Embryonic stem cells have been proposed as an interesting model system to investigate molecular and cellular mechanisms involved in mammalian development. The present review is focused on extrinsic soluble factors, intrinsic transcription factors, receptors, signal transduction pathways, and genes regulating the development of cardiovascular system in vivo and in vitro. Special emphasis has been given to cardiovascular genomics including gene expression studies on the cardiovascular system under developmental and pathophysiological conditions.


docid: nhbofufv

title: Bone marrow transplantation for thalassemia

text: Early trials of allogeneic bone marrow transplantation (BMT) for homozygous beta-thalassemia and the analyses of results of transplantation in patients less then 16 years old have allowed us to identify three classes of risk using the criteria of degree of hepatomegaly, the degree of portal fibrosis and the quality of the chelation treatment given before the transplant. Patients for whom all three criteria were adverse constituted class 3, patients with none of the adverse criteria constituted class one and patients with one or various association of the adverse criteria formed Class 2. Most patients older than 16 years have disease characteristics that place them in class 3 with very few in class 2. For all the patients with an HLA identical donor we are actually using two Protocols for BMT to whom the patients are assigned on the base of the class they belong to at the time of BMT and independently on the age of the patient. For class 1, class 2 and for class 3 the probabilities of survival and of event-free-survival are respectively of 98% and 94%, 87% and 84%, 100% and 67%. For those patients that were older than 16 years at the time of the transplant, the probabilities of survival are 82% and the probabilities of event-free survival are 79%. Bone marrow transplantation is a new form of radical treatment of thalassemia in those patients with an HLA identical donor.


docid: blonveub

title: Life-threatening complications of adult-onset Still’s disease

text: Adult-onset Still’s Disease (AOSD) since its description in 1971 has proven to be a very complex and challenging disease entity. This rare auto-inflammatory disease is classically described by the “Still’s triad” of fever, rash, and arthritis, although the atypical cases frequently outnumber the typical ones. The exact pathogenesis and etiologic factors responsible for the clinical features remain largely obscure, despite recent suggestive cytokine biology findings. Diagnosis is made on clinical grounds, following the exclusion of mimickers of infectious, autoimmune or neoplastic etiology, with the additional consideration of non-specific laboratory abnormalities such as peripheral leukocytosis and elevation of serum ferritin and other acute phase reactants. The disease manifestations are protean and can include diverse complications, affecting multiple organ systems. Moreover, the severity of the organ involvement can vary considerably, representing a wide spectrum from the self-limited to severe. The mainstay of therapy has evolved from the traditional use of corticosteroids and oral immunosupressants to the newer targeted treatments with biologic agents. The scope of this review is to alert the clinician to the existence of life-threatening AOSD complications, namely the macrophage activation syndrome, disseminated intravascular coagulopathy, thrombotic thrombocytopenic purpura, diffuse alveolar hemorrhage, and pulmonary arterial hypertension. Such knowledge may lead in earlier recognition, prompt treatment, and, ideally, improved patient outcomes.


title: Characterization and changes of a chromosomal-scaffolding protein in human epithelia

text: Chromosomal-scaffolding proteins exert DNA structural functions during mitosis, and gene regulatory functions such as RNA splicing/polymerization and DNA replication in interphase, allowing the progression of the cell cycle. Recently, it has been reported that topoisomerases play a key role in DNA repair, suggesting an additional regulatory mechanism of the chromosome structure on DNA metabolism and cell cycle checkpoints. Despite the progress made toward the understanding of the genome organization and expression, few changes have been reported in the chromosome scaffold of malignant cells associated with the cancer phenotype. In a previous work, we reported LFM-1 protein (Licensing Factor Model-1) as a chromosomal-scaffold component transiently associated with mitotic chromosomes in MDCK (Madin Darby canine kidney) epithelial cells (Vega-Salas and Salas 1996). In this work, we explore LFM-1 expression in human epithelia with contrasting tumorigenicity during the progression of the cell cycle. Although cell metabolic labeling shows synthesis of a common 87-kDa LFM-1 precursor during G(2)-phase in both non-tumorigenic and cancer cells, surprisingly, the post-translational LFM-1 chromosome-bound polypeptide displays a different apparent molecular weight and binding to chromosomes in the cancer phenotype. The finding of a highly phosphorylated LFM-1 60-kDa form with abnormal binding to chromosomes in human carcinoma cells suggests a structural/regulatory role(s) of the chromosome-scaffold/matrix in DNA metabolism in cancer-related events of cell proliferation.


