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1.
Front Digit Health ; 6: 1359776, 2024.
Article in English | MEDLINE | ID: mdl-38606036

ABSTRACT

Introduction: Clinical assessment of upper limb sensorimotor function post-stroke is often constrained by low sensitivity and limited information on movement quality. To address this gap, recent studies proposed a standardized instrumented drinking task, as a representative daily activity combining different components of functional arm use. Although kinematic movement quality measures for this task are well-established, and optical motion capture (OMC) has proven effective in their measurement, its clinical application remains limited. Inertial Measurement Units (IMUs) emerge as a promising low-cost and user-friendly alternative, yet their validity and clinical relevance compared to the gold standard OMC need investigation. Method: In this study, we conducted a measurement system comparison between IMUs and OMC, analyzing 15 established movement quality measures in 15 mild and moderate stroke patients performing the drinking task, using five IMUs placed on each wrist, upper arm, and trunk. Results: Our findings revealed strong agreement between the systems, with 12 out of 15 measures demonstrating clinical applicability, evidenced by Limits of Agreement (LoA) below the Minimum Clinically Important Differences (MCID) for each measure. Discussion: These results are promising, suggesting the clinical applicability of IMUs in quantifying movement quality for mildly and moderately impaired stroke patients performing the drinking task.

3.
Plasma Sources Sci Technol ; 29(9): 095018, 2020 Sep.
Article in English | MEDLINE | ID: mdl-34149205

ABSTRACT

Atmospheric pressure plasmas have been ground-breaking for plasma science and technologies, due to their significant application potential in many fields, including medicinal, biological, and environmental applications. This is predominantly due to their efficient production and delivery of chemically reactive species under ambient conditions. One of the challenges in progressing the field is comparing plasma sources and results across the community and the literature. To address this a reference plasma source was established during the 'biomedical applications of atmospheric pressure plasmas' EU COST Action MP1101. It is crucial that reference sources are reproducible. Here, we present the reproducibility and variance across multiple sources through examining various characteristics, including: absolute atomic oxygen densities, absolute ozone densities, electrical characteristics, optical emission spectroscopy, temperature measurements, and bactericidal activity. The measurements demonstrate that the tested COST jets are mainly reproducible within the intrinsic uncertainty of each measurement technique.

4.
Sci Rep ; 8(1): 7736, 2018 05 16.
Article in English | MEDLINE | ID: mdl-29769633

ABSTRACT

Reactive oxygen and nitrogen species released by cold physical plasma are being proposed as effectors in various clinical conditions connected to inflammatory processes. As these plasmas can be tailored in a wide range, models to compare and control their biochemical footprint are desired to infer on the molecular mechanisms underlying the observed effects and to enable the discrimination between different plasma sources. Here, an improved model to trace short-lived reactive species is presented. Using FTIR, high-resolution mass spectrometry, and molecular dynamics computational simulation, covalent modifications of cysteine treated with different plasmas were deciphered and the respective product pattern used to generate a fingerprint of each plasma source. Such, our experimental model allows a fast and reliable grading of the chemical potential of plasmas used for medical purposes. Major reaction products were identified to be cysteine sulfonic acid, cystine, and cysteine fragments. Less-abundant products, such as oxidized cystine derivatives or S-nitrosylated cysteines, were unique to different plasma sources or operating conditions. The data collected point at hydroxyl radicals, atomic O, and singlet oxygen as major contributing species that enable an impact on cellular thiol groups when applying cold plasma in vitro or in vivo.

