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PubMed1975

Metabolism of systematically given corticosteroids.

In the metabolism of a systemically administered corticosteroid, one of three possible main pathways is determined by the position in the molecule of the substituents which are added in the drugs to the naturally occurring ones. (I) Chiefly, hydrogenation in ring A and/or the 20-position: cortisol, cortisoine, prednisolone, prednisone, and 6alpha-methylprednisolone (II) In the presence of a substituent in the 16-position mainly 6beta-hydroxylation: dexamethasone, betamethasone, and triamcinolone. (III) In the presence of a substituent in the 16-position, and fluorine in the 6alpha-position principally defluorination in the 6alpha-position and 6beta-hydroxylation: fluocortolone and paramethasone. Complete metabolism, in long-term use, can be expected in the case of the substances mentioned under II and III, but not of those under I. Enzyme induction, both actively and passively, is negligible in group I and marked in groups II and III.

Adrenal Cortex Hormones↗
PubMed2001

Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial.

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

Adrenal Cortex Hormones↗
PubMed1989

Failure of corticosteroid therapy to prevent induction of ventricular tachycardia in sarcoidosis.

Programmed ventricular stimulation was performed in a patient with sarcoidosis who exhibited an episode of sustained ventricular tachycardia. Sustained rapid ventricular tachyarrhythmias requiring cardioversion for termination were induced by double right ventricular apical extrastimuli during control, and treatment with disopyramide, quinidine, and fluocortolone. In contrast, only four repetitive ventricular complexes were induced during combined therapy with quinidine, mexiletine and amiodarone. While receiving the latter regimen, the patient has been asymptomatic during 28 months of follow-up.

Adult↗
PubMed1976

In vitro studies on enzymatic cleavage of steroid esters in the female organism.

The decreasing water-solubility of steroid esters concomitant with increasing chain lenth of monocarboxylic acids provides a prolonged therapeutic effect of the steroid. Whether a slow release of the steroid from an oily depot in the muscle or a secondary storage of the enter in the body fat ("deep compartment") are responsible for this prolonged action, is open to discussion. The aim of this study was to investigate the steriod ester cleaving enzyme activity of human subcutaneous fatty tissue. The followeing steroid esters were investigated: Testosterone acetate and oenanthate, metenolone acetate and oenanthate, norethisterone acetate and oenanthate, dehydroepiandrosterone acetate and oenanthate, fluocortolone acetate and caproate. In the 10000 X g supernatant phase of the female subcutaneous fatty tissue the rate of enzymatic cleavage of the long-chain oenanthates was considerably greater than that of the corresponding short-chain steroid esters. The nature and position of the ester group in the steroid molecule exhibited a marked effect on the rate of enzymatic cleavage of steroid esters. The cleavage rate of long- and short-chain steroid esters in human myometrium and endometrium resembled that in the fatty tissue. On the other hand, the gastric mucosa, recuts musculature, placenta and vaginal mucosa split the short-chain steroid esters more rapidly than the long-chain esters. The marked differences in the relation of the cleavage rate of long- and short-chain steoid esters in the various tissues allow the assumption that long- and short-chain steroid esters are cleaved by different enzymes.

Adipose Tissue↗
PubMed1992

Prevention of miscarriage in antiphospholipid syndrome.

Recurrent adverse pregnancy outcome may be the final result of different causes, including autoimmune diseases, as the Antiphospholipid Syndrome. Antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) were found in 16% of 197 patients with prior unexplained recurrent miscarriages. During our study 22 out of 32 antiphospholipid antibodies positive women became pregnant again. To prevent abortion relapses, 16 of them were treated with acetylsalicylic acid (50 mg x 2/day) and/or fluocortolone (20 mg/day for 5 days/week). Such therapy started as soon as pregnancy was diagnosed in 14 patients. Two patients began the therapeutic regimen during the third month of gestation. Six patients, who didn't accept this therapeutic approach, represent our control group. All the 14 early treated patients ended pregnancy with success. The 2 women that began the therapy later presented abortion relapses. Among the 6 not treated patients, 5 presented spontaneous abortion and only one gave birth to a baby. No side effect was observed neither in treated mothers nor in their babies. In conclusion, even if further studies would be necessary to standardise a therapeutic protocol, our results encourage the clinical care of patients with antiphospholipid antibodies and adverse pregnancy outcomes.