title: The role of intestinal transplantation in the Management of intestinal failure

text: Significantly reduced morbidity and mortality is needed before intestinal transplantation will be applicable in most patients with intestinal failure who are on long-term total parenteral nutrition (TPN). However, transplantation does play a role if TPN fails, with failure defined by Medicare as liver failure, frequent line sepsis, major central vein thrombosis, or recurrent dehydration. Of these complications, the relationship between liver failure and subsequent death in high-risk subgroups of long-term TPN patients has been shown clearly. Patients with less than 100 cm of postduodenal small bowel, an end-jejunostomy, no ileocecal valve or cecum, or persistently elevated liver function levels are at high risk for end-stage liver disease (ESLD). Early referral to experienced centers is suggested in these circumstances. High-risk patients may also take part in clinical trials of promising therapies to increase intestinal adaptation and prevent liver failure. Living donors should be considered for transplant candidates to minimize waiting time and optimize HLA matching. ESLD patients need a liver-intestine transplant. Because their waiting-list mortality is very high, their status on the liver waiting list should be elevated if possible. High incidence of early death from sepsis is reported after intestinal transplant, even at experienced centers. Aggressive measures should be taken if uncontrolled sepsis occurs, including discontinuing immunosuppression and removing the graft. Further research is needed in intestinal immunology and in development of strategies to decrease the need for aggressive immunosuppression in these transplant recipents. The ultimate role of intestinal transplantation will be determined by its capacity to show superiority, both in effectiveness and safety, to long-term TPN.


title: Influenza A virus: radiological and clinical findings of patients hospitalised for pandemic H1N1 influenza

text: PURPOSE: This paper describes the radiological and clinical findings identified in a group of patients with H1N1 influenza. MATERIALS AND METHODS: Between May and mid-November 2009, 3,649 patients with suspected H1N1 influenza presented to our hospital. Our study population comprised 167 (91 male, 76 female patients, age range 11 months to 82 years; mean age 29 years) out of 1,896 patients with throat swab positive for H1N1 and clinical and laboratory findings indicative of viral influenza. All 167 patients were studied by chest X-ray (CXR), and 20 patients with positive CXR and worsening clinical condition also underwent computed tomography (CT). The following findings were evaluated on both modalities: interstitial reticulation (IR), nodules (N), ground-glass opacities (GGO), consolidations (CONS), bacterial superinfection and pulmonary complications. RESULTS: Ninety of 167 patients had positive CXR results. Abnormalities identified on CXR, variously combined and distributed, were as follows: 53 IR, 5 N, 13 GGO, 50 CONS; the predominant combination was represented by six GGO with CONS. Of the 20 CXR-positive cases also studied by CT, 17 showed pathological findings. The abnormalities identified on CT, variously combined and distributed, were as follows: 14 IR, 2 N, 5 GGO; the predominant combination was 10 GGO with CONS. Despite the differences between the two modalities, the principle radiological findings of bacterial superinfection were tree-in-bud pattern, consolidation with air bronchogram, and pleural and pericardial effusion. Fifteen of the 20 patients studied by both CXR and chest CT showed respiratory complications with bilateral and diffuse CONS on CXR and CT. Six of 15 died: 4/6 of acute respiratory distress syndrome and 2/6 of multiple organ failure. CONCLUSIONS: Our study describes the radiological and clinical characteristics of a large population of patients affected by H1N1 influenza. CXR and chest CT identified the site and extent of the pulmonary lesions and documented signs of bacterial superinfection and pulmonary complications.


title: Lemierre’s syndrome and other disseminated Fusobacterium necrophorum infections in Denmark: a prospective epidemiological and clinical survey

text: In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre’s syndrome and disseminated non-head-and-neck-associated F. necrophorum infections. Fifty-eight cases of Lemierre’s syndrome were reported in previously healthy persons, with an incidence of 14.4 cases per million per year in youngsters aged 15–24 years old. There was no increase during the study period. Lemierre’s syndrome originating from an oropharyngeal infection was seen in 37 youngsters. An otogenic variant of Lemierre’s syndrome was seen in 5 children with dissemination to nearby regions, and other variants of Lemierre’s syndrome, e.g. from the sinuses and teeth, were seen in 16 adults. Patients often had metastatic infections already on admission and needed prolonged hospitalisation. The overall mortality of Lemierre’s syndrome was 9%. Forty-two elderly patients had disseminated F. necrophorum infections originating from foci in lower parts of the body. They frequently had predisposing diseases, e.g. abdominal or urogenital cancers, which contributed to the high mortality of 26%. This study shows that the incidence of Lemierre’s syndrome is higher than that previously found and has a characteristic age distribution. Early suspicion of the diagnosis, several weeks of antibiotic therapy, often combined with surgical drainage, is mandatory to lower the mortality. In disseminated non-head-and-neck-associated F. necrophorum infections, underlying cancers must be considered.


title: Pulmonary nuclear medicine

text: This article reviews the contribution made by nuclear imaging to the assessment, diagnosis and monitoring of patients with respiratory disease. It focuses on several specific areas including the diagnosis of pulmonary embolism, the investigation of intrapulmonary infection and neoplasm and the role of positron emission tomography (PET) scanning.