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Prednisone
Kinds of Prednisone Terms modified by Prednisone Selected AbstractsPrednisone induces immunophenotypic modulation of CD10 and CD34 in nonapoptotic B-cell precursor acute lymphoblastic leukemia cells,CYTOMETRY, Issue 3 2008Giuseppe Gaipa Abstract Background: Immunophenotypic modulation is induced by steroids in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients during remission induction therapy. Methods: We cultured BCP-ALL blasts from diagnostic bone marrow (BM) samples (n = 20) in the presence of prednisone on stroma layer obtained from BM-derived mesenchymal cells to maintain viability. Antigen expression was assessed by multiparametric flow cytometry. Results: Leukemia samples that sustained the treatment in vitro with prednisone, showed significative reduction of CD10 and CD34 expression compared with control, and it was comparable with that observed in residual leukemic cells of the same patients in BM at day 15 of treatment. Modulated cells were viable as determined by Annexin V staining and preserved light scattering properties. Of note, the extent of antigen modulation in vitro correlated with response to prednisone in vivo. Conclusions: The prednisone-induced immunophenotypic modulation can be reproduced in vitro and this phenomenon may reflect sensitivity to chemotherapy. © 2008 Clinical Cytometry Society [source] Large B-cell lymphoma of the legINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2001Elsa Vasquez-del-Mercado MD A 74-year-old Mexican man presented with an 18-month history of multiple, violaceous, coalescing, firm, tender nodules with an ulcer in the anterior aspect of the right leg (Fig. 1) and slightly infiltrated, ill-defined erythematous plaques affecting the left leg and both forearms. He had not received any treatment for his condition. Past medical history was relevant for noninsulin-dependent diabetes mellitus and hypertension without formal treatment and a history of heavy alcohol intake in his youth. A biopsy specimen of both plaque-type lesions of the forearm and tumorous lesions of the leg showed a diffuse, nonepidermotropic mononuclear infiltrate throughout the dermis and extending to the subcutis. The infiltrate was composed of pleomorphic, atypical, large mononuclear cells (Fig. 2). Immunostaining with CD20 was positive for the atypical cells while CD3 was positive for normal appearing lymphocytes, characterized as reactive T cells. Additional laboratory and image studies ruled out extracutaneous involvement. The diagnosis of primary cutaneous large B cell lymphoma of the leg (LBCLL) was made. The patient was initiated on radiotherapy localized to the right leg with a very good initial response, nevertheless resolution was not achieved and the plaques in the rest of the limbs remained unchanged. Thus, the patient started chemotherapy with CHOP (Cyclophosphamide, Vincristine, Doxorubicin, Prednisone). He has currently finished his fourth cycle with this chemotherapy regimen. The tumorous lesions involuted leaving only residual hyperpigmentation (Fig. 3) and the plaques in the rest of the limbs disappeared, the area of the ulcer diminished considerably. There is still no evidence of extracutaneous involvement. Figure 1. Nodules and ulcer in the anterior aspect of the right leg Figure 2. Atypical lymphocytes, with large, pleomorphic nuclei and multiple nucleoles. Positivity for CD20 antigen was demonstrated by immunohistochemical analysis (hematoxylin and eosin; X 600) Figure 3. Residual hyperpigmentation and granulation tissue after chemotherapy [source] Quinacrine and hydroxychloroquine, a forgotten combination for patients with active systemic lupus erythematosus in Australasia?INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2003Daniel W. T. Ching Abstract In 1994, A 39-year-old Female Patient With Systemic Lupus Erythematosus (Sle) Was Diagnosed As Having Lupus-induced Serositis. She Was Commenced On Hydroxychloroquine (Hcq) And Prednisone. Her Disease Kept Relapsing Whenever She Was Tailed Off Prednisone. In 1997, Quinacrine (Qn) Was Commenced, And Prednisone Was Gradually Stopped. Her Disease Has Remained In Remission On The Combination Of Hcq And Qn. In December 2000 She Ran Out Of Qn For A Week, And Within This Period She Started To Experience Fatigue And Polyarthralgia Again. Quinacrine Is Available From Compounding Pharmacies, And Is Relatively Cheap. The Combination Of Hcq And Qn In The Treatment Of Sle Should Be Considered More Often. [source] Effects of Low-Dose Prednisone on Bone Metabolism,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2005Francine N Ton MD Abstract Prednisone 5 mg/day suppresses multiple indices of bone formation in a randomized placebo-controlled trial in healthy postmenopausal females. This suggests that even low doses of prednisone may reduce bone repair or renewal and may have adverse effects on bone mass and/or bone strength. Introduction: High doses of chronic glucocorticoids are known to have adverse effects on bone, and measures to prevent bone loss are well established for doses >7.5 mg daily, because these doses can cause premature or exaggerated osteoporosis. However, it is unclear if chronic prednisone doses of 5 mg daily have the same effects on bone. There are no established recommendations for preventing glucocorticoid-induced osteoporosis in people taking prednisone 5 mg daily, a dose used frequently in medical practice to treat diseases of the lungs, joints, skin, muscles, eyes, nerves, etc. Our