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PubMed1994

Added salmeterol versus higher-dose corticosteroid in asthma patients with symptoms on existing inhaled corticosteroid. Allen & Hanburys Limited UK Study Group.

Guidelines on asthma management recommend that in patients who still have symptoms on treatment with low-dose inhaled corticosteroids the first step should be an increase in inhaled corticosteroid dose. The addition of long-acting inhaled beta 2-adrenoceptor agonists is another option. We have compared these two strategies in a randomised, double-blind, parallel-group trial. We studied 429 adult asthmatic patients who still had symptoms despite maintenance treatment with 200 micrograms twice daily inhaled beclomethasone dipropionate (BDP). 3 did not provide verifiable data. Of the others, 220 were assigned salmeterol xinafoate (50 micrograms twice daily) plus BDP and 206 were assigned higher-dose BDP (500 micrograms twice daily) for 6 months. The mean morning peak expiratory flow increased from baseline in both groups, but the increase was greater in the salmeterol/BDP group than in the higher-dose BDP group at all time points (differences 16-21 L/min, p < 0.05). Mean evening PEF also increased with salmeterol/BDP but not with higher-dose BDP. There were significant differences in favour of salmeterol/BDP in diurnal variation of PEF (all time points) and in use of rescue bronchodilator (salbutamol) and daytime and night-time symptoms (some time points). There was no significant difference between the groups in adverse effects or exacerbations of asthma, indicating that in this group of patients regular beta 2-agonist therapy was not associated with any risk of deteriorating asthma control over 6 months. This study suggests a need for a flexible approach to asthma management.

Administration, Inhalation↗
PubMed2003

The effect of antenatal corticosteroids on gut peptides of preterm infants--a matched group comparison: corticosteroids and gut development.

BACKGROUND: Postnatal glucocorticosteroid administration has trophic effects on the gastrointestinal tract of preterm infants. The aim of the present study was to investigate whether antenatal glucocorticosteroids affect the secretion of gastrointestinal peptides that are involved in the regulation of secretion, motility and mucosal protection of the gastrointestinal tract. METHODS: Plasma levels of gastrin, motilin and vasoactive intestinal peptide (VIP) were estimated in 28 preterm infants with a mean birth weight of 1280 g, and mean gestational age of 30.5 weeks, whose mothers had received a full course of antenatal glucocorticosteroids (GC group) and in 17 preterm infants with mean birth weight of 1200 g, mean gestational age of 30.2 weeks, whose mothers had not received corticosteroids (control group). GI peptides were estimated on two occasions: (a) Immediately after birth and (b) following the initiation of enteral feeding. RESULTS: Gastrin levels in the GC group were significantly higher both immediately after birth (early measurement) and also after receiving enteral feeding (late measurement) (p<0.001, p<0.05, respectively) but the increase in plasma gastrin concentration was identical in both groups (32 vs. 33 pg/ml). Motilin levels in the GC group were also significantly higher as compared to the control group but only in the late measurement (p<0.001). Gastrin and motilin levels in both groups were significantly higher in the late measurement as compared to the early measurement (GC group: p<0.001, p<0.001, respectively; CONTROLS: p<0.001, p<0.01, respectively). There was no significant difference in VIP levels between the two groups both in the early and the late measurements. CONCLUSION: Antenatal glucocorticoids (GCs) stimulate gastrin secretion in the fetus but not in the neonate. Contrary to this, corticosteroid effect on motilin is seen only postnatally following the introduction of enteral feeding. Glucocorticosteroids appear to have no effect on VIP levels. Plasma gastrin and motilin levels increase significantly following the introduction of enteral feeding regardless of the use of steroids.

Adult↗
PubMed1996

Corticosteroid receptor mRNA expression is unaffected by corticosteroids in rat kidney, heart, and colon.

Hormones can regulate the expression of their own receptor. We have examined whether adrenalectomy (ADX) and hormone replacement by physiological doses of aldosterone or dexamethasone could modulate the expression of glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) at the mRNA level in the rat kidney, distal colon, and heart. Adult rats were adrenalectomized and received or did not receive an infusion of aldosterone (5 micrograms.100 g-1.day-1) or dexamethasone (10 micrograms.100 g-1.day-1). No significant change in steady-state levels of both MR and GR mRNA was detectable by using ribonuclease (RNase) protection assay (RPA) after either ADX or hormone replacement. Because the kidney is heterogeneous with regard to MR expression, RPA was adapted for measurements on microdissected nephron segments. GR mRNA is expressed at comparable levels all along the nephron, whereas MR mRNA is restricted to the distal nephron. No effect of ADX or GR and MR mRNA levels was detected in any nephron segment that was either aldosterone sensitive or insensitive. In situ hybridization confirmed the absence of corticosteroid-dependent modulation of MR mRNA in all kidney cell types. We conclude that variations of corticosteroid status do not affect MR and GR mRNA steady-state levels in heart, colon, and kidney and thus do not participate to the functional adaptations that are known to depend on hormonal status.

