Efficacy of ceftaroline fosamil against penicillin-sensitive and -resistant streptococcus pneumoniae in an experimental rabbit meningitis model.

Ceftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain of S. pneumoniae in an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

Efficacy of Ceftaroline Fosamil against Escherichia coli and Klebsiella pneumoniae strains in a rabbit meningitis model.

In this study, the efficacy of ceftaroline fosamil was compared with that of cefepime in an experimental rabbit meningitis model against two Gram-negative strains (Escherichia coli QK-9 and Klebsiella pneumoniae 1173687). The penetration of ceftaroline into inflamed and uninflamed meninges was also investigated. Both regimens were bactericidal, but ceftaroline fosamil was significantly superior to cefepime against K. pneumoniae and E. coli in this experimental rabbit meningitis model (P < 0.0007 against K. pneumoniae and P < 0.0016 against E. coli). The penetration of ceftaroline was approximately 15% into inflamed meninges and approximately 3% into uninflamed meninges.

Evaluation of ceftobiprole activity against a variety of gram-negative pathogens, including Escherichia coli, Haemophilus influenzae (ß-lactamase positive and ß-lactamase negative), and Klebsiella pneumoniae, in a rabbit meningitis model.

Ceftobiprole medocaril, a new cephalosporin, is highly active against a broad spectrum of Gram-positive and Gram-negative clinical pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant pneumococci. In this study, we tested ceftobiprole against various Gram-negative pathogens in a rabbit meningitis model and determined its penetration into the cerebrospinal fluid (CSF). In this animal model, ceftobiprole produced an antibacterial activity similar to that of cefepime against an Escherichia coli strain, a Klebsiella pneumoniae strain, and a ß-lactamase-negative Haemophilus influenzae strain. Against a ß-lactamase-positive H. influenzae strain, ceftobiprole was significantly superior. The penetration of ceftobiprole through inflamed meninges reached about 16% of serum levels compared to about 2% of serum levels through uninflamed meninges.

Combination of daptomycin plus ceftriaxone is more active than vancomycin plus ceftriaxone in experimental meningitis after addition of dexamethasone.

We examined the cerebrospinal fluid penetration of daptomycin after the addition of dexamethasone and its bactericidal efficacy with and without ceftriaxone in an experimental rabbit model of pneumococcal meningitis. The combination of daptomycin with ceftriaxone was the most efficacious regimen for pneumococcal meningitis. The previous addition of dexamethasone affected the antibacterial activity of daptomycin only marginally, either as monotherapy or combined with ceftriaxone, although the penetration of daptomycin into inflamed meninges was significantly reduced from 6 to 2%. Daptomycin with ceftriaxone might be a potential candidate for the empirical therapy of bacterial meningitis, although the activity of this regimen against Listeria monocytogenes remains to be demonstrated.

Developing ICF Core Sets for persons with sleep disorders based on the International Classification of Functioning, Disability and Health.

BACKGROUND: With the International Classification of Functioning, Disability and Health (ICF), we can now rely on a globally agreed-upon framework and system for classifying the typical spectrum of problems in the functioning of persons given the environmental context in which they live. ICF Core Sets are subgroups of ICF items selected to capture those aspects of functioning that are most likely to be affected by sleep disorders. OBJECTIVE: The objective of this paper is to outline the developmental process for the ICF Core Sets for Sleep. METHODS: The ICF Core Sets for Sleep will be defined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies, namely (a) a systematic literature review regarding the outcomes used in clinical trials and observational studies, (b) focus groups with people in different regions of the world who have sleep disorders, (c) an expert survey with the involvement of international clinical experts, and (d) a cross-sectional study of people with sleep disorders in different regions of the world. CONCLUSION: The ICF Core Sets for Sleep are being designed with the goal of providing useful standards for research, clinical practice and teaching. It is hypothesized that the ICF Core Sets for Sleep will stimulate research that leads to an improved understanding of functioning, disability, and health in sleep medicine. It is of further hope that such research will lead to interventions and accommodations that improve the restoration and maintenance of functioning and minimize disability among people with sleep disorders throughout the world.