primary objective was to test whether prednisone 5 mg daily affects serum and urine indices of bone metabolism in healthy postmenopausal women. Our secondary objectives were to determine if prednisone 5 mg affected systolic or diastolic blood pressure or causes side effects. Materials and Methods: A double-blinded randomized placebo-controlled 8-week trial in 50 healthy postmenopausal women was conducted at the Massachusetts General Hospital Outpatient General Clinical Research Center. Patients were randomly assigned to prednisone 5 mg daily or matching placebo for 6 weeks, followed by a 2-week recovery phase. Markers of bone formation and resorption were determined at weeks 0, 2, 4, 6, and 8. Indices of osteoblast activity included serum propeptide of type I N-terminal procollagen (PINP), propeptide of type I C-terminal procollagen (PICP), osteocalcin, and bone-specific alkaline phosphatase (BSALP). Indices of osteoclast activity included urine and serum type I collagen N-telopeptide (NTX) and free urinary deoxypyridinoline (DPD). Results and Conclusions: Prednisone rapidly and significantly decreased serum PINP (p < 0.01), PICP (p < 0.01), and osteocalcin (p < 0.01) and free urinary deoxypyridinoline (p = 0.017). These changes were largely reversed during the recovery period. Side effects were indistinguishable in the two groups. Neither systolic nor diastolic blood pressure changed significantly throughout the study between the two groups. In conclusion, low-dose prednisone significantly decreases indices of bone formation and may decrease indices of bone resorption in postmenopausal women. Further studies are needed to assess the effects of low-dose prednisone on BMD and fracture risk. [source] Prednisone Prevents Inducible Atrial Flutter in the Canine Sterile Pericarditis ModelJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2008ROBERT N. GOLDSTEIN M.D. Background: Atrial fibrillation (AF) and atrial flutter (AFL) are common following cardiac surgery and are associated with significant morbidity. We tested the hypothesis that suppression of the inflammatory response with steroids would significantly modify the inducibility of postoperative AF/AFL in the canine sterile pericarditis model. Methods: Twenty-three dogs were studied daily from creation of pericarditis to the fourth postoperative day: 11 dogs were treated with oral prednisone (PRED) starting 2 days preoperatively until the end of the study; 12 dogs were controls (CON). EP testing was performed daily using epicardial electrodes placed at initial surgery. High-resolution (404 sites) epicardial mapping was performed during the terminal study. Baseline and daily CRP levels were obtained in all dogs. Results: Sustained AFL was absent in PRED (0%) versus CON dogs (91%; P < 0.001); AF induced in the early postoperative course in PRED dogs was of very short CL (mean 66 ms). Tissue inflammation was significantly attenuated in PRED dogs. Thresholds were lower in PRED versus CON dogs, significantly so on postoperative day (POD) 3. There was a trend toward lower ERPs in the PRED group at all CLs. CRP levels were markedly reduced in PRED versus CON dogs (peak CRP 78 ± 7 mg/L vs 231 ± 21 mg/L, P < 0.001), and returned to baseline in PRED dogs by POD 4, correlating with a virtual absence of sustained arrhythmia. During open chest mapping studies on POD 4, PRED dogs showed only nonsustained AF/AFL. Conclusions: Prednisone eliminated postoperative AFL, affected all EP parameters studied, and attenuated the inflammatory response associated with pericarditis. [source] Comparison of Oral Prednisone and Prednisone Combined with Metronidazole for Induction Therapy of Canine Inflammatory Bowel Disease: A Randomized-Controlled TrialJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2010A.E. Jergens Background: Although prednisone and metronidazole are commonly used to treat canine inflammatory bowel disease (IBD), no randomized-controlled trials have been performed. Hypothesis: Combination drug therapy with prednisone and metronidazole will be more effective than prednisone alone for treatment of canine IBD. Reduction in disease severity will be accompanied by decreased canine IBD activity index (CIBDAI) scores and serum C-reactive protein (CRP) concentrations. Animals: Fifty-four pet dogs diagnosed with IBD of varying severity. Methods: Dogs were randomized to receive oral prednisone (1 mg/kg; n = 25) or prednisone and metronidazole (10 mg/kg; n = 29) twice daily for 21 days. Clinical (CIBDAI) scores and serum CRP were determined at diagnosis and after 21 days of drug therapy. The primary efficacy measure was remission at 21 days, defined as a 75% or greater reduction in baseline CIBDAI score. Results: Differences between treatments in the rate of remission (both exceeding 80%) or the magnitude of its change over time were not observed. CRP concentrations in prednisone-treated dogs were increased because of many dogs having active disease. Both treatments reduced CRP in comparison with pretreatment concentrations. An interaction between CIBDAI and CRP was identified in 42 of 54 dogs (78%), whereas 8 of 54 dogs (15%) showed disagreement between these indices. Conclusions and Clinical Importance: Prednisone is as effective as combined treatment with prednisone and metronidazole for induction therapy of canine IBD. CRP may be normal or increased in dogs with IBD and may be useful in assessing the response of individual dogs to treatment along with changes in the CIBDAI. [source] A Case of Juvenile Bullous