Biomedical subjects

J Barth

Publications and source records attributed to J Barth.

At least 73 records · Page 4Linked to original sources

PubMed1996

[Health locus of control and health related risk behavior--an analysis of locus of control patterns].

In this study we related health locus of control beliefs to risk-behavior (little physical exercise, overweight and smoking) in a sample of n = 956 persons, First, we used a correlative method and later we analysed health locus of control patterns. The sample is divided in eight different health locus of control beliefs patterns by the three dimensions (internal, social external and fatalistic external). The hypothesis that some subgroups have a different risk-behavior can't supported. Only the subgroup with high internal and high social external health locus of control showed in tendency lower risk-behavior. Finally we discuss different possibilities for the interpretation of the results.

Adult↗

PubMed1995

[Fatal Aspergillus sepsis following orthotopic heart transplantation].

In a 64-year-old man heart transplantation had been performed for ischaemic heart disease. 7 months later severe vascular disease in the transplant necessitated a second transplantation. Both procedures had been performed under immunosuppression (cyclosporine, azathioprine, prednisolone, antithymocyte globulin), with a subsequent prednisolone maintenance dose of 10 mg daily. At first there were no complications, but 31 days after the re-transplantation atrial flutter developed. Although this was quickly terminated by drugs, circulatory failure set in. Because of signs of infection (white blood cell count 29,800/microliters, 17% stab cells, C-reactive protein 24 mg/l) broad-spectrum antibiotics were administered, but without response. As a trial anti-rejection treatment was started (prednisolone 250 mg daily: antithymocyte globulin 100 mg daily for 4 days). When cytomegalovirus (CMV) infection was demonstrated, ganciclovir and CMV hyperimmunoglobulin were administered and slow improvement was noted. The finding of Aspergillus in tracheal secretion was interpreted as apathogenic colonization. The patient died from cardiorespiratory failure 57 days after the second transplantation. Autopsy revealed Aspergillus sepsis.

Aspergillosis↗

PubMed1995

Regulation of mitochondrial energy generation in health and disease.

In mammalian cytochrome c oxidase (COX) three of the ten nuclear coded subunits (VIa, VIIa, VIII) occur in tissue-specific isoforms. The isoform distribution, however, varies in liver and heart of different species. Subunit VIII is different in liver and heart of bovine, dog, rat and chicken, but identical in human (liver-type) on one hand, and sheep, rabbit and rainbow trout (heart-type) on the other hand, as determined by N-terminal sequencing. Two moles of trinitrophenyl-ATP bind to monomeric COX from bovine heart and one to COX from bovine liver with dissociation equilibrium constant (Kd) values of about 3 microM. One binding site at the heart enzyme is blocked by a monoclonal antibody to subunit VIa-H. ATP (and/or ADP) interact with COX at two or three high-affinity binding sites, as shown by titration of the spectral changes of COX. Isolated COX from bovine heart was reconstituted with variable intraliposomal ATP/ADP ratios. By measuring the RCR (respiratory control ratio) and RCRVal (related to the valinomycin-respiration), which is a direct measure of the H+/e(-)-stoichiometry (Wilson and Prochaska, Arch. Biochem. Biophys. 282 (1990) 413-420), almost complete inhibition of the proton pump activity of COX by high intraliposomal ATP concentrations was found. The vectorial of protons for the formation of water, however, appears to be unaffected by nucleotides. This regulatory mechanism is assumed to have physiological significance for thermogenesis in muscle at rest. COX of fibroblasts from patients suffering from Leigh's syndrome, which is associated with a decreased COX activity, are suggested to have an incompletely assembled enzyme complex. This suggestion is further corroborated by the higher temperature-sensitivity of the enzyme when compared with COX from normal control fibroblasts. Defective regulation of COX via nuclear coded subunits is also proposed to cause mitochondrial diseases.

Amino Acid Sequence↗

PubMed1995

Pharmacokinetic and pharmacodynamic evaluation of triamcinolone acetonide after intravenous, oral, and inhaled administration.

