THE LARYNGOSCOPE, Issue 9 2004
Natasha Mirza MD
Educational Objective: At the conclusion of this article, the readers should be able to 1) describe the laryngeal findings in patients who use combination therapy for asthma, 2) discuss the mechanism of laryngeal irritation from the use of inhalers, and 3) describe possible mechanisms for reducing laryngeal irritation and secondary dysphonia from the use of inhalers. Objectives: To describe voice changes and laryngeal findings in patients who are started on combination corticosteroid and bronchodilator therapy in the form of a dry powder inhaler (DPI). Study Design: Retrospective, single-subject design. Methods: Retrospective review of 10 consecutive patients meeting inclusion criteria, who presented at the voice center with more than 4 weeks of dysphonia after being started on a combination form of asthma medication for control and maintenance therapy. All patients were nonsmokers and without history of previous identification or excision of vocal pathology. All patients were treated previously with a proton pump inhibitor for gastroesophageal reflux. Laryngeal videostroboscopic evaluations were performed on all patients. Patients were asked to complete a questionnaire regarding their perceived voice change and history of medical maintenance therapy for asthma. Results: Dysphonia was present in the patients selected for greater than 4 weeks. Patients had been switched to combination therapy after previously using traditional two-drug asthma regimens. In eight of nine patients, the vocal folds demonstrated areas of hyperemia, with plaque-like changes on the surface mucosa. Reduced amplitude of vibration and a reduction in mucosal wave propagation were present on videostroboscopy. Questionnaires revealed that all patients were initiated on combination DPI treatment within the last 6 months. Conclusions: Dysphonia caused by a change in the surface mucosa is a side effect from the use of DPI therapy for asthma. The high-impact force during inhalation of the medication and carrier leads to deposition of particles in the upper airway. We believe the extent of mucosal irritation can be minimized by patient education in the proper delivery of DPI. In some cases, however, return of the two medications delivered separately was necessary. The irritation of the laryngeal mucosa and return of normal vibratory parameters occurred in all patients. [source]

Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung disease

ACTA PAEDIATRICA, Issue 12 2000
B Jónsson
We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23,29) and birthweight 805 g (525,1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2± 0.3. The budesonide (PulmicortÔ dose was 500 ,g bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed Conclusion: We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects. [source]

Effect of previous topical corticosteroid on patch testing

CONTACT DERMATITIS, Issue 5 2007
Cathy Green
No abstract is available for this article. [source]

Single doses of local betamethasone do not suppress allergic patch test reactions to nickel sulfate

CONTACT DERMATITIS, Issue 4 2004
Gerd Molander
Topical corticosteroids are usually banned on test areas prior to patch testing. The previous literature on the effect of topical corticosteroids is conflicting. Patients allergic to nickel sulfate were patch tested on 4 sites with nickel on day (D) 0. Intracutaneous betamethasone was injected to test sites on D,1, D0 and D1. NaCl injection on D,1 was control. The patch test reactions were evaluated clinically and with laser Doppler. There were no differences in patch test reaction intensities on sites treated with intracutaneous betamethasone as compared to control. A single local dose of potent corticosteroid does not suppress allergic patch reactions to nickel. The current practice of avoiding topical corticosteroid use prior to patch testing should be re-evaluated. [source]

FS09.3 Can Flutivate® cream be safely used in formaldehyde-allergic patients?

CONTACT DERMATITIS, Issue 3 2004
Marléne Isaksson
Objectives:, To study the healing time of an experimental eczema treated with Flutivate® cream, a potent corticosteroid containing a formaldehyde releasing preservative, in patients allergic to formaldehyde and controls not allergic to formaldehyde. Methods:, 24 individuals allergic to nickel, 7 of whom were also allergic to formaldehyde, had a nickel-allergic contact dermatitis experimentally induced on both upper arms. The dermatitis was treated twice daily for a maximum of 3 weeks or until healing with either Flutivate® cream or Betnovate® cream, a corticosteroid with the same potency but containing another preservative, which was tolerated by all 24 study persons. The study was double-blind and randomized. Results:, In 12/17 controls (71%) the nickel-allergic contact dermatitis healed completely when treated with Flutivate® cream compared to 2/7 formaldehyde-allergic patients (29%)(p < 0.05). Conclusion:, Flutivate® cream should not be used by individuals allergic to formaldehyde. [source]

COLORECTAL INVOLVEMENT OF KAPOSI'S SARCOMA IN A HIV-NEGATIVE CASE

DIGESTIVE ENDOSCOPY, Issue 2 2008
Mehmet Bektas
A case of Kaposi's sarcoma (KS) in a 70-year-old man who was using corticosteroid for the treatment of asthma is presented. KS lesions occurred in the skin, colon, and rectum. Macroscopic appearances of the lesions varied from polypoid, hemorrhagic mucosal nodules and ulcers to red macules in the mucosal plane to plaque-like indurations of the wall. As the case was HIV negative, it is believed that KS developed due to corticosteroid-induced immunosuppression. [source]

Concentration of methylprednisolone in the centrodistal joint after administration of methylprednisolone acetate in the tarsometatarsal joint