Pemphigoid, Successful Treatment with Diaminodiphenylsulfone and PrednisonePEDIATRIC DERMATOLOGY, Issue 1 2009Karen A. Marcus M.D. Because of the wide variety of bullous disorders and the considerable clinical overlap between them, it is difficult to differentiate one from the other on clinical features alone. Appropriate additional investigations are required to confirm the diagnosis. These include routine histologic examination of the skin, in addition to immunohistochemical staining and immune serology. Here, we present a rare case of juvenile bullous pemphigoid, which we will use to illustrate the difficulties encountered in the diagnostic process and to show how acquired blistering disorders of childhood should be approached. [source] Maintenance therapy with dose-adjusted 6-mercaptopurine in idiopathic pulmonary hemosiderosis,PEDIATRIC PULMONOLOGY, Issue 11 2008Xue-Qun Luo MD Abstract There are challenges for diagnosis and treatment of idiopathic pulmonary hemosiderosis (IPH). This clinical trial was to review the diagnosis and evaluate the efficacy of maintenance therapy with dose-adjusted 6-mercaptopurine (6MP) in IPH children. Fifteen children were enrolled. Prednisone was administered at 2 mg/kg/day for 4 weeks in acute phase of the disease followed by taper. 6MP was also started at 60 mg/m2/day simultaneously and continued for 3 years in outpatient. The delay in diagnosis of IPH is common and probably due to a lack of classical triad of IPH in most children. All the patients exhibited response to the initial treatment. Only one of eight patients with relative leukopenia on 6MP maintenance recurred while 5 of 7 others recurred (P,<,0.05) during median 4.5-year follow-up. Of the latter five patients who recurred, 4 remained recurrence-free after adjusting the dose of 6MP upwards to keep relative leucopenia. It suggests that children with IPH could achieve steroid-free long term remission on 6MP maintenance therapy, and relative lekopenia on 6MP might be a simple maker of predicting clinical response in most IPH children. Pediatr Pulmonol. 2008; 43:1067,1071. © 2008 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Cell-Surface CD200 May Predict Efficacy of Paternal Mononuclear Leukocyte Immunotherapy in Treatment of Human Recurrent Pregnancy LossAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009David A. Clark Problem, The allogeneic leukocytes in transfused blood can modulate the recipient's immune system so as to induce TGF-,-producing suppressor cells, and the cell-surface CD200 tolerance-signaling molecule on mononuclear dendritic cells is required for this effect. A subset of couples with unexplained recurrent pregnancy loss appears to benefit from transfusion of allogeneic paternal blood leukocytes (LIT), and considerable effort has been devoted to characterizing those who may benefit. Some data has been accumulated for LIT as sole therapy in patients with classical spontaneous abortions with respect to dose,response, duration of protection, need for boosting, excluding patients with autoimmunity, and inefficacy of paternal mononuclear cells stored at 4°C overnight before use which causes loss of cell-surface CD200. Recent data emphasize an important role of expression of the CD200 tolerance-signaling molecule on cells used to prevent abortions both in mice and humans. Method of study, An observational study of outcome as a function of the number of CD200+ paternal mononuclear cells was performed. Fourteen patients constituted the pilot group. Patients with autoimmunity who had failed inspite of treatment with IVIG + Heparin + Aspirin ± Prednisone were allowed to have paternal mononuclear cells added to their therapy. CD200 on purified paternal blood mononuclear cells was measured by flow cytometry. Results, The number of CD200+ cells administered was significantly greater in women achieving pregnancy (39.2 × 106 versus 20.8 × 106, P < 0.025) and in those who achieved a live birth (50.2 × 106 versus 20.8 × 106, P < 0.005) compared to those who did not achieve pregnancy, and % of paternal cells that were CD200+ was greater (11,12.5% versus 5.6%, P < 0.01). Amongst those achieving pregnancy which failed, the CD200+ cell dose was not significantly different from the non-pregnant group (30.5 × 106 versus 20.8 × 106). Conclusion, The number of CD200+ paternal mononuclear leukocytes may be an important determinant of subsequent reproductive outcome in a subset of patients. A lower % CD200+ cell number may also reflect hitherto unappreciated paternal factors bearing on reproductive success. It is feasible to recruit women to enter observational studies and to obtain useful data as a foundation for further studies. More complete patient characterization in a larger study is needed. [source] The efficacy and safety of abatacept in patients with non,life-threatening manifestations of systemic lupus erythematosus: Results of a twelve-month, multicenter, exploratory, phase IIb, randomized, double-blind, placebo-controlled trial,ARTHRITIS & RHEUMATISM, Issue 10 2010J. T. Merrill Objective To evaluate abatacept therapy in patients with non,life-threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis. Methods In a 12-month, multicenter, exploratory, phase IIb randomized, double-blind, placebo-controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (,10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper. Results A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference ,3.5 [95% CI ,15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept-treated