Adrenalectomy↗
PubMed1977

Studies of the diurnal pattern of plasma corticosteroids and gonadotropins in two cases of feminizing adrenal carcinoma: measurements of estrogen and corticosteroid production.

Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.

Adrenal Cortex Hormones↗
PubMed1977

Effect of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. An experimental approach to a possible mechanism of action of corticosteroids in myasthenia gravis.

We studied the effect of intraperitoneally administered corticosteroids on the neuromuscular transmission in the sciatic nerve-tibialis anterior muscle preparation of the anesthetized rat stimulated at a rate of 10 Hz. Administered simultaneously with hemicholinium-3 (HC-3), 80 mug per kilogram (that is, half the lethal dose for 50 percent survival), prednisolone and dexamethasone cause a marked reversal of the block of the neuromuscular transmission caused by HC-3. The effect of aldosterone is very small. The blocking action of d-tubocurarine is not antagonized by either prednisolone or dexamethasone. Choline provides total protection against the HC-3 blockade, whereas physostigmine, in a just sublethal dose, is ineffective. We tentatively conclude that in myasthenia gravis the carrier-mediated transport of choline into the nerve endings may be deficient and that the beneficial effect of corticosteroids in this condition is based on their ability to ameliorate the deficient choline transport.

Animals↗
PubMed2001

Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients : a 4-year longitudinal study.

BACKGROUND: It is not certain whether inhaled corticosteroid (ICS) therapy reduces bone mineral density (BMD) in asthmatic patients. In addition, the potential risk of osteoporosis associated with the rescue use of short courses of oral corticosteroids (SC-OCS) is unclear. OBJECTIVE: To evaluate the effect of inhaled beclomethasone dipropionate (BDP) and SC-OCS on BMD in asthmatic patients. DESIGN: A 4-year longitudinal study. METHOD: Lumbar BMD was measured twice by dual-energy x-ray absorptiometry at a mean (+/- SD) interval of 4.2 +/- 0.1 years in 35 asthmatic adults (15 men and 20 postmenopausal women; mean age at the second evaluation, 60.6 +/- 11.5 years) who had been treated with BDP and SC-OCS. RESULTS: The average period of BDP treatment was 7.7 +/- 2.2 years (range, 4.8 to 13.0 years) at the second evaluation. During the study period, the daily dose of BDP was 765 +/- 389 microg (range, 100 to 1,730 microg), and the frequency of SC-OCS was 1.9 +/- 2.7 courses per year (range, 0.0 to 8.9 courses per year). As a whole, lumbar BMD was unchanged during the course of the study, whereas the Z score (ie, the percentage of normal value predicted from age and sex) increased significantly. Changes in BMD and Z scores in patients receiving high doses of BDP (ie, > 1,000 microg/d; n = 9) were not significantly different from those of patients receiving lower doses (ie, 2.5 courses per year; n = 9) showed a significantly greater loss in BMD and Z score compared with those receiving sporadic courses (ie, <or= 2.5 courses per year; n = 26) (p = 0.002 and p = 0.035, respectively). CONCLUSIONS: ICS therapy per se does not affect BMD, whereas frequent SC-OCS may do so.

Absorptiometry, Photon↗
PubMed2002

Replacement of oral corticosteroids with inhaled corticosteroids in the treatment of acute asthma following emergency department discharge: a meta-analysis.

OBJECTIVES: Oral corticosteroids (CS) are standard treatment for patients discharged from the emergency department (ED) after treatment for acute asthma. Several recent, relatively small trials have investigated the replacement of CS with inhaled corticosteroids (ICS), with varied results and conclusions. This systematic review examined the effect of using ICS in place of CS on outcomes in this setting. METHODS: Only randomized controlled trials were eligible for inclusion. Studies in which patients were treated for acute asthma in the ED or its equivalent, and on discharge compared ICS therapy to standard CS therapy, were eligible for inclusion. Trials were identified using the Cochrane Airways Review Group register, searching abstracts and bibliographies, and contacting primary authors and pharmaceutical companies. Data were extracted and methodologic quality assessed independently by two reviewers, and missing data were obtained from authors. RESULTS: Seven trials, involving a total of 1,204 patients, compared high-dose ICS therapy vs CS therapy after ED discharge. There were no significant differences demonstrated between the treatments for relapse rates (odds ratio, 1.00; 95% confidence interval, 0.66 to 1.52) or in the secondary outcomes of beta-agonist use, symptoms, or adverse events. However, the sample size was not adequate to prove equivalence between the treatments, and severe asthmatics were excluded from these trials. CONCLUSIONS: There is some evidence that high-dose ICS therapy alone may be as effective as CS therapy when used in mild asthmatics on ED discharge; however, there is a significant possibility of a type II error in drawing this conclusion.