Triamcinolone acetonide (TCA) is a corticosteroid that is frequently used in the treatment of asthma. After inhalation, TCA can become systemically available when the inhaled formulation is swallowed, causing undesirable systemic effects. A clinical study was conducted to determine the systemic side effects of TCA after intravenous (2 mg as phosphate ester), oral (5 mg), and inhaled (2 mg) administration. Blood samples were collected at appropriate times over 24 hours, and TCA concentrations in plasma were measured by high-performance liquid chromatography and radioimmunoassay. Free drug concentrations were determined by ultrafiltration for correlating pharmacokinetics and pharmacodynamics. The free fraction of TCA (+/- standard deviation) was 29.0 +/- 1.3% and was independent of the investigated concentration range up to 1,000 ng/mL. Pharmacodynamic parameters were determined by monitoring lymphocytes, granulocytes, and cortisol. Pharmacokinetic/pharmacodynamic modeling was performed using a modified Emax model for lymphocytes and granulocytes. A novel linear release rate model was used to characterize the cortisol data. The E50 values determined from all three pharmacodynamic endpoints were not significantly different for the three treatments, indicating that these effects can be explained based on systemic steroid concentrations.

Administration, Inhalation↗

PubMed1995

Pharmacokinetics of triamcinolone acetonide after intravenous, oral, and inhaled administration.

The pharmacokinetics of triamcinolone acetonide were studied after intravenous (2 mg), oral (5 mg), and inhaled (2 mg) administration. Triamcinolone acetonide concentrations were measured in plasma by high-performance liquid chromatography/radioimmunoassay. After intravenous administration, triamcinolone acetonide was eliminated with a total body clearance of 37 L/h and a half-life of 2.0 hours. The volume of distribution was 103 L, and oral bioavailability averaged 23%. Absorption was rapid, achieving maximum triamcinolone acetonide levels of 10.5 ng/mL after 1 hour. After inhalation, bioavailability averaged 22% with maximum levels of 2.0 ng/mL observed after 2.1 hours. The resulting systemic levels for all three treatments caused a significant decrease in the number of lymphocytes in blood.

Administration, Inhalation↗

PubMed1995

Alveolar macrophages from bronchoalveolar lavage of patients with pulmonary histiocytosis X: determination of phenotypic and functional changes.

In recent years the alveolar macrophage has been found to play a central role in interstitial lung disease. Pulmonary histiocytosis X is characterized by infiltrating fibroblasts, mononuclear cells, and CD-1-positive Langerhans cells. Bronchoalveolar lavage (BAL) fluid displays an increase of CD-1-positive cells and a remarkable exaggeration of the total cell count with only slight changes in the differential cell count. Changes of alveolar macrophage phenotype and functional activity occurring in pulmonary histiocytosis X have not yet been characterized. The BAL fluid of nine patients with histologically proven isolated pulmonary histiocytosis X was compared with that of 16 control patients. Immunophenotyping of alveolar macrophages by monoclonal maturation and differentiation markers of monocyte/macrophage lineage cells [Ki-M2, Ki-M6 (CD-68), Ki-M8, Ki-M1 (CD-11c)] revealed a significant increase of immature macrophages with a more monocyte-like phenotype. The proliferation marker Ki-67 revealed an increased proportion of proliferating macrophages. Functional analysis by measuring oxygen radical release revealed an increase both in baseline and stimulated luminol-enhanced chemiluminescence. Fibronectin production was elevated in alveolar macrophage supernatants from pulmonary histiocytosis X patients. These findings are consistent with phenotypic changes of alveolar macrophages in other interstitial lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis. Local proliferation and the fresh influx of blood monocytes seem to be responsible for the increase in immature and functionally activated alveolar macrophages. The increase in oxygen radical release and fibronectin production suggests an augmented tissue injuring and fibrosing capacity of alveolar macrophages in pulmonary histiocytosis X.

