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1.
Chem Commun (Camb) ; 52(88): 13035-13038, 2016 Oct 27.
Article in English | MEDLINE | ID: mdl-27757451

ABSTRACT

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).

2.
Integr Biol (Camb) ; 6(12): 1132-40, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25205504

ABSTRACT

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.


Subject(s)
Hydrochloric Acid , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/pathology , Microfluidic Analytical Techniques/instrumentation , Pulmonary Alveoli/injuries , Respiratory Mucosa/injuries , Respiratory Mucosa/pathology , Animals , Disease Models, Animal , Equipment Design , Equipment Failure Analysis , Feasibility Studies , Flow Injection Analysis/instrumentation , Flow Injection Analysis/methods , Gastroesophageal Reflux/chemically induced , Gastroesophageal Reflux/pathology , Humans , Microfluidic Analytical Techniques/methods , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/pathology , Respiratory Mucosa/drug effects
3.
Antimicrob Agents Chemother ; 57(12): 5808-10, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24002097

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/pharmacology , Klebsiella Infections/drug therapy , Meningitis, Escherichia coli/drug therapy , Animals , Anti-Bacterial Agents/cerebrospinal fluid , Anti-Bacterial Agents/pharmacokinetics , Cefepime , Cephalosporins/cerebrospinal fluid , Cephalosporins/pharmacokinetics , Disease Models, Animal , Escherichia coli/drug effects , Escherichia coli/physiology , Klebsiella Infections/cerebrospinal fluid , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/physiology , Meninges/drug effects , Meninges/metabolism , Meninges/microbiology , Meningitis, Escherichia coli/cerebrospinal fluid , Meningitis, Escherichia coli/microbiology , Permeability , Rabbits , Treatment Outcome , Ceftaroline
4.
Antimicrob Agents Chemother ; 57(10): 4653-5, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23836180

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cephalosporins/therapeutic use , Meningitis/drug therapy , Penicillins/pharmacology , Streptococcus pneumoniae/pathogenicity , Animals , Penicillin Resistance , Rabbits , Streptococcus pneumoniae/drug effects , Ceftaroline
5.
Praxis (Bern 1994) ; 102(4): 233-6, 2013 Feb 13.
Article in German | MEDLINE | ID: mdl-23399608

ABSTRACT

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.


Subject(s)
Anemia, Iron-Deficiency/etiology , Gastrointestinal Hemorrhage/diagnosis , Turner Syndrome/diagnosis , Adult , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/genetics , Capsule Endoscopy , Diagnosis, Differential , Dilatation, Pathologic/diagnosis , Female , Gastrointestinal Hemorrhage/genetics , Hemangioma/diagnosis , Humans , Ileum/blood supply , Jejunum/blood supply , Telangiectasis/diagnosis , Turner Syndrome/genetics , Veins/pathology
6.
Praxis (Bern 1994) ; 101(22): 1441-4, 2012 Oct 31.
Article in German | MEDLINE | ID: mdl-23117965

ABSTRACT

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.


Subject(s)
Fatigue/etiology , Giant Cell Arteritis/diagnosis , Military Personnel , Weight Loss , Aortitis/diagnosis , Aortitis/pathology , Biopsy , Giant Cell Arteritis/pathology , Humans , Male , Middle Aged , Temporal Arteries/pathology
7.
Praxis (Bern 1994) ; 101(12): 793-8, 2012 Jun 06.
Article in German | MEDLINE | ID: mdl-22669783

ABSTRACT

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.


Subject(s)
Accidents, Occupational , Fires , Lung/drug effects , Petroleum/toxicity , Pneumonia, Aspiration/chemically induced , Follow-Up Studies , Humans , Male , Middle Aged , Pneumonia, Aspiration/diagnostic imaging , Pneumonia, Aspiration/rehabilitation , Respiratory Function Tests , Tomography, X-Ray Computed
8.
Antimicrob Agents Chemother ; 56(2): 921-5, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22064544

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Cephalosporins/administration & dosage , Disease Models, Animal , Gram-Negative Bacteria/drug effects , Meningitis, Bacterial/drug therapy , beta-Lactamases/metabolism , Animals , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/cerebrospinal fluid , Cephalosporins/blood , Cephalosporins/cerebrospinal fluid , Escherichia coli/drug effects , Escherichia coli/enzymology , Gram-Negative Bacteria/enzymology , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Haemophilus influenzae/drug effects , Haemophilus influenzae/enzymology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Meningitis, Bacterial/microbiology , Microbial Sensitivity Tests , Rabbits , Treatment Outcome
10.
Antimicrob Agents Chemother ; 53(7): 3030-3, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19364870

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Ceftriaxone/therapeutic use , Daptomycin/therapeutic use , Dexamethasone/therapeutic use , Meningitis, Bacterial/drug therapy , Vancomycin/therapeutic use , Animals , Chromatography, High Pressure Liquid , Drug Therapy, Combination , Rabbits
11.
Praxis (Bern 1994) ; 98(5): 245-6, 2009 Mar 04.
Article in German | MEDLINE | ID: mdl-19266449
12.
Praxis (Bern 1994) ; 97(24): 1301-3, 2008 Dec 03.
Article in German | MEDLINE | ID: mdl-19048509

ABSTRACT

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).