Abortion, Habitual↗
PubMed1976

[Collagen disease with pure red cell anemia and perimembraneous glomerulonephritis (author's transl)].

Record on a case of collagen disease with pure red cell anemia and perimembraneous glomerulonephritis. The direct antiglobulin tests with anti-IgG and anti-kappaserum were positive as were the tests on antinuclear serum-antibodies. During therapy with fluocortolon and azathioprin the anemia remitted completely even when therapy was stopped. The antiglobulin tests became negative, the glomerulitis remained active, there was no deterioration of renal function.

Adult↗
PubMed1976

[Studies on the Pharmacology of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolon valerate) (author's transl)].

The topical and systemic anti-inflammatory action of 6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) was studied in the rat in comparison with fluocortolone, diflucortolone and some other corticoids. In addition the effect of the compounds studied on the following parameters of corticoid activity was examined in the rat: body weight and weights of thymus, spleen and adrenals; blood sugar concentration and liver glycogen content; diuresis and Na+ and K+ elimination with the urine; the binding of diflucortolone and some diflucortolone-21-esters to the cytoplasmic corticoid receptor of the rat's thymus was also determined. In all tests diflucortolone was shown to be a corticoid with very potent topical and systemic action. Diflucortolone valerate showed the same potent anti-inflammatory action on topical application as the unesterified compound. After subcutaneous administration, however, the systemic corticoid action of the valerate was considerably inferior to that of diflucortolone on account of the kinetics of the more lipid soluble ester.

Adrenal Glands↗
PubMed1990

Steroid responsive familial neuropathy with liability to pressure palsies.

Autosomal dominant motor and sensory neuropathy with liability to pressure palsies was studied in three members of the same family. Only one of two monozygotic twin sisters was clinically affected. She developed unilateral peroneal palsy twenty minutes following local pressure. Electromyography revealed a weak intermediate innervation pattern with very rapid action potentials in the right anterior lower leg muscle. A 25-70 per cent reduction of motor and sensory conduction velocity was recorded in the clinically unaffected twin sister and in the father. The electrophysiological findings in the mother were normal. The sural nerve biopsy revealed "sausage-like" formations. The palsy persisted for two months and disappeared after eight weeks of fluocortolon treatment. It is possible that the myelin sheaths acted as antigen.

Biopsy↗
PubMed1990

[The symptomatic therapy of hemorrhoids and anal eczema--a report of experiences from proctology practice].

Besides the various operative procedures, which nowadays have come into use in hemorrhoidal disorders, drug therapy as well continues to keep an important place. Its main conditions of application are inflammatory processes before, between and after hemorrhoidal sclerosis or proctological operations. In a clinical study suppositories with the corticoid fluocortolone-21-pivalate and the local anesthetic lidocaine hydrochloride as well as a cream with the same substances and in addition, chlorquinaldol were tested in 92 patients with hemorrhoidal diseases and their concomitant conditions. In 92% of the cases efficacy of the preparations proved to be good or very good, and in all cases they were well tolerated.

Administration, Topical↗
PubMed1988

[Development of multiple precancerous conditions and malignant skin tumors in immunosuppressive therapy].

A 45-year-old patient developed squamous cell carcinoma 4 years after renal transplantation and immunosuppressive therapy with azathioprine and fluocortolone. During the following 3 years, the patient developed on sun-exposed skin several premalignant hyperkeratoses, Bowen's carcinoma, basal cell carcinoma, as well as squamous cell carcinoma and carcinoma of the eccrine sweat glands, both showing the clinical picture of keratoacanthoma.

Azathioprine↗
PubMed1977

[Experimental studies in animals on the influence of fluocortin butylester on the course of generalized infections (author's transl)].

