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Therapeutic outcome of prednisone medication and of orbital irradiation in patients with Graves' ophthalmopathy.

Response to treatment was evaluated prospectively in 58 patients with Graves' ophthalmopathy. Prednisone, administered to 44 patients, resulted in a favourable response in 29 patients (66%): excellent in 3, good in 10 and fair in 16 subjects; 15 patients (34%) did not respond. Orbital irradiation was administered to 39 patients of whom all except 4 had been treated previously with steroids. Six months later, 25 patients (64%) had responded favourably (excellent in 0, good in 9 and fair in 16 subjects) and 14 patients had not responded (36%). A favourable response to prednisone or irradiation was reflected in a general shift to lower grades in each of the classes 2-6 of the NOSPECS system. Responders were not different from non-responders with regard to age, sex, NOSPECS classification, ophthalmopathy index, interval between the onset of eye disease (or of thyroid disease if present) and the start of treatment, or the presence of thyroid disease. In conclusion, (1) the ratio of responders to non-responders is 2:1 for both prednisone treatment and orbital irradiation in Graves' ophthalmopathy, (2) the response is seen in all classes of the NOSPECS system, and (3) the response is not dependent on age, sex, severity or duration of eye disease, or the presence of thyroid disease.

Female↗

Long-term hemodynamic follow-up of cardiac transplant patients treated with cyclosporine and prednisone.

To evaluate the long-term hemodynamic results in cardiac transplant patients treated with cyclosporine and prednisone, 19 patients were studied by cardiac catheterization and endomyocardial biopsy 13 +/- 3 months after transplantation. Immunosuppression consisted of 6 +/- 4 mg/kg/day cyclosporine and 20 +/- 8 mg/day prednisone. Eighteen patients were asymptomatic but had developed postoperative systemic hypertension (17 on antihypertensive therapy). These patients were compared with a normotensive control group of 18 patients without cardiovascular disease. Significant differences were found in heart rate; right atrial, pulmonary arterial, pulmonary arterial wedge, systemic arterial, and left ventricular end-diastolic pressures; cardiac index and stroke volume index; systemic and pulmonary vascular resistance; and end-diastolic volume index and left ventricular ejection fraction. The most frequent hemodynamic abnormalities included an elevated arterial pressure in 10 patients (56%), an elevated left ventricular end-diastolic pressure in six patients (33%), and a reduced ejection fraction in five patients (28%). Hemodynamic abnormalities tended to resolve or improve in the five patients restudied 2 years after transplantation. There was no significant relationship between fibrosis or inflammation on endomyocardial biopsy and hemodynamic abnormalities. We conclude that mild-to-moderate hemodynamic abnormalities are common in asymptomatic cardiac transplant patients receiving cyclosporine and prednisone.

Adult↗

Comparison of agents producing a neutrophilic leukocytosis in man. Hydrocortisone, prednisone, endotoxin, and etiocholanolone.

To study the potential application of glucocorticosteroid administration for the measurement of the bone marrow neutrophil reserve response, blood neutrophil count changes were measured in normal subjects after the administration of intravenous hydrocortisone (25, 50, 100, 200, and 400 mg) and oral prednisone (5, 10, 20, 40, and 80 mg). The upper three doses of both steroids increased the blood neutrophil count by approximately 4,000 cells/mm3. The neutrophilia occurring after hydrocortisone (200 mg) and/or prednisone (40 mg) was compared with that observed after endotoxin (0.8 ng/kg) and etiocholanolone (0.1 mg/kg) in 14 normal subjects, 7 patients with Wegener's granulomatosis on cyclophosphamide therapy and 10 patients with chronic idiopathic neutropenia. The normal responses (mean increase of blood neutrophils/mm3 above base line +/- 1 SEM) were: hydrocortisone 4,220 +/- 320, prednisone 4,610 +/- 360, endotoxin 6,060 +/- 880, and etiocholanolone 3,780 +/- 440. In the patient studies, etiocholanolone gave the smallest mean responses, but, in general, the results were similar for all agents. These data indicate that these glucocorticosteroids can be used as equivalent agents to endotoxin and etiocholanolone for measuring the neutrophil reserve response.

