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Biomedical subjects

M Kolb

Publications and source records attributed to M Kolb.

At least 19 recordsLinked to original sources
PubMed2006

Assessment of the environmental impact of landfill sites with open combustion located in arid regions by combined chemical and ecotoxicological studies.

Two different waste disposal sites in Jordan were investigated in order to determine the environmental situation in context with waste disposal techniques. One landfill, located at Marka/Amman, had been closed about 25 years ago and covered with soil. Here, the waste had been actively open combusted and openings in the cover, still emitting smoke, indicated that waste was still smoldering inside the landfill's body. The second disposal site close to Ekeeder/Irbid is still operated. On this ground, the solid waste is not intentionally burned, although spontaneous fires frequently come up. Samples of waste, soil, and entrained dust were collected and analyzed. From the solid samples, respectively, their eluates, sum parameters, ecotoxicological effects as well as contents of elements/heavy metals and organic pollutants (PAH, PCDD/F) were determined. In general, the Ekeeder-samples were low-contaminated. The investigation of the Marka-samples showed higher contamination of the site's center, clearly being influenced by combustion processes. A significant contamination of the landfill's vicinity by its emissions could not be derived from the analytical data. Ecotoxicological investigations, applying a bio-test battery, revealed correlations with the sum parameters but not with the trace pollutants. Thus, the Marka-samples with the highest measured values of sum parameters caused adverse effects on three different test species, whereas other samples from Marka and Ekeeder had small or no effects. The results of these investigations depict the influence of different disposal techniques on the contamination situation of a landfill and they shall contribute to assess the conditions of other disposal sites in (semi)arid regions.

Benzofurans↗
PubMed2003

[The role of cytokines and growth factors in fibroproliferative lung disease].

A new hypothesis of the pathogenesis of fibroproliferative lung disease suggests that fibrosis is caused by abnormal and excessive wound healing and pathologic tissue remodelling. Inflammation is possibly an epiphenomenon. Cytokines are critical players in the pathologic process and attractive targets for pharmacological intervention. TGF beta is a key profibrotic growth factor, a variety of approaches are known to modify and inhibit its activity. This article reviews the basic pathological concepts of pulmonary fibrogenesis and outlines its potential clinical benefit.

Cytokines↗
PubMed2001

Budesonide enhances repeated gene transfer and expression in the lung with adenoviral vectors.

The immune response with generation of neutralizing antiviral antibodies is an obstacle to effective repeated adenoviral gene transfer. Different immunosuppressive drugs facilitate repeat administration of adenovectors, but the clinical utility is uncertain because of systemic side effects. We investigated the use of topical corticosteroid in improving gene expression after repeated injection of adenovectors into mouse lungs. Using a vector expressing murine interleukin-6 (mIL-6) as a marker cytokine for gene expression, we show that budesonide given around exposure to adenovirus to the lung significantly maintained high levels of expressed transgene protein in bronchoalveolar lavage fluid (BALF) after as many as four consecutive injections of virus at two weekly intervals (p = 0.02 versus saline). Differences between treatment groups were most obvious 4 and 6 wk after the initial exposure to adenovirus (equivalent to three and four total exposures). In Week 4, transgene mIL-6 concentration was 2,327 +/- 955 pg/ml in budesonide compared with 336 +/- 246 pg/ml in saline-treated mice (p = 0.001). However, budesonide did not significantly protect transgene expression beyond Week 8 (four prior exposures). The improved transgene expression in budesonide-treated compared with saline-treated animals was associated with a reduction, but not prevention of neutralizing antiviral antibodies (BALF p < 0.001, serum p = 0.04). We conclude that budesonide can be valuable in gene therapy of the lung where repeated transient gene transfer is necessary.

Adenoviridae↗
PubMed2001

Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung.

Transforming growth factor (TGF)-beta is a key cytokine in the pathogenesis of pulmonary fibrosis, and pharmacological interference with TGF-beta can ameliorate the fibrotic tissue response. The small proteoglycans decorin and biglycan are able to bind and inhibit TGF-beta activity in vitro. Although decorin has anti-TGF-beta properties in vivo, little is known about the physiological role of biglycan in vivo. Adenoviral gene transfer was used to overexpress active TGF-beta, decorin, and biglycan in cell culture and in murine lungs. Both proteoglycans were able to interfere with TGF-beta bioactivity in vitro in a dose-dependant manner. In vivo, overexpression of TGF-beta resulted in marked lung fibrosis, which was significantly reduced by concomitant overexpression of decorin. Biglycan, however, had no significant effect on lung fibrosis induced by TGF-beta. The data suggest that differences in tissue distribution are responsible for the different effects on TGF-beta bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung.

