Methylprednisolone pulse therapy in acute severe asthma

Methylprednisolone pulse therapy (MPPT) has been shown to possess a long-lasting effect in other immune-inflammatory diseases without the well-known side effects caused by long-term treatment with glucocorticosteroids. In an attempt to reduce the long-term use of oral steroids in asthmatics, we conducted this double-blind, double-dummy study to compare the use of MPPT (1 g of methylprednisolone intravenously) (8 patients) with a short course of oral prednisolone (10 patients) in asthmatics presenting with acute severe asthma. Both treatments were effective in relieving the acute attack of asthma. The MPPT-treated patients did not show a faster resolution than did the orally treated group. No patients needed assisted ventilation, and no deaths occurred. One week after the treatment FEV1 tended to decrease in the methylprednisolone group compared with the oral prednisolone group (P = 0.06). The patients initially receiving MPPT needed supplementary prednisolone earlier and in higher doses than did the patients receiving oral prednisolone as initial treatment. At the end of the 12 weeks' study period, the groups reached identical FEV1. In conclusion, we did not find intravenous methylprednisolone superior to oral prednisolone in the treatment of acute attacks of severe asthma, but methylprednisolone pulse therapy had a shorter duration as regards protection against future asthma attacks.     

甲基强的松龙在颈椎病围手术期的疗效观察

目的探讨甲基强的松龙（MP）在脊髓型颈椎病围手术期的疗效。方法将因脊髓型颈椎病行单纯前路减压的117例患者随机分为3组：A组40例,减压手术前在持续心电监护下于30 m in内以30 mg/kg剂量快速静脉滴注MP,术后1-3 d按照3 mg·kg^-1·d^-1剂量静滴MP;B组39例,仅术后1-3 d按照3 mg·kg^-1·d^-1剂量静滴MP;C组38例,仅术后1-3 d以10 mg地塞米松静脉滴注。术后常规给予脱水、预防溃疡及神经营养药物治疗。于术后3 d、7 d、180 d对3组患者的脊髓神经功能恢复情况及并发症发生率进行统计学分析。结果3组术前JOA评分无显著差异,术后A组神经功能恢复率优于B组和C组,B组术后1周内优于C组。术后各时相点JOA评分较术前显著提高（P〈0.01）,各组之间术后并发症发生率无显著差异。结论脊髓型颈椎病围手术期给予MP治疗对于神经功能的恢复有良好疗效,且术前给予大剂量冲击治疗较单纯术后使用MP疗效更好。     

High-performance size-exclusion chromatographic analysis of dextran-methylprednisolone hemisuccinate in rat plasma

A size exclusion chromatographic method is presented for the measurement of the concentrations of a macromolecular prodrug of methylprednisolone (MP), dextran-methylprednisolone succinate (DEX-MPS), in rat plasma. After precipitation of the plasma (100 microl) proteins with perchloric acid, the samples are injected into a size exclusion column with a mobile phase of water:acetonitrile:glacial acetic acid (75:25:0.2) and a flow-rate of 1 ml/min. The DEX-MPS conjugate, detected at 250 nm, elutes at a retention time of approximately 6.5 min, free of endogenous peaks. Excellent linear relationships (r2=0.997) were found between the detector response and the concentrations of DEX-MPS in the range of 2-100 microg/ml (MP equivalent), with intra- and inter-run C.V.s of <6% and error values of <5%. The application of the assay was also demonstrated by measurement of the plasma concentrations of DEX-MPS after single 5 or 10 mg/kg doses of the conjugate administered intravenously to rats.     

Effect of low-dose troleandomycin on glucocorticoid pharmacokinetics and airway hyperresponsiveness in severely asthmatic children

Fifteen hospitalized asthmatic children (8 to 18 years old) completed a 2-week randomized, parallel, double-blind placebo-controlled comparison of combination methylprednisolone and placebo troleandomycin, prednisone and troleandomycin (P-TAO) or methylprednisolone-TAO (MPn-TAO). Troleandomycin (250 mg once daily or every other day) and glucocorticoid doses were reduced by a standard protocol. Symptom scores, blood chemistries, pulmonary function tests, airway response to methacholine, and glucocorticoid pharmacokinetics were compared. In each group, a steroid dose reduction of 50% was achieved without a deterioration in symptom scores. Methacholine response was unchanged in all five on methylprednisolone alone, but decreased 3-fold to 30-fold in two of five on combination P-TAO, and four of five on combination MPn-TAO. Troleandomycin decreased MPn clearance by an average of 62% but did not alter prednisolone clearance. Low-dose TAO combined with MPn has a significant effect on methylprednisolone clearance in children, an effect equivalent to that reported with higher dose TAO (1000 mg/d) therapy. In addition, this preliminary study suggests that TAO may decrease bronchial hyperresponsiveness to methacholine in severely asthmatic children.     