EQUINE VETERINARY JOURNAL, Issue 2 2005
A. SERENA
Summary Reasons for performing study: The centrodistal (CD) and tarsometatarsal (TMT) joints are often injected individually with a corticosteroid to resolve lameness caused by osteoarthritis (OA). There are no data available regarding diffusion of methylprednisolone (MP) from the TMT joint to the CD joint. Hypothesis: A therapeutic concentration of MP diffuses into the CD joint after methylprednisolone acetate (MPA) is administered into the TMT joint. Objective: To measure the concentration of MP in the CD joint after MPA was administered into the TMT joint. Methods: MPA was administered into a TMT joint of 16 horses. At different times, the ipsilateral CD joint of these horses was injected with a small amount of saline and recovered saline was measured for concentration of MP using high performance liquid chromatography. Results: Six hours after administration of MPA into the TMT joint, a therapeutic concentration of MP was found in all 10 CD joints sampled at this time. Conclusions: Horses with pain arising from the distal 2 joints of the hock can be treated by administering MPA into the TMT joint alone. Potential relevance: Administering MPA into the TMT joint only, to treat OA of the distal 2 hock joints, reduces the difficulties and risks associated with centesis of the CD joint. [source]

A phenotypically distinct subset of immature B cells exhibits partial activation, increased survival, and preferential expression of VhS107

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2003
Emily
Abstract We have observed that immature B cells (IgMlowIgD,) in the bone marrow of adult BALB/c mice exhibit heterogeneity, with a distinct subpopulation (,4,10%) expressing the CD43/S7 surface protein. These CD43/S7+ immature B cells often express other surface antigens associated with B cell activation (CD5, CD11b, PD-1). Generation of optimal numbers of CD43/S7+ immature B cells requires expression of a functional Btk protein, consistent with activation as a requisite for the CD43/S7+ immature B cell phenotype. Like typical CD43/S7, immature B cells, the CD43/S7+ immature B cells are predominantly resting cells, which are derived from cycling bone marrow B cell precursors. The CD43/S7+ immature B cell population exhibits enhanced survival in vivo upon administration of the apoptosis-inducing corticosteroid, dexamethasone. Finally, CD43/S7+ immature B cells show a fourfold increase in incidence of VhS107 , heavy chain expression compared to the CD43/S7, immature B cells. Therefore, in adult murine bone marrow, the presence of a phenotypically distinct immature B cellpopulation can be demonstrated which has undergone partial activation leading to increased survival and BCR-dependent Vh repertoire selection. [source]

High-dose methylprednisolone influences the physiology and virulence of Candida albicans ambiguously and enhances the candidacidal activity of the polyene antibiotic amphotericin B and the superoxide-generating agent menadione

FEMS YEAST RESEARCH, Issue 2 2007
Ágnes Gyetvai
Abstract Although exposure of Candida albicans cells to high-dose (4 mM) methylprednisolone stimulated microbial growth, germination rate in serum and phospholipase release, it also promoted the recognition of C. albicans cells by polymorphonuclear leukocytes. Pretreatment of C. albicans cells with methylprednisolone did not result in any increase in the pathogenicity of the fungus in intraperitoneal and intravenous mouse assays. Therefore, the virulence of C. albicans is unlikely to increase in patients treated with comparably high-dose methylprednisolone on skin and mucosal membranes. Methylprednisolone treatments also increased the production of conjugated dienes and thiobarbituric acid-reactive substances, and the menadione sensitivity of C. albicans cells, which can be explained by a significant decrease in the specific activities of several antioxidant enzymes. The combination of methylprednisolone with oxidants, e.g. in topical applications, may be of clinical importance when the predisposition to candidiasis is high. Methylprednisolone treatments negatively affected membrane fluidity and decreased the antifungal effects of both the polyene antibiotic nystatin and the ergosterol biosynthesis inhibitor lovastatin, and also enhanced the deleterious effects of the polyene antimycotic amphotericin B on C. albicans cells. These corticosteroid,polyene drug interactions should be considered in the treatment of C. albicans infections in patients with prolonged topical application of corticosteroids. [source]

Putting flesh and polish on autoimmune hepatitis and moving the disease of exclusion to inclusion,

HEPATOLOGY, Issue 4 2010
Albert J. Czaja
Autoimmune hepatitis emerged during an era when concepts of neonatal immune tolerance, clonal selection of lymphocytes, and "forbidden clones" of activated immune cells were forming. The diagnosis had to be deduced from circumstantial evidence and by exclusion of other conditions. The goals of this review are to demonstrate how a clinician nonscientist can contribute to the maturation of autoimmune hepatitis and to illustrate the principles of clinical investigation that can be applied broadly to other projects. Autoimmune hepatitis initially had to be distinguished from other diseases, and improvements in the tests for viral and immune markers were instrumental in this regard. Diversification of the clinical phenotype to accommodate acute severe, asymptomatic, elderly, and variant forms enhanced the pertinence of the disease, and the formation of the International Autoimmune Hepatitis Group standardized the diagnosis, interconnected investigators, and promoted global acceptance of the condition. Subsequent studies refined current corticosteroid-based therapies, identified prognostic markers, assessed genetic predispositions, explored new pharmacological agents, and forecast the emergence of cellular and molecular interventions. Good fortune, stimulating mentors, career dedication, practical goal selection, protocol compliance, compulsive record keeping, personal resilience, and strong collaborations were the bases for progress. Autoimmune hepatitis exemplifies an evolutionary process in the science of autoimmunity and the people committed to its study. Lessons derived from this experience can be far-reaching. (HEPATOLOGY 2010;52:1177-1184) [source]