Adult↗

Terbutaline-induced desensitization of human lymphocyte beta 2-adrenoceptors. Accelerated restoration of beta-adrenoceptor responsiveness by prednisone and ketotifen.

We investigated, in 36 healthy volunteers, the effects of prednisone and ketotifen on recovery of lymphocyte beta 2-adrenoceptor density (determined by (-)-125iodocyanopindolol binding) and responsiveness (assessed by lymphocyte cyclic AMP [cAMP] responses to 10 microM (-)-isoprenaline) after desensitization by the beta 2-agonist terbutaline. Terbutaline (3 X 5 mg/d) decreased lymphocyte beta 2-adrenoceptor density by approximately 40-50%; concomitantly, lymphocyte cAMP responses to 10 microM (-)-isoprenaline were significantly reduced. After withdrawal of terbutaline beta 2-adrenoceptor, density and responsiveness gradually increased, reaching predrug levels after 4 d. Prednisone (1 X 100 mg orally) accelerated beta 2-adrenoceptor recovery; only 8-10 h after administration of the steroid beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached values not significantly different from pretreatment levels. Similar effects were obtained with ketotifen (2 mg; thereafter 2 X 1 mg/d for 4 d): 24 h after application of the drug beta 2-adrenoceptor density and cAMP responses to (-)-isoprenaline had reached pretreatment levels. Furthermore, ketotifen simultaneously applied with terbutaline completely prevented terbutaline-induced decrease in lymphocyte beta 2-adrenoceptor density and responsiveness. Prednisone (1 X 100 mg orally) or ketotifen (2 mg; thereafter 2 X 1 mg/d for 2 d) had no significant influence on lymphocyte beta 2-adrenoceptor density in healthy volunteers not pretreated with terbutaline, but shifted the ratio high-to-low affinity state of the lymphocyte beta 2-adrenoceptor toward high affinity state. We conclude that glucocorticoids as well as ketotifen can accelerate recovery of density and responsiveness of lymphocyte beta 2-adrenoceptors desensitized by long-term treatment with beta 2-agonists. Such an effect may have clinical implications for preventing tachyphylaxis of asthmatic patients against therapy with beta 2-agonists.

Adult↗

Relative hyperglucagonemia in L-asparaginase-and prednisone-induced glucose intolerance in management of acute lymphocytic leukemia.

Ten children with acute lymphocytic leukemia developed transient diabetes mellitus during treatment with L-asparaginase and prednisone. Serum glucose, plasma insulin, and plasma glucagon levels were measured when the patients were hyperglycemic. Six of the children were restudied several months later when there were no clinical or laboratory signs of glucose intolerance. Hyperglycemia induced by L-asparaginase and prednisone was associated with depression of plasma insulin and, despite the inhibiting action of L-asparaginase on protein synthesis, a corresponding elevation of plasma glucagon. Thus patients with diabetes mellitus induced by L-asparaginase and prednisone have relative hyperglucagonemia similar to other patients with diabetes mellitus.

Adolescent↗

Bone mineral content in nephrotic children on long-term, alternate-day prednisone therapy.

Bone mineral content (BMC) was measured by single-photon absorptiometry in 24 children with steroid-dependent, minimal-lesion nephrotic syndrome after 1 to 6.3 years of alternate-day prednisone therapy and in a sex- and age-matched control group. Bone mineral content was -0.002 +/- 1.2 standard deviation scores in patients and 0.3 +/- 1.4 in controls (t = 1.17; P = 0.25). No significant relation was found between BMC in patients and the amount of prednisone taken or the duration of therapy. Alternate-day prednisone therapy at doses usually needed to keep children with steroid-dependent nephrotic syndrome under control does not significantly affect BMC.

Absorptiometry, Photon↗

Retrospective analysis of alternate-day prednisone maintenance therapy for Crohn's disease.