The influence of butyl 6alpha-fluoro-11beta-hydroxy-16alpha-methyl-3,20-dioxo-1,4-pregnadien-21-oate (fluocortin butylester, Vaspit), a new corticosteroidal compound with a marked dissociation between local antiinflammatory and systemic action, upon resistance against infections was studied in experimental bacterial and fungal infections in mice. The results of the experiments showed, that fluocortin butylester, even after repeated s.c. or oral administration of dosages up to 100 mg/kg did not depress the resistance of the animals against microbial infections. The relevance of the animal models was checked by parallel experiments with fluocortolone, hydrocortisone, prednisolone and cyclophosphamide.

Animals↗
PubMed1982

[Periodic application of topical corticosteroids. Practicability and therapeutic value in daily practice].

Therapeutic efficacy and practicability of an interval treatment were investigated in a multi-center study in a total of 1573 patients with psoriasis or eczema, respectively. Fluocortolone monohydrate as Syracort and Syracerin as steroid-free "partner drug" were applied at 4-/3-day intervals. The findings and established results substantiate equivalent therapeutic success in comparison with consistent treatment. Starting from the premise that the risk of steroidinduced skin lesions can be reduced, if not avoided, by interval application of topical corticosteroids one may consider steroid application at intervals as superior to consistent therapy.

Administration, Topical↗
PubMed1982

[On the question of interval application of topical corticoids/Practicability and efficacy (author's transl)].

Therapeutic efficacy and practicability of an interval treatment were investigated in a multi-center study in a total of 1573 patients with psoriasis or eczema, respectively. Fluocortolone monohydrate as Syracort and Syracerin as steroid-free "partner drug" were applied at 4-13-day intervals. The findings and established results substantiate equivalent therapeutic success in comparison with consistent treatment. Starting from the premise that the risk of steroid-induced skin lesions can be reduced, if not avoided, by interval application of topical corticoids one may consider steroid application at intervals as superior to consistent therapy.

Administration, Topical↗
PubMed1980

[Primary amyloidosis with nephrotic syndrome: 5 year follow-up under polychemotherapy. A case report (author's transl)].

A patient with primary amyloidosis had infiltration of liver, bone and bone marrow and a nephrotic syndrome with massive proteinuria. In addition, there was evidence for a plasma cell dyscrasia with an increased number of plasma cells and other lymphoreticular cell elements in the bone marrow and an impairment of immunoglobulin synthesis without M-gradient. The course of disease was observed over a period of five years. The patient was treated intermittently with a combination of penicillamine, melphalan, fluocortolone and fluoxymesterone. Under treatment the nephrotic syndrome disappeared and liver size decreased. Hemopoiesis remained sufficient but bone marrow infiltration by amyloid did not respond to therapy and massive osteoporosis developed. Comparison of our with other reported cases treated with the same regime suggests that response to this treatment may be influenced by factors such as sex and clinical manifestation of the disease.

Amyloidosis↗
PubMed2001

Systemic mycophenolate mofetil in comparison with systemic cyclosporin A in high-risk keratoplasty patients: 3 years' results of a randomized prospective clinical trial.

BACKGROUND: With the use of systemic cyclosporin A (CsA), graft prognosis after high-risk penetrating keratoplasty has improved considerably. However, the application of CsA is limited owing to a variety of severe side effects. In this prospectively randomized study mycophenolate mofetil (MMF), a safe and efficient immunosuppressive medication after renal transplantation, was compared with CsA after high-risk penetrating keratoplasty. METHODS: Twenty-nine high-risk keratoplasty patients were treated with MMF 2x 1 g daily; another 27 patients received CsA, aiming at blood trough levels of 120-150 ng/ml. Systemic immunosuppression was scheduled for 6 months. In both groups oral corticosteroids (fluocortolone 1 mg/kg) were administered for 3 weeks postoperatively. RESULTS: During the first year after operation, no graft failure was recorded. Two years postoperatively 92%/82% and 3 years postoperatively 74%/69% of grafts were clear in the MMF and CsA group, respectively (Kaplan Meier P=0.33, logrank test). In total, two graft failures were recorded in the MMF group and four in the CsA group. Three years postoperatively 53% of the grafts were rejection-free in the MMF group and 73% in the CsA group (Kaplan Meier P=0.46, log-rank test). Eight endothelial immune reactions were observed in the MMF group (three under systemic immunosuppression/five thereafter; six mild/two severe) and five in the CsA group (three under systemic immunosuppression/two thereafter; three mild/two severe). Side effects occurred in six patients under MMF and 11 under CsA. CONCLUSIONS: Concerning efficacy, no statistically significant difference between systemic MMF and systemic CsA administered for 6 months after high-risk penetrating keratoplasty could be shown. Systemic MMF was proven to be at least as safe as CsA. The main mechanism in improving graft survival is a shift from severe to milder endothelial immune reactions, as already demonstrated for CsA. Thus, MMF may become an alternative to CsA for immunosuppression after penetrating high-risk keratoplasty. About 2 years postoperatively, pharmacologically induced relative immunological tolerance slowly decreases. Therefore, long-term administration of systemic MMF should be evaluated in further studies.