Oral mesalamine and clinical remission are associated with a decrease in the extent of long-standing ulcerative colitis

INFLAMMATORY BOWEL DISEASES, Issue 7 2006
Michael F. Picco MD
Abstract Objective: To compare colonoscopy alone with surveillance biopsy for the determination of anatomic extent in long-standing ulcerative colitis (UC). To assess the influences of mesalamine use and clinical disease activity on the change of histologic extent with time. Materials and Methods: Disease extent (proctosigmoiditis, left-sided colitis, or pancolitis) measured by colonoscopy and surveillance biopsy was compared among 212 consecutive patients with long-standing UC. Among the 102 patients who had 2 consecutive colonoscopies with surveillance biopsies, the following influences on change in histologic extent were determined: disease activity, mesalamine use, age at disease onset, folic acid, corticosteroid and azathioprine/6-mercaptopurine use, and time between colonoscopies. Results: Agreement between gross and microscopic findings was poor (, = 0.39). Colonoscopy underestimated and overestimated extent in 25.9% and 8.5%, respectively. Microscopic distribution between consecutive colonoscopies remained the same in 60.8%. Where distribution changed, an increase was twice as common as a decrease in extent. There was no difference in age at onset, time between colonoscopies, or disease duration among those with an increase, decrease, or no change in extent. Clinical remission and oral mesalamine were independently associated with 10.7 and 5.8 times the odds of a decrease in disease extent, respectively. Folic acid, topical mesalamine, corticosteroids, and immunomodulators did not influence change in extent. Conclusions: UC extent is best determined by surveillance biopsy. Among patients with long-standing UC, histologic extent fluctuates with time. Disease remission and oral mesalamine were independently associated with decreases in disease extent. [source]

Infliximab efficacy in pediatric ulcerative colitis,

INFLAMMATORY BOWEL DISEASES, Issue 3 2005
Alexandra P Eidelwein MD
Abstract Background: The effects of infliximab, a tumor necrosis factor-alpha (TNF-,) antibody, have been well established in adult patients with inflammatory and fistulizing Crohn's disease. This study evaluates short- and long-term efficacy of infliximab in children with ulcerative colitis. Methods: All pediatric patients with ulcerative colitis who received infliximab between July 2001 and November 2003 at the Johns Hopkins Children's Center were identified. Short- and long-term outcomes and adverse reactions were evaluated. Results: Twelve pediatric patients with ulcerative colitis received infliximab for treatment of fulminant colitis (3 patients), acute exacerbation of colitis (3), steroid-dependent colitis (5), and steroid-refractory colitis (1). Nine patients had a complete short-term response, and 3 had partial improvement. The mean per patient dose of corticosteroid after the first infliximab infusion decreased from 45 mg/day at the first infusion to 22.2 mg/day at 4 weeks (P = 0.02) and 7.8 mg/day at 8 weeks (P = 0.008). Eight patients were classified as long-term responders with a median follow-up time of 10.4 months. Of the 4 long-term nonresponders, 3 underwent colectomy, and the fourth has ongoing chronic symptoms. Three of 4 long-term nonresponders were steroid-refractory compared with 1 of 8 long-term responders. Patients receiving 6-mercaptopurine had a better response to infliximab. Conclusion: Infliximab should be considered in the treatment of children with symptoms of acute moderate to severe ulcerative colitis. [source]

A case of mucosal leishmaniasis: beneficial usage of polymerase chain reaction for diagnosis

