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Biomedical subjects

J Barth

Publications and source records attributed to J Barth.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inhibition of HLA-DR expression on activated human blood eosinophils by transforming growth factor-beta1.

Peripheral blood, bronchoalveolar lavage and sputum eosinophils of patients with asthma but not peripheral blood eosinophils from normal controls have been shown to express human leucocyte antigen (HLA)-DR on their cell surface. Cytokines implicated in the activation of eosinophils, such as interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), can up-regulate HLA-DR expression. However, little is known about antagonistic factors that might down-regulate HLA-DR expression on eosinophils. In this study we investigated whether transforming growth factor-beta (TGF-beta), which has been shown to reduce survival of activated eosinophils, can also modulate HLA-DR expression on eosinophils. For this purpose, isolated peripheral blood eosinophils were stimulated with IL-3 and GM-CSF for 24 h and HLA-DR expression was measured by flow cytometry. We found that while isolated eosinophils expressed low levels of surface HLA-DR, incubation with GM-CSF and IL-3 increased HLA-DR expression on eosinophils. TGF-beta alone did not change HLA-DR expression on isolated eosinophils. However, co-incubation of eosinophils with TGF-beta and either GM-CSF or IL-3 significantly decreased HLA-DR expression compared to eosinophils incubated with either GM-CSF or IL-3 alone and this was not reversed by addition of IL-5. This effect of TGF-beta on IL-3-induced HLA-DR expression was attenuated dose-dependently in the presence of monoclonal anti-TGF-beta antibodies. Our results suggest that TGF-beta can reduce cytokine-induced HLA-DR expression on eosinophils and could thus influence eosinophil activation.

Cells, Cultured↗
PubMed1998

Gene expression of profibrotic mediators in bronchiolitis obliterans syndrome after lung transplantation.

Bronchiolitis obliterans syndrome (BOS) develops in one-third of lung transplant recipients. A fibroproliferative process involving mesenchymal cells is observed histopathologically. In order further to evaluate the pathomechanisms of BOS, the gene expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta 1 in bronchoalveolar lavage (BAL) cells of six lung transplant recipients and appropriate controls was studied. Equal amounts of total RNA were submitted to semiquantitative reverse transcription/polymerase chain reaction (RT-PCR), amplifying actin, PDGF-B and TGF-beta 1 using established protocols and primer sets. The signal/actin ratio was calculated based on laser densitometry measurements. TGF-beta 1 transcripts were detected in all samples, and a slight increase in BOS patients was observed. PDGF-B mRNA was increased in BAL samples from BOS patients compared to unaffected recipients and controls. Plotting the FEV1 in percent of vital capacity and the PDGF expression in BOS patients revealed an increased PDGF signal preceding lung function deterioration. The data were consistent with the hypothesis based mainly on in vitro findings that PDGF and TGF-beta contribute to the development of BOS.

Adult↗
PubMed1998

Dermatology in Germany.

In Germany, dermatology has a long tradition as a medical specialization. The first dermatological university departments were established about 120 years ago. From the beginning, venerology was integrated in this field. Today it also covers andrology, allergy, medical cosmetology, mycology, dermatosurgery, phlebology and photodermatology. This broad spectrum more and more gives rise to competition with other medical fields. About 77% (n = 3281) of all German dermatologists (n = 4240 in 1997) work in private practices. The others are employed in clinical departments. The official number of working physicians in Germany in 1997 was 343,556; about 1.5% of them were dermatologists. This means that one dermatologist takes care of 20,000 people. The overwhelming majority of dermatological patients directly contacts the specialist and are not referred by general practitioners (GPs) who comprise about 40% of all German physicians. This is a great advantage over those countries in which patients primarily have to consult the GP. At present, there is a discussion initiated by GPs to change this system in Germany and to reestablish the GP's role as "gatekeeper". Dermatologists together with other specialists are trying to prevent this an to maintain the traditional broad spectrum of German dermatology.

Dermatology↗
PubMed1998

[Internal consistency and validity of work disability duration].