Adult↗

PubMed1995

[AgNOR expression in skin tumors. Studies of melanocytic, epidermal and fibrohistiocytic lesions].

Nucleolus organizer regions are segments of DNA-coding ribosomal genes, which can be visualized histologically by a special silver staining technique as so-called AgNORs. Determination of the number and size of AgNORs provides quite a precise reflection of current cellular proliferation activity. We have examined the AgNOR expression in 228 melanocytic, epidermal and fibrohistiocytic lesions. Dysplastic naevi and Spitz naevi showed a significantly lower AgNOR expression than melanomas, and there were analogous differences between keratoacanthomas and carcinomas. Furthermore, there were also significant differences between the groups of melanomas and carcinomas, as there were between benign and non-benign fibrohistiocytic lesions. The AgNOR expression in more cellular fibrohistiocytic lesions differed from at in more fibrous lesions. Analysis of AgNOR areas was not so informative as AgNOR counting. The results of PCNA examinations correlated with the degree of AgNOR expression. It was found that the AgNOR technique is useful in differential diagnosis and for histological determinations of proliferation activity in melanocytic, epidermal and fibrohistiocytic lesions. The AgNOR method is easy to apply and can be applied in paraffin-embedded tissue.

Antigens, Nuclear↗

PubMed1995

Health counseling and health promotion of musculoskeletal disorders.

The steady increase in the number of musculoskeletal disorders has heightened the importance of health promotion accordingly. In Germany, health promotion efforts have become the responsibility of health insurers. Commissioned by the health insurance organization, Hamburg-Münchener Ersatzkasse, we developed and evaluated a new health counseling service for persons with musculoskeletal (rheumatic) complaints. In order to draft the scope and principles of the counseling program, we questioned more than 1000 enrollees per questionnaire. The aim of the survey was to estimate the actual demand for participation in the health counseling. The results show that the subjective need for health counseling is strongly linked to the kind of physical limitation involved, so that it can be assumed that particularly persons with relevant complaints and musculoskeletal disorders will participate in the program. To evaluate the counseling sessions, a range of measurements was developed. The aim was to obtain a comprehensive and precise record of the problems and complaints of those taking part in the program. The evaluation shows that the new service is used mainly by persons who have suffered limitations to their health for years due to musculoskeletal disorders. Especially middle-aged persons use the counseling service, with women showing the most interest. When participants were asked after counseling which health support measures they had taken or were planning, their answers indicated that in most cases the recommendations of the counselor were being put into practice. We conclude that health counseling can be considered a meaningful option for health promotion.

Adult↗

PubMed1995

Pharmacokinetic/pharmacodynamic evaluation of deflazacort in comparison to methylprednisolone and prednisolone.

PURPOSE: The pharmacokinetics and pharmacodynamics of deflazacort after oral administration (30 mg) to healthy volunteers were determined and compared with those of 20 mg of methylprednisolone and 25 mg of prednisolone. METHODS: Methylprednisolone, prednisolone and the active metabolite of deflazacort, 21-desacetyldeflazacort, were measured in plasma using HPLC. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was applied to link corticosteroid concentrations to the effect on lymphocytes and granulocytes. RESULTS: Deflazacort is an inactive prodrug which is converted rapidly to the active metabolite 21-desacetyldeflazacort. Maximum concentrations of 21-desacetyldeflazacort averaged 116 ng/ml and were observed after 1.3 h. The average area under the curve was 280 ng/ml.h, and the terminal half-life was 1.3 h. 21-Desacetyldeflazacort was cleared significantly faster than both methylprednisolone and prednisolone. The PK-PD-model was suitable to describe time course and magnitude of the observed effects. The results were consistent with reported values for glucocorticoid receptor binding affinities for the investigated compounds. CONCLUSIONS: Due to the short pharmacokinetic half-life of its active metabolite, pharmacodynamic effects of deflazacort are of shorter duration than those of methylprednisolone and prednisolone. The PK-PD model allows good prediction of pharmacodynamic effects based on pharmacokinetic and receptor binding data.