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2001
Hironori Onuma MD
A 36-year-old woman, who had emigrated from Japan to Paraguay as a 4-year-old child before returning to Japan in 1991, visited our clinic on November 10, 1997. She had suffered from a persistent ulcer on her forearm as a 6-year-old child and received intravenous injections for a few months, although she did not remember the details of therapy. Since May 1997, she had been aware of redness and swelling on her nose and had been treated with topical corticosteroid, but no improvement had been noted. Physical examination revealed erythematous plaque with crust from the left internal naris to nasolabial region (Fig. 1a). The atrophic plaque that had resulted from prolonged ulceration was found on the right forearm (Fig. 1b). In a biopsy specimen from the erythematous plaque on the nasolabial region, mononuclear dermal infiltrate, consisting of lymphocytes and histiocytes, was seen (Fig. 2a). The histiocytes were filled with Leishman-Donovan (L-D) bodies on a Giemsa staining sample (Fig. 2b). Fiberscopic examination revealed white plaque in the pharynx. The biopsy from the affected mucosa showed the same histopathological finding as with the skin. Figure 1. (a) Erythematous plaque with crust from the left internal naris to nasolabial region. (b) Atrophic plaque on the right forearm Figure 2. (a) In the biopsy specimen from the erythematous plaque on the nasolabial region, a mononuclear dermal infiltrate consisting of lymphocytes and histiocytes was seen. (Hematoxylin-Eosin stain, × 100) (b) The histiocytes were filled with Leishman-Donovan bodies. (Giemsa staining, × 400) Total DNA was purified from the skin biopsy specimen for polymerase chain reaction (PCR) analysis using a specific primer for L (V) braziliensis.1,2 A 70-bp product was amplified (Fig. 3a); furthermore, the specificity of the PCR product was confirmed by Southern hybridization with the probe for L (V) braziliensis (Fig. 3b) and DNA sequence analysis (data not shown). From December 2, 1997, the patient received 20 mg/kg/day sodium stibogluconate (PentostamTM) intravenously for 20 days. After 5 days of treatment, the redness and swelling of the skin lesion was improved, and faint erythema remained at the end of 20 days' treatment. After a 2-week interval, since the erythema remained, another 20-day treatment was performed. All of the skin lesion became scar tissue and L-D bodies could not be found in a skin biopsy specimen. However, L-D bodies were still found in a biopsy from the pharyngeal mucosa that had a normal appearance. Though another additional treatment was planned, the patient refused it. Figure 3. (a) The results of PCR. 70-bps bands appear in lanes 2 and 6. Lane 1, a size marker (pUC19/HapII); lane 2, DNA extracted from the formalin-fixed patient's sample; lane 3, DNA extracted from a formalin-fixed control sample; lane 4, DNA (,); lane 5, DNA extracted from L (V) tropica; lane 6, DNA extracted from L (V) braziliensis. (b) Results of Southern blotting using the PCR products. The PCR products were transferred from agarose gel as shown in Fig. 3 (a). Specific probes were hybridized with 70-bps bands on lanes 2 and 6 [source]

A double blind, randomized, placebo controlled study to evaluate the efficacy of erythromycin in patients with knee effusion due to osteoarthritis

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2009
Shahram SADREDDINI
Abstract Objective:, The efficacy of erythromycin in treatment of knee effusion due to osteoarthritis was evaluated. Method:, We assessed efficacy and safety of erythromycin during 16 weeks in patients enrolled in a randomized double-blind study. One hundred and eight patients with knee effusion due to osteoarthritis (OA) received 12-week courses of erythromycin or placebo allocated randomly, and were followed for 4 months. Acetaminophen 650 mg/day was used in both groups, while they received no other anti-inflammatory drugs (such as corticosteroid or nonsteroidal anti-inflammatory drugs) during the course of the study. Our patients were divided in two groups, erythromycin in doses of 200 mg four times per day was given to the first group (51 patients) over the first 3 months of the study and in the second group we used placebo with the same dosage and schedule (53 patients). Outcomes improvement for the erythromycin-treated group was assessed by a significantly higher mean score from baseline to the end of the trial, compared with placebo group. Patients were examined monthly during the treatment period. Measurement values included recording of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire subscales (pain, stiffness and function), range of motion and knee circumference. Results:, Erythromycin produced a higher response rate than placebo in treatment of knee effusion due to OA. Significant reduction in knee circumference (P < 0.0005) and pain (P < 0.001) with functional improvement (P < 0.0005) were seen. At the first month after treatment, 11.8% (6 patients) in erythromycin and 9.4% (5 patients) in placebo groups had 50% pain reduction, which was not significant (P = 0.75). At the fourth month, 50% reduction of pain was seen in 45.1% (23 patients) of the erythromycin and 11.3% (6 patients) of the placebo group. This was statistically significant (P < 0.0005). Erythromycin treatment was well tolerated and mild adverse events caused no discontinuation during the study. Conclusion:, This is a placebo-controlled study of macrolid efficacy on knee effusion due to OA in a short period. Results of this research showed the better efficacy of erythromycin in controlling effusion and pain with functional improvement in patients with knee effusion due to OA. [source]

Scalp necrosis and giant cell arteritis: case report and issues in wound management

INTERNATIONAL WOUND JOURNAL, Issue 4 2005
Stefan J Landis
Abstract Scalp necrosis is rare in patients with giant cell arteritis. Here, we report the case of an 81-year-old woman who presented with a management problem that required a truly multidisciplinary approach to treatment. A combined approach of effective wound bed preparation with selective debridement, prolonged antimicrobial therapy, corticosteroid use and careful dressing choices resulted in a successful outcome in a potentially disastrous situation. [source]

Life-threatening systemic toxicity and airway compromise from a common European adder bite to the tongue

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009
L. C. G. HOEGBERG
A 24-year-old man was bit on the tongue by a European common adder. Within 15 min following envenomation, he experienced tongue swelling, hypotension and impaired consciousness. Antihistamine, corticosteroid and crystalloids were administered. Within 105 min of envenomation, increasing oral, pharyngeal and facial oedema compromised the airway, leading to respiratory failure, concomitant with circulatory failure related to hypoxaemia and systemic toxic effects. Acute tracheotomy secured the airway, and two doses of antivenom successfully treated the systemic, toxic effects. The reaction was severe due to rapid and suspected high-dose uptake of venom, underlining the need for early advanced symptomatic treatment with airway control and early and eventually repeated dosing of antivenom. [source]