In this study results of a survey taken of persons insured under the public health care system were presented. The main objective of the survey was to determine the health of the insured on the basis of their subjective data, as well as to assess their prevention behaviour and their wish that the health insurance should offer prevention programmes. In addition, the health insurance provided data on how often the insured persons were unable to work for health reasons during a period of seven years. The data of work absenteeism are used to divide the group of respondents according to their health. To determine internal consistency it was first investigated whether persons with periods of disablement during one year (cross-section) also had long periods of disablement in the years before or after (longitudinal section). It was found that in the cross-section, persons with serious health problems (more than six weeks of disablement) differed little from those with average disablement periods (from one to six weeks) in the long-term development of disablement. The study also examined the correlation of periods of disablement and subjective data (validity). A mean correlation was found between the respondents' subjective assessment of their health and the length of disablement periods. There was also a significant negative correlation between internal health locus of control beliefs and the length of disablement. The results are discussed, and the ways and limits of using periods of disablement for empirical studies are presented.

Absenteeism↗
PubMed1997

Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation.

The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of charcoal. A placebo group was used to assess the endogenous cortisol, granulocyte, and lymphocyte baseline levels. Flunisolide plasma levels were determined by high-performance liquid chromatography using a tandem mass spectrometer as detector (HPLC/MS/MS). Cortisol plasma levels and differential white blood cell counts were obtained over 12 hours. An integrated pharmacokinetic/pharmacodynamic (PK/PD) model was applied to link the flunisolide plasma concentrations with the effects on lymphocytes, granulocytes, and cortisol. Maximum concentration levels of 3 to 9 ng/mL of flunisolide were observed after 0.2 to 0.3 hours for all of the investigated doses. The terminal half-life ranged from 1.3 to 1.7 hours. There was no statistical difference between treatments in the presence or absence of orally administered charcoal. The pharmacokinetic/pharmacodynamic (PK/PD) models satisfactorily described the time-courses of the effects on granulocytes, lymphocytes, and cortisol suppression. The resulting E50-values (concentrations to induce 50% of the maximum effect) concurred with the reported values of in vitro receptor binding affinities. The duration of the systemic effects were short because of the short half-life of the drug. Cumulative cortisol suppression increased with dose administration and ranged from 20% to 36%. The PK/PD simulations resulted in a smaller degree of cortisol suppression for the drug administered at 10 PM. The cumulative change from baseline was slightly smaller for the effects on granulocytes and lymphocytes than those on cortisol. This information promotes the comparison with other inhaled glucocorticoids.

Administration, Inhalation↗
PubMed1997

Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral administration.

The pharmacokinetics of methylprednisolone and prednisolone were evaluated in 24 healthy men after oral administration of single and multiple doses for 3 days. For each drug, 6 different administration regimens with doses ranging from 1 to 80-mg of methylprednisolone and 1.25 to 100-mg of prednisolone, and administration intervals ranging from 3 to 24 hours for both were investigated. Plasma was assayed using a normal phase high-performance liquid chromatography (HPLC) method. Methylprednisolone showed linear pharmacokinetics with no apparent dose or time dependency. Prednisolone showed marked dose dependency with higher clearance and volume of distribution for higher doses. This can be explained by its saturable protein binding of plasma, because unbound clearance and unbound volume of distribution were not dose-dependent. After multiple administration, prednisolone showed significant time-dependent pharmacokinetics with increased unbound clearance and increased unbound volume of distribution. Due to the complicated pharmacokinetic properties of prednisolone, it is extremely difficult to determine the dose needed to obtain a desired target concentration. The pharmacokinetics of methylprednisolone are more predictable because methylprednisolone concentrations are proportional to dose, and no determination of plasma protein binding is needed.

Administration, Oral↗
PubMed1997

Dependency of cortisol suppression on the administration time of inhaled corticosteroids.

Endogenous cortisol suppression is one of the major systemic side effects of inhaled corticosteroids in the treatment of asthma. A previously developed pharmacokinetic/ pharmacodynamic approach was used to evaluate the influence of administration time on the cumulative cortisol suppression (CCS) after single doses of the inhaled corticosteroids flunisolide and fluticasone propionate. Administration time-dependent simulations of CCS were performed with drug-specific pharmacokinetic and pharmacodynamic parameters obtained from previous clinical trials. Both drugs showed similar diurnal variation in CCS, dependent on the administration time, with maximum suppression when administered in the early morning at approximately 3 AM. The optimum administration time for minimized CCS was in the afternoon but was shifted from 3 PM for fluticasone propionate to later time points around 7 PM for flunisolide, probably because of the shorter terminal elimination half-life of flunisolide. Regarding peak to trough fluctuation, however, CCS after fluticasone propionate showed only half the administration time dependency as after flunisolide. Therefore, the ratio between CCS after flunisolide and after fluticasone propionate also followed administration time-dependent variations. This led to the conclusion that administration time has to be considered as a pivotal influential factor in clinical studies comparing CCS among different inhaled corticosteroids.