We reviewed the medical records of 98 children with Crohn's disease followed at Children's Hospital of Pittsburgh from 1983 to 1993 to evaluate the merits of alternate-day prednisone (AD) maintenance therapy once initial remission was achieved. Of the 98 children, 35 had adequate data recorded for eligibility to the study. Of these, 11 were in the AD group and 24 were in a group whose maintenance regimen did not include prednisone (NO). The dependent variables were frequency of flares and linear growth over time. AD therapy reduced mean symptomatic flares (0.23 +/- 0.1 vs 0.69 +/- 0.14 flares/patient/year; p = 0.04) over a 2-year follow-up period but did not delay significantly the onset of a flare after remission was achieved (16.5 +/- 3.4, vs 13.4 +/- 1.8 months; p = 0.4). Site of disease involvement had no impact on frequency of flares. Fewer patients in the AD group experienced flares, but this finding did not achieve statistical significance (4/11, 36%, vs 17/24, 71%; p = 0.07). Linear growth, measured in height percentile and growth velocity (cm/year), was not significantly reduced by the second year of either therapy. This small retrospective study suggests that AD prednisone therapy may be effective in reducing symptomatic flares in Crohn's patients without a resultant inhibition of linear growth.

Adolescent↗

Prednisone is not a mouse carcinogen.

The carcinogenic potential of prednisone, a synthetic corticosteroid used as an anti-inflammatory and immunosuppressive agent, was investigated by feeding it to Crl:CD-1(ICR) mice (50/sex/dose) at doses of 0.25, 0.50, 1.0, and 5.0 mg/kg/day for 18 months. Prednisone did not significantly increase the incidence of neoplasms (p less than or equal to 0.05); on the contrary, it significantly decreased the incidence of hepatocellular tumors (p = 0.002 in males, p = 0.027 in females), male lacrimal/Harderian gland tumors (p = 0.05), female pulmonary adenomas (p = 0.047), female endothelial cell tumors (p = 0.035), and female lymphosarcomas (p = 0.02). This study suggests that long-term (lifetime) prednisone use does not increase cancer risk and may actually reduce it.

Animals↗

Treatment of Sydenham's chorea with intravenous immunoglobulin, plasma exchange, or prednisone.

Sydenham's chorea has been established as a postinfectious autoimmune neuropsychiatric disorder. Corticosteroids have been used to treat patients with severe disease but are not always effective, and relapses are frequent after cessation. Eighteen subjects were entered into this randomized-entry controlled trial designed to determine if intravenous immunoglobulin or plasma exchange would be superior to prednisone in decreasing the severity of chorea. Mean chorea severity for the entire group was significantly lower at the 1-month follow-up evaluation (overall 48% improvement). Although the between-group differences were not statistically significant, clinical improvements appeared to be more rapid and robust in the intravenous immunoglobulin and plasma exchange groups than in the prednisone group (mean chorea severity scores decreased by 72% in the intravenous immunoglobulin group, 50% in the plasma exchange group, and 29% in the prednisone group). Larger studies are required to confirm these clinical observations and to determine if these treatments are cost-effective for this disorder.

Adolescent↗

Effects of combination therapy of beta-interferon 1a and prednisone on serum immunologic markers in patients with multiple sclerosis.

Beta-interferon (beta-IFN) has a proven treatment effect on relapsing-remitting multiple sclerosis (MS), presumably through its regulatory properties on T-cell activation and cytokine production. This paper examines whether combination therapy of beta-IFN with prednisone would enhance immunoregulatory effects of beta-IFN by measuring serum levels of selected proinflammatory cytokines and soluble T-cell activation markers associated with MS. The selected markers were analyzed in MS patients treated with beta-IFN alone (n = 22) and beta-IFN combined with a low daily dose of prednisone (n = 33), as compared with those in 27 healthy controls at baseline and at a three-month interval for one year. The study confirmed that beta-IFN treatment inhibited serum levels of tumor necrosis factor-alpha (TNFalpha) and intracellular adhesion molecule-1 (ICAM-1) in patients with MS. However, combination therapy did not significantly enhance the inhibitory effect of beta-IFN treatment on the production of TNFalpha, interleukin (IL)-12, IL-2R, and ICAM-1, while the addition of prednisone antagonized the effect of beta-IFN on up-regulation of IL-10 and soluble CD95. No difference in the occurrence of binding antibodies to beta-IFN was found between the two treatment groups. The findings are important for the understanding of the role of combination therapy in the treatment of MS.