Simplified System for Absolute Fracture Risk Assessment: Clinical Validation in Canadian Women,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2009
William D Leslie
Abstract Absolute 10-yr fracture risk based on multiple factors is the preferred method for risk assessment. A simplified risk assessment system from sex, age, DXA, and two clinical risk factors (CRFs),prior fracture and systemic corticosteroid (CS) use-has been used in Canada since 2005. This study was undertaken to evaluate this system in the Canadian female population. A total of 16,205 women ,50 yr of age at the time of baseline BMD (1998,2002) were identified in a database containing all clinical DXA test results for the Province of Manitoba, Canada. Basal 10-yr fracture risk from age and minimum T-score (lumbar spine, femur neck, trochanter, total hip) was categorized as low (<10%), moderate (10,20%), or high (>20%). Health service records since 1987 were assessed for prior fracture codes (N = 5224), recent major CS use (N = 616), and fracture codes after BMD testing (mean, 3.1 yr of follow-up) for the hip, vertebrae, forearm, or humerus (designated osteoporotic, N = 757). Fracture risk predicted from age and minimum T-score alone showed a significant gradient in observed fracture rates (low 5.1 [95% CI, 4.1,6.4], moderate 11.5 [95% CI, 10.1,13.0], high 25.4 [95% CI, 23.2,27.9] per 1000 person-years; p -for-trend <0.0001). There was an incremental increase in incident fracture rates from a prior fracture (13.9 [95% CI, 11.3,16.4] per 1000 person-years) or major CS use (11.2 [95% CI, 4.1,18.2] per 1000 person-years). This simplified fracture risk assessment system provides an assessment of fracture risk that is consistent with observed fracture rates. [source]

Use of Inhaled Corticosteroids and Risk of Fractures

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2001
T. P. Van Staa
Abstract Treatment with systemic corticosteroids is known to increase the risk of fractures but little is known of the fracture risks associated with inhaled corticosteroids. A retrospective cohort study was conducted using a large UK primary care database (the General Practice Research Database [GPRD]). Inhaled corticosteroid users aged 18 years or older were compared with matched control patients and to a group of noncorticosteroid bronchodilator users. Patients with concomitant use of systemic corticosteroids were excluded. The study comprised 170,818 inhaled corticosteroid users, 108,786 bronchodilator users, and 170,818 control patients. The average age was 45.1 years in the inhaled corticosteroid, 49.3 years in the bronchodilator, and 45.2 years in the control groups. In the inhaled corticosteroid cohort, 54.5% were female. The relative rates (RRs) of nonvertebral, hip, and vertebral fractures during inhaled corticosteroid treatment compared with control were 1.15 (95% CI, 1.10,1.20), 1.22 (95% CI, 1.04,1.43), and 1.51 (95% CI, 1.22,1.85), respectively. No differences were found between the inhaled corticosteroid and bronchodilator groups (nonvertebral fracture RR = 1.00; 95% CI, 0.94,1.06). The rates of nonvertebral fractures among users of budesonide (RR = 0.95; 95% CI, 0.85,1.07) and fluticasone propionate (RR = 1.03; 95% CI, 0.71,1.49) were similar to the rate determined for users of beclomethasone dipropionate. We conclude that users of inhaled corticosteroids have an increased risk of fracture, particularly at the hip and spine. However, this excess risk may be related more to the underlying respiratory disease than to inhaled corticosteroid. [source]

Circadian and age-related changes in stress responsiveness of the adrenal cortex and erythrocyte antioxidant enzymes in female rhesus monkeys

JOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2008
Nadezhda D. Goncharova
Abstract Background, The objective of this study was to evaluate the role of the adrenal cortex in the regulation of antioxidant enzyme defense and to characterize this regulation in different age periods. Methods, Five young and five old female rhesus monkeys were subjected to 2 hours squeeze cage restraint stress at 0900 or 1500 hours. Plasma levels of corticosteroids and activities of erythrocyte antioxidant enzymes were measured before the stress and 30, 60, 120, 240 minutes after beginning of the stress. Results, Young monkeys showed a circadian rhythm in stress responsiveness as measured by corticosteroids and glutathione reductase. The rhythm was attenuated in old animals. Age-related changes in the overall level of response to the afternoon stress were also seen in the corticosteroid and glutathione reductase measures. Conclusions, The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age. [source]

The Anti-Inflammatory Effect of Bee Venom Stimulation in a Mouse Air Pouch Model Is Mediated by Adrenal Medullary Activity