Administration, Inhalation↗
PubMed1997

Stimulus size effects in Boston naming test performance in younger and older adults.

Thirty undergraduates and 31 older adults named the Boston Naming Test (BNT) stimulus pictures. Across younger and older participants, all 60 BNT pictures were presented in their standard size, in sizes 1.5 times larger than standard, and in sizes 1.5 times smaller than standard. BNT picture size had no effect on naming performance accuracy.

Journal Article↗
PubMed1997

Analysis of immunoglobulins in sarcoidosis.

BACKGROUND: Assessment of local immunoglobulin(Ig)-production in sarcoidosis may be indicative of disease activity. However, in interstitial lung disease an increase in protein leakage across the alveolar-capillary membrane complicates determination of local Ig-production. In order to overcome this problem, techniques successfully used for the evaluation of local Ig-production in cerebrospinal fluid were applied to bronchoalveolar lavage (BAL)-analysis. METHODS: Ten patients with biopsy-proven sarcoidosis, seven patients with respiratory infections and ten patients as controls without any sign of interstitial lung disease or infection underwent BAL. Equal amounts of total protein (2 micrograms/lane) from BAL and serum samples were run on SDS-PAGE gradient-gel and blotted to a nitro-cellulose membrane. The blots were stained for total protein, IgA, IgM, IgG and IgG1-4-subgroups. RESULTS: Densitometric analysis revealed a significant increase of the IgG/albumin-ratio in BAL of sarcoidosis patients compared to the control group. In all control patients a single IgG band of identical molecular weight was detected both in serum and BAL. In sarcoidosis and pneumonia the serum showed multiple bands distinct from the BAL-band in regard to molecular weight. Subclass analysis of this group revealed an increased band intensity and different molecular weight of IgG1, IgG2 and IgG4-bands in BAL compared to serum indicative of local production. IgA and IgM were detected in all samples without any significant differences between the three groups. CONCLUSIONS: Molecular weight analysis of IgG-subgroups revealed local production of IgG1,2+4 in sarcoidosis and respiratory infection. This technique may prove useful with regard to the assessment of disease activity in sarcoidosis.

Adult↗
PubMed1997

Clinical PK/PD modelling as a tool in drug development of corticosteroids.

Corticosteroids are used for the treatment of a variety of different diseases both locally and systemically. Most therapeutic effects result from glucocorticoid receptor-mediated events, and there seems to be no substance-specific difference in the post-receptor reaction cascade. Therefore, the extent and duration of glucocorticoid effects depend only on the availability of the respective steroid at the receptor site and its affinity to the receptor. This makes glucocorticoids an ideal candidate for PK/PD modelling. Availability at the receptor site is governed by pharmacokinetic parameters such as bioavailability, clearance, protein binding, and volume of distribution. The receptor affinity can easily be measured in vitro. A suitable indirect-response PK/PD model is presented that allows description of the receptor-mediated drug effects such as endogenous cortisol suppression as a function of time. Furthermore, this model allows prediction of the systemic activity of newly developed corticosteroids based on their pharmacokinetics and their respective receptor-binding affinity. The model can also be applied in order to study systemic steroid effects after topical administration or to investigate the effect of the time of dosing on cortisol suppression. Comparison of predictions based on this model and results from large clinical studies are in excellent agreement. Corticosteroids may represent an ideal class of drugs for the successful use of PK/PD modelling during drug development allowing to save time and expenses.

Adrenal Cortex Hormones↗
PubMed1997

[Analysis of lymphocyte populations with flow cytometry in routine bronchoalveolar lavage diagnosis: comparison of a 3-color method with the alkaline phosphatase anti-alkaline phosphatase immunohistochemistry].