and placebo-treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician-assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient-reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease-related events occurring during the first 6 months of the study (including the steroid taper period). Conclusion Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non,life-threatening manifestations of SLE. The increased rate of SAEs requires further assessment. [source] Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial,ARTHRITIS & RHEUMATISM, Issue 1 2010Joan T. Merrill Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ,1 British Isles Lupus Assessment Group (BILAG) A score or ,2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ,1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. [source] P58 Multisensitization to plants: clinical caseCONTACT DERMATITIS, Issue 3 2004António Luís Santos We observed a 65 years old male patient with pruritus, scaling erythema and liquenification areas on the face, neck, forearms and hands. For six years he had a story of episodic crisis of exsudative erythema associated with farm work. The skin biopsy showed irregular acantosis with slight hyperkeratosis and a mild multifocal lymphohistiocytic infiltrate, with many eosinophils. The patch tests with the Contact Dermatitis Portuguese Group of Study standard tray were positive for colophony, perfume mix and lactone mix. The patch tests with plant series were positive to atranorin, usnic acid, alantolactone, Parthenolide, lichen mix, Frulania dilatata, Achillea millefolium and Tanacetum extracts. Treatment was started with oral prednisone and hydroxyzine plus topical hydrocortisone and emollient cream with great improvement. The patient was advised about the avoidance of possible allergens sources. This kind of multisensitization to plants is an uncommon finding and poses diagnostic and therapeutic problems. This patient had a sustained recovery by avoiding farm work and by removal of in house plants. [source] Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus,CYTOMETRY, Issue 4 2009Susana Mellor-Pita Abstract Objective To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE). Methods Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNF,), interferon gamma (IFN,), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated. Results Serum IL10, IL6, and TNF, levels were increased in patients (P , 0.01), and a higher spontaneous (without stimuli) intracellular expression of IL10 in CD4+ and CD8+ T lymphocytes (P < 0.05) and of IL6 in monocytes (P = 0.01) were found. After stimulation, patients presented a higher percentage of CD4+ and CD8+ T lymphocytes producing IL4 and IL10 (P , 0.01), and of monocytes producing IL6 (P = 0.04) and IL10 (P = 0.008). The SLEDAI score was positively correlated with the percentage of CD4+IL10+ and CD8+IL10+ T lymphocytes (P < 0.01), and inversely correlated with CD8+TNF,+ (P= 0.02), CD4+IFN,+ (P = 0.04) and CD8+ IFN,+ (P = 0.002) T lymphocytes. Patients receiving high dose prednisone produced higher IL10, but they also were the patients with a more active disease. Conclusion Monocytes and T lymphocytes (CD4+ and CD8+) contribute to an overproduction of IL6 and IL10 in SLE; this correlates with the disease activity but is independent of the treatment the patients are receiving. © 2009 Clinical Cytometry Society [source] Prednisone induces immunophenotypic modulation of CD10 and CD34 in nonapoptotic B-cell precursor acute lymphoblastic leukemia cells,CYTOMETRY, Issue 3 2008Giuseppe Gaipa Abstract Background: Immunophenotypic modulation is induced by steroids in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients during remission induction therapy. Methods: We cultured BCP-ALL blasts from diagnostic bone marrow (BM) samples (n = 20) in the presence of prednisone on stroma layer obtained from BM-derived mesenchymal cells to maintain viability. Antigen expression was assessed by multiparametric flow cytometry. Results: Leukemia samples that sustained the treatment in vitro with prednisone, showed significative reduction of CD10 and CD34 expression compared with control, and it was comparable with that observed in residual leukemic cells of the same patients in BM at day 15 of treatment. Modulated cells were viable as determined by Annexin V staining and preserved light scattering properties. Of note, the extent of antigen modulation in vitro correlated with response to prednisone in vivo. Conclusions: The prednisone-induced immunophenotypic modulation can be reproduced in vitro and this phenomenon may reflect sensitivity to chemotherapy. © 2008 Clinical Cytometry Society [source] A Case of Multiple Keratoacanthoma Centrifugum MarginatumDERMATOLOGIC SURGERY, Issue 5 2004Cristina Mangas MD Background. Keratoacanthoma centrifugum marginatum is a rare variety of keratoacanthoma, usually presented and classified as solitary keratoacanthoma. Reported cases of multiple keratoacanthoma centrifugum marginatum are exceptional in the literature. Observations. A 21-year-old man presented for evaluation of erythematous papules and plaques on both legs that had had a peripheral growth over the past year. Clinical and histologic examination showed typical features of keratoacanthoma centrifugum marginatum. Owing to the multiplicity and size of the lesions, treatment with oral isotretinoin was started. It was ineffective. Subsequent treatment with methotrexate combined with oral prednisone led to the regression of all lesions. Conclusions. The