Adjuvants, Immunologic↗

Etoposide (VP-16) with prednisone and vincristine for the treatment of refractory acute lymphoblastic leukemia.

Fifty children with acute lymphoblastic leukemia (ALL) in first to fifth relapse were treated with a three-drug reinduction regimen consisting of prednisone (40 mg/m2/d for seven days), vincristine (1.5 mg/m2 on day 1) and etoposide (VP-16, 250 mg/m2 on days 1 through 3). The intent was to assess the efficacy of VP-16 in an otherwise conventional reinduction plan, especially in patients who had previously received teniposide (VM-26), the close congener of VP-16. Among the 46 patients who received at least two courses of the therapy, 16 (0.34) achieved complete remission. Seven others showed improvement in their bone marrow status. Each child had been heavily pretreated with prednisone and vincristine, and 14 had received VM-26. That seven patients judged to be clinically resistant to VM-26 had complete responses to prednisone-vincristine-VP-16 indicates that prior treatment with one podophyllotoxin derivative does not preclude responses to the other. We are uncertain about the pharmacologic basis of these results but suggest that the increased dosage and more frequent administration of VP-16, relative to that of VM-26, was sufficient to overcome apparent resistance to the latter compound. Remission durations ranged from one to eight months (median, four months), emphasizing the need to devise more effective continuation therapy, including investigational agents such as the epipodophyllotoxins.

Acute Disease↗

An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.

Antineoplastic Combined Chemotherapy Protocols↗

Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer.

PURPOSE: This phase II study was designed to assess the effects of mitoxantrone with prednisone in patients with metastatic prostate cancer who had progressed on hormonal therapy. The methods of assessment included quality-of-life analyses, pain indices, analgesic scores, and the National Prostatic Cancer Project (NPCP) criteria. PATIENTS AND METHODS: Patients received mitoxantrone 12 mg/m2 intravenously every 3 weeks plus prednisone 10 mg orally daily. All had a castrate serum testosterone and Eastern Cooperation Oncology Group (ECOG) performance status < or = 3, and had not received prior chemotherapy. Every 3 weeks, analgesic intake was scored, and a present pain intensity (PPI) record and visual analog scale (VAS) describing pain were collected. Every 6 weeks, the European Organization for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire plus a prostate-specific module were completed. A palliative response was defined as a decrease in analgesic score by > or = 50% or a decrease in PPI by > or = two integers without any increase in the other. RESULTS: Twenty-seven patients were entered onto the study. Nine of 25 (36%) assessable patients achieved a palliative response maintained for > or = two cycles (range, two to eight or more). Improvements in mean PPI and VAS pain scores after each cycle of therapy (P < .05) were seen. Quality-of-life analysis showed improvements in social and emotional functioning, and in pain and anorexia. Using NPCP criteria, one patient achieved a partial response (PR) and 12 had stable disease; one of seven patients with measurable disease had a PR. No serious nonhematologic toxicity was experienced, and there were no episodes of febrile neutropenia. CONCLUSION: Mitoxantrone with low-dose prednisone is a well-tolerated treatment regimen that has some beneficial effects on disease-related symptoms and quality of life for patients with advanced prostate cancer.

Aged↗

Interferon versus interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study.