Absorption↗

PubMed1995

Anti-inflammatory activity of croconazole, a broad-spectrum antimycotic agent, in the arachidonic acid-induced mouse ear swelling test.

Investigations on croconazole, a novel imidazole compound, suggested antiphlogistic properties in vitro. Hence, its anti-inflammatory capacity was tested in vivo using the arachidonic acid-induced mouse ear swelling test, which is a suitable model for screening inhibitors of the lipoxygenase and/or the cyclooxygenase. Topical application of croconazole (1%/0.01%) to the mouse ear induced a maximal inhibition of edema (inhibition: 39%/33%; p = 0.01) which was as strong as the reference nordihydroguaiaretic acid (inhibition: 38.9%; p = 0.01). These results justify further investigations on croconazole to study potential inhibitory effects on proinflammatory arachidonic acid metabolites.

Animals↗

PubMed1995

Croconazole: an inhibitor of eicosanoid synthesis in A23187-stimulated human polymorphonuclear leukocytes and human whole blood.

The aim of this investigation was to ascertain possible inhibitory effects of the antimycotic agent croconazole on eicosanoid biosynthesis. Human polymorphonuclear leukocytes (PMN) and whole blood of healthy donors were pretreated with croconazole in different concentrations (0.8-100 microM) for 5 min followed by the addition of Ca ionophore A23187 (10 microM) and subsequent incubation for 10 min (PMN) and 30 min (whole blood), respectively. Thereupon the eicosanoids were determined by reversed-phase high-performance liquid chromatography. Croconazole exhibited dose-dependent inhibitory activity on the 5-lipoxygenase (5-LOX) of neutrophils. The mean half maximum inhibition concentration (IC50) of croconazole for synthesis of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) was determined as 7.8 +/- 1.7 and 7.6 +/- 0.3 microM, respectively. The mean IC50 value for LTB4 estimated in whole blood was distinctly higher (27.0 +/- 3.1 microM) compared with that determined in PMN. Additionally, an inhibitory effect (IC50 9.8 +/- 2.0 microM) on the production of the cyclooxygenase (COX) product 12-hydroxyheptadecatrienoic acid (HHT) was demonstrated, whereas the production and/or releasing of 12-hydroxyeicosatetraenoic acid (12-HETE) was not attenuated by the azole. Our results in the cell-free 5-LOX system favor a direct inhibitory action of croconazole on 5-LOX, with a relatively high portion (45-77%) of reversibility. In spite of distinctly lower inhibitory potency compared with reference inhibitors such as nordihydroguaiaretic acid and indomethacin, croconazole is an effective inhibitor of arachidonic acid metabolism. Our results suggest that croconazole may be of some benefit in anti-inflammatory therapy.

Antifungal Agents↗

PubMed1995

Modulation of fibroblast activity in histiocytosis X by platelet-derived growth factor.

Platelet-derived growth factor (PDGF) was shown to modulate fibroblast activity in interstitial lung diseases like idiopathic pulmonary fibrosis (IPF). The role of PDGF in fibrosing mechanisms in histiocytosis X is unclear. Eight patients with histiocytosis X, five patients with idiopathic pulmonary fibrosis (IPF), and nine patients with no evidence of interstitial lung disease underwent bronchoalveolar lavage (BAL). The c-sis gene (a proto-oncogen encoding for the B-chain of PDGF) expression was measured by gene hybridization revealing an upregulated c-sis transcript in the group of histiocytosis X and patients, whereas no c-sis expression was detectable in the control group. The alveolar macrophage supernatants from histiocytosis X patients and from the control group were incubated with a human lung fibroblast cell line (WI-38). The mitosis rate was measured by tritiated thymidine incorporation and collagen production was estimated by determining the procollagen III peptide concentration in fibroblast supernatants. Tritiated thymidine uptake was increased 1.6 times in histiocytosis X compared with the control group (p < 0.01). Procollagen-III-peptide levels in fibroblast supernatants after incubation with alveolar macrophage supernatants from histiocytosis X were elevated 2.5 times compared with the control group (p < 0.01). Prior to incubation with the WI-38 cell line, the cell supernatant then was preincubated with nonpreserved anti-human PDGF (AA- and BB-chain) resulting in an 80% decrease of tritiated thymidine uptake and procollagen-III-peptide production in the group of histiocytosis X patients compared with native supernatants. No significant change in fibroblast activity was seen in the control group. Preincubation with nonpreservated Ki-T2 antibodies as pan T-lymphocyte marker did not show significant differences in both groups excluding unspecific antibody inhibition. These findings suggest increased PDGF production by alveolar macrophages in histiocytosis X patients. The PDGF is in part responsible for increased fibroblast replication and collagen production.