JOURNAL OF NEUROENDOCRINOLOGY, Issue 1 2003
Y.-B. Kwon
Abstract Cutaneous electrical or chemical stimulation can produce an anti-inflammatory effect, which is dependent on adrenal medullary-sympathetic activation. We have previously shown that peripheral injection of bee venom (BV) also produces a significant anti-inflammatory effect that is neurally mediated. In the present study, we examined whether this anti-inflammatory effect is also dependent on the adrenal gland using the mouse inflammatory air pouch model. Subcutaneous (s.c.) BV injection produced a marked suppression of leucocyte migration and tumour necrosis factor (TNF)- , concentration induced by zymosan injection into the air pouch. The role of the adrenal gland in this suppression was evaluated in adrenalectomized mice. Adrenalectomy significantly reversed the suppression of leucocyte migration and TNF- , elevation caused by BV. Serum concentrations of corticosteroid were increased in mice with zymosan-induced air-pouch inflammation and this increase was reduced by BV administration, suggesting that adrenal corticosteroid release is not involved in mediating the anti-inflammatory effects of BV. To test this hypothesis, the corticosteroid receptor antagonist (RU486) was administered and found not to affect the BV-induced inhibition of leucocyte migration. By contrast, pretreatment with the , -adrenergic antagonist propranolol reversed the BV-induced inhibitory effect on leucocyte migration. These results suggest that the anti-inflammatory effect of s.c. BV administration is mediated in part by the release of catecholamines from the adrenal medulla. [source]

Postnatal corticosteroids in preterm infants: Systematic review of effects on mortality and motor function

JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 2 2000
LW Doyle
Background: Postnatal corticosteroid therapy has been proved in randomized controlled trials to reduce ventilator dependence and the rate of chronic lung disease in preterm infants with few serious short-term side effects. However, there are other consequences that might follow postnatal corticosteroid therapy that are more important, including mortality or cerebral palsy. Objectives: To review the evidence from reported randomized controlled trials on the effects of postnatal corticosteroid on long-term mortality and motor dysfunction, including cerebral palsy. Methods: The methods involved a meta-analysis of reported randomized controlled trials, following guidelines of the Cochrane Collaboration, including calculation of event rate differences (ERD) and 95% confidence intervals (CI). Results: The mortality rate difference was non-significant both statistically and clinically (ERD , 0.1% favouring corticosteroids, 95% CI ,2.9% to 2.8%). There were no subgroups in which a beneficial effect of postnatal corticosteroids on survival could be demonstrated. The rate of motor dysfunction in survivors was significantly higher in survivors from the postnatal corticosteroid group (ERD 11.9% favouring controls, 95% CI 4.6% to 19.2%). The rate of survival, free of motor dysfunction, was significantly lower in the postnatal corticosteroid group (ERD 7.8% favouring controls, 95% CI 0.5% to 15.1%). Conclusions: Although postnatal corticosteroids have short-term benefits, they do not increase the survival rate, and they may cause motor dysfunction in survivors. A large-scale, placebo-controlled randomized trial, with survival free of sensorineural impairments and disabilities as the major endpoint, is urgently needed. [source]

Pharmacodynamic interaction of recombinant human interleukin-10 and prednisolone using in vitro whole blood lymphocyte proliferation

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002
Abhijit Chakraborty
Abstract Prednisolone, a commonly used synthetic corticosteroid, and IL-10, a cytokine under investigation for strong antiinflammatory properties, are being contemplated as a potential joint therapeutic regimen in immune disorders. Their pharmacodynamic interactions were examined in blood from healthy adult male and female volunteers using an in vitro phytohemagglutinin (PHA)-stimulated whole,blood lymphocyte proliferation technique. Isobolograms along with parametric competitive and noncompetitive interaction models were used to determine the nature and intensity of interactions. Single drug effects show prednisolone more efficacious in inhibiting lymphocyte proliferation with an IC50 of 3.3 ng/mL and Imax value of 1, signifying complete suppression. Analogous parameters for IL-10 were 16.2 ng/mL for IC50 and 0.89 for Imax. There were no significant differences in the single drug immunosuppressive effects among genders. Their joint effects showed additive interaction based on isobolographic analysis. Parametric analysis using the competitive interaction model described their interaction as slightly synergistic, while the noncompetitive interaction modeling indicate a small degree of antagonism. Also, the joint effects in females tend to be more antagonistic than males. Concomitant use of prednisolone and IL-10 should thus reflect the net additive responses to concentrations of each agent. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1334,1342, 2002 [source]

Assessment of corticosteroid-induced alkaline phosphatase as a prognostic indicator in canine lymphoma

JOURNAL OF SMALL ANIMAL PRACTICE, Issue 4 2005
A. L. Wiedemann
Objectives: To examine the incidence of elevated corticosteroidinduced alkaline phosphatase (sALP) in dogs with lymphoma and to determine if sALP is a reliable prognostic indicator in canine lymphoma. Methods: The medical records of 62 canine lymphoma patients treated with a combination chemotherapy protocol from 1994 to 2003 at the University of Illinois Veterinary Teaching Hospital were examined. Variables assessed with respect to response rate and remission duration included age, bodyweight, sex, breed, World Health Organization stage (I to V), substage (a or b), pretreatment administration of corticosteroid, and serum levels of alkaline phosphatase, sALP and alanine aminotransferase. Results: sALP was not statistically significant with respect to response rate or duration of remission, nor was preinduction glucocorticoid administration. Stage was significant with respect to achieving remission. Clinical Significance: It was found that sALP is not a useful prognostic indicator for response rate and remission duration in dogs with lymphoma. [source]