PURPOSE: We evaluated the vincristine, doxorubicin, and dexamethasone (VAD) regimen alone or with chemosensitizers for remission induction and interferon (IFN) versus IFN plus prednisone (IFN/P) for remission maintenance in previously untreated multiple myeloma. PATIENTS AND METHODS: Two hundred thirty-three patients were registered for remission-induction therapy with VAD or VAD plus the chemosensitizers verapamil and quinine. Patients who achieved remission were randomized to maintenance therapy with IFNalpha 3 MU in the evening three times weekly or IFN plus 50 mg of prednisone (IFN/P) on the morning after IFN until relapse. RESULTS: Two hundred twenty-nine patients were eligible for induction. Fatal toxicities in nine patients who received VAD plus verapamil and quinine led to closure of this arm after 47 registrations. Subsequently, all patients received VAD induction. Despite the high early mortality rate on VAD plus sensitizers, overall survival by induction arm did not differ for median or 5-year survival with approximately 40% of patients surviving 5 years. Eighty-nine eligible patients who achieved remission were randomized to maintenance. Patients who received IFN/P had improved progression-free survival (median, 19 v9 months for IFN; P = .008). After 48 months, progression-free survival on IFN/P was at the thirtieth percentile, whereas it was below the tenth percentile on IFN alone. Median survival from start of maintenance was long on both arms (57 months for IFN/P v 46 months for IFN; P = .36). CONCLUSION: IFN/Pwas more effective than IFN alone. Improved relapse-free survival may be attributable to IFN/P or to the use of prednisone for maintenance. This latter alternative is currently being studied.

Adult↗

Liposome-encapsulated doxorubicin in combination with standard agents (cyclophosphamide, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma: results of therapy and correlates of response.

PURPOSE: To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. PATIENTS AND METHODS: Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m(2) was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. RESULTS: Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm(3) (range, 19/mm(3) to 791/mm(3)). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P =.027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. CONCLUSION: Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evidence that prednisone-induced myopathy is reversed by physical training.

Treatment with glucocorticoids causes wasting of proximal skeletal muscles. There is evidence that physical training improves muscle mass and strength in glucocorticoid-treated rats. Whether this is also true in humans is not known. The present investigation was designed to establish in what respect moderate physical training may alter muscle mass and function as assessed quantitatively by computed tomography (CT) and an isokinetic dynamometer (Cybex II). Compared with matched normal subjects (n = 12), patients (n = 12) treated with prednisone [12.6 +/- 3.3 (+/- SD) mg/day] had a 20% lower midthigh muscle area and a 36% increase in midthigh fat to muscle ratio. The mean peak torque and the total work output of the thigh muscle were lower by more than 20%. Baseline measurements of total work output or peak torque at all tested velocities increased with midthigh muscle area (r = 0.73; n = 24; P less than 0.001). Fifty days of isokinetic training in 12 patients increased the thigh muscle area, decreased the thigh fat area, and normalized the mean peak torque and total work output. The increase in peak torque was inversely correlated with the daily dose of prednisone (r = 0.60; n = 12; P less than 0.05). Thus, glucocorticoid-induced muscle wasting can be reversed by increasing physical activity in patients taking a low to moderate dose of prednisone.

Adult↗

Long-term benefit from prednisone therapy in Duchenne muscular dystrophy.

Two successive, 6-month, randomized, double-blind, controlled trials of prednisone showed that 0.75 mg/kg/d was the optimal dose to improve strength in boys with Duchenne muscular dystrophy (DMD). We attempted to maintain 93 boys on that dose for an additional 2 years. During the 3 years of observation, the decline in average muscle strength scores of all boys taking prednisone was 0.072 units/yr, as compared with an expected decline of 0.341 units/yr from natural history controls. The occurrence of side effects in some boys prevented maintenance of the full dose, which may have lessened the response. At the time of last visit, dosages ranged from 0.15 mg/kg to 0.75 mg/kg. In addition to maintaining their strength, several of the boys actually improved their performance in lifting kilogram weights and in some timed function tests. Treatment of DMD with prednisone significantly slows the progression of weakness and loss of function for at least 3 years.

Adolescent↗

Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group.

A recent double-blind, placebo-controlled trial has shown that prednisone improves strength in patients with Duchenne muscular dystrophy. To determine whether immunosuppressant effects were important in mediating this improvement, we performed immunohistochemical analyses on muscle biopsies obtained at the conclusion of the trial. We studied 33 patients: 12 from the placebo group, nine from the low-dose prednisone group (0.75 mg/kg/d), and 12 from the high-dose group (1.5 mg/kg/d). There was a significant difference in total T cells (CD2+) between the placebo group and both treatment groups. Similarly, the number of CD8+ cytotoxic/suppressor T cells was significantly decreased in both