Adenoviridae↗
PubMed2001

Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin.

Pulmonary fibrosis is a chronic progressive disease with no effective therapy. Transforming growth factor beta (TGF-beta) is thought to be a key profibrotic mediator and blocking its activity is therefore one of the targets of new treatment strategies for fibrosis. Decorin is an endogenous proteoglycan and one of the known inhibitors of TGF-beta. The short half-life of peptide-based therapeutics makes gene transfer a promising approach to achieve prolonged protein levels in the lung. Replication-deficient adenovirus was used to deliver decorin transgene (AdDec) to the airways by a single intranasal injection in a murine bleomycin model of lung fibrosis. The ability of vector-derived decorin to inhibit TGF-beta was examined in a bioassay and its effect on bleomycin-induced pulmonary fibrosis was determined by histomorphology and lung hydroxyproline. In vitro, supernatant from cells infected with AdDec abrogated the bioactivity of TGF-beta in a dose-dependent manner whereas control virus (AdDL70) had no effect. In vivo, treatment of bleomycin-injected mice with AdDec substantially reduced the fibrogenic response compared with control virus (hydroxyproline: bleomycin/AdDec, 1.96 microg/mg; bleomycin/AdDL70, 3.05 microg/mg; p = 0.0005). These results suggest that a single administration of AdDec was able to generate a local pulmonary environment that effectively blocked the fibrogenic response to bleomycin by inhibition of TGF-beta.

Adenoviridae↗
PubMed2001

Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis.

IL-1beta is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic diseases. Although it is considered to participate in wound repair, no major role has been attributed to IL-1beta in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1beta in rat lungs after intratracheal administration. The high expression of IL-1beta in the first week after injection was accompanied by local increase of the proinflammatory cytokines IL-6 and TNF-alpha and a vigorous acute inflammatory tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-beta1 were increased in lung fluid samples 1 week after peak expression of IL-1beta. Although PDGF returned to baseline in the third week, TGF-beta1 showed increased concentrations in bronchoalveolar lavage fluid for up to 60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin. These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory cytokine, IL-1beta, converts to progressive fibrotic changes. IL-1beta should be considered a valid target for therapeutic intervention in diseases associated with fibrosis and tissue remodeling.

Acute-Phase Reaction↗
PubMed2001

A chronic inflammatory infusion model of peritoneal dialysis in rats.

OBJECTIVES: Peritoneal membrane changes are related to daily exposure to non physiologic dialysate and recurrent acute inflammation. We modified a daily infusion and inflammation model and evaluated it for fibrotic and angiogenic features. The feasibility of adenovirus-mediated gene transfer in the model was also assessed. METHODS: Peritoneal catheters were implanted in rats. Over a period of 4 weeks, the animals received a daily infusion of Dianeal 4.25% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) with an initial three doses of lipopolysaccharide (LPS) or physiologic saline. Peritoneal fluid was assayed for transforming growth factor beta (TGFbeta) and vascular endothelial growth factor (VEGF). Animals were humanely killed at week 5. Net ultrafiltration was then measured, and tissue samples were immunostained for factor VIII. Mesenteric tissue was assayed for hydroxyproline content. Adenovirus-mediated gene transfer of beta-galactosidase was assayed by intraperitoneal administration of the virus, 4 days before the end of the experiment. RESULTS: Animals treated with either Dianeal or physiologic saline showed peritoneal membrane thickening and increased vascularity. Fibrosis was demonstrated by increased hydroxyproline concentration. Ultrafiltration was impaired. We found increased concentrations of VEGF and TGFbeta in the peritoneal fluid of animals treated with LPS and daily infusion. Adenovirus-mediated gene transfer to the peritoneal membrane was demonstrated in the model. CONCLUSIONS: Exposure to LPS and daily Dianeal or physiologic saline leads to peritoneal fibrosis and neoangiogenesis. Vascularization and glucose transport correlate with ultrafiltration failure. The present animal model mimics changes seen in humans on peritoneal dialysis and may be valuable for evaluating short-term interventions to prevent membrane damage.

Adenoviridae↗
PubMed2000

Application of model-predictive control based on artificial neural networks to optimize the fed-batch process for riboflavin production.