Effectiveness and safety of a prevention-of-flare-progression strategy with pimecrolimus cream 1% in the management of paediatric atopic dermatitis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 11 2008
B Sigurgeirsson
Abstract Objective, This study was performed to investigate the efficacy and safety of a prevention-of-flare-progression strategy with pimecrolimus cream 1% in children and adolescents with atopic dermatitis (AD). Methods, A 26-week multi-centre, randomized, double-blind, vehicle-controlled study was conducted in 521 patients aged 2,17 years, with a history of mild or moderate AD, who were clear/almost clear of disease before randomization to pimecrolimus cream 1% (n = 256) or vehicle cream (n = 265). Twice-daily treatment with study medication was started at the first signs and/or symptoms of recurring AD. If, despite the application of study medication for at least 3 days, AD worsened (as confirmed by the investigator), treatment with a moderately potent topical corticosteroid (TCS) was allowed in both groups. The primary efficacy end point was the number of days on study without TCS use for a flare. Results, The mean number of TCS-free days was significantly higher (P < 0.0001) in the pimecrolimus cream 1% group (160.2 days) than in the control group (137.7 days). On average, patients on pimecrolimus cream 1% experienced 50% fewer flares requiring TCSs (0.84) than patients on vehicle cream (1.68) (P < 0.0001). Patients on pimecrolimus cream 1% also had fewer unscheduled visits (87) than patients on vehicle cream (246). Conclusions, In children and adolescents with a history of mild or moderate AD but free/almost free of signs or symptoms of the disease, early treatment of subsequent AD exacerbations with pimecrolimus cream 1% prevented progression to flares requiring TCS, leading to fewer unscheduled visits and reducing corticosteroid exposure. [source]

Late-onset Behçet's disease does not correlate with indolent clinical course: report of seven Taiwanese patients

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2008
J Tsai
Abstract Background, Behçet's disease (BD) is a recurrent multisystem disease of uncertain aetiology. The young adults are most often affected, usually during the third decade. Late occurrence of the disease is considered uncommon and less frequently investigated. Objective, The aim of this study was to examine the clinical features of BD patients with disease onset at a later age and compare them with the usual age of onset group. Methods, Retrospective review of clinical charts of BD patients was conducted. Patients with age of onset at or after 40 years of age were identified. The clinical profiles and medications required to control the disease activity were documented. Comparisons of clinical features and the medications used were made between patients with disease onset before and after 40 years of age. Results, Seven late-onset BD patients were identified. Among them, five patients required the use of systemic immunosuppressant in addition to colchicine and corticosteroid for adequate disease control. There is no significant difference in clinical profiles between patients with disease onset before and after 40 years of age, but the incidence of uveitis, an indicator of unfavourable prognosis, was surprisingly high. More specifically, it was noted in four of seven patients identified. Conclusion, Our findings indicate that the clinical course of BD is not indolent in the patients with late-onset BD. More importantly, physicians should be aware that BD can occur in older patients, and close attention regarding their disease activities is warranted as their clinical courses may not be as benign as previously believed. [source]

Double-blind clinical study reveals synergistic action between alpha-hydroxy acid and betamethasone lotions towards topical treatment of scalp psoriasis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2000
K Kostarelos
Abstract Objective A double-blind, single-site, split-face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17-valerate) scalp application against conditions of psoriasis. Background,-hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side-effects most frequently associated with use of the latter. Methods Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double-blind, split-face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four-grade scale, prior to treatment and after 2, 4, 6 and 8 weeks. Results Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment. Conclusions The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy. [source]

Withdrawal of corticosteroids in inflammatory bowel disease patients after dependency periods ranging from 2 to 45 years: a proposed method

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009
S. J. MURPHY
Summary Background, Even in the biologic era, corticosteroid dependency in IBD patients is common and causes a lot of morbidity, but methods of withdrawal are not well described. Aim, To assess the effectiveness of a corticosteroid withdrawal method. Methods, Twelve patients (10 men, 2 women; 6 ulcerative colitis, 6 Crohn's disease), median age 53.5 years (range 29,75) were included. IBD patients with quiescent disease refractory to conventional weaning were transitioned to oral dexamethasone, educated about symptoms of the corticosteroid withdrawal syndrome (CWS) and weaned under the supervision of an endocrinologist. When patients failed to wean despite a slow weaning pace and their IBD remaining quiescent, low dose synthetic ACTH stimulation testing was performed to assess for adrenal insufficiency. Multivariate analysis was performed to assess predictors of a slow wean. Results, Median durations for disease and corticosteroid dependency were 21 (range 3,45) and 14 (range 2,45) years respectively. Ten patients (83%) were successfully weaned after a median follow-up from final wean of 38 months (range 5,73). Disease flares occurred in two patients, CWS in five and ACTH testing was performed in 10. Multivariate analysis showed that longer duration of corticosteroid use appeared to be associated with a slower wean (P = 0.056). Conclusions, Corticosteroid withdrawal using this protocol had a high success rate and durable effect and was effective in patients with long-standing (up to 45 years) dependency. As symptoms of CWS mimic symptoms of IBD disease flares, gastroenterologists may have difficulty distinguishing them, which may be a contributory factor to the frequency of corticosteroid dependency in IBD patients. [source]

