[The indications for acetazolamide].
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Biomedical subjects
Publications and source records attributed to J Barth.
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The influence of a 2-h neuropsychological stress test on plasma catecholamines, cortisol, and on the distribution of lymphocyte subpopulations was studied in 14 patients with systemic lupus erythematosus (SLE), 10 patients on prednisone treatment (without collagenosis), and 14 sex-and-age-matched healthy controls. Psychological stress induced comparably significant increases in plasma adrenaline and noradrenaline levels as compared with baseline values (P less than 0.05) in all three groups, whereas plasma cortisol remained unchanged. The rise in plasma catecholamines was accompanied by a significant cell mobilization in healthy subjects and prednisone-treated patients, but not in patients with SLE. CD19+ cells increased significantly in number from baseline in healthy subjects and prednisone-treated controls (P less than 0.05), while remaining unchanged in SLE patients. In conclusion, SLE patients showed a reduced cell mobilization due to psychological stress despite hormonal alterations paralleling those of healthy subjects or prednisone-treated patients without collagenosis.
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An elderly woman receiving long term treatment with prednisone and azathioprine for cryptogenic chronic active hepatitis developed granulomatous lipophagic panniculitis and temporal arteritis. The lymphoplasmahistiocytic inflammatory reaction pattern is common to this patient's three diseases. It is suggested that an aberration of the defence mechanisms, immunological or otherwise, is responsible for this unusual occurrence. The triple association of chronic active hepatitis, granulomatous panniculitis and temporal arteritis has not been reported previously.
In this study various precipitation methods have been used to concentrate the proteins from broncho-alveolar-lavages. The highest percentage of proteins was recovered from the broncho-alveolar-lavages using the method of Wessel & Flügge (Anal. Biochem. 138 (1984) 141-143). The recovered proteins were further analysed by SDS-polyacrylamide gel electrophoresis. Except for low molecular mass proteins, the method of Wessel & Flügge proved to be the most effective for the recovery of individual proteins. In general, the method of Wessel & Flügge seems to be the superior method for concentrating proteins of broncho-alveolar-lavages for further analysis.
A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure. Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand. This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably. Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful' disease. On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again. This result fits well into the general observation of stress-induced down-regulation of immune responses.
To reveal the underlying mechanisms in the therapeutic effectiveness of ultraviolet (UBV)- and psoralen plus UVA phototherapy, the photostability of leukotriene B4 (LTB4), 12-hydroxyeicosatetraenoic acid (12-HETE) and 5-HETE was investigated in the presence and absence of photosensitizers (8-methoxypsoralen and 5-methoxypsoralen). Arachidonic lipoxygenase products were irradiated with doses of narrow-band UVB (311 nm) ranging from 0.5-3.2 J/cm2, UVB and UVA (305-400 nm) ranging from 0.6-6.3 J/cm2 and UVA ranging from 5.0-60.0 J/cm2, respectively. High-performance liquid chromatography demonstrated a dose-dependent decrease of LTB4, 12-HETE, and 5-HETE. The photostability of 12-HETE was much higher than that of LTB4 and 5-HETE. Two products of transformation of LTB4 were identified as 5(S), 12(R)-dihydroxy-(6E, 8E, 10E, 14Z)-eicosatetraenoic acid [6-trans-LTB4] and 5(S), 12(R)-dihydroxy-(6E, 8Z, 10E, 14Z)-eicosatetraenoic acid [5(S), 12(R)-DiHETE]. There was no significant increase in photodegradation after addition of photosensitizing psoralens.
Sarcoidosis is a granulomatous disorder which can be characterized by various immunologic abnormalities including lymphocyte dysfunctions. The purpose of this study was to investigate the B-lymphocyte reactivity in the peripheral blood of 29 various patients with pulmonary sarcoidosis. A significant decrease in the production of IgG, IgM and IgA in supernatants of cultivated sarcoidosis B-cells both after stimulation with a T-cell dependent polyclonal B-cell activator (pokeweed mitogen) and with a T-cell independent polyclonal B-lymphocyte activator (Klebsiella pneumoniae) was seen, which suggested a disturbance in the B-cell differentiation of sarcoidosis patients. Those patients which were known to have a clinically active disease or a high intensity alveolitis in the bronchoalveolar lavage fluid showed a greater reduction in the B-cell differentiation response. Further evaluation of Ig-G subclasses displayed a significant decrease in the secretion of IgG1, IgG3 and IgG4. In contrast to the differentiation, the proliferation response of sarcoidotic peripheral blood lymphocytes to different mitogens did not differ from healthy controls.
The pharmacokinetics and pharmacodynamics of prednisolone were investigated according to four different routes of administration: 20 and 40 mg prednisolone orally in the morning, 20 mg prednisolone orally in the evening and 40 mg prednisolone intravenously in form of prednisolone phosphate in the morning. The plasma levels of prednisolone were followed using HPLC. To study the pharmacodynamics of prednisolone, glucose levels and various blood cell parameters such as erythrocytes, leukocytes, segmented neutrophilic granulocytes, eosinophils, basophils, monocytes and lymphocytes were followed. To summarize the data, the area under the effect-time-curve (AUCE) was calculated by the trapezoidal rule. The results show that the pharmacokinetics of prednisolone is dose-dependent (non-linear) and time-dependent. Prednisolone concentrations in plasma after a 20 mg and 40 mg dose are very similar, indicating that the pharmacokinetics of prednisolone are non-linear and dose-dependent with a higher clearance for higher concentrations. The comparison of 20 mg administered in the morning with the same dose given in the evening shows that the pharmacokinetics of prednisolone after oral administration of equal doses changes during the day with higher concentrations in the morning than in the evening. Furthermore, the results of the present study confirm the presence of pharmacodynamic corticosteroid effects on blood cell count and blood glucose. No statistically significant differences were observed for the four different treatments. In summary, it can be concluded that due to the complex pharmacokinetics of prednisolone, it is difficult to make accurate predictions of the expected effect-time relationships.
The influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL-2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study.
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Aside from the well established modes of topical treatment, systemic treatments are also required in cases of recalcitrant and/or severe topic eczema. The following methods already introduced in clinical practice are discussed: Substitution of gamma-linoleic acid and intake of eicosapentaenoic acid respectively, UV-irradiation with suitable wavelength bands, Cyclosporin A-treatment. Finally the different therapeutic possibilities which could effect the atopic inflammatory infiltrate are pointed out.
To prove the clinical usefulness of cortisol measurements in saliva for the exact assessment of a patient's corticoid status under therapeutic hormone substitution, we measured simultaneously total cortisol in serum and non-protein-bound cortisol in saliva after administration of different forms of hydrocortisone (cortisol) in eight cortisol-suppressed, healthy male volunteers. The intravenous and oral administration of 20 mg of cortisol exceeds the binding capacity of the corticosteroid-binding globulin (CBG), leading to an increase of the ratio between salivary and serum cortisol at the higher cortisol concentrations in blood. After rectal administration of 100 mg of cortisol acetate, the serum cortisol concentration does not exceed the binding capacity of CBG, so the ratio between salivary and serum cortisol remains nearly constant. However, this ratio was higher after rectal administration than after intravenous and oral administration, probably because of weaker binding of the acetate form of cortisol to CBG. Thus, the salivary measurement of the non-protein-bound (i.e., biologically active) cortisol offers a convenient way to monitor the effectiveness of various forms of systemic corticoid substitution.
The human VH5 family consists of two functional genes and one pseudogene. We have found a novel 1.2-kb VH5 gene transcript in normal fetal liver and cord blood and in transformed B lineage cells. VH5-positive cDNA clones were isolated from precursor B acute lymphoblastic leukemia, B chronic lymphoblastic leukemia, Epstein-Barr Virus-transformed B cell lines, and cord blood, and were identified as transcripts of unrearranged VH5 genes (germline transcripts). The cDNA clones were derived from both functional and pseudo-VH5 genes. Most germline transcripts appear to initiate at the normal VH promoter and are cleaved and polyadenylated at sites several hundred bases downstream of the VH5 coding region. Correct splicing of the leader intron was observed in all clones. In functional and pseudo-VH5 cDNAs, an open translational reading frame extends from the leader to a termination codon in the nonamer. Only limited polymorphisms were observed in the coding as well as flanking regions of the VH5 transcripts. Functional and pseudo-VH5 transcripts and previously identified murine germline VHJ558 transcripts are discussed.
The pharmacokinetics of 20 mg hydrocortisone were studied after IV and oral administration. Endogenous hydrocortisone was suppressed by dexamethasone administration. Hydrocortisone concentrations were measured in plasma and saliva. After IV administration, hydrocortisone was eliminated with a total body clearance of 18 L/hr and a half-life of 1.7 hr. The volume of distribution was 34 L. Oral bioavailability averaged 96%. Absorption was rapid, achieving maximum hydrocortisone levels of 300 ng/mL after 1 hour. Saliva levels were not proportional to plasma levels, but could be shown to reflect free, non-protein bound hydrocortisone concentrations in plasma.
The pharmacokinetics and bioavailability of hydrocortisone after rectal administration of a hydrocortisone acetate foam was determined. Endogenous hydrocortisone was suppressed by dexamethasone administration. Plasma levels were compared with those observed after iv and oral administration. Only a very small part of the rectal dose (100 mg) was absorbed; the mean absolute bioavailability was 2%. There was substantial intersubject variability. Maximum hydrocortisone levels were reached after 2 h and averaged 35 ng/mL. These levels were 10-fold lower than those obtained after oral administration of a fivefold lower dose (20 mg) of hydrocortisone in the same subjects.
Systemic retinoids are effective in a variety of inflammatory dermatoses. Disorders in which polymorphonuclear leukocytes (PMN) are involved, such as psoriasis and acne, respond particularly well to various retinoids. However, side-effects restrict the use of systemic retinoids to severe manifestations. Topical application might provide the possibility of avoiding the systemic side-effects of these compounds. In this communication we report on the modulation of transepidermal migration of PMN by topical application of all-trans-retinoic acid, 13-cis-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone. Test areas of healthy volunteers were pretreated with these retinoids in a cream base and with corresponding placebo creams, and intraepidermal accumulation of PMN was quantified 24 h after epicutaneous challenge with leukotriene B4 (LTB4), using elastase as a marker enzyme. Topical treatment with 13-cis-retinoic acid resulted in a marked and statistically significant inhibition of the LTB4-induced migration of PMN. All-trans-retinoic acid, arotinoid methyl sulphone and arotinoid ethyl sulphone reduced the accumulation of PMN slightly, but not statistically significantly. Topical treatment with arotinoid methyl sulphone had no effect.