Adult↗

PubMed1995

Pharmacokinetic interaction between endogenous cortisol and exogenous corticosteroids.

A problem in the evaluation of pharmacokinetic interactions between prednisolone and cortisol is that both steroids bind to cortisol binding globulin (CBG) and albumin. The binding of both steroids to CBG is saturable in the therapeutic concentration range. General drug binding equations were applied to two drugs and two binding sites and two implicit cubic equations were derived. These equations cannot be solved algebraically. However, the free concentration can be calculated using spreadsheet programs on a personal computer. A spreadsheet for these equations was developed using EXCEL 5.0 and its SOLVER option. Free concentrations of prednisolone and cortisol were determined as a function of total concentrations of both ligands. The simulations show that the protein binding of cortisol remains relatively constant in the physiological range but changes when exogenous corticosteroid is present. However, the degree of protein binding of exogenous corticosteroids that bind to CBG depends on the cortisol concentration which competes for binding sites. At the same time, the exogenous corticosteroid suppresses the release of endogenous cortisol. The presented approach is able to take all of these pharmacokinetic and pharmacodynamic interactions into account leading to a more accurate estimation of active free corticosteroid concentrations.

Adult↗

PubMed1995

Anti-CENP-B response in sera of uranium miners exposed to quartz dust and patients with possible development of systemic sclerosis (scleroderma).

OBJECTIVE: To look for anti-CENP-B antibodies and their diagnostic relevance in patients negative and positive for anticentromere antibodies (ACA) with different risk for the development of systemic sclerosis (SSc), including uranium miners exposed to quartz dust. METHODS: We studied sera of 107 patients with SSc, 121 patients with possible SSc, 202 uranium miners heavily exposed to quartz dust, 14 patients with vibration induced white fingers, and 240 control patients. Subjects were screened for ACA by indirect immunofluorescence on HEp-2 cells (IIF-ACA) and then for anti-CENP-B autoantibodies by an ELISA using eukaryotically expressed human full length recombinant CENP-B protein. RESULTS: All IIF-ACA positive sera of "idiopathic" SSc (N = 19), "idiopathic possible" SSc (N = 6) and other patients (N = 11), and 17 of 19 IIF-ACA positive sera of miners exposed to silica with (N = 13) and without (N = 6) symptoms of SSc reacted with CENP-B in this assay. Of the 622 IIF-ACA negative sera, 28 were found positive for anti-CENP-B. There was a significant increase of the prevalence of anti-CENP-B antibodies in IIF-ACA negative patients with possible SSc (11 of 109) and in miners exposed to silica (11 of 196) compared to a group of men older than 60 years with diseases or symptoms not related to SSc (1 of 138). CONCLUSION: (1) CENP-B is also the major target of the IIF-ACA response in diseases other than scleroderma and in the risk group of miners exposed to quartz dust. (2) Anti-CENP-B antibodies can be found in IIF-ACA-negative sera, particularly in those at risk for SSc. (3) The detection of anti-CENP-B antibodies in miners exposed to quartz dust may indicate a high risk group for developing SSc and reveals possibilities for the study of early pathogenetic changes as well as exogenic and endogenic factors involved in the development of this disease.

Autoantibodies↗

PubMed1994