Prescription rates of protective co-therapy for NSAID users at high GI risk and results of attempts to improve adherence to guidelines

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009
L. LAINE
Summary Background, Protective co-therapy is recommended in NSAID users with GI risk factors, but adherence is poor. Aim, To assess the proportion of NSAID users receiving co-therapy and strategies to improve adherence. Methods, Arthritis patients ,50 years of age received etoricoxib or diclofenac in a double-blind randomized trial. Reminders that high-risk patients (age , 65; previous ulcer/haemorrhage; corticosteroid, anticoagulant, aspirin use) should receive co-therapy were given at study initiation. Free PPI was provided. An intervention midway through the study included a written reminder and required written response regarding co-therapy. Results, 16 244/23 504 (69%) patients had GI risk factors. Pre-intervention, co-therapy was most common with previous ulcer/haemorrhage [706/1107 (64%)] and 3,4 risk factors [331/519 (64%)]. In the 10 026 patients enrolled pre-intervention and remaining in the study ,6 months after, co-therapy in high-risk patients increased from 2958/6843 (43%) to 4177/6843 (61%) (difference = 18%; 95% CI 16%,19%). The increase was greater outside the US (22%; 19%,24%) than in the US (15%; 13%,17%). Conclusions, Less than 50% of NSAID users with GI risk factors are given protective co-therapy , even if prescribers are given reminders and cost is not an issue. Direct communication requiring written response significantly increased adherence to guidelines, but achieving higher levels of adherence will require additional strategies. [source]

Infliximab and other immunomodulating drugs in patients with inflammatory bowel disease and the risk of serious bacterial infections

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009
S. SCHNEEWEISS
Summary Background, There remain concerns about the safety of infliximab therapy in patients with inflammatory bowel disease (IBD). Aim, To assess the association between the initiation of infliximab and other immunomodulating drugs and the risk of serious bacterial infection in the treatment of IBD. Methods, We assembled a cohort study of patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC). All patients initiating an immunomodulating drug between January 2001 and April 2006 were identified in British Columbia from linked health care utilization databases. Exposure of interest was initiation of infliximab or corticosteroids compared with initiation of other immunosuppressive agents, including azathioprine, mercaptopurine (MP) and methotrexate (MTX). Outcome of interest was serious bacterial infections requiring hospitalization, including Clostridium difficile. Results, Among 10 662 IBD patients, the incidence rate of bacteriaemia ranged from 3.8 per 1000 person-years (95% confidence interval 2.1,6.2) for other immunosuppressive agents to 7.4 (3.3,19.3) for infliximab with slightly higher rate for serious bacterial infections resulting in an adjusted relative risk 1.4 (0.47,4.24). Clostridium difficile infections occurred in 0/1000 (0,5.4) among 521 infliximab initiations and 14/1000 (10.6,18.2) for corticosteroids. Corticosteroid initiation tripled the risk of C. difficile infections (RR = 3.4; 1.9,6.1) compared with other immunosuppressant agents. This corticosteroid effect was neither dose-dependent nor duration-dependent. Bacteriaemia and other serious bacterial infections were not increased by corticosteroids or infliximab (5 events). Conclusions, In a population-based cohort of patients with IBD, we found no meaningful association between infliximab and serious bacterial infections, although some subgroups had few events. Corticosteroid initiation increased the risk for C. difficile infections in these patients. [source]

Red Maple (Acer rubrum) Leaf Toxicosis in Horses: A Retrospective Study of 32 Cases

JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2006
Ashley Alward
Background:Ingestion of wilted red maple leaves by horses can result in severe hemolytic anemia and methemoglobinemia. Little is known about what factors influence the outcome of red maple leaf toxicosis in horses. Hypothesis:Our hypothesis was that physical examination findings, clinicopathologic variables or therapeutic modalities may predict outcome in horses with red maple leaf toxicity. Animals:Horses with red maple leaf toxicosis presented to referral hospitals in the southeast region of the United States. Methods:A multi-institutional retrospective study was designed to identify factors that predict mortality in horses with red maple toxicosis. Results:Thirty-two horses with red maple toxicosis were identified, 19 of which died. Twenty-nine horses presented with anemia and 24 had clinicopathologic evidence of systemic inflammation. Renal insufficiency was identified in 12/30 (41%) horses. Laminitis (9/28) and colic (13/30) also were identified in horses with red maple toxicosis, but development of these 2 conditions did not have a negative effect on short-term survival. Horses with red maple toxicosis that survived to discharge were likely to have developed pyrexia during hospitalization (P= .030). Horses that were treated with a corticosteroid had a significantly increased likelihood of death (P= .045). There was no significant relationship between initial serum hemoglobin concentration, methemoglobin concentration, or percentage methemoglobin and mortality in this horse series. Conclusions and Clinical Importance: This study suggests that information obtained on initial examination cannot be used to accurately predict survival in horses with red maple toxicosis, but horses that receive corticosteroids are unlikely to survive. [source]