Intravenous methylprednisolone pulse therapy in ankylosing spondylitis

For several years the medical treatment of active ankylosing spondylitis (AS) has been NSAID because gold, penicillamine, antimalarials and steroids have been without efficacy. In 1981, Mintz et al reported that methylprednisolone pulse therapy (MPPT) had an excellent effect in patients with AS. Seven patients with active AS and insufficient efficacy of NSAID for three months were treated with one gram methylprednisolone daily given intravenously for three successive days. Mobility and pain were recorded before, during, and after treatment. Significant pain relief and improvement of mobility of the spine for at least six weeks were clearly demonstrated (p less than 0.05). Finger to floor distance and chin manubrium distance improved significantly for at least six months (p less than 0.05). We conclude that intravenous MPPT is a useful treatment in patients with active AS when NSAID is insufficient.     

Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease.

Clinical and preclinical data indicate that tumor necrosis factor (TNF)-alpha is an important mediator of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation. We completed a study using etanercept, a fusion protein capable of neutralizing TNF-alpha, for the initial treatment of aGVHD. Etanercept (25 mg subcutaneously) was administered twice weekly for 16 doses, along with methylprednisolone (2 mg/kg) and tacrolimus for biopsy-proven aGVHD. Twenty patients with a median age of 47 years (range, 8-63 years) were enrolled. Fourteen patients with grade II aGVHD (11 family donors and 3 unrelated donors) and 6 patients with grade III aGVHD (3 family donors and 3 unrelated donors) were treated. Twelve patients completed 16 doses of therapy, and 8 received 5 to 15 doses. Reasons for not completing all doses of etanercept included progression of aGVHD (n = 4), relapsed leukemia (n = 2), progression of pulmonary and central nervous system lesions (n = 1), and perforated duodenal ulcer (n = 1). Fifteen (75%) of 20 patients had complete resolution of aGVHD within 4 weeks of therapy. Increasing levels of soluble TNF receptor 1 plasma concentration during the first 4 weeks of therapy indicated progression of aGVHD in 5 patients. In contrast, for 15 responding patients, soluble TNF receptor 1 plasma concentration levels returned to baseline. These data demonstrate the feasibility of using cytokine blockade in the early treatment of aGVHD.     

Effects of atropine, trimedoxime and methylprednisolone on the development of organophosphate-induced delayed polyneuropathy in the hen.

In this study we have examined the effects of atropine, trimedoxime (TMB-4) and methylprednisolone (MP) on the development of organophosphate-induced delayed polyneuropathy (OPIDP) in the hen. The birds were treated with standard neuropathic dose of diisopropylfluorophosphate (DFP) (1.1 mg/kg, sc), which produced OPIDP that could be graded as 5 on the 8-point scale, and the development of OPIDP was observed for the next 22 days. The results obtained have shown that atropine (20 mg/kg, ip), TMB-4 (15 mg/kg, im) and MP (2 or 10 mg/kg, ip) either alone or in different combinations are able to improve the condition of the birds. The most potent effect was obtained with atropine, TMB-4 (given 20 min before DFP) and MP (2 mg/kg, sc, given 20 min before and at 48 hour intrevals after poisoning) since the signs of OPIDP could hardly be seen (grade 1 at the 8-point scale). When TMB-4 and MP were given 15 or 40 min after DFP the protective/therapeutic effects of these drugs appeared to be diminished since walking disorders were more serious and graded as 2 or 4, respectively. The possible mechanisms of the action of the drugs in respect to OPIDP are discussed. In conclusion, the results of this study have shown that it is possible to prevent the development of DFP-induced OPIDP in the hen by treatment with atropine, trimedoxime and methylprednisolone when they were given before or soon after DFP.     

