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Intraperitoneal administration of prednisolone (2 mg/kg body weight every day) early after onset of GVHD from day +10 until day +42 resulted in reduced clinical GVHD severity and improved survival of allogeneic recipients. Although the liver was barely affected by prednisolone treatment, aGVHD-related histopathologic injury of the gastrointestinal tract was strongly reduced in association with diminished expression of interferon-γ, tumor necrosis factor, CXCL 9-11, CCL2-3, mucosal addressin cell adhesion molecule-1, and intercellular adhesion molecule-1. Prednisolone-induced reduction of adhesion molecule expression in the gut manifested earlier than seen for cytokines or chemokines. Interestingly, when starting steroid treatment on day +28, the course of GVHD was unchanged and no major differences in cyto- or chemokine expression in gastrointestinal tract or liver on day +42 were seen.
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Prednisone is a well-established treatment option in rheumatoid arthritis. Low-dose glucocorticoid therapy alleviates disease signs and symptoms, is better tolerated than high-dose therapy, and its addition to disease-modifying anti-rheumatic drugs (DMARDs) inhibits radiographic disease progression. A low-dose, modified-release (MR) formulation of prednisone, administered in the evening, was developed to counter the circadian rise in pro-inflammatory cytokine levels that contributes to disease activity. In a 12-week, randomized trial (CAPRA-2) in adult patients with rheumatoid arthritis who were receiving stable DMARD therapy, the addition of MR prednisone reduced disease signs and symptoms by ≥20 % according to the American College of Rheumatology criteria (in 48 % of patients vs. 29 % with placebo; p < 0.002 [primary endpoint]). In another 12-week trial (CAPRA-1), addition of evening MR prednisone to stable DMARD therapy reduced the mean duration of morning stiffness to a greater extent than addition of morning immediate-release (IR) prednisone (22.7 vs. 0.4 %; p = 0.045 [primary endpoint]). The improvement in morning stiffness with MR prednisone was maintained for 9-12 months during the open-label extension of CAPRA-1. These findings were supported by data from observational studies in various adult populations with rheumatoid arthritis. Treatment with evening MR prednisone for up to 12 months was generally well tolerated, with an overall similar tolerability profile compared with evening placebo or morning IR prednisone, and no new safety concerns. MR prednisone was estimated to be cost effective relative to IR prednisone in patients with rheumatoid arthritis in a UK pharmacoeconomic model.
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After decades of disuse because of its teratogenic effects, thalidomide has had a resurgence of use as a promising therapeutic agent for multiple myeloma. Its mechanism of action involves activation of the immune system, antiangiogenic effects, and inhibition of cytokines. Thalidomide does not interact with the cytochrome oxidase system. It is not significantly metabolized, but it does undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive. Despite the potential adverse effects of peripheral neuropathy, constipation, deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide is an effective first-line agent for multiple myeloma in combination with dexamethasone or melphalan and prednisone. It has also been studied in the palliative care of patients with cytokine-based syndromes such as anorexia-cachexia syndrome. This review describes its use in oncology, hematology, and palliative care.
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Lymphoma is a malignant neoplasm of lymphoid tissue classified into Hodgkin's and non-Hodgkin's types. It mostly affects lymph nodes although a considerable proportion of Non-Hodgkin's cases occur in extranodal sites.
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Stage 4 disease, large mediastinal mass, albumin (<3.5), and fever were independent predictors of EFS that were each assigned one point in the CHIPS. Four-year EFS was 93.1% for patients with CHIPS = 0, 88.5% for patients with CHIPS = 1, 77.6% for patients with CHIPS = 2, and 69.2% for patients with CHIPS = 3.
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Treatment with docetaxel every three weeks is an effective and well tolerated therapeutic option in patients with mHRPC.
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Optic perineuritis (OPN) is an inflammatory condition involving the optic nerve sheath because of a variety of causes. We describe three patients in whom OPN was secondary to Wegener's granulomatosis (WG) and compare the clinical findings in these cases with those of idiopathic OPN.
Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.