The fed-batch process for commercial production of riboflavin (vitamin B2) was optimized on-line using model-predictive control based on artificial neural networks (ANNs). The information required for process models was extracted from both historical data and heuristic rules. After each cultivation the process model was readapted off-line to include the most recent process data. The control signal (feed rate), however, was optimized on-line at each sampling interval. An optimizer simulated variations in the control signal and assessed the forecasted model outputs according to an objective function. The optimum feed profile for increasing the product yield (YB2/S) and the amount of riboflavin at the time of harvesting was adjusted continuously and applied to the process. In contrast to the control by set-point profiles, the novel ANN-control is able to react on-line to variations in the process and also to incorporate the new process information continuously. As a result, both the total amount of riboflavin produced and the product yield increased systematically by more than 10% and the reproducibility of seven subsequently optimized batches was enhanced.

Algorithms↗
PubMed2000

[Adverse (cardio-)vascular effects of vinorelbine in non-small-cell bronchial carcinoma].

Vinorelbin is an important tumouricidal substance. The (cardio-)vascular side effects are not well known. We report on four patients in highly palliative situations who were treated with vinorelbine for non-small cell lung cancer. Case one presented with myocardial infarction eleven days after onset of therapy. The second and third cases had to be admitted immediately after the beginning of vinorelbine treatment because of hypertension and angina pectoris. The fourth case suffered from angina abdominalis. A critical review of the literature showed 17 cardiac ischaemias with seven myocardial infarctions, three of them with lethal outcome.

Aged↗
PubMed2000

Cardiovascular load of competitive golf in cardiac patients and healthy controls.

PURPOSE: Sports in cardiovascular patients (CVP) should serve for risk factor management, increase of exercise capacity, and reintegration into daily life. Competition of cardiac patients with healthy sportsmen is often discouraged and thus reintegration hampered. Golf, with its endurance component and exceptional rules (e.g., the handicap) should be an alternative. METHODS: In 20 male golfers (65.2 +/- 6.1 yr, 1.4 +/- 0.3 W x kg(-1) body weight (approximately 4.8 METs)) with cardiovascular diseases and eight controls (C) (62 +/- 5 yr, 2 +/- 0.4 W x kg(-1) body weight (approximately 6.9 METs)), the performance assessed in the laboratory (ergospirometry, serum lactate) allowed for comparison of the cardiovascular load on the golf course (lactate, Holter monitoring, blood pressure, urine catecholamines). RESULTS: In comparison with in the hospital, resting heart rates were significantly (P < 0.001) elevated in both groups immediately before the tournament (CVP: 76.1 +/- 10.8 vs 90.1 +/- 8.6 bpm; C: 74.8 +/- 6.3 vs 92.3 +/- 9.7 bpm). On the course, the mean heart rates of the patients were closer (P < 0.01) to the anaerobic threshold (105.4 +/- 11.0 vs 115.3 +/- 10.8 bpm) in comparison with controls (100.5 +/- 7.3 vs 125.6 +/- 16.6 bpm) corresponding to 0.9 +/- 0.3 W x kg(-1) (approximately 3.1 METs) or 76.0 +/- 13.1%VO2max (CVP) and to 0.9 +/- 0.2 W x kg(-1) (approximately 3.1 METs) or 55.3 +/- 9.1%VO2max (C). Serum lactate levels were 1.36 +/- 0.7 mmol x L(-1) (approximately 12.4 +/- 6.4 mg x dL(-1)) (CVP) and 1.1 +/- 0.4 mmol x L(-1) (approximately 9.1 +/- 3.6 mg x dL(-1)) (C). In patients, arrhythmias were lower in quantity and quality (LOWN) in comparison with other activities as registered by means of the 24-Holter-ECG. CONCLUSION: In cardiovascular patients, competitive golf reaches an intensity that may positively influence cardiovascular risk factors, depending on the type of the course and may provide patients the desired integration with healthy sportsmen.

Aged↗
PubMed2000

Newborn hearing testing at Wisconsin hospitals: a review of the need for universal screening.

Every year, an estimated 200 babies are born in Wisconsin with hearing impairment. Early identification of hearing loss is associated with better language development. This study describes the prevalence of newborn hearing screening at Wisconsin hospitals. Ninety-six percent of all 107 acute care hospitals with newborn delivery services responded to a mailed survey. In 1997, 10% of newborns in Wisconsin had hearing tested. In 1997 and 1998, two and then seven hospitals, respectively, established universal hearing screening programs. Nurses performed hearing tests on most newborns using automated auditory brainstem response equipment. Universal newborn hearing screening can be done by nurses or other personnel at community hospitals prior to discharge.

Data Collection↗
PubMed1999

Fracture in disordered media and tensile strength of microcrystalline cellulose tablets at low relative densities.