肾移植后不同抗排斥治疗方案感染及急性排斥发生率的比较

背景：目前对肾移植围手术期采用何种免疫抑制治疗方案(特别是抗体的使用)既可以减少急性排斥反应,又不增加受体感染的风险尚无统一的认识。 目的：比较肾移植后6个月内6种不同免疫抑制诱导治疗方案的感染及急性排斥发生率差异。 方法：采用前瞻性队列研究设计,将113例同种异体肾移植后患者分为甲基泼尼龙组、甲基泼尼龙+抗人T细胞免疫球蛋白组、甲基泼尼龙+抗胸腺细胞球蛋白组、甲基泼尼龙+赛尼哌组、甲基泼尼龙+抗胸腺细胞球蛋白+赛尼哌组、甲基泼尼龙+抗人T细胞免疫球蛋白+赛尼哌组,各组免疫抑制诱导治疗后均联合环孢素A+吗替麦考酚酯+泼尼松三联维持免疫抑制治疗。 结果与结论：①感染发生率：甲基泼尼龙+抗胸腺细胞球蛋白组最低,甲基泼尼龙+抗胸腺细胞球蛋白+赛尼哌组最高。各组间差异无显著性意义。②急性排斥发生率：甲基泼尼龙组最高,甲基泼尼龙+抗胸腺细胞球蛋白+赛尼哌组最低。甲基泼尼龙组明显高于甲基泼尼龙+抗胸腺细胞球蛋白+赛尼哌组及甲基泼尼龙+抗人T细胞免疫球蛋白+赛尼哌组(P < 0.05)。表明联合单克隆与多克隆抗体免疫抑制诱导治疗方案与单用甲基泼尼龙组或单独使用单克隆或多克隆抗体治疗组比较,不增加感染的发生,且急性排斥反应发生率较低。     

Antigenic charge as a factor in resistance to immunosuppressive therapy.

This study examines the effects of methylprednisolone (MP) on the glomerular lesions induced by the injection of cationic bovine serum albumin (BSA) in rabbits. Male New Zealand white rabbits (n = 55) were treated with cationic BSA alone (n = 13), cationic BSA plus MP (n = 26), native BSA alone (n = 8), or native BSA plus MP (n = 8). Animals receiving BSA alone developed subepithelial immune complex deposits after injections of cationic BSA or mesangial immune complex deposits after injections of native BSA. Subepithelial deposits were inhibited in only 10 of 26 rabbits receiving MP and cationic BSA. Glomerular lesions occurred rather predictably in this group unless complete ablation of antibody production was achieved. Even minimal amounts of detectable antibody were sufficient to support the development of the full-blown renal lesion. Proteinuria was diminished in all animals receiving cationic BSA and MP in whom a beneficial histologic effect was observed. MP inhibited the development of mesangial deposits in all of the animals given native BSA. This inhibition was associated with almost complete ablation of anti-BSA antibody production in this group. Renal perfusion studies (n = 8) demonstrated that the beneficial effects of MP on the development of immune deposits were related to systemic immunosuppression and not to local structural alterations in the glomerulus. Our findings confirm that the pattern of immune response to native and cationic antigens differ. In addition, they demonstrate that cationic antigens appear to require only small amounts of free circulating antibody in order to produce glomerular immune complexes and cause proteinuria.     

A study of the effects of systemic administration of adrenal glucocorticoids in an experimental model of hypersensitivity pneumonitis

To study the effects of steroids on the pulmonary lesions in experimental hypersensitivity pneumonitis, rabbits were sensitized to ovalbumin (OA) by injections of OA into footpads and 3 weeks later they were subjected to two successive aerosol challenges with OA at an interval of 48 hr. Injections of hydrocortisone sodium succinate 10 mg twice daily (but not at the reduced dosage of 5 mg twice daily) or methylprednisolone acetate 5 mg twice daily beginning 30 min before the first challenge and continued to the time of killing reduced the extent and intensity of vasculitis in both the treated groups and showed less alveolar septal thickening in the hydrocortisone treated group and less alveolar consolidation in the methylprednisolone treated group compared to the pulmonary lesions in the rabbits which were sensitized and then subjected to OA aerosol challenges, but received no treatment. In view of the observation that even in a steroid sensitive species like the rabbit, extensive pulmonary changes like alveolar consolidation, septal thickening and vasculitis persisted in spite of treatment with relatively large doses of these steroids, it was felt that in human hypersensitivity pneumonitis steroids might only suppress the warning symptoms without substantially affecting the progress of the pulmonary lesions.     