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Adult T-cell leukaemia lymphoma (ATLL) is an aggressive T-cell malignancy caused by the human T-lymphotropic virus type-1 (HTLV-1) and is associated with a very poor prognosis. Combination chemotherapy has had little impact on the long term survival of these patients. ATLL cells are characterised by the expression of CD25 (IL-2Rα), which is not expressed in normal resting T-cells. Daclizumab (Zenapax(®)) is a humanised murine anti-CD25 monoclonal antibody, which contains 10% murine CDR sequences. In this prospective trial 15 patients with aggressive ATLL were treated with CHOP-Zenapax (CHOP-Z) to determine the tolerability and feasibility of this novel regimen as well as evaluate its efficacy. Eleven patients had acute ATLL and four had the lymphoma subtype. The main presenting features were elevated LDH (100%), lymphocytosis (73%), lymphadenopathy (67%), skin lesions (40%), hypercalcaemia (53%), and hepato-splenomegaly (27%). Ten (67%) patients received the six scheduled cycles. Complete response (CR) lasting for two months or more was seen in 5 (33%), partial response in 3 (20%), minor response in 1 (7%), and no response in 6 (40%) patients. The median overall survival was 10 months (95% CI: 0.05-20.88) but this was significantly longer among responders (18 months) compared to non responders (3 months) (P = 0.019). For patients who achieved CR the disease free survival (DFS) was 15 months while the event-free survival (EFS) was 5 months. In conclusion CHOP-Z is safe and in those who achieve a complete response it was associated with prolonged overall survival.
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Multimodal postoperative analgesia employs multiple medications given perioperatively to block the generation and perception of pain at different points in the nociceptive pathway. This retrospective study examines its effect on the length of stay for patients undergoing hindfoot and ankle fusions.
After 9 years the overall patient survival rate was 94.12%, whereas the graft survival rate was 63.35%. Normal glucose and insulin levels were maintained either fasting or during oral glucose tolerance test (OGTT). The group of recipients of pediatric organs was compared with patients receiving organs from adult donors (n = 125); the mean glucose values were lower in the pediatric group, whereas insulin production was higher in the adult patients. Early venous thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher exact test, P = not significant [NS]).
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A total of 117 adult well-characterized DLBCL cases were included. The panel of antibodies comprised CD45, CD20, CD79a, CD3, BCL2, BCL6, and p53. PCR was also employed to correlate the events at the DNA level in BCL2.
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A 16-year-old girl presenting with systemic and cutaneous symptoms of hemorrhagic Henoch-Schonlein purpura continued to develop bullae on top of old scars. Past history was significant for bullae on the feet and legs after trauma. Based on history, physical examination, disease course, and biopsy, the patient, her mother, and other family members were diagnosed with dominant dystrophic epidermolysis bullosa, explaining the severe course and complications of her Henoch-Schonlein purpura.
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The majority of patients benefited from treatment for AIED. Four patients (6 ears) received intratympanic therapy as part of their treatment.
During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.
Myasthenia Gravis Foundation America postintervention status and changes in treatment and antibody titers were periodically determined. Lymphocyte subpopulations, total immunoglobulin, immunoglobulin G (IgG) anti-MuSK subclasses, and anti-tetanus toxoid IgG before and after treatment were also studied.
In vitro, CMC-544 was more potent in causing growth inhibition of various BCL than cyclophosphamide, doxorubicin, vincristine or dexamethasone. In vivo, treatment with CHOP or CVP inhibited growth of BCL xenografts for up to 40 days after which BCL relapsed. Tumor growth inhibition by CMC-544 (>100 days) lasted longer than that by CHOP or CVP. BCL xenografts that relapsed after the treatment with CHOP or CVP were far less responsive to CHOP or CVP re-treatment but regressed upon subsequent treatment with CMC-544. CVP could be co-administered with suboptimal doses of CMC-544, while CHOP could be administered on alternant days with CMC-544 to cause enhanced regression of established BCL xenografts.
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A total of 42 patients with nephrotic syndrome caused by IMN were randomly divided into short-term (n = 20) and long-term (n = 22) groups. All patients received initial treatment with tacrolimus and prednisone for 6 months, and afterward only the long-term patient group was tapered with low-dose tacrolimus until 24 months.