Hydrodynamic thermal confinement: creating thermo-chemical microenvironments on surfaces.

We present a new, general concept termed Hydrodynamic Thermal Confinement (HTC), and its implementation for the creation of microscale dynamic thermo-chemical microenvironments on biological surfaces. HTC is based on a scanning probe and operates under physiological conditions. The temperature can be regulated between 30° and 80 °C with ±0.2 °C precision and temperature ramps of 5 °C s-1 over a footprint of ∼50 µm × 80 µm in a volume of ∼50 × 80 × 15 µm3 (∼50 pl).

Monitoring of BCR-ABL expression using real-time RT-PCR in CML after bone marrow or peripheral blood stem cell transplantation.

To analyze the value of real time RT-PCR for monitoring of bcr-abl expression in CML patients after allogeneic or autologous stem cell transplantation (SCT), we generated pairs of PCR-primers and TaqMan probes specific for either the b2a2- or the b3a2-variant of bcr-abl. Either variant could be detected specifically from cDNA from a single K562 (b3a2) and BV173 (b2a2) cell with the respective TaqMan probe. Bcr-abl expression was normalized by comparison with GAPDH expression, and samples were quantitated using standard cDNA dilutions from K562 or BV173 cells. In a retrospective analysis 13 patients with CML after allogeneic (n = 10) or autologous (n = 3) SCT including patients with relapsed or persistent CML were analyzed by both real-time and conventional nested RT-PCR. In addition chimerism was monitored by FISH analysis of sex chromosomes in three patients with relapsed disease. The bcr-abl/GAPDH ratio dropped at least 1000-fold in all seven patients evaluable prior to and after allogeneic SCT as estimated by real-time RT-PCR, and conventional RT-PCR became negative in 6/7 patients. In five patients with relapsed or persistent disease after allogeneic SCT the bcr-abl/GAPDH ratio eventually increased again, and real-time RT-PCR was as sensitive as conventional RT-PCR for detection of bcr-abl. Donor lymphocyte infusions (DLI) were given to all five patients, and the bcr-abl/GAPDH ratio dropped to undetectable levels in two patients both remaining in continuing molecular remission. In contrast, in three other patients the bcr-abl/GAPDH ratio decreased only or did not change significantly after DLI. In three patients undergoing autologous SCT the bcr-abl/GAPDH ratio dropped only 1.1 to 30-fold, and the patients were tested positive with real-time RT-PCR at all time points. These data demonstrate that real-time RT-PCR is valuable to quantitate bcr-abl expression in CML patients after transplantation.

Donor cell-derived acute myeloid leukemia developing 14 months after matched unrelated bone marrow transplantation for chronic myeloid leukemia.

We report a patient with Ph-positive CML who developed a Ph-negative AML in donor cells 14 months after BMT from an HLA-identical male unrelated donor. The Ph translocation could not be detected by either conventional cytogenetics, FISH or RT-PCR analysis excluding relapse of CML in myeloid blast crisis. Chimerism studies were performed by variable number of tandem repeats (VNTR) analysis. These revealed donor-type hematopoiesis in both unseparated mononuclear cells and CD34+ selected blasts proving the leukemia to be of donor origin. The patient received three cycles of polychemotherapy with mitoxantrone, topotecan and ara-c resulting in CR after the first treatment cycle and reconstitution with donor hematopoiesis. A second transplant from a female alternative matched unrelated donor was performed after conditioning with fludarabine and 200 cGy TBI and was well tolerated. Nine months after the second transplant the patient is at home and in CR. T cell chimerism was studied by sex chromosome analysis and revealed complete female donor chimerism.

Intra- and inter-individual comparison of Porphyromonas gingivalis genotypes.