Steroid dose sparing: Pharmacodynamic responses to single versus divided doses of methylprednisolone in man

Inhibitory drug interactions affecting the metabolism of methylprednisolone (MP) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid. This phenomenon can be mimicked by administering MP in divided doses. Two types of responses were compared after a single MP dose (40 mg bolus) and a divided regimen (20 mg bolus and a 5 mg bolus 8 hours later) in six healthy male volunteers. The suppression of basophils measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours. The 37.5% reduction in dose produced a 23% overall decreased blood histamine response. A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens. A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of basophil cell return to blood. The 50% inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens. The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours. The 50% inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml. Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the "dose-sparing" effects that were achieved by prolonging MP plasma concentrations. This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized.     

Effect of tiagabine on sleep in elderly subjects with primary insomnia: a randomized, double-blind, placebo-controlled study

SUBJECT OBJECTIVE: This study further evaluated the effects of tiagabine on sleep in elderly subjects with primary insomnia. METHODS: Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights. Efficacy was assessed using standard polysomnography and a postsleep questionnaire. Additional assessments included the Assessment of Daily Functioning, Digit Symbol Substitution Test (for residual effects), and visual analog scale (for sleepiness/alertness). RESULTS: A total of 207 subjects were randomly assigned to study medication (tiagabine: 2 mg, n = 43; 4 mg, n = 38; 6 mg, n = 45; 8 mg, n = 43; placebo, n = 38). Tiagabine did not significantly effect wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo (P > .05). Significant increases in Stage 3+4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05). At 6 and 8 mg, tiagabine also significantly reduced the number of awakenings and increased the ratio of Stage 3+4/(Stage 1 +wake after sleep onset). In general, there were no significant effects on subjects' ratings of sleep or daily functioning with tiagabine 2, 4, and 6 mg versus placebo. These 3 doses had tolerability profiles comparable with that of placebo and were not associated with significant residual effects or reduced alertness. The 8-mg dose, however, significantly decreased subjective total sleep time and refreshing quality of sleep, as well as daily functioning. This dose was associated with troublesome adverse events, significant residual effects, and reduced alertness. CONCLUSIONS: In elderly subjects with primary insomnia, tiagabine did not have a significant effect on wake after sleep onset, latency to persistent sleep, total sleep time, or the subjective rating of sleep. Tiagabine 4, 6, and 8 mg significantly increased slow-wave sleep, with a corresponding significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles generally similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events, residual effects, and reduced alertness.     

Oral versus intravenous corticosteroids in children hospitalized with asthma

BACKGROUND: Previous studies have demonstrated that in the emergency treatment of an asthma exacerbation, corticosteroids used in conjunction with beta-agonists result in lower hospitalization rates for children and adults. Furthermore, orally administered corticosteroids have been found to be effective in the treatment of outpatients with asthma. However, similar data in inpatients is lacking. OBJECTIVE: The purpose of this study was to determine the efficacy of oral prednisone versus intravenous methylprednisolone in equivalent doses for the treatment of an acute asthma exacerbation in hospitalized children. METHODS: We conducted a randomized, double-blind, double-placebo study comparing oral prednisone at 2 mg/kg/dose (maximum 120 mg/dose) twice daily versus intravenous methylprednisolone at 1 mg/kg/dose (maximum 60 mg/dose) four times daily in a group of patients 2 through 18 years of age hospitalized for an acute asthma exacerbation. All patients were assessed by a clinical asthma score 3 times a day. The main study outcome was length of hospitalization; total length of stay and time elapsed before beta-agonists could be administered at 6-hour intervals. Duration of supplemental oxygen administration and peak flow measurements were secondary outcome measures. RESULTS: Sixty-six patients were evaluated. Children in the prednisone group had a mean length of stay of 70 hours compared with 78 hours for the methylprednisolone group (P =.52). Children in the prednisone group were successfully weaned to beta-agonists in 6-hour intervals after 59 hours compared with 68 hours for the methylprednisolone group (P =.47). Patients receiving prednisone required supplemental oxygen for 30 hours compared with 52 hours for the methylprednisolone group (P =.04). CONCLUSION: There was no difference in length of hospital stay between asthmatic patients receiving oral prednisone and those receiving intravenous methylprednisolone. Because hospitalization charges are approximately 10 times greater for intravenous methylprednisolone compared with oral prednisone, the use of oral prednisone to treat inpatients with acute asthma would result in substantial savings.     