Adolescent↗
PubMed1996

Simultaneous determination of triamcinolone acetonide and hydrocortisone in human plasma by high-performance liquid chromatography.

A validated HPLC method for the simultaneous determination of triamcinolone acetonide and hydrocortisone has been established to monitor the plasma levels of the compounds in healthy volunteers following intramuscular (i.m.) administration of triamcinolone acetonide. Plasma (1.0 ml) was extracted with dichloromethane after addition of the internal standard, fluocortolone. The compounds were separated using a LiChrospher RP 18 column and detected by UV absorbance. Specificity, linearity, as well as the repeatability, intermediate precision and accuracy of the method were established. The limit of quantification was 0.6 ng/ml for triamcinolone acetonide (C.V. = 8.7%, R.E. = 2.6%, n = 6) and 2.0 ng/ml for hydrocortisone (C.V. = 8.3%, R.E. = 2.8%, n = 6). Data on the stability of triamcinolone acetonide in human plasma are presented. Recovery of the compounds and the internal standard have been studied. The results of quality control samples (n = 126) determined during routine analysis of volunteer samples are described. Plasma levels of triamcinolone acetonide after i.m. administration of 40 mg of triamcinolone acetonide are presented.

Administration, Topical↗
PubMed1993

Premature ovarian failure--the prognostic application of autoimmunity on conception after ovulation induction.

OBJECTIVE: To assess whether the presence of autoimmune activity in patients with premature ovarian failure (POF) can predict the response to ovulation induction and conception. DESIGN: Assessment of autoimmune activity in patients with POF, correlating the response to ovulation induction with this autoreactivity. SETTING: Tertiary care academic center. PATIENTS: Forty women with POF, 15 of them treated by ovulation induction because of infertility. INTERVENTIONS: All patients were tested for the presence of autoimmune activity, antibodies against various tissues, and 15 of them were treated with combinations of hMG/hCG, glucocorticosteroids as immunosuppressant, and some of them also with a long-acting GnRH agonist. Those patients not interested in infertility were put on hormone replacement therapy (HRT). MAIN OUTCOME MEASURES: Serum E2 and P were measured during ovulation induction as well as follicular diameter monitoring by transvaginal sonography. Achievement of gestations and their outcome were monitored in the group in which ovulation induction was accomplished. RESULTS: Antibodies against thyroglobulin, nuclear antigens, heart, tissue gluten, or increased levels of immunoglobulin (Ig)M, or decreased levels of complement C3 and C4 were significantly different in the patients with POF than in the control population. Autoreactivity of at least one class of the tested antibodies was found in 31 of 40 patients (77%). In 15 patients with autoimmune activity who have undergone ovulation induction using hMG/hCG, 14 pregnancies were achieved in 8 patients. Two of the pregnancies were spontaneous, and 12 were generated by hMG/hCG and fluocortolone, with or without pretreatment with GnRH-a. Twelve healthy babies were generated by 10 gestations, 3 ended in spontaneous abortions (23%), and 1 is ongoing. All the nonspontaneous pregnancies were achieved in the first three cycles of ovulation induction. CONCLUSIONS: Patients with POF and autoimmune activity, suggesting an autoimmune etiology to the ovarian failure, may respond to ovulation induction and have a conception rate of approximately 40% in three cycles. Those who do not conceive in three treatment cycles have a very low probability to conceive; therefore, further attempts of ovulation induction should be discouraged. However, some patients may spontaneously conceive in association with HRT.

Adult↗