BACKGROUND: Identification of lymphocyte phenotypes in bronchoalveolar lavage (BAL) plays a crucial role in the diagnosis of interstitial lung disease. Cells staining positive for specific monoclonal antibodies may be detected by immunocytochemistry or flow cytometry (FCM). The present study compares a three-colour FCM-approach to a standard APAAP protocol for immunocytochemistry. METHODS: BAL-specimens of 22 patients with various lung diseases were investigated. Inclusion criteria was a lymphocytosis of > 10% of all BAL-cells. After the preparation of cytocentrifuge slides, staining was performed with monoclonal antibodies to CD3, CD4 and CD8 following the APAAP-protocol. FCM-analysis was performed with the following panel of conjugates: CD3-FITC, CD4- or CD8-PE, CD45-perCP. Lymphocytes were gated by their SSC/CD45 characteristics. T-helper and T-suppressor percentages were evaluated by quadrant analysis of CD3/CD4 or CD3/CD8 histograms. RESULTS: With the exception of CD3, where the range of values was quite narrow (10% variance), the correlation between the two methods was excellent (CD4: r = 0.98; CD8: r = 0.99; CD4/CD8: r = 0.96; p < 0.0001). CONCLUSION: Flow cytometry reveals similar results compared to immunocytochemistry in the determination of lymphocyte subsets characterised by CD3, CD4 and CD8 antigens.

Adult↗
PubMed1996

Sustained cough in methotrexate therapy for rheumatoid arthritis.

Sustained cough is a frequent complaint in methotrexate (MTX) treatment for rheumatoid arthritis and can be a symptom of incipient MTX-induced pneumonitis. This study was performed to characterize MTX-associated cough clinically and to clarify by which means this condition can be distinguished from incipient MTX pneumonitis. Three patients with MTX-induced pneumonitis and 10 patients with sustained cough unassociated with pneumonitis were examined clinically, by pulmonary function testing, and bronchoalveolar lavage (BAL). In MTX pneumonitis, cough was associated with progressive dyspnoea, constitutional symptoms, impaired pulmonary function, and interstitial infiltration of variable degree by chest X-ray. BAL cytology invariably showed lymphocytic alveolitis while transbronchial biopsy revealed active interstitial inflammation in only one patient. Ten patients had sustained, nonprogressive cough in the absence of constitutional symptoms, progressive dyspnoea and impaired pulmonary function. Neither X-ray nor BAL nor transbronchial biopsy revealed any evidence of interstitial lung disease. In the majority of these patients, cough abated with symptomatic treatment with or without temporary discontinuation of MTX. It is concluded that MTX-associated cough can be a reflection of isolated airway disease. Clinically, absence of constitutional symptoms, impaired pulmonary function, and interstitial infiltration on X-ray distinguished this condition from incipient MTX pneumonitis. Cough without pulmonary parenchymal involvement appears to result from an irritant effect of MTX on the airways.

Aged↗
PubMed1996

Biologically weighted personal UV dosimetry.

People are exposed to natural or artificial UV radiation in different ways; unintentionally or intentionally, at their workplace on their spare time. To quantify the amount of individual UV exposure, a personal dosimetry is necessary. In research, polysulphone film (PSF) dosimeters are the most frequently used personal UV dosimeters. We use calculated weighting factors in the measurement processing of polysulphone film dosimeters. The special weighting factor transforms the dosimeter reading from an equivalent UV dose to the biologically effective UV dose. The factor depends on the investigated problem (action spectrum of the photobiological effect and spectral distribution of the incident UV source), the calibration of PSF was carried out once by a monochromatic radiation (gamma = 295 nm). The equivalent dose readings are available from this calibration curve for any investigated question. A presented result of this method is the seasonal measurement of erythemally effective UV exposure by ambient solar radiation, and the individual exposure level in a "normal" person concerning UV exposure and also in groups with the risk of a lack of sunshine. Further applications are occupational measurements of the risk of health damage by UV radiation (with respect to the limit of the maximum permissible 8 h-exposure according to IRPA/INIRC-guidelines). We controlled the extent of UV exposure in workers in the area of arc welding workplaces. The biological weighting of PSF readings simplifies a routine use of PSF in personal UV monitoring to investigators without the expending special measurement technology (e.g. spectroradiometer).

Film Dosimetry↗
PubMed1996

Colorectal adenocarcinoma in Crohn's disease.