Maleic vinyl ether anhydride nephropathy: altered glomerular permeability due to an immunomodulating agent

The polyanionic immunomodulatory polymer, maleic vinyl ether anhydride (MVE-2), enhances antitumor macrophage activity and causes heavy proteinuria. The effects of this compound on renal function and renal morphology were investigated in a rat model. Rats were given daily intravenous infusions of MVE-2, 100 mg/kg, over 2-4 hr on each of three consecutive days. Renal function and morphology in MVE-2-infused rats were examined by standard techniques and compared to control rats given saline. On the average, MVE-2 rats had a significant reduction in inulin clearance to 62% of control values. MVE-2 rats developed heavy proteinuria 1-3 days after the first infusion (mean +/- 1 SEM, 387 +/- 91 mg/24 hr). By light microscopy, the only finding was intratubular protein casts; glomeruli were normal. Immunofluorescence showed no deposition of antibody, complement, or fibrin. Electron microscopy revealed foot process effacement, epithelial cell vacuolization, and subepithelial ring-shaped structures; no immune-complex deposits were present. MVE-2 rats had no increase in the number of glomerular Ia(+) cells. To examine further the mechanism of MVE-2 nephropathy, the ability of MVE-2 to induce proteinuria in animals pretreated with radiation (750 rad), methylprednisolone (MP) or cyclosporine (CyA) was determined. Animals pretreated with radiation or MP had significantly less proteinuria after MVE-2 treatment compared to animals receiving no immunosuppressive therapy, while CyA pretreated rats developed heavy proteinuria. These results are compatible with the hypothesis that MVE-2 induces proteinuria via an effect on steroid- and radiation-sensitive cells, perhaps related to production of circulating factors which alter glomerular permeability.     

A 12‐week, placebo‐controlled study of the efficacy and safety of ebastine, 10 and 20 mg once daily, in the treatment of perennial allergic rhinitis

This double-blind, placebo-controlled, multicentre study investigated the ability of ebastine, 10 and 20 mg once daily, to control symptoms of perennial allergic rhinitis (PAR) over a 12-week period, and assessed additional benefits of the 20-mg dose. Following a 2-week baseline period, patients (12-63 years) were randomized to treatment with ebastine 10 mg (n=88) or 20 mg (n=102), or placebo (n=100). Patients scored symptom severity (0-3) twice daily, and mean changes from baseline scores showed ebastine to be significantly effective in week 1. Control of symptoms persisted over the 12 weeks, the average daily total nasal symptom score for nasal stuffiness plus nasal discharge plus sneezing plus itchy nose being reduced by both doses, with statistical significance at 20 mg (P=0.015 vs placebo) despite decreased usage of sodium cromoglycate rescue medications. Patient and clinician final opinions of treatment also significantly favoured ebastine, both 10 and 20 mg, over placebo. No serious adverse events occurred, and study treatments were well tolerated with a low incidence of central nervous system-related adverse events and headache. In conclusion, ebastine 10 or 20 mg once daily was rapidly effective in relieving symptoms of PAR in adult and adolescent patients; additional benefits of the 20-mg dose became apparent in the longer term.     

Daily glucose injections facilitate performance of a win-stay water-escape working memory task in mice.

In an experiment that compared 3 versions of a working memory task, male C57BL/6 mice given either 3 (n = 7) or 5 (n = 7) opportunities (test runs) per trial to choose the escape choice section of a maze acquired a win-stay (spatial matching-to-sample) water-escape task. Mice given only 1 test run per trial (n = 6) were unable to perform above chance level. In a 2nd experiment, 14 mice from the 1st experiment were tested for performance on the 3-test-run version of the task. Each mouse was tested for 12 consecutive days with each of 4 doses of glucose (0, 50, 100, & 250 mg/kg ip) given 30 min before testing. The two higher doses increased the percentage of correct test run choices on all 3 daily test runs across the 12 days of testing. Daily glucose injections facilitated the use of trial-dependent information.     