Acute Disease↗
PubMedDate not supplied

Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases.

This randomized, double-blind, parallel, multi-center study was designed to determine whether the addition of salmeterol to existing inhaled corticosteroid therapy provides greater therapeutic benefit than doubling the dose of inhaled corticosteroids in symptomatic patients with asthma. A total of 514 adults were randomized to either beclomethasone 168 micrograms plus salmeterol 42 micrograms twice daily or beclomethasone 336 micrograms twice daily for 24 weeks. Both treatments resulted in significantly improved symptom control and increased pulmonary function. However, beclomethasone plus salmeterol provided greater improvements than doubling the dose of beclomethasone (p < or = 0.05) in FEV1 and in daily-recorded measurements of morning (38 L/minute versus 20 L/minute after treatment with higher dose beclomethasone) and evening peak expiratory flow, asthma symptom scores, symptom-free days, supplemental albuterol use, and days and nights not requiring albuterol. There were no significant differences between treatment groups in the number of patients with abnormal response to corticotropin stimulation at Treatment Week 24. No treatment differences in asthma exacerbation and adverse event frequency rates were seen. Beclomethasone 168 micrograms plus salmeterol 42 micrograms administered twice daily was superior to beclomethasone 336 micrograms taken twice daily in patients symptomatic on beclomethasone 168 micrograms, with no added safety risks.

Administration, Inhalation↗
PubMed1999

Salmeterol added to inhaled corticosteroid therapy is superior to doubling the dose of inhaled corticosteroids: a randomized clinical trial.

This randomized, double-blind, double-dummy, parallel group clinical trial compared the efficacy and safety of adding salmeterol xinafoate to concurrent inhaled beclomethasone dipropionate therapy with doubling the dose of beclomethasone dipropionate in patients experiencing symptoms on low-dose beclomethasone. Salmeterol added to low-dose beclomethasone was superior (p < or = 0.05) to doubling the dose of beclomethasone in improving peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1), and in reducing symptoms of asthma, sleep loss, nighttime awakenings, and use of albuterol. Both treatment regimens had comparable safety profiles. In asthma patients inadequately controlled despite the use of low-dose inhaled corticosteroids (i.e., less than 400 microg per day), the addition of salmeterol may be a more effective treatment option than doubling the dose of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1992

The use of corticosteroids in dermatological practice.

OBJECTIVE: To discuss the various uses of corticosteroids in patients with skin diseases. DATA SOURCES: All relevant literature published since 1950 was reviewed and 33 studies were selected. CONCLUSIONS: Systemic and topical corticosteroid preparations are used commonly in patients with skin diseases. Oral administration of steroids is particularly useful in acute hypersensitivity diseases, connective tissue diseases, immunological blistering diseases, and the commoner dermatoses when they are very severe and widespread. Topical steroid preparations are mainly used in the different forms of dermatitis, but are also useful in psoriasis and a number of other skin diseases. If potent topical steroid preparations are used for too long, or in excessive quantities, side effects will be encountered as a direct effect on the skin, for example atrophy, and as a result of systemic absorption, for example, hypothalamic-pituitary-adrenal suppression and Cushing's syndrome.

Administration, Oral↗
PubMed2004

Corticosteroid regulation of colonic ion transport during postnatal development: methods for corticosteroid analysis.

Many mammalian species including human are immature at birth and undergo major developmental changes during suckling and weaning period. This problem is also conspicuous for the gastrointestinal tract that undergoes abrupt transitions coinciding with birth and weaning. This review deals with the maturation of ion transport functions in colon, the intestinal segment that plays an important role in sodium and potassium absorption and secretion. The purpose of the present review is to summarize the mechanism of sodium and potassium transport pathways and show how these transport processes change postnatally and how hormones, particularly corticosteroids, modify the pattern of development. Finally we describe some of the ways, how to analyze corticosteroid metabolism in target tissue.