The purpose of this study is to establish a theoretical basis for the tensile strength of low density tablets. In a first step, a lattice model based on percolation theory is presented. As a theoretical result, a power law is obtained for the lattice strength. The exponent in this law is expected to be universal and as a numerical value Tf congruent with 2.7 is proposed. The result is identical with an earlier theoretical finding from an alternative approach proposed by. In a second step, the new model equation is applied to the tensile strength of low density tablets. The compacts were manufactured and tested with an universal testing instrument Zwick UPM 1478 (Zwick-Roell). Different types of microcrystalline cellulose Emcocel 50M, Emcocel 90M, Avicel PH101 and Avicel PH102 were assayed as model excipients because of their ability to form tablets at comparatively low relative densities (rhor). For determination of the tensile strength, two different strain rates 0.5 and 25 mm min-1 were examined. All experimentally determined exponents were in the same range with an average of Tf=3.2+/-0.1 and the critical solid fractions (rhorc), yielded values close the relative bulk densities. In a third step, the new model is compared to the Ryshkewitch-Duckworth equation. This exponential relationship of the tensile strength and porosity was found to have an inferior fitting adequacy than the new power law. As a conclusion, the lattice model presented is able to explain the power law behaviour of the tensile strength as a function of the relative density with an exponent close to three. The expected universal character of this exponent was supported by the results of the assayed substances at two different strain rates. Plus, in the case of the tested substances, the new relationship between the tensile strength and the relative density should be preferred to the often used exponential function. However, further studies have to be conducted to know more about the validity of the new model.

Cellulose↗
PubMed1999

Modulation of base hydroxylation by bile acids and salicylates in a model of human colonic mucosal DNA: putative implications in colonic cancer.

Bile acids are believed to be involved in the formation of colonic cancer, and 5-aminosalicylic acid and other salicylates may have a protective role. The precise mechanisms of both actions are not known, but modifications (stimulation or inhibition) of basal or oxygen-radical induced DNA base hydroxylation as potential early events in tumor formation by these compounds may be involved in such actions. We, therefore, investigated whether: (1) bile acids in concentrations as they occur systemically or intraluminally are able to enhance basal or OH*-radical-stimulated base hydroxylation in DNA from calf thymus; (2) 5-aminosalicylic acid, its main intestinal metabolite N-acetyl-aminosalicylic acid and salicylate, the main aspirin metabolite, are able to inhibit this hydroxylation; and (3) DNA from calf thymus can be used as a model by comparing its base composition and hydroxylation with DNA from normal human colonic mucosa. We found an enhancement of the OH*-radical-induced DNA hydroxylation especially 8-OH adenine with 214.0%. On the other hand 5-ASA, N-acetyl-ASA, and salicylate showed a concentration-dependent inhibition of OH*-stimulated hydroxylation with IC50 between 0.04 +/- 0.01 mM (X +/- SD) and 1.3 +/- 0.1 mM. No effects were observed on basal hydroxylation. Electron spin resonance spectroscopy studies showed reduction of the corresponding base signals pointing to a scavenger mechanism. In DNA isolated from normal human colonic mucosa (N = 7) a similar base distribution was found as in calf thymus; hydroxylation was < or = 1.0% in both systems. From our results we conclude that DNA from calf thymus may serve as a model for human colonic mucosal DNA and that one of the carcinogenic actions of bile acids may be enhancement of oxygen-radical-induced DNA base hydroxylation, especially 8-OH adenine. The absence of effects under unstimulated conditions supports their role as cocarcinogens. The concentration-dependent inhibition of OH*-stimulated DNA hydroxylation by 5-ASA, salicylate, and N-acetyl-ASA may be a possible mechanism of chemoprevention.

Animals↗
PubMed1999

[Autocrine activation of fibroblasts following irradiation].