The incidence of corticosteroid side effects in chronic steroid-dependent asthmatics on TAO (troleandomycin) and methylprednisolone

The purpose of this study was to determine the effect of troleandomycin (TAO)-methylprednisolone (MP) regimens on the incidence of corticosteroid-induced side effects. Retrospective analysis was performed on the charts of 29 adult chronic steroid-dependent asthmatics on regimens of TAO-MP. These 29 met our criteria of a minimum of 1 year on TAO-MP and at least 6 to 12 months on daily or alternate-day corticosteroids before TAO-MP was instituted. Charts were reviewed for nine known corticosteroid (CS) side effects, all previously identified side effects were excluded. Charts were also reviewed for TAO dose, MP dose, and dose/duration on CS therapy before TAO-MP regimen began. Patients on TAO at an average dose of 250 mg/d were able to wean to an average MP dose of 10.8 mg every other day from an average MP equivalent dose of 16.8 mg every other day before TAO. In spite of lower MP doses on TAO we found that 35% showed an increase in CS-induced side effects, some (three) had more than one side effect. Three patients developed cataracts (10%), two become hypertensive (6.8%), one developed diabetes (3%), one had a psychotic episode (3%), and one patient developed TB (3%) and had a spinal compression fracture. Sixty percent of these patients were on 8 mg or less of MP on an alternate-day basis. We found that in this group of 29 chronic steroid-dependent asthmatics the incidence of corticosteroid-related side effects was increased on TAO-MP regimens despite a reduction in corticosteroid dose.     

Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.     

Peritransplant use of ultraviolet-B irradiation (UV-B) therapy is detrimental to allogeneic stem cell transplantation outcome.

Whole-body UV-B phototherapy has been used for the treatment of graft-versus-host disease (GVHD) of the skin and has systemic immunosuppressive and tolerogenic effects. We hypothesized that whole-body UV-B therapy would improve donor engraftment and decrease the incidence and severity of GVHD that is associated with decreased intensity allogeneic hematopoietic stem cell transplantation. This study tested the feasibility of using UV-B phototherapy that was initiated before grafting and continued until engraftment to determine its effect on transplantation outcome. Eight patients (median age, 55.5 years; range, 32-65 years) with hematologic malignancies were included. Allogeneic peripheral blood stem cells were obtained from matched related (n=5) or matched unrelated (n=3) donors. Conditioning regimen was fludarabine 30 mg/m2 intravenously for 5 days, cyclophosphamide 1 g/m2/d intravenously for 2 days, and equine antithymocyte globulin 30 mg/kg/d for 2 days. GVHD prophylaxis included cyclosporine, methylprednisolone, and escalating doses of narrowband UV-B (311 nm) according to skin tolerance, 3 days a week, from 10 days before to 28 days after transplantation. The conditioning regimen and the UV-B therapy were well tolerated. Two patients received all 14 prescribed UV-B treatments (cumulative doses of 2000 and 3260 mJ/cm2, respectively) and 6 patients received 8 to 13 treatments with a cumulative dose range of 528-3465 mJ/cm2. There was a rapid decrease in epidermal CD1a+ cells by day of transplantation. Myeloid engraftment was rapid. One patient had secondary engraftment failure at 3 months and another had mixed chimerism at day 100. Seven of 8 patients developed severe acute GVHD (grade III, n=5; grade IV, n=2). Six had skin involvement, 5 had gastrointestinal involvement, and 1 had liver involvement. Four patients died (2 from sepsis, 1 from acute GVHD, and 1 from chronic GVHD). Four patients are alive (130-287 days), 3 with extensive chronic GVHD. We conclude that extended peritransplant UV-B therapy at the standard minimally erythemogenic dose is detrimental to the outcome of allogeneic stem cell transplantation. It is unclear how UV-B at this immunsuppressive dose might have altered skin and systemic cytokine and immune cell compositions in the host and increased GVHD- and treatment-related mortalities. Different UV-B dose and schedules should be further explored. However, although other phototherapeutic modalities may be effective against GVHD, extended UV-B therapy should not be used during early phases of decreased conditioning allogeneic transplantation.     

A combination of methylprednisolone and quercetin is effective for the treatment of cardiac contusion following blunt chest trauma in rats

Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg⁻¹·day⁻¹), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.