Subject(s)
Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antidiuretic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Deamino Arginine Vasopressin/therapeutic use , Diabetes Insipidus/complications , Diabetes Insipidus/diagnosis , Diabetes Insipidus/drug therapy , Diagnosis, Differential , Humans , Lung/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Palliative Care , Polyuria/complications , Radiography, Thoracic , Radiotherapy Dosage , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinblastine/therapeutic use , Vinorelbine
14.
Praxis (Bern 1994) ; 97(8): 437-42, 2008 Apr 16.
Article in German | MEDLINE | ID: mdl-18551914

ABSTRACT

From medical view the main problems of investigation and convicts are in particular in the range of the drugs and alcohol illnesses to see transferable diseases (HIV, hepatitis B - C and tuberculosis) and psychological illnesses. These complex diseases require a close meshed and intensive support of each individual patient and represent actually the main problem during an arrest. The development of the health service could address the new requirements making possible cost-conscious acting in handling with resources in the health service. In the canton Berne 957197 inhabitants live on a total area of 5959 km2. The police and military management operates the regional and district prisons as well as the transportation service for prisoners in the canton Berne for prisoners. The canton Berne has altogether 327 places. Since May 1971 persons from the regional and district prison and the penal institutions needing hospitalisation can be accepted. In the University hospital Berne on a specially equipped guard station and be cared for their medical problems. The prisoners profit in such a way from the entire range of the university facilities.


Subject(s)
Delivery of Health Care/organization & administration , Health Services Accessibility/organization & administration , Prisoners/statistics & numerical data , Prisons , Ambulatory Care/organization & administration , Ambulatory Care/statistics & numerical data , Communicable Disease Control/organization & administration , Comorbidity , Cross-Sectional Studies , Delivery of Health Care/statistics & numerical data , Female , HIV Infections/epidemiology , Health Services Accessibility/statistics & numerical data , Hepatitis B/epidemiology , Hepatitis C/epidemiology , Hospitalization/statistics & numerical data , Hospitals, University/organization & administration , Hospitals, University/statistics & numerical data , Humans , Male , Mental Disorders/epidemiology , Security Measures/organization & administration , Substance-Related Disorders/epidemiology , Switzerland
15.
Sleep Med ; 9(2): 191-8, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17644416

ABSTRACT

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.


Subject(s)
Disability Evaluation , Health Status , International Cooperation , Sleep Wake Disorders/classification , Sleep Wake Disorders/prevention & control , Humans , Sleep Wake Disorders/therapy , World Health Organization
18.
Cytotherapy ; 9(1): 35-43, 2007.
Article in English | MEDLINE | ID: mdl-17354100

ABSTRACT

BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.


Subject(s)
Bone Marrow Cells/cytology , Cell Separation/methods , Myocardial Infarction/therapy , Antigens, CD34/analysis , Bone Marrow Cells/immunology , Cell Separation/standards , Clinical Laboratory Techniques/standards , Flow Cytometry/methods , Flow Cytometry/standards , Quality Control , Reproducibility of Results
19.
Praxis (Bern 1994) ; 96(10): 383-5, 2007 Mar 07.
Article in German | MEDLINE | ID: mdl-17385283

ABSTRACT

Diseases associated with cobalamin deficiency often present a variety of neurological disorders apart from the well known megaloblastic anaemia as haematological manifestation. The peripheral and the central nervous system can be affected in different levels by the metabolic changes due to an impaired Vitamin B12 metabolism. Based upon an observed case we discuss the manifestation of cerebral convulsion possibly due to a secondarily acquired cobalamin deficiency. We conclude that in de novo cerebral convulsion in the elderly a cobalamin deficiency could play an important role.


Subject(s)
Epilepsy, Complex Partial/etiology , Vitamin B 12 Deficiency/diagnosis , Aged , Diagnosis, Differential , Female , Humans , Mental Status Schedule , Neurologic Examination
20.
Antimicrob Agents Chemother ; 51(6): 2249-52, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17371817

ABSTRACT

Daptomycin monotherapy was superior to ceftriaxone monotherapy and was highly efficacious in experimental pneumococcal meningitis, sterilizing the cerebrospinal fluid (CSF) of three of three rabbits after 4 to 6 h. With daptomycin therapy only a negligible release of [(3)H]choline as marker of cell wall lysis was detectable in the CSF, peaking around 250 cpm/min after 4 h, compared to a peak of around 2,400 cpm/min after 4 to 6 h for the ceftriaxone-treated rabbits.


Subject(s)
Anti-Bacterial Agents , Ceftriaxone , Cell Wall/drug effects , Daptomycin/therapeutic use , Meningitis, Pneumococcal/drug therapy , Streptococcus pneumoniae/drug effects , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacteriolysis , Ceftriaxone/administration & dosage , Ceftriaxone/pharmacology , Ceftriaxone/therapeutic use , Cerebrospinal Fluid/metabolism , Cerebrospinal Fluid/microbiology , Choline/metabolism , Daptomycin/administration & dosage , Daptomycin/pharmacology , Disease Models, Animal , Humans , Meningitis, Pneumococcal/microbiology , Microbial Sensitivity Tests , Penicillin Resistance , Rabbits , Treatment Outcome , Tritium/metabolism
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