5.
J Dairy Sci ; 101(6): 5159-5165, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29525317

ABSTRACT

We conducted 2 experiments to determine lysine loss from 2 lipid-coated lysine products after mixing with silage. In our first experiment, we mixed 2 lipid-coated lysine products, crystalline lysine or crystalline lysine and amounts of lipid identical to amounts included in lipid-coated lysine products, with alfalfa or corn silage that had 2 different amounts of acidity. Lysine appeared to disassociate from lipid-coated lysine products in a nonlinear manner after mixing with either alfalfa or corn silage at different amounts of acidity. Additionally, silage source and acidity affected amounts of lysine released from lipid-coated lysine products after mixing. In a corresponding experiment, in vitro estimates of lysine available to ruminal microbiota after mixing with alfalfa or corn silage at different amounts of acidity were measured by ammonia release. In vitro measures were conducted with or without monensin to allow estimates of effects of monensin on amounts of lysine released from the 2 lipid-coated lysine products. It is unclear whether in vitro estimates of lysine fermentation from lipid-coated lysine are truly reflective of ruminal degradation of lysine from lipid-coated lysine because amounts of time needed to measure differences between different lysine sources were greater than typical estimates of mean ruminal particulate retention time. Nonetheless, monensin apparently reduced ammonia release from lysine, but ammonia release from lipid-coated lysine did not differ from crystalline lysine. Clearly, methods of manufacture together with physical and chemical characteristics of diet can affect amounts of lysine provided from lipid-coated lysine products to ruminants.


Subject(s)
Digestion/physiology , Drug Carriers , Fermentation , Lysine/metabolism , Animals , Diet , Female , Lactation , Lipids , Lysine/administration & dosage , Medicago sativa , Rumen , Silage , Zea mays
6.
BMC Public Health ; 17(1): 130, 2017 01 28.
Article in English | MEDLINE | ID: mdl-28129759

ABSTRACT

BACKGROUND: Sub-Saharan Africa is undergoing an epidemiological transition from a predominance of infectious diseases to non-communicable and lifestyle related conditions. However, the pace of this transition and the pattern of disease epidemiology are uneven between affluent urban and rural poor populations. To address this question for a remote rural region located in the central African rainforest region of Gabon, this study was conducted to assess reasons for health care attendance and to characterize the epidemiology of malaria and other major infectious diseases for the department of Tsamba Magotsi. METHODS: Major causes for health care attendance were collected from local hospital records. Cross sectional population based surveys were performed for the assessment of local malaria epidemiology. Pregnant women attending antenatal care services were surveyed as a sentinel population for the characterization of chronic viral and parasitic infections in the community. RESULTS: Infectious diseases were responsible for 71% (7469) of a total of 10,580 consultations at the formal health care sector in 2010. Overall, malaria - defined by clinical syndrome - remained the most frequent cause for health care attendance. A cross sectional malaria survey in 840 asymptomatic individuals residing in Tsamba Magotsi resulted in a Plasmodium spp. infection prevalence of 37%. The infection rate in 2-10 year old asymptomatic children - a standard measure for malaria endemicity - was 46% (100 of 217) with P. falciparum as predominant species (79%). Infection with other plasmodial species (P. ovale and P. malariae) presented most commonly as coinfections (23.2%). Prevalence of HIV, HBV, and syphilis were 6.2, 7.3, and 2.5%, respectively, in cross-sectional assessments of antenatal care visits of pregnant women. Urogenital schistosomiasis and the filarial pathogens Loa loa and Mansonella perstans are highly prevalent chronic parasitic infections affecting the local population. CONCLUSIONS: Despite major improvements in the accessibility of Tsamba Magotsi over the past decade the epidemiological transition does not appear to have majorly changed on the spectrum of diseases in this rural Gabonese population. The high prevalence of Plasmodium infection indicates a high burden of malaria related morbidity. Infectious diseases remain one of the most important health issues and further research activities in the field of tropical medicine and infectious diseases could help improve health care for the local population.


Subject(s)
Malaria/epidemiology , Maternal Health/statistics & numerical data , Pregnancy Complications, Infectious/epidemiology , Rural Population/statistics & numerical data , Adult , Cross-Sectional Studies , Female , Gabon/epidemiology , Humans , Pregnancy , Pregnancy Complications, Parasitic/epidemiology , Pregnant Women , Prenatal Care/statistics & numerical data , Prevalence
7.
Transl Anim Sci ; 1(3): 311-319, 2017 Sep.
Article in English | MEDLINE | ID: mdl-32704656

ABSTRACT

We conducted 2 experiments to determine lysine bioavailability from 2 lipid-coated lysine products. In an in vitro experiment we mixed each lipid-coated lysine product with either alfalfa- or corn-silage at different amounts of acidity. Scanning electron micrographs indicated that surface structure of each lipid-coated lysine particle was eroded after mixing with silage. Additionally, visual evaluation of scanning electron micrographs suggested that peripheral surface abrasion of lipid-coated lysine may be greater when lipid-coated lysine was mixed with alfalfa silage in comparison to corn silage. In a corresponding experiment, in vivo measures of lysine bioavailability to sheep from 2 lipid-coated lysine products and lysine-HCl were determined after mixing in corn silage. Plasma lysine concentrations increased linearly (P < 0.01) in response to abomasal lysine infusion indicating that our model was sensitive to increases in metabolizable lysine flow. Bioavailability of each lipid-coated lysine source and dietary lysine-HCl were calculated to be 23, 15, and 18%, respectively. Even though each dietary source of lysine increased plasma lysine, rates of increases in plasma lysine from one lipid-coated lysine source (linear; P = 0.20) and lysine-HCl (linear; P = 0.11) were not different from plasma lysine levels supported by diet alone. However, the rate of plasma lysine increase in response to lysine from the other lipid-coated lysine source was greater (P = 0.04) than plasma lysine from feed alone. Nonetheless, the rate of plasma lysine increase in response to lipid-coated lysine did not differ (P ≥ 0.70) from the rate of plasma lysine increase from lysine-HCl. Clearly, methods of manufacture, together with physical and chemical characteristics of diet, can impact amounts of metabolizable lysine provided from lipid-coated lysine products. Direct measures of lysine bioavailability from lipid-coated lysine products after mixing with diets should be based on measurements with the products treated similarly to the method of feeding.

8.
Gesundheitswesen ; 79(12): 1043-1049, 2017 Dec.
Article in German | MEDLINE | ID: mdl-26695539

ABSTRACT

BACKGROUND: In spite of a nationwide implementation of performance indicators (PI) for monitoring inpatient medical care, a systematic evaluation of their development over time is still missing. METHODS: A trend analysis of annual rates of PI from 2006/07 to 2013 of Bavarian hospitals was conducted; 123 out of a total of 245 PI selected from 15 distinct clinical fields were available and comparable over the entire period and evaluated. Joinpoint regression was used to estimate annual percentage changes (APC) in regional averages. Individual hospital rates were inspected with box plots for selected indicators. RESULTS: 99 PI (80.5%) showed improvement over time, 67 (54.5% of all PI) were statistically significant. A change from positive to negative trend was found in 15 indicators (12.2%); the negative trend was significant only once. A continuous negative trend was observed in 9 cases (7.3%) (3 significant). Extreme values of hospital rates were present throughout the entire period of observation with results generally far below the national average. CONCLUSION: The majority of indicators improved continuously, which may be interpreted as indicating effectiveness of quality assurance programs, and could also give a strong impetus to further quality improvement measures.


Subject(s)
Quality Assurance, Health Care , Quality Indicators, Health Care , Germany , Hospitals/standards , Humans , Quality Improvement
9.
Prog Brain Res ; 229: 303-323, 2016.
Article in English | MEDLINE | ID: mdl-27926445

ABSTRACT

Knowledge of performance can activate the striatum, a key region of the reward system and highly relevant for motivated behavior. Using functional magnetic resonance imaging, striatal activity linked to knowledge of performance was measured during the training of a repetitive arc-tracking task. Knowledge of performance was given after a random selection of trials or after good performance. The third group received knowledge of performance after good performance plus a monetary reward. Skill learning was measured from pre- to post- (acquisition) and from post- to 24h posttraining (consolidation). Our results demonstrate an influence of feedback on motor skill learning. Adding a monetary reward after good performance leads to better consolidation and higher ventral striatal activation than knowledge of performance alone. In turn, rewarding strategies that increase ventral striatal response during training of a motor skill may be utilized to improve skill consolidation.


Subject(s)
Corpus Striatum/physiology , Feedback, Psychological/physiology , Motor Skills/physiology , Reward , Adult , Corpus Striatum/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Oxygen/blood , Photic Stimulation , Young Adult
10.
Euro Surveill ; 20(16)2015 Apr 23.
Article in English | MEDLINE | ID: mdl-25953271

ABSTRACT

Onchocerca lupi, a nematode parasite infecting dogs and cats with a hitherto unknown arthropod vector, is also being recognised as a parasite also responsible for human eye infections. Here we describe a case of human eye infection diagnosed molecularly by nematode 12S rDNA PCR in a German patient who had travelled to Tunisia and Turkey. The patient recovered after treatment with antibiotic and anti-inflammatory therapy.


Subject(s)
Onchocerca/genetics , Onchocerca/isolation & purification , Onchocerciasis, Ocular/diagnosis , Travel , Adult , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , DNA, Ribosomal/genetics , Germany , Humans , Male , Onchocerca/classification , Onchocerciasis, Ocular/drug therapy , Onchocerciasis, Ocular/parasitology , Polymerase Chain Reaction , Treatment Outcome , Tunisia , Turkey
11.
Klin Padiatr ; 227(1): 41-4, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25565197

ABSTRACT

Here we report on a case of primary cryptococcal skin infection in an immunocompetent 8-year-old boy. The infection first manifested itself as a subcutaneous abscess around the proximal joint of his right thumb after a minor injury from contact with a thorny shrub. After surgical incision and drainage was performed, Cryptococcus neoformans var. neoformans was the only pathogen cultured from the lesion. An agglutination test for the capsular antigen in serum displayed negative results and the immunological work-up revealed no underlying immunodeficiency. A "watch and wait" strategy - one without systemic antifungal treatment - was adopted and this resulted in uneventful healing. In summary, primary cryptococcal skin infections in immunocompetent hosts may be managed successfully by surgical treatment in combination with careful clinical follow-up. This approach may help avoid unnecessary antimicrobial treatments.


Subject(s)
Abscess/therapy , Antifungal Agents/administration & dosage , Cryptococcosis/therapy , Cryptococcus neoformans , Dermatomycoses/therapy , Drainage , Immunocompetence , Thumb , Abscess/diagnosis , Child , Combined Modality Therapy , Cryptococcosis/diagnosis , Dermatomycoses/diagnosis , Follow-Up Studies , Humans , Male , Thumb/injuries
12.
Infection ; 41(6): 1163-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23661288

ABSTRACT

PURPOSE: The detection of galactomannan in serum is a cornerstone for the diagnosis of invasive fungal disease (IFD). Because a delay in treatment initiation is associated with a poor outcome, the results have to be available promptly. However, due to methodological and economic reasons, the test frequencies of the commonly used galactomannan assays vary between daily to weekly, meaning that results may be available too late to be clinically useful. The novel Aspergillus lateral-flow device (Aspergillus-LFD) is a rapid test that may overcome these limitations. METHODS: We compared the diagnostic performance of the Aspergillus-LFD and the Platelia® Aspergillus EIA (GM-EIA) in serum from 101 patients during and after allogeneic haematopoietic stem cell transplantation (HSCT). Clinical data and sera were collected prospectively and patients classified according to the European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) 2008 guidelines. RESULTS: By the end of hospitalisation, one proven, nine probable and 20 possible cases of IFD were identified. Depending on the number of positive serum samples required for test positivity, the sensitivities, specificities and diagnostic odds ratios in patients with proven and probable IFD were as follows. One positive serum required: Aspergillus-LFD 40.0 %, 86.8 % and 3.03; GM-EIA 40.0 %, 89.0 % and 3.64. Two positive sera required: Aspergillus-LFD 20.0 %, 97.8 % and 11.13; GM-EIA 30.0 %, 98.9 % and 38.57. Although the GM-EIA was positive in a higher percentage of samples, this did not result in an earlier diagnosis. CONCLUSIONS: If used as a screening test (one positive serum required for test positivity) or to rule out IFD, the Aspergillus-LFD has shown a comparable diagnostic performance to the GM-EIA. However, if the results have to be confirmed by a second positive serum, the GM-EIA exhibited superior sensitivity. In terms of practicability, the Aspergillus-LFD has demonstrated to be a quick (15 min) and easy-to-use test for single-patient detection of Aspergillus antigens.


Subject(s)
Aspergillosis/diagnosis , Hematopoietic Stem Cell Transplantation/adverse effects , Mannans/blood , Adult , Aged , Aspergillus/isolation & purification , Biomarkers/blood , Chromatography, Affinity/instrumentation , Chromatography, Affinity/methods , False Positive Reactions , Female , Galactose/analogs & derivatives , Humans , Immunoenzyme Techniques/instrumentation , Immunoenzyme Techniques/methods , Male , Middle Aged , Reagent Kits, Diagnostic , Young Adult
13.
Mucosal Immunol ; 5(3): 299-310, 2012 May.
Article in English | MEDLINE | ID: mdl-22333910

ABSTRACT

T helper (Th)1 and Th2 cells play decisive roles in the regulation of resistance vs. susceptibility to pulmonary cryptococcosis. To study the function of interleukin (IL)-4 receptor (IL-4R) on Th cells in pulmonary cryptococcosis, we infected mice specifically lacking IL-4Rα on CD4(+) T cells (Lck(Cre)IL-4Rα(-/lox) mice) and IL-4Rα(-/lox) controls. Lck(Cre)IL-4Rα(-/lox) mice developed enhanced resistance accompanied by reduced pulmonary allergic inflammation and diminished production of the Th2 cytokines IL-4, IL-5, and IL-13 as compared with IL-4Rα(-/lox) mice. Polyfunctional antigen-specific Th2 cells producing simultaneously two or three Th2 cytokines were reduced in infected Lck(Cre)IL-4Rα(-/lox) mice, pointing to a critical role of polyfunctional Th2 cells for disease progression. Reduced Th2 polyfunctionality was associated with fewer pulmonary alternatively activated macrophages. This work is the first direct evidence for a critical contribution of the IL-4R on Th cells to Th2-dependent susceptibility during allergic bronchopulmonary mycosis. Moreover, the data demonstrate that the quality of the Th2 response has an impact on type 2 inflammation. The analysis of polyfunctional Th2 cells may be useful for monitoring the course of the disease.


Subject(s)
Cryptococcosis/immunology , Cryptococcus neoformans/immunology , Invasive Pulmonary Aspergillosis/immunology , Lung/metabolism , Macrophages/immunology , Receptors, Interleukin-4/metabolism , Th2 Cells/immunology , Animals , Cryptococcosis/complications , Cryptococcus neoformans/pathogenicity , Cytokines/metabolism , Disease Susceptibility , Humans , Invasive Pulmonary Aspergillosis/etiology , Lung/immunology , Lung/pathology , Macrophage Activation/genetics , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Transgenic , Receptors, Interleukin-4/genetics , Receptors, Interleukin-4/immunology , Th1 Cells/immunology , Virulence
14.
Scanning ; 34(4): 221-9, 2012.
Article in English | MEDLINE | ID: mdl-22076793

ABSTRACT

We report the investigation of the interfaces between microneedle arrays and cell cultures in patch-on-chip systems by using Focused Ion Beam (FIB) preparation and Scanning Electron Microscopy (SEM). First, FIB preparations of micro chips are made to determine the size and shape of the designed microneedles. In this essay, we investigate the cell-substrate interaction, especially the cell adhesion, and the microneedle's potential cell penetration. For this purpose, cross-sectional preparation of these hard/soft hybrid structures is performed by the FIB technology. By applying the FIB technology followed by high-resolution imaging with SEM, new insights into the cell-substrate interface can be received. One can clearly distinguish between cells that are only in contact with microneedles and cells that are penetrated by microneedles. A stack of slice images is collected by the application of the slice-and-view setup during FIB preparation and is used for three-dimensional reconstruction of cells and micro-needles.


Subject(s)
Cell Adhesion , Fibroblasts/physiology , Microscopy, Electron, Scanning/methods , Specimen Handling/methods , Animals , Mice
15.
Clin Microbiol Infect ; 17(7): 1118-22, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21446990

ABSTRACT

Serum (1→3)-ß-D-Glucan (BG) is a biomarker for Pneumocystis jirovecii pneumonia (PJP). However, information concerning its usefulness for monitoring the clinical course is lacking. We conducted a retrospective study to investigate whether consecutive BG-measurements can be used to assess treatment response in PJP. Analysis of sera from 18 patients during PJP therapy shows that decreasing BG-levels strongly correlate with a favourable clinical course. In contrast, increasing BG-levels were associated with treatment failure or fatal outcome is only 44% of patients. As a consequence, BG-kinetics might be used to confirm treatment success but seem to be of limited value for the identification of treatment failure.


Subject(s)
Drug Monitoring/methods , Pneumocystis carinii/chemistry , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy , beta-Glucans/blood , Biomarkers/blood , Humans , Middle Aged , Proteoglycans , Retrospective Studies , Treatment Outcome
16.
Clin Microbiol Infect ; 17(4): 595-602, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20673271

ABSTRACT

Pneumocystis jirovecii (carinii) pneumonia (PJP) is a major cause of disease in immunocompromised individuals. However, until recently no reliable and specific serological parameters for the diagnosis of PJP have been available. (1 → 3)-ß-D-Glucan (BG) is a cell wall component of P. jirovecii and of various other fungi. Data from the past few years have pointed to serum measurement of BG as a promising new tool for the diagnosis of PJP. We therefore conducted a retrospective study on 50 patients with PJP and 50 immunocompromised control patients to evaluate the diagnostic performance of serum BG measurement. Our results show an excellent diagnostic performance with a sensitivity of 98.0% and a specificity of 94%. While the positive predictive value was only 64.7%, the negative predictive value was 99.8% and therefore a negative BG result almost rules out PJP. BG levels were already strongly elevated in an average of 5 days and up to 21 days before microbiological diagnosis demonstrating that the diagnosis could have been confirmed earlier. BG levels at diagnosis and maximum BG levels during follow-up did not correlate with the outcome of patients or with the P. jirovecii burden in the lung as detected by Real-Time PCR. Therefore, absolute BG levels seem to be of no prognostic value. Altogether, BG is a reliable parameter for the diagnosis of PJP and could be used as a preliminary test for patients at risk before a bronchoalveolar lavage is performed.


Subject(s)
Biomarkers/blood , Pneumonia, Pneumocystis/diagnosis , Serum/chemistry , beta-Glucans/blood , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Proteoglycans , Retrospective Studies , Sensitivity and Specificity , Time Factors , Young Adult
17.
Parasitol Res ; 104(6): 1459-64, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19172294

ABSTRACT

Glycerol derivatives are a class of compounds, which are easy and inexpensive to produce with potent anti-malarial activities against blood stages of Plasmodium falciparum in vitro. In the present study, one of these compounds, termed 1t, which had the lowest IC(50) values, was assessed in a murine malarial model. Nuclear magnetic resonance imaging and Balb/c mice infected with Plasmodium berghei ANKA strain were treated in a 4-day suppressive test. Mice received a once-daily intraperitoneal administration of 50 mg/Kg of the drug for 4 days. Although no parasitaemia clearance was reached, a slower parasite proliferation and a slightly longer survival time compared with the placebo group were observed.


Subject(s)
Amino Alcohols/therapeutic use , Antimalarials/therapeutic use , Malaria/drug therapy , Plasmodium berghei/drug effects , Amino Alcohols/administration & dosage , Amino Alcohols/pharmacology , Animals , Antimalarials/administration & dosage , Antimalarials/pharmacology , Female , Inhibitory Concentration 50 , Injections, Intraperitoneal , Male , Mice , Mice, Inbred BALB C , Parasitemia/drug therapy , Survival Analysis
18.
Anaesthesist ; 51(2): 110-5, 2002 Feb.
Article in German | MEDLINE | ID: mdl-11963302

ABSTRACT

INTRODUCTION: The aim of this study was the detection and understanding of weak points in the ergonomic design of anaesthesia workplaces in a multidisciplinary operating room facility. METHODS: Analysis of workplaces and of working processes by means of observations, computer-supported task recording and video-photo documentation. During guided interviews the participants were provided with material for naming-by-pointing and drawing. Subsequently, the background of the problems encountered and possible improvements were visualised. RESULTS: Important deficits were devices not positioned within reach and view, difficulties in operating the lines connecting the patient and the devices, and inconsistent workplace layouts. These were caused by erroneous planning of the facility and disregarding ergonomic principles in equipment design. The initial improvements implemented were the development of a new concept for a flexible equipment positioning and the design of a tool for cable handling. DISCUSSION AND CONCLUSION: Although from the very beginning of the study the anaesthesia personnel quoted the handling of the lines connecting patients and devices as the main cause for working difficulties, the external ergonomist could contribute to a broader view of the problems. The method presented here initiated a mutual learning process between ergonomist and users and resulted in a common understanding of the problems and their causes. Compared to the traditional consulting process, more time and efforts were necessary but were offset by the users' acceptance of the improvements and the prevention of design errors.


Subject(s)
Anesthesia , Anesthesiology/instrumentation , Ergonomics , Operating Rooms/organization & administration , Workplace , Interviews as Topic
19.
Hepatology ; 34(4 Pt 1): 758-67, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11584373

ABSTRACT

Hepatitis C virus (HCV) infection is a major cause of liver disease characterized by inflammation, cell damage, and fibrotic reactions of hepatocytes. Apoptosis has been implicated in the pathogenesis, although it is unclear whether proteases of the caspase family as the central executioners of apoptosis are involved and how caspase activation contributes to liver injury. In the present study, we measured the activation of effector caspases in liver biopsy specimens of patients with chronic HCV infection. The activation of caspase-3, caspase-7, and cleavage of poly(ADP-ribose)polymerase (PARP), a specific caspase substrate, were measured by immunohistochemistry and Western blot analysis by using antibodies that selectively detect the active truncated, but not the inactive precursor forms of the caspases and PARP. We found that caspase activation was considerably elevated in liver lobules of HCV patients in comparison to normal controls. Interestingly, the immunoreactive cells did yet not reveal an overt apoptotic morphology. The extent of caspase activation correlated significantly with the disease grade, i.e., necroinflammatory activity. In contrast, no correlation was observed with other surrogate markers such as serum transaminases and viral load. In biopsy specimens with low activity (grade 0) 7.7% of the hepatocytes revealed caspase-3 activation, whereas 20.9% of the cells stained positively in grade 3. Thus, our results suggest that caspase activation is involved in HCV-associated liver injury. Moreover, measurement of caspase activity may represent a reliable marker for the early detection of liver damage, which may open up new diagnostic and therapeutic strategies in HCV infection.


Subject(s)
Caspases/metabolism , Hepatitis C, Chronic/pathology , Liver/pathology , Adult , Apoptosis , Biopsy , Caspase 3 , Caspase 7 , DNA Fragmentation , Enzyme Activation , Female , Hepatitis C, Chronic/enzymology , Humans , In Situ Nick-End Labeling , Liver/enzymology , Male , Middle Aged , Poly(ADP-ribose) Polymerases/metabolism , Tumor Cells, Cultured , fas Receptor/biosynthesis
20.
Drug Resist Updat ; 4(4): 243-52, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11991679

ABSTRACT

Induction of apoptosis in tumor cells is a major goal for chemotherapy and radiation treatment strategies. However, disordered gene expression often leads to apoptosis resistance rendering tumor cells insensitive to various conventional treatments. TNF-related apoptosis-inducing ligand (TRAIL) is a recently identified cytokine of the TNF superfamily that induces apoptosis in tumor cells upon binding to different receptors. Remarkably, the majority of tumor cell lines are sensitive to TRAIL-induced apoptosis, while most nontransformed cell types are TRAIL-resistant. Furthermore, a combination treatment of TRAIL with ionizing irradiation or chemotherapeutic agents induces apoptosis in a highly synergistic manner, particularly in those cells that are otherwise resistant to a sole treatment. In contrast to other TNF members, TRAIL apparently does not exert overt systemic toxicity in murine and primate models, although unexpected concerns about a potential hepatotoxicity of TRAIL have been recently raised. While the molecular mechanisms of TRAIL sensitivity and resistance are poorly understood, TRAIL seems to be a promising biological agent for combination therapy with chemotherapeutic drugs or irradiation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Membrane Glycoproteins/administration & dosage , Neoplasms/drug therapy , Tumor Necrosis Factor-alpha/administration & dosage , Animals , Antineoplastic Combined Chemotherapy Protocols/metabolism , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Apoptosis/physiology , Apoptosis Regulatory Proteins , Drug Resistance, Neoplasm/physiology , Humans , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/pharmacology , Neoplasms/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology , TNF-Related Apoptosis-Inducing Ligand , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/metabolism , Tumor Necrosis Factor-alpha/pharmacology
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