BACKGROUND: The most important limitation of thoracic radiotherapy is radio-toxicity of the normal lung. We distinguish the pneumonitis with acute clinical onset, histologically characterised by infiltration of inflammatory cells to alveoli and interstitium, from fibrosis, which is slowly progressive and characterised by fibroblast proliferation and collagen deposition in the interstitium. Radiogenetic fibrosis can occur without evidence of alveolitis, an active role of mesenchymal lung cells in the pathogenesis of this special disorder is assumed. METHODS: Human lung fibrobasts were irradiated in vitro with single doses of 4, 7 and 10 Gy and afterwards observed or incubated together with non-irradiated cells in a co-culture system. After 3, 6, 9, and 12 days cells were counted, and TGF beta 1 and fibronectin was measured in supernatants. RESULTS: Cell growth of irradiated fibroblasts was inhibited as expected. In contrast, we observed a significant stimulation of cell growth of the non-irradiated fibroblasts, which were incubated together with the irradiated cells. This effect was obvious from day 1 until day 9 following irradiation and was dose dependent. In irradiated cells TBF beta 1 was increased in culture supernatants up to five-fold compared to sham-irradiated cells from day 6 until day 12. Fibronectin was elevated in dose dependent manner. CONCLUSION: Irradiation of fibroblasts in vitro induces synthesis of substances which stimulate cell growth. TGF beta 1 and fibronectin may be involved in this act of "self-activation".

Cell Division↗
PubMed1998

Lesion location influences perception of homonymous scotomata during flickering random dot pattern stimulation.

An attempt was made to clarify whether the site of postchiasmal lesions affects subjective perception of homonymous visual field defects during stimulation with flickering random dot patterns (white noise-field). Out of 56 patients with homonymous hemianopia, 38 (68%) perceived scotomata in this situation, but 18 (32%) discerned none at all. Neuroradiologic superposition of cerebral lesions detected by computed tomography (CT) or magnetic resonance imaging (MRI) showed that nearly all patients who perceived their scotomata had lesions involving the primary visual cortex or the perigeniculate region, whereas those who received no scotoma had lesions centered within the optic radiation. Functional MRI of six normal subjects during stimulation with flickering random dot patterns indicated predominant activation of the primary visual cortex. Since noise-field defects were most frequently perceived by patients whose lesion involved the primary visual cortex, it appears that the sensitivity of noise-field campimetry depends on the site of damage in the visual pathway. The explanation for this may be that damage to long-range horizontal connections impairs filling-in processes.

Adolescent↗
PubMed1998

Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. Response to treatment is infrequent and the use of immunosuppressive agents other than corticosteroids is the subject of ongoing discussion because of uncertain efficacy and side-effects. To determine the efficacy and safety of cyclophosphamide pulse therapy in IPF, this study retrospectively analysed 18 patients with progressive IPF who were treated with intermittent i.v. cyclophosphamide (1-13 g x month(-1)) and additional oral prednisolone for 1 yr. Static lung volumes, arterial oxygen tension (Pa,O2) at rest, clinical symptoms and potential treatment-related side-effects were recorded. Cyclophosphamide had to be stopped in one patient, owing to repeated pulmonary infection; 11 patients were responders (five improving, six stabilizing) and six patients deteriorated. The change in vital capacity (VC) of responders was +6.7+/-18.0% (mean +/-SD), compared with -20.6+/-18.2% in nonresponders (p=0.008). Pa,O2 remained constant in responders (+0.13+/-0.88 kPa (+1.0+/-6.6 mmHg)), while it decreased in nonresponders (-2.08+/-1.92 kPa (-15.6+/-14.4 mmHg, p=0.008)). Additional prednisolone was reduced by 19.1+/-13.4 mg in responders, compared with 6.7+/-16.3 mg in nonresponders (p=0.02). VC at initiation of therapy was higher in responders (60.2+/-10.2 versus 40.3+/-12.9% predicted; p=0.004). No side-effects occurred, other than respiratory tract infection. These data demonstrate that intravenous cyclophosphamide pulse therapy may be a favourable regimen for certain patients with progressive idiopathic pulmonary fibrosis. Patients with a vital capacity of more than 50% predicted and a shorter duration of disease may benefit most.

Administration, Oral↗
PubMed1997

[Magnetic resonance tomography and magnetic resonance angiography in diagnosis of complicated popliteal artery aneurysm].

Regarding the frequency of aneurysms, the popliteal artery comes third behind the abdominal aorta and the iliac arteries. In up to 50% of cases a sudden limb-threatening thrombotic occlusion may occur. Early surgical intervention is the therapy of choice. We report the case of a 56-year-old patient whose popliteal aneurysms (PAs) in both legs had been bypassed with a venous graft some years previously. He presented with acute pain and tumescence in the left popliteal fossa combined with inflammatory symptoms. Neither ultrasonography nor DSA could distinguish between an extravascular inflammatory process, an anastomotic aneurysm and a partial reperfusion of the original PA due to a leaking anastomosis. The correct diagnosis was provided by MRI in combination with MRA, confirmed by the intraoperative findings. The value of MRA in the diagnostic imaging of the vasculature of the lower extremities is discussed and compared alternative methods.

Anastomosis, Surgical↗