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At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes.
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Following Institutional Review Board approval, we conducted a retrospective review of patients with angiographically-confirmed SAVF who received intravenous, oral, or epidural corticosteroids for treatment of their symptoms. We studied patient-reported motor and sensory function following steroid administration using both the modified Rankin Scale and the Aminoff Motor Disability Scale.
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Arsenic trioxide (ATO) combined with dexamethasone, melphalan or other cytostatic agents had been used to treat refractory or relapsed multiple myeloma (MM) patients. We assessed the safety and efficacy of ATO combined with vindesine/cyclophosphamide/melphalan/prednisone (VCMP) or vindesine/doxorubicin/dexamethsone (VAD) chemotherapy for MM patients who failed more than two different prior regimens. All patients received ATO (0.25 mg/kg day) for 10 days/cycle combined with VCMP or VAD in 30-day cycles. Vindesine (1.4 mg/m(2)) was given intravenously on day 1, cyclophosphamide (400 mg/m(2) day) was given intravenously on days 2, 4, 6, 8, 10, melphalan (6 mg/day) and prednisone (1 mg/kg day) were given orally day 1 to day 10 for VCMP regimen. VAD regimen consisted of vindesine 1 mg/day and doxorubicin 10 mg/day intravenously drip for 4 days with oral dexamethasone 40 mg/day for days 1-4, 9-12, 17-20. Patients who completed at least one cycle were evaluated for response to treatment. Objective responses occurred in 35 of 63 (56 %) patients, including seven complete, 14 partial and 14 minor responses. Median progression-free survival and overall survival were 6 and 23 months respectively. 12 patients had elevated serum creatinine levels (SCr) at baseline, and 9 of 12 (75 %) showed decreased SCr levels during treatment. Frequent Grade 3/4 non-hematological adverse events included arrhythmia, hypertension, fatigue and neuropathy. These results indicate that ATO combined with VCMP or VAD was effective and well tolerated as a new therapeutic option for patients with relapsed or refractory MM.
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Ninety-four young patients (age, 18-60) with stage III-IV diffuse large B-cell lymphoma at intermediate/high or high risk according to the age-adjusted International Prognostic Index were enrolled into a phase II trial. The treatment was as follows: four courses of bi-weekly rituximab-cyclophosphamide-epirubicin-vincristine-prednisone (R-MegaCEOP14), two courses of rituximab-mitoxantrone-cytarabine-dexamethasone (R-MAD) and carmustine-etoposide-cytarabine-melphalan (BEAM) with autologous stem cell transplantation.
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The illicit use of dexamethasone as growth-promoting agent in animal breeding is still practiced within the EU constituting a health risk for meat consumers. An experimental study was developed to assess dexamethasone urinary excretion and tissue distribution (liver, kidney, and muscle) in male calves after therapeutic and growth-promoting administration. Urine and tissue samples collected from treated and untreated bovines were also investigated for the presence of other natural and synthetic corticosteroids (prednisolone, prednisone, hydrocortisone, and cortisone), in order to study a possible correlation with dexamethasone administration and to clarify prednisolone origin. Analyses were performed by a multi-residue LC-MS/MS method developed and validated according to the Commission Decision 2002/657/EC. The results confirm the rapid rate of dexamethasone urinary excretion, irrespective of the dosage, the duration and the route of administration, and the disappearance of cortisone and hydrocortisone during the treatment. Dexamethasone was distributed to the tissues where the elimination rate proceeded relatively slower as suggested by the presence of residues one month after the withdrawal of the therapeutic treatment. An increase in the number of positive findings for prednisolone, in association with higher levels of cortisone and hydrocortisone, was observed in urine samples collected from slaughterhouse rather than those collected at the farm. Prednisone residues were found only in one urine sample that showed the highest levels of prednisolone, hydrocortisone, and cortisone. The occurrence of prednisolone residues in urine and even in tissue samples confirms the endogenous nature of this molecule.