exceptional case of a man with multiple keratoacanthoma centrifugum marginatum is reported. Treatment with methotrexate combined with oral prednisone was effective. This case illustrates how some variants of keratoacanthomas do not really fit into the current classification and how complex the treatment of these tumors is. [source] Environment and prednisone interactions in the treatment of recurrent airway obstruction (heaves)EQUINE VETERINARY JOURNAL, Issue 5 2000C. A. Jackson Summary Recurrent airway obstruction (RAO) or heaves is a manifestation of a hypersensitivity to dust, moulds, and spores in the environment of a susceptible horse. Although in the majority of RAO-affected horses, clinical remission can be achieved by keeping horses at pasture to reduce their allergen exposure, this often is not practicable. For this reason, we investigated if changing the environment of a single stall in a 4 stall stable was sufficient to improve lung function and reduce inflammation in RAO-affected horses. In addition, we determined if addition of oral prednisone provided additional benefit. Twelve RAO-susceptible horses were stabled, fed hay, and bedded on straw until they developed airway obstruction. At this point, bedding was changed to wood shavings and they were fed a pelleted diet for 2 weeks. Lung function was measured and bronchoalveolar lavage was performed before and 3, 7, and 14 days after environmental modification. In a crossover design, horses were treated for the 14 days with prednisone tablets (2.2 mg/kg bwt, q. 24 h). Horses then returned to pasture for 30 days. Airway obstruction was greatest before environmental modification. Significant improvement in lung function occurred within 3 days of the change in environment and continued to Day 7. Airway function was best after 30 days at pasture. The clinical response achieved by environmental modification was not significantly improved by addition of oral prednisone. The total number of cells, total neutrophils, and percent neutrophils was greatest before environmental modification. In the absence of prednisone, total and percent neutrophils did not decrease until Day 14 and total cell number until 30 days at pasture. In the presence of prednisone, total cells and total and percent neutrophils decreased by Day 3 and again at pasture. The fact that lung function can be improved within 3 days by environmental management alone emphasises the need for allergen reduction as the cornerstone of treatment of RAO. Although prednisone induced a more rapid reduction in airway inflammation, this was not associated with a more rapid improvement in airway function. [source] Saliva DHEA and cortisol responses following short-term corticosteroid intakeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010L. Jollin Eur J Clin Invest 2010; 40 (2): 183,186 Abstract Background, Given the high correlation between the serum and saliva hormone values demonstrated at rest, saliva provides a convenient non-invasive way to determine dehydroepiandrosterone (DHEA) and cortisol concentrations. However, to our knowledge, pituitary adrenal recovery following short-term suppression with corticosteroids has never been investigated in saliva. The aim of this study was therefore to examine how steroid hormone concentrations in saliva are influenced by short-term corticosteroid administration. Materials and methods, We studied saliva DHEA and cortisol concentrations before, during (day 1,day 7) and following (day 8,day 16) the administration of oral therapeutic doses of prednisone (50 mg daily for 1 week) in 11 healthy recreationally trained women. Results, Mean saliva DHEA and cortisol concentrations decreased immediately after the start of prednisone treatment (P < 0·05). Three days after concluding prednisone administration, both saliva DHEA and cortisol had returned to pretreatment levels. Conclusions, These data are consistent with previous studies on blood samples and suggest that non-invasive saliva samples may offer a practical approach to assessing pituitary-adrenal function continuously during and after short-term corticosteroid therapy. [source] Elevated exhalation of hydrogen peroxide in patients with systemic sclerosisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2003uczyñska Abstract Background Systemic sclerosis is accompanied by an influx of activated phagocytes into distal airways. These cells release H2O2, which may evaporate from the airways surface and be detected in expired breath condensate. We tested whether patients with systemic sclerosis exhale more H2O2 than healthy subjects and whether breath condensate H2O2 levels correlate with some clinical parameters. Material and methods H2O2 was measured fluorimetrically in the expired breath condensate of 27 patients (22 women, five men, mean age 49 ± 13·1 years) with systemic sclerosis and 27 age- and sex- matched healthy controls. Results Exhaled H2O2 levels were 3·5-fold higher (0·88 ± 0·62 µM vs. 0·25 ± 0·17 µM, P < 0·001) in the patients with systemic sclerosis than in the controls. Treatment with cyclophosphamide and/or prednisone (29 ± 50 months, range 3,168 months) did not significantly decrease H2O2 exhalation (0·78 ± 0·50 µM, n= 10 vs. 0·94 ± 0·67 µM, n= 17, P > 0·05). No significant difference was found between patients with limited and diffuse scleroderma (1·03 ± 0·69 µM, n= 17 vs. 0·63 ± 0·41 µM, n= 10, P > 0·05). H2O2 levels correlated with disease duration (r = 0·38, P < 0·05) and time from the first Raynaud's episode (r = 0·44, P < 0·05). Conclusions