Genetic analysis of 31 clinical strains of Porphyromonas gingivalis isolated from nine subjects, 2-6 strains per subject, was performed by Southern hybridization. Chromosomal DNA was extracted by the method of Moncla et al. [1] and digested to completion with restriction endonucleases PstI, ClaI and BglI. The DNA fragments were separated electrophoretically on agarose gels, transferred to nylon membranes and hybridized to the non-radioactively labelled plasmid pKK 3535 which contains the rmB ribosomal RNA operon of the Escherichia coli chromosome. Of the three enzymes, BglI was the most suitable for the genetic analysis of P. gingivalis. With this enzyme, the intra-individual strains were shown to be identical in eight of the nine subjects, whereas inter-individual strains were different.

[Ex vivo increase in hematopoietic progenitor cells for clinical use]. / Ex-vivo-Vermehrung von hmatopoetischen Progenitorzellen für die klinische Anwendung.

BACKGROUND: The clinical use of ex vivo expanded hematopoietic progenitor cells is currently explored. MATERIAL AND METHODS: In this study the culturing of G-CSF mobilized and purified CD34+ blood cells was investigated. The interleukins IL-1 beta, IL-3 and IL-6 (each at a dose of 300 U/ml) and stem cell factor (25 ng/ml) without or with erythropoietin (1 U/ml) were used. Cells of 10 healthy sibling donors and 10 patients with solid tumors were incubated under small-scale (n = 15, 2 ml) and large-scale (n = 7, 50 ml) culture conditions at 37 degrees C for 5 and 4 weeks, respectively. The cell density was adjusted to about 1 x 10(5) cells/ml. RESULTS: The nucleated cell counts increased approximately 7-fold and 10- to 70-fold after 1 and 2 weeks of incubation. Numbers of CD34+ cells doubled to triplicated within this time interval, without any significant changes in their clonogenicity (CFU-GM and BFU-E output). Thereafter a depletion of the CD34+ cell pool was noticed. However the numbers of CD34+/CD38(-)- or CD34+/ HLA-DR(-)- cells were reduced to a lesser extent. The expanded cells generated predominantly myeloid and almost no lymphoid cells. More glycophorin-A+ cells were produced when erythropoietin was added. Replacement of non-human additives with heat-inactivated autologous plasma had no influence on cell growth. Almost no proliferation was obtained with a 10-fold higher cell density (1.7 x 10(6)/ml in 100 ml), but the cells maintained their viability for 13 to 16 days. CONCLUSIONS: This study suggests, that the chosen culture conditions might be feasible for a large-scale ex vivo expansion of hematopoietic progenitor cells for clinical application. The impact of the ex vivo generated cells on hematopoietic regeneration after chemotherapy is currently under clinical investigation.

[Evaluation of surgical risk in patients with COPD]. / Die Beurteilung der Operabilität bei Patienten mit COPD.

In this overview general risk factors for postoperative complications are discussed with special reference to pulmonary complications, which frequently occur in patients with chronic obstructive pulmonary disease (COPD). In a second part the functional evaluation of lung resection candidates is presented. Pulmonary complications are the most frequent cause of postoperative morbidity and mortality. Risk factors include: underlying respiratory disease, especially COPD, current smoking, duration of anaesthesia, type of surgical procedure (upper abdominal or thoracic surgery), age and obesity. The preoperative evaluation of patients at risk is discussed. For non-thoracic surgery preoperative pulmonary function testing and a preoperative chest radiograph are indicated for high-risk patients only, whereas they are mandatory for all lung resection candidates. There are no cut-off values in pulmonary function testing which would preclude non-thoracic surgical procedures. In patients with COPD, laparascopic procedures are recommended; and regional or epidural anaesthesia have less adverse effects on pulmonary function than general anaesthesia. Prevention of postoperative pulmonary complications includes smoking cessation at least eight weeks before surgery, and, if indicated preoperative treatment with antibiotics, beta2-agonists, steroids (steroid-trial) and intensive perioperative chest physiotherapy (incentive spirometry). The functional reserves of lung resection candidates is assessed with an algorithm based on the forced expiratory volume in one second (FEV1), the transfer factor of the lung for carbon monoxide (DLCO), and the maximal oxygen uptake on exercise (VO2max). In critical patients additional split function studies are necessary to estimate the remaining pulmonary function depending on the extent of resection.

The potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries.

Idiopathic pulmonary fibrosis (IPF) remains a major clinical challenge to date. Repeated alveolar epithelial microinjuries are considered as the starting point and the key event in both the development and the progression of IPF. Various pro-fibrotic agents have been identified and shown to cause alveolar damage. In IPF, however, no leading cause of alveolar epithelial microinjuries can be identified and the exact etiology remains elusive. New results from epidemiologic studies suggest a causal relation between IPF and frequent episodes of gastric refluxes resulting in gastric microaspirations into the lung. The effect of gastric contents on the alveolar epithelium has not been investigated in detail. Here, we present a microfluidic lung epithelial wounding system that allows for the selective exposure of alveolar epithelial cells to gastric contents. The system is revealed to be robust and highly reproducible. The thereby created epithelial microwounds are of tiny dimensions and best possibly reproduce alveolar damage in the lung. We further demonstrate that exposure to gastric contents, namely hydrochloric acid (HCl) and pepsin, directly damages the alveolar epithelium. Together, this novel in vitro wounding system allows for the creation of in vivo-like alveolar microinjuries with the potential to study lung injury and alveolar wound repair in vitro.

[28-year-old patient with iron deficiency anemia]. / 28-jährige Patientin mit Eisenmangelanämie.

We report the case of a 28-years-old woman with Turner's syndrome and iron deficiency anaemia. The faecal occult blood test was intermittently positive whereas earlier upper and lower endoscopy revealed no source of bleeding. Capsule endoscopy showed multiple vascular malformations on the jejunum and ileum. Our case report emphasizes the importance of capsule endoscopy in the localising occult bleedings in the small bowel. We discuss the different diagnostic modalities and possible treatments.

[A 58-year-old soldier with a history of weight loss and exercise intolerance. Giant cell arteritis]. / 58-jähriger Berufssoldat mit Gewichtsverlust und reduzierter Leistungsfähigkeit. Riesenzellarteriitis.

We report the case of a 58-years-old soldier with a history of movement related neck pain, weight loss and exercise intolerance. Blood tests presented signs of an inflammatory syndrome. The CT-scan showed extended thickening of the aortic wall characteristic for aortitis. The diagnosis of giant cell arteritis could be histologically confirmed by biopsy of the temporal arteries. Our case report emphasizes the importance of the various imaging modalities. We discuss the different forms of disease evolution and the treatment regimen.

[Consequences of an accidental aspiration of petroleum in a case of a fire eating man]. / Folgen einer akzidentellen Aspiration von Petroleum bei einem Feuerspucker.

Fire-eater's pneumonitis, caused by aspiration of petroleum, is an infrequent clinical problem in our region. It is an acute inflammatory response of the lungs to the accidental aspiration of hydrocarbons, as shown in our patient. Despite the severe initial clinical und radiological presentation, fire-eater's pneumonitis usually shows a favourable evolution with "restitutio ad integrum". Acute mortality rate is less than 1%. Fire-eater's lung is a medical emergency and needs medical support and surveillance. There is no good evidence that systemic cortico-steroids and antibiotics are effective in the treatment of hydrocarbon aspiration. Concerning chronic lung injury after fire-eater's pneumonitis, there are favorable results from short observational series.

[Atypical case of bronchus carcinoma]. / 47-jähriger Patient mit Sehstörungen, Polydipsie und Polyurie.

Bronchuscarcinoma ist the most frequent death cause with tumor patients. At time of diagnosis the stadium is often already advanced, the patient is inoperable. We present a patient (non-smoker) with polydipsia, visual troubles and polyuria. The lab results confirmed diabetes insipidus, but the following x-rays proved multiple intracerebral spots. And also multiple spots in the lungs, the mediastinum, in the liver, the coloumn and the adrenals. Histological diagnosis was non small cell lung cancer (NSCLC).