Adrenal Cortex Hormones↗
PubMed2006

Topical management of psoriasis - corticosteroids and sparing corticosteroid therapy.

Psoriasis is a complex disease that requires safe, long-term treatment. Topical steroid therapy, topical non-steroid therapy only, and a combination of various topical therapies in the treatment of mild to moderate forms of psoriasis are presented. Topical therapy includes corticosteroids, vitamin D3 analogs, retinoids, tars, anthralin, keratolytics, and topical immunomodulators. While most medications are approved for use as a single agent in the treatment of psoriasis, some of these drugs are most effective when used in combination with topical corticosteroids. Topical therapy is generally administered for mild and localized forms of psoriasis, whereas phototherapy and systemic therapy are reserved for extensive lesions and more severe forms of the disease. Individual approach is absolutely necessary in each patient with psoriasis.

Administration, Topical↗
PubMed1988

Mucous membrane manifestations of pemphigus vulgaris. A 25-year survey of 185 patients treated with corticosteroids or with combination of corticosteroids with methotrexate or heparin.

One hundred and eighty-five patients with pemphigus vulgaris were treated and followed up over a period of 25 years, from 1962 to 1987, at the Department of Dermatology of Moscow Medical Stomatological Institute. In all these patients the diagnosis was confirmed clinically, histologically and cytologically, and in 152 patients by means of direct and indirect immunofluorescence. The patients were treated with corticosteroids or with a combination of corticosteroids with methotrexate or heparin. The initial manifestations of the disease and their development at the period before the treatment and during therapy were studied. The optimum regimens of the maintenance treatment were investigated including those in 31 patients whom the treatment could be discontinued. The treatment-related complications and 28 cases with fatal outcome are analysed.

Adrenal Cortex Hormones↗
PubMed1989

Serum osteocalcin in the assessment of corticosteroid induced osteoporosis. Effect of long and short term corticosteroid treatment.

Serum osteocalcin was measured in patients receiving corticosteroid for long and short term at different doses. Low osteocalcin levels were observed in treated patients compared to age and sex matched controls (p less than 0.001). The effect was dose dependent and paralleled the adrenal inhibition assessed by morning cortisol. Short term administration resulted in a rapid decline of baseline osteocalcin which was maintained during the treatment period and was reversible after withdrawal. Osteocalcin appeared as a sensitive index of the inhibitory effect of corticosteroid on osteoblasts.

Adolescent↗
PubMed1995

Corticosteroids plus pulse cyclophosphamide and plasma exchanges versus corticosteroids plus pulse cyclophosphamide alone in the treatment of polyarteritis nodosa and Churg-Strauss syndrome patients with factors predicting poor prognosis. A prospective, randomized trial in sixty-two patients.

OBJECTIVE: To define the most effective treatment for severe polyarteritis nodosa (PAN) and Churg-Strauss syndrome (CSS) and to investigate the indication for plasma exchange treatment. METHODS: We conducted a prospective, randomized, multicenter trial in which 62 patients were randomly assigned to receive either prednisone plus cyclophosphamide (intravenous bolus) (group A; n = 28) or prednisone plus cyclophosphamide (intravenous bolus) plus plasma exchanges (group B; n = 34) as first-line treatment for severe PAN or CSS. Factors predicting poor prognosis were renal symptoms, gastrointestinal tract involvement, cardiomyopathy, central nervous system involvement, weight loss > 10% of body weight, and age > 50 years old. Patients with hepatitis B virus-related PAN were not included in this study. The end point of the study was control of the disease (recovery or remission) or death. RESULTS: Clinical symptoms and laboratory findings did not differ significantly in the 2 groups. Initial control of the disease was similar in both groups. Relapse after initial control of the disease was observed in 7 patients (4 in group A and 3 in group B). The mean +/- SD followup period was 31.1 +/- 20 months for group A and 35.9 +/- 16.8 months for group B. At 5 years of followup, 38 patients (61.3%) were cured (16 in group A and 22 in group B), and 5 (8.1%) were in remission without treatment but had not yet completed the cure-defining period of 18 months (3 in group A and 2 in group B). Eight (12.9%) (2 in group A and 2 in group B) were considered to be in clinical remission and required a maintenance regimen of low-dose corticosteroids. Eleven patients died during the study period (7 in group A [25%], 4 in group B [11.8%]). Uncontrolled vasculitis was responsible for 4 deaths (2 in each group), and treatment side effects caused the death of 1 patient in group A. There was no significant difference between the 5-year cumulative survival rates of the 2 groups (75% and 88%, respectively). CONCLUSION: Based on our data, combined treatment with prednisone, cyclophosphamide, and plasma exchanges is not superior to treatment with prednisone and cyclophosphamide alone, and plasma exchanges should not be systematically proposed for initial treatment of severe PAN or CSS.