OBJECTIVE: The authors' aim was to review the clinical features and estimate the long-term survival of patients with colorectal carcinoma complicating Crohn's disease. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a significantly increased risk of colorectal carcinoma in patients with Crohns disease. METHODS: The authors reviewed retrospectively the medical records of 30 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1989 in whom colorectal adenocarcinoma developed. All patients were operated on and follow-up was complete for all patients to 10 years after operation, to the time of death, or to the closing date of the study in December 1989. RESULTS: The 30 patients in the series had 33 colorectal adenocarcinomas; three patients (10%) presented with two synchronous cancers. The patients were relatively young (mean age, 53 years) and had long-standing Crohn's disease (duration >20 years in 87%). The 5-year actuarial survival was 44% for the overall series: 100% for stage A, 86% for stage B, 60% for stage C. All five patients with excluded bowel tumor died of large bowel cancer within 2.4 years; by contrast, the actuarial 5-year survival for patients with in-continuity tumors was 56%. CONCLUSIONS: The incidence, characteristics, and prognosis of colorectal carcinoma complicating Crohn's disease are similar to the features of cancer in ulcerative colitis, including young age, multiple neoplasms, long duration of disease, and greater than a 50% 5-year survival rate (without excluded loops). These observations suggest the advisability of surveillance programs for Crohn's disease of the colon similar to those for ulcerative colitis of comparable duration and extent.

Adenocarcinoma↗
PubMed1996

Pulmonary sarcoidosis coexisting with systemic lupus erythematosus.

A 23 year old female presented with fatigue, Raynaud's syndrome, symmetric polyarthritis, lymphocytopenia, hypocomplementemia, IgG elevation, and antinuclear antibodies with anti-U1RNP specificity. A diagnosis of systemic lupus erythematosus (SLE) was made. Disseminated micronodular infiltration in the chest X-ray, a pattern of lymphocytic alveolitis by bronchoalveolar lavage, histologic demonstration of non-caseating epitheloid microgranulomas, and rapid reversal of lung disease upon low-dose methylprednisolone treatment led to a diagnosis of concomitant sarcoidosis. Clues to the diagnosis of sarcoidosis coexisting with SLE are discussed.

Adult↗
PubMed1996

Pharmacokinetics and pharmacodynamics of cloprednol.

The pharmacokinetics and pharmacodynamics of cloprednol after oral administration in doses of 2.5 to 15 mg to healthy volunteers were determined. The half-life of cloprednol ranged from 1.8 h to 2.7 h, the oral clearance (CL/F) was determined to be 15-22 l/h. Since cloprednol shows nonlinear plasma protein binding, the plasma concentrations were converted to their free, unbound concentrations for the PK/PD-analysis. Due to this nonlinearity, the half-life of free, unbound cloprednol was shorter than that of the total drug. For the assessment of pharmacodynamics, differential white blood cell counts were obtained over 24 hours. An integrated pharmacokinetic-pharmacodynamic (PK/PD) approach using a modified Emax-model was applied to link unbound corticosteroid concentrations to the effect on lymphocytes and granulocytes. The E50 value for unbound cloprednol ranged from 3.6 to 4.7 ng/ml and 1.2 to 4.6 ng/ml for granulocytes and lymphocytes, respectively. The PK/PD model allowed a good prediction of the observed effects and was consistent with reported values for glucocorticoid receptor binding affinities for cloprednol.

Administration, Oral↗
PubMed1996

Phytohemagglutinin-dependent T-cell proliferation is not impaired by morphine.

Opioids have been reported in the literature to have immunosuppressive properties. Thus, we investigated the influence of morphine, morphine-3-glucuronide and morphine-6-glucuronide in vitro on phytohemagglutinin-stimulated proliferation of peripheral mononuclear cells from healthy humans. Furthermore, the effects of a 1-week treatment with morphine in a range of 30-240 mg/day on proliferation of lymphocytes from patients with chronic pain syndromes were evaluated. In addition, human peripheral mononuclear cell membranes were tested for specific opioid radioligand binding. The results show that i) morphine and its main metabolites do not influence mitogen-induced T-cell proliferation, ii) treatment of patients with sustained release morphine for 1 week did not impair the lymphocyte proliferative response, and iii) no specific binding of mu-, delta- and kappa-radioligands could be demonstrated to membranes of peripheral lymphocytes obtained from healthy humans. These results do not indicate an impairment of phytohemagglutinin-induced T-cell proliferation during pain treatment with sustained release morphine.

Analgesics, Opioid↗