Patients with systemic sclerosis exhale more H2O2 than healthy controls, suggesting involvement of reactive oxygen species in disease processes. Lack of significant intergroups differences in H2O2 levels may have resulted from the small number of patients analyzed. [source] Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Fortunato Morabito Abstract The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front-line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review. [source] Central nervous system involvement in diffuse large B-cell lymphomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010Wataru Yamamoto Abstract Background:,Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B-cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) -CHOP chemotherapy. Patients and methods:,We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R-CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results:,CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions:,The incidence of CNS involvement dose not decrease in rituximab-era. [source] Results of the PETHEMA ALL-96 trial in elderly patients with Philadelphia chromosome-negative acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Juan-Manuel Sancho Abstract Background and aim:,Only 20,30% of elderly patients with acute lymphoblastic leukemia (ALL) are enrolled in clinical trials because of co-morbid disorders or poor performance status. We present the results of treatment of Philadelphia chromosome-negative (Ph,) ALL patients over 55 yr treated in the PETHEMA ALL-96 trial. Patients and methods:,From 1996 to 2006, 33 patients 55 yr with Ph, ALL were included. Induction therapy was vincristine, daunorubicin, prednisone, asparaginase, and cyclophosphamide over 5 weeks. Central nervous system (CNS) prophylaxis involved triple intrathecal (IT) therapy, 14 doses over the first year. Consolidation-1 included mercaptopurine, methotrexate, teniposide and cytarabine, followed by one consolidation-2 cycle similar to the induction cycle. Maintenance consisted of mercaptopurine and methotrexate up to 2 yr in complete remission (CR) with monthly reinduction cycles (vincristine, prednisone and asparaginase) during the first year. Results:,Median (range) age was 65 yr (56,77). Phenotype (30 patients): early-pre-B 7, common/pre-B 18, T 5. Cytogenetics (28 patients): normal 12, complex 10, t(4;11) 2 and other 4. CR was achieved in 19/33 (57.6%) patients, early death occurred in 12 (36.4%) and 2 (6%) were resistant. Overall survival and disease-free survival probabilities (2 yr, 95% CI) were 39% (21%,57%) and 46% (22%,70%), respectively (median follow up of 24 months). Removal of asparaginase and cyclophosphamide from the induction decreased induction death (OR 0.119, CI 95% 0.022,0.637, P = 0.013) and increased survival (20% vs. 52%, P = 0.05). Conclusions:,The prognosis of elderly Ph, ALL patients is poor. In this study, less intensive induction decreased toxic death, allowing delivery of planned consolidation therapy and increased survival probability. [source] Do cytogenetic abnormalities precede morphologic abnormalities in a developing malignant condition?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Jill K. Northup Abstract Cytogenetic evaluation of bone marrow and neoplastic tissues plays a critical role in determining patient management and prognosis. Here, we highlight two cases in which the cytogenetic studies challenge the common practice of using hematologic and morphologic changes as key factors in malignant disease management. The first case is that of a lymph node sample from a 40-yr-old non-Hodgkin's lymphoma (NHL) patient sent for determination of disease progress. Hematologic studies showed no evidence of transformation to high-grade NHL (>15% blasts with rare mitotic figures). Cytogenetic studies of lymph node showed multiple clonal abnormalities, most notably a der(18) from a t(14;18) which is associated with high-grade NHL. After two cycles of chemotherapy with fludarabine, the patient did not show any clinical response, suggesting possible progression to high-grade lymphoma. The second case is of a patient with a history of human immunodeficiency virus and blastic natural killer leukemia/lymphoma. Hematologic studies of ascitic fluid classified the patient as having pleural effusion lymphoma whereas bone marrow analysis showed no malignancy. Bone marrow cytogenetic studies showed multiple clonal abnormalities including a t(8;14), which is commonly associated with Burkitt's lymphoma (BL). To our knowledge, this is the first case wherein a morphologically normal bone marrow showed presence of clonal abnormalities consistent with BL or Pleural effusion lymphoma. After two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, the patient's general condition and ascitis improved and she was discharged. These studies clearly demonstrate that genetic changes often precede morphologic changes in a developing malignant condition. Therefore, the critical information needed for care of patients with malignant disorders may be incomplete or inaccurate if cytogenetic evaluation is overlooked. [source] PET-CT imaging of combined brachial and lumbosacral neurolymphomatosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2005Pazit Kanter Abstract:, Neurolymphomatosis is a rare manifestation of progressive non-Hodgkin's lymphoma. A 44-yr-old man with diffuse large B-cell lymphoma presented with unilateral progressive peripheral sensorimotor neuropathy after the 7th cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. No