Adolescent↗
PubMed1992

Type I corticosteroid receptor-like immunoreactivity in the rat salivary glands and distal colon: modulation by corticosteroids.

A 167 amino acid fragment of the N-terminal domain of the human type I corticosteroid (mineralocorticoid) receptor was fused to the glutathione S-transferase gene using the Gex expression plasmid and the fusion protein used to raise the monospecific polyclonal antibody, MINREC4. Immunostaining experiments showed that MINREC4 specifically bound type I receptor in the distal tubule of the kidney, the ductal elements of the salivary glands and the epithelium of the distal colon in the rat. Adrenalectomy abolished staining in the parotid and colon, and reduced immunoreactivity in the submandibular gland. Administration of corticosterone or aldosterone resulted in partial restoration of immunostaining in the parotid, and a complete restoration of staining to intact levels in the submandibular gland and colon. These results suggest that adrenocorticoid binding to the type I receptor may result in tissue specific conformational changes in the binding protein and that the MINREC4 antibody may be used to study the effects.

Aldosterone↗
PubMed1991

Corticosteroid side-chain oxidations--I. Structural effects on the excreted isotope ratios of 4-14C- and 21-3H-labelled corticosteroid metabolites in rabbit urine.

The metabolic fates of 4-14C- and 21-3H-labelled corticosteroids have been investigated in the rabbit by analysis of the normalized isotope ratios of neutral and acidic metabolites excreted in the urine. Isotope ratios of excreted radioactivity declined in the order cortisol (F) greater than corticosterone (B) greater than 11-desoxycortisol (S) greater than deoxycorticosterone (DOC). Steroid acids, isolated in alumina fraction C, represented 19.0, 15.0, 9.7 and 2.7% of the doses of DOC, B, S and F, respectively, and the isotope ratios declined in the order F greater than B greater than S greater than DOC. HPLC of steroid acid methyl ester derivatives indicated generally low isotope ratios for DOC and S steroid acids, consistent with complete side-chain oxidation to 20-oxo-21-oic acids and/or 17-carboxylic acids. Several B metabolite methyl esters peaks also exhibited low isotope ratios, but both B and F metabolites gave methyl esters that retained significant tritium consistent with the presence of 20-hydroxysteroid acids. The 21-hydroxy-steroid metabolite fractions had isotope ratios of F = S greater than B greater than DOC. HPLC showed that 20-oxo (tetrahydro) metabolites of B and F had reduced isotope ratios unlike the C-20 reduced (hexahydro) metabolites of DOC and S. It may be concluded that the metabolic fate of the corticoid side-chain in the rabbit is dependent on the steroid structure and may result in the excretion of both 20-oxo and 20-hydroxysteroid acids.

Adrenal Cortex Hormones↗
PubMed1998

Establishing a therapeutic index for the inhaled corticosteroids: part I. Pharmacokinetic/pharmacodynamic comparison of the inhaled corticosteroids.

The inhaled corticosteroids contain physicochemical differences that alter both glucocorticoid receptor-binding characteristics and the pharmacokinetic variables of these drugs. Differences in receptor-binding affinity translate into differences in potency for different drugs. Differences in pharmacokinetics, however, determine the topical effect to systemic effect ratio, or the "pulmonary targeting" of the drug. Beneficial pharmacokinetic properties that may improve pulmonary targeting include low oral bioavailability, rapid systemic clearance, and slow absorption from the lung. Delivery devices can produce clinically significant differences in topical activity by altering the dose deposited in the lung and, for orally absorbed drugs, the amount deposited in the oropharynx and swallowed. Clinical trials have confirmed that differences in potency or drug delivery of 2-fold or more can be detected in patients with asthma. However, because of the relatively flat nature of the dose-response curve for morning peak expiratory flow and forced expiratory volume in 1 second, the trials must be adequately powered and well controlled. The use of bronchial provocation measures are problematic because of the prolonged lag time for response. Study design flaws can lead to misinterpretation of results. Clinical studies have indicated the following relative potency differences: fluticasone propionate > budesonide = beclomethasone dipropionate > triamcinolone acetonide = flunisolide. Current evidence suggests that potency differences can be overcome by giving larger doses of the less potent drug. However, because of these potency differences, studies of systemic effects should not be done in isolation of adequate topical activity studies to define the pulmonary targeting of the drugs.

Administration, Inhalation↗