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Biomedical subjects

C Moser

Publications and source records attributed to C Moser.

At least 19 recordsLinked to original sources

Cyclophosphamide pulse therapy followed by azathioprine or methotrexate induces long-term remission in patients with steroid-refractory Crohn's disease.

BACKGROUND: In patients with steroid-refractory Crohn's disease, the therapeutic goal is to achieve both rapid remission and maintenance of clinical response. AIM: To evaluate the long-term benefit in patients treated with cyclophosphamide pulse therapy and azathioprine or methotrexate, a combination shown to be effective in a recent pilot study. METHODS: Sixteen patients with acute steroid-refractory Crohn's disease participated in a prospective open-labelled uncontrolled pilot study between December 1998 and June 2003. All had a median number of 4 monthly pulses of intravenous cyclophosphamide (750 mg) and were followed until relapse of the disease. RESULTS: Thirteen of 16 patients (81%) achieved remission within 8 weeks after two pulses of cyclophosphamide in combination with azathioprine or methotrexate, with a Crohn's Disease Activity Index decrease from 294 to 111 (median). Remission sustained for 19 months (median, range: 1-45). Moreover, eight patients with pyoderma gangrenosum and erythema nodosum who responded to cyclophosphamide have maintained their remission for up to 30 months. CONCLUSIONS: In steroid refractory patients with Crohn's disease, cyclophosphamide is highly effective to induce remission. This uncontrolled study indicates that cyclophosphamide-induced remission is long-lasting under standard immunosuppressive therapy.

Adult↗

Inflexal V--the influenza vaccine with the lowest ovalbumin content.

The antigen used in influenza vaccines is directly derived from influenza viruses. It is produced in embryonated chicken eggs for both inactivated and live attenuated influenza vaccines. As a consequence, all influenza vaccines contain varying amounts of residual egg proteins, depending on the specific manufacturing process of the vaccine. The degree of purity of influenza vaccines can be assessed by quantifying the total amount of protein in relation to the amount of specific antigen. Alternatively, ovalbumin can be used as surrogate marker, representing the amount of egg-derived proteins present in the vaccine. Egg proteins, such as ovalbumin, are classified as sensitising agents. Their presence in a vaccine may be linked to adverse reactions. Such a vaccine is not suitable for subjects with a known history of egg-allergy. This population is currently excluded from influenza vaccination programs. Influenza vaccines are intended for annual re-immunisation. This repeated administration may lead to an immunity against ovalbumin and other egg proteins, which in turn may provoke increased local and systemic reactions and a reduced tolerability profile of the product. Comparing several influenza vaccines present on the market, ELISA and Western blot analysis showed clearly a very low level of ovalbumin in Inflexal V. Furthermore, data showed, that Inflexal V is the influenza vaccine with the lowest ovalbumin content.

Blotting, Western↗

Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia.

BACKGROUND: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs is reflected as a migration of PMNs through the blood in chronically infected CF patients. METHODS: Blood and sputum samples from 37 stable, chronically (CF+P) and 6 non-infected (CF-P) CF patients without exacerbations were compared using FACS, leukocyte counting, and ELISA. Within the CF+P patients, the blood parameters were compared to the lung function (FEV1 and FVC) and to the sputum. Similar measurements were performed on 15 chronically infected CF patients before and after elective antibiotic treatment. RESULTS: In the CF+P patients the concentration of G-CSF in the sera and PMNs in the blood was increased and correlated to poor lung function. However, only the concentration of G-CSF in the sera was correlated to the concentration of TNF-alpha in the sputum. After the antibiotic treatment, the lung function was improved and the concentration of PMNs in the blood and G-CSF in the sera was reduced. CONCLUSION: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status.

Adolescent↗

Filter cubes with built-in ultrabright light-emitting diodes as exchangeable excitation light sources in fluorescence microscopy.

The use of ultrabright light-emitting diodes as a potential substitute for conventional excitation light sources in fluorescence microscopy is demonstrated. We integrated ultrabright light-emitting diodes in the filter block of a conventional fluorescence microscope together with a collimating Fresnel lens, a holographic diffuser and emission filters. This setup enabled convenient changes between different excitation light sources and resulted in high excitation efficiencies. Quantitative comparison of image intensities of test samples revealed that light-emitting diodes yielded intensities in the range of a mercury arc lamp depending on the wavelength. The use of ultrabright light-emitting diodes also enabled luminescence lifetime imaging without the need for image intensification.

Journal Article↗

[About fruits and vegetables: the paradise does not come back].

An increased fruit and vegetable consumption might be associated with a protection for the development of chronic diseases. The postulated mechanisms of this protection are multiple and no single mechanism can be identified. It is important to remember that the protection is mediated by the ideal combination of nutrients and phytochemicals in fruits and vegetables and not by a single chemical component. Accordingly it is more wise to eat fruits and vegetables instead of isolated compounds in pharmacological dosage.

Adult↗

Comparative analysis of expressed sequence tags from different organs of Vitis vinifera L.

Expressed sequence tags (ESTs) are providing a valuable approach to sampling organism-expressed genomes, especially when studying large genomes such as those of many plants. We report on the comparison of 8,647 ESTs generated from six different grape (Vitis vinifera L.) organs: berry, root, leaf, bud, shoot and inflorescence. Clustering and assembly of these ESTs resulted in 4,203 unique sequences and revealed that at this level of EST sampling, each organ shares a low percentage of transcripts with the others. To define organ relationships based on EST counts, we calculated a distance matrix of pairwise correlation coefficients between the libraries which indicated bud, inflorescence and shoot as a group distinct from the other organs considered in this study. A putative function was identified for about 85% of the unique sequences. By assigning them to specific functional classes, we were able to highlight strong differences between organs in the metabolism, protein biosynthesis and photosynthesis categories. This grape EST collection has also proven to be a valuable source for the development of 'functional' simple sequence repeats (SSRs) markers: a total of 405 SSRs have been identified. EST sequences and annotation results have been organised in the IASMA-grape database, freely available at the address http://genomics.iasma.it.

DNA, Complementary↗

[Fruit and vegetable].

An increased fruit and vegetable intake is associated with a reduced risk for chronic diseases. The protective effects are due to different mechanisms such as an increased intake of essential micronutrients as well as different non-nutritive phytochemicals. A dietary pattern characterised by a high intake of fruits and vegetables has a much higher protective effect than the intake of pharmacological doses of single nutrients or phytochemicals.

Chronic Disease↗

Development of ulcerative colitis after heart transplantation during immunosuppressive therapy.

BACKGROUND: Cardiac transplantation has become an accepted treatment modality for end-stage heart failure. Immunosuppressive agents, which are used after transplantation, are considered as therapeutic options for inflammatory bowel disease. CASE REPORT: We report on a 53-year-old patient who was treated for 2 years with cyclosporine A, azathioprine and prednisolone after heart transplantation. He developed a distal colitis with all features of ulcerative colitis. An infectious or ischemic etiology was carefully excluded. In spite of high-dose treatment with prednisolone the patient's abdominal symptoms worsened and he developed a progression of the inflammation in the entire colon and a colectomy with ileostomy was necessary. The histology was consistent with ulcerative colitis. After colectomy he recovered and remained in a good state of health. CONCLUSIONS: This report supports the concept that new onset inflammatory bowel disease can develop in a heart transplantation recipient in spite of immunosuppression.

Biopsy↗

Duodenal angiolipoma -- endoscopic diagnosis and therapy.

We report on two patients with upper gastrointestinal bleeding owing to duodenal angiolipomas, and their endoscopic diagnosis and therapy. In both cases the bleeding source was a pedunculated tumour. Diagnosis and definitive therapy was made by endoscopic snare polypectomy. After stopping the bleeding from the mucosal defect by injection therapy in one patient, the further course was uneventful in both. A colonic angiolipoma in one of the patients was also treated by polypectomy. Gastrointestinal angiolipomas are exceedingly rare, however, these case reports show that duodenal angiolipomas do exist and that they, as lipomas, may lead to substantial gastrointestinal bleeding and may be treated successfully by standard polypectomy techniques.

Adenomatous Polyps↗

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection.

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.

Animals↗

Safety and efficacy of intravenous pulse cyclophosphamide in acute steroid refractory inflammatory bowel disease.

BACKGROUND AND AIMS: One major problem in the management of steroid refractory attacks of patients with inflammatory bowel disease (IBD) is the establishment of a rapidly acting immunosuppressive regimen. Based on its well known efficacy in systemic vasculitis, intravenous cyclophosphamide pulse therapy was used in refractory IBD patients to evaluate both its efficacy and safety. METHODS: Between December 1998 and May 2001, seven patients (Crohn's disease, n=5; indeterminate colitis, n=1) with severe steroid refractory IBD (Crohn's disease activity index (CDAI) 264-479 points) received 4-6 cycles of monthly treatment with intravenous cyclophosphamide (750 mg) in a prospective uncontrolled pilot study. RESULTS: All patients improved after two intravenous pulses of cyclophosphamide and six of seven patients achieved complete remission (CDAI <150 points). One patient with Crohn's disease of the small and large bowel showed an impressive clinical response but did not enter into remission. Tapering to low dose steroids was possible in all responders. Remission was maintained in all patients for 18 months (median) but required a second course of intravenous pulse cyclophosphamide in one patient. The drug was well tolerated except for two episodes of candida oesophagitis. CONCLUSIONS: Intravenous pulse cyclophosphamide may be a safe and effective treatment in patients with severe IBD unresponsive to steroid treatment and merits evaluation in a controlled trial.

Acute Disease↗

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.

Animals↗

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response.

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.

Agar↗

Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis.

Exercise can stimulate catabolic inflammatory cytokines even in healthy children. For patients with cystic fibrosis (CF), this may be problematic because CF is characterized by increased inflammation and suppressed growth. We examined fitness and the response to brief exercise of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 +/- 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 +/- 0.5 yr of age, NS). Subjects performed brief intermittent, constant work rate protocol (scaled to each individual's exercise capacity) with blood and urine sampling. Peak V O(2) was correlated with IGF-I (r = 0.68, p < 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p < 0.05) and IGF-I was 47% lower than in control subjects (p < 0.05). Post hoc analysis revealed a progressive increase in the IL-6 response to exercise, with the lowest increase observed in control subjects (11.8 +/- 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 +/- 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 +/- 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-alpha. Exercise also significantly increased IGFBP-1 in both control subjects and subjects with CF. Brief exercise can increase even chronically elevated inflammatory mediators in CF, and this response may be attenuated by ibuprofen.

Adolescent↗

Limited signal transduction repertoire of human Y(5) neuropeptide Y receptors expressed in HEC-1B cells.

In HEC-1B cells transfected with human Y(5) neuropeptide Y (NPY) receptors (but not in non-transfected cells) NPY inhibited forskolin-stimulated cAMP accumulation in a pertussis toxin-sensitive manner (-log EC(50) 8.88 +/- 0.25). Elevations of intracellular Ca(2+) were largely restricted to very high NPY concentrations and similar in transfected and nontransfected cells. NPY did not increase inositol phosphate accumulation and did not activate a variety of isoforms of protein kinase C or mitogen-activated protein kinases. We conclude that at least upon expression in HEC-1B cells the signal transduction of Y(5) NPY receptors is limited to inhibition of cAMP accumulation.

Analysis of Variance↗

Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth.

The biofilm mode of growth is the survival strategy of environmental bacteria like Pseudomonas aeruginosa. Such P. aeruginosa biofilms also occur in the lungs of chronically infected cystic fibrosis patients, where they protect the bacteria against antibiotics and the immune response. The lung tissue damage is due to immune complex mediated chronic inflammation dominated by polymorphonuclear leukocytes releasing proteases and oxygen radicals.

Animals↗