pathology in the nervous system was evident by computerized tomography (CT), magnetic resonance imaging (MRI) of the head, spinal axis and plexuses and by repeated analysis of cerebrospinal fluid. However, the hybrid modality of positron emission tomography (PET) of fluorinated deoxyglucose (FDG) combined with CT scan (PET-CT) showed unilateral involvement of both the brachial and lumbosacral nervous plexuses. A complete recovery of neurological manifestations and normalization of PET-CT followed intensive chemotherapy with autologous stem cell transplantation. The diagnosis and localization of neurolymphomatosis may be supported by PET-CT imaging. [source] First case of immune-mediated haemolytic anaemia associated to imatinib mesylateEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003Marcia C. Zago Novaretti Abstract: Imatinib mesylate is a specific inhibitor of protein tyrosine kinase activity secondary to bcr-abl, mostly indicated for the treatment of patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML). Generally, the undesirable effects of imatinib administration observed in clinical trials were of mild-to-moderate degree, and no haemolysis has been associated with this drug. We report here a case of immune-mediated haemolytic anaemia associated to imatinib mesylate successfully treated with prednisone in a patient with CML. Laboratory investigation showed anaemia [haemoglobin (Hb) of 59 g/L], reticulocyte of 61 × 109/L and a positive direct antiglobulin test. Anti-drug in vitro studies revealed a positive result with gel microcolumn assay by an adsorption mechanism. Seventy-four days after prednisone therapy, the patient's Hb level was of 110 g/L with negative direct antiglobulin test and drug in vitro studies. This case demonstrated that patients treated with imatinib mesylate can present immune-mediated haemolysis and adequate management of this event can be done maintaining the drug and associating corticosteroids. [source] Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOPEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2002A Hellenic Co-operative Oncology Group Study Abstract:Introduction: During the last few years epirubicin (E) and mitoxantrone (M) (Novantrone) have been used in the treatment of non-Hodgkin's lymphoma (NHL), because of their favorable principal profile. In particular, M has less severe non-hematological toxicity. Patients and methods: A randomized multicenter phase III study was conducted in order to compare the efficacy and toxicity of CEOP and CNOP in intermediate- and high-grade NHL. CEOP (arm A) consisted of cyclophosphamide 1000 mg m,2, vincristine 2 mg, E 70 mg m,2 on day 1 and prednisone 60 mg on days 1,7. The CNOP regimen (arm B) was identical to CEOP except for replacement of E by M at a dose of 12 mg m,2. Randomization was stratified according to stages I,IV. From September 1993 to March 1999, 249 patients registered for the trial. Patient characteristics were equally distributed in the two arms, except for age and International Prognostic Index (IPI) groups. Results: There were no significant differences between the two groups in the rates of complete (CR) and partial response (PR). The overall response rate was 78% in arm A (57% CR, 21% PR) and 82% in arm B (60% CR, 22% PR). With a median follow-up time of 47.3 months, the median survival was not reached in arm A, while it was 39.5 months in arm B (P = 0.09). Three-year survival rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference regarding the time to progression between the two groups (29.7 vs. 18.5 months); furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP, respectively (P = 0.07). The therapeutic efficacies of both regimens were equivalent among the four IPI groups. More alopecia was observed in arm A. WHO grade >2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF was given to 22 and 24 patients, respectively. Conclusion: There were no significant differences in terms of overall response rates, overall survival and time to progression between CEOP and CNOP in the treatment of intermediate- and high-grade NHL. Patients with low or low intermediate IPI risk treated with either CEOP or CNOP showed significantly better survival, response rates and time to progression than those with high intermediate or high IPI risk. Therefore, new improved therapeutic approaches should be developed for the treatment of high IPI risk patients. [source] Headache attributed to spontaneous low CSF pressure: report of three cases responsive to corticosteroidsEUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2004S. Gentile The therapy of headache attributed to spontaneous low CSF pressure (previously defined as spontaneous intracranial hypotension) is still a matter of debate. Epidural blood patch is considered the most effective treatment. However, pharmacological strategies may be considered before blood patch. We report three patients with headache attributed to spontaneous low CSF pressure that were successfully treated with oral prednisone. Additional studies may be useful to prove the effectiveness of corticosteroids in this syndrome. [source] Combination of rituximab with chemotherapy in diffuse large B-cell lymphoma.HEMATOLOGICAL ONCOLOGY, Issue 3 2008Evaluation in daily practice before, after approval of rituximab in this indication Abstract Randomized trials have demonstrated improved outcome from adding rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) for patients with diffuse large B-cell lymphoma (DLBCL). This retrospective study compared the outcomes of 224 patients with DLBCL treated in our institution before (Period 1, 1996,2002) and after (Period 2, 2002,2005) approval of rituximab in this indication to evaluate the impact of the drug in daily practice in unselected patients receiving different types of chemotherapy. We treated 131 patients in Period 1 versus 93 in Period 2 (median follow-up, 75 and 29 months, respectively) with no difference in patient characteristics between the two periods. Event-free and overall survivals (EFS and OS) were significantly improved in Period 2 for elderly patients and a significant shift in the selection of regimens was observed at the time when rituximab became available. More patients received the CHOP regimen in Period 2 than in Period 1 (82 vs. 57%, p,<,0.007) with CHOP being substituted for epirubicin-based regimens. In younger patients treated mostly with the ACVBP regimen (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) these differences were not observed, suggesting that combination of rituximab with dose-dense chemotherapy may deserve further evaluation in this age group. Copyright © 2008 John Wiley & Sons, Ltd. [source] Themes of liver transplantation,HEPATOLOGY, Issue 6 2010Thomas E. Starzl Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV. HEPATOLOGY 2010 [source] Development of autoimmune hepatitis in patients with typical primary biliary cirrhosis,HEPATOLOGY, Issue 1 2006Raoul Poupon Primary biliary cirrhosis (PBC),autoimmune hepatitis (AIH) overlap syndrome is a clinical entity characterized by the occurence of both conditions at the same time in the same patient. In addition to PBC-AIH overlap syndrome, transitions from one autoimmune disease to another have been reported, but no systematic series have been published. We report a series of 12 patients with consecutive occurrence of PBC and AIH (i.e., PBC followed by AIH). Among 282 PBC patients, 39 were identified who fulfilled criteria for probable or definitive AIH. AIH developed in 12 patients (4.3%). The baseline characteristics of the patients were similar to those of patients with classical PBC. Time elapsed between the diagnosis of PBC and the diagnosis of AIH varied from 6 months to 13 years. Patients with multiple flares of hepatitis at the time of diagnosis of AIH had cirrhosis on liver biopsy. Ten patients were given prednisone ± azathioprine; short-term as well as sustained remissions were obtained in 8 of these, while two had multiple relapses and eventually died 8 and 7 years after diagnosis of AIH. In conclusion, the development of superimposed AIH could not be predicted from baseline characteristics and initial response to UDCA therapy. If not detected early, superimposed AIH can result in rapid progression toward cirrhosis and liver failure in PBC patients. (HEPATOLOGY 2006;44:85,90.) [source] Long-term clinical outcome of living-donor liver transplantation for primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Etsuko Hashimoto Aim:, We described the recurrence of primary biliary cirrhosis (PBC) after living donor liver transplantation (LDLT) (Liver Transplantation, 7, 2001: 588). However, since the follow-up period in that study was insufficiently long (median 35.5 months), we performed a long-term study to further characterize recurrence of PBC after LDLT. Patients:, From 1991 to 2006, 15 patients with end-stage PBC underwent LDLT at Tokyo Women's Medical University. Of these patients, we studied 8 PBC patients (age 29 to 51 years, all females) who survived LDLT for more than 5 years. The follow-up period for these patients ranged form 68 to 120 months. Immunosuppression was maintained with tacrolimus and prednisone. Laboratory examinations performed in every patient and donor before LDLT included routine biochemical studies, antimitochondrial antibody (AMA) by immunofluorescence (IF), anti-M2 by enzyme-linked immunosorbent assay as well as antinuclear antibody (ANA) by IF, and immunoglobulin. After LDLT, the same laboratory examinations were performed in patients every 6 months. Liver biopsy was performed when patients exhibited clinical or biochemical signs of graft dysfunction. In addition, protocol biopsy was performed every 1 to 2 years after LDLT. Results:, At the time of LDLT, all patients had end-stage cholestatic liver failure. Seven patients were positive for AMAand anti-M2 while 1 patient was negative for these markers but strongly positive for ANA. Donors were blood relatives in 6 cases, and 2 donors who were not blood relatives still exhibited multiple HLA matches with the recipients. At the end of the study in May 2006, all patients were doing well. On laboratory examination, mild abnormal liver function test results were found in 4 patients: 3 were probably due to recurrence of PBC, 1 resulted from nonalcoholic steatohepatitis. Comparison of the AMA titer between before LDLT and the most recent follow-up visit showed an increase in three patients, a decrease in two patients and no change in three patients. In contrast, the ANA titer increased in five patients. Histologically, strong evidence of recurrent PBC was found in 4 patients, and findings compatible with PBC were present in 2 additional patients. Conclusions:, Although the number of our patients is small, our findings confirm that PBC can recur at high frequency after LDLT. However, this complication has not developed to advanced stages and has not caused appreciable symptoms in our patients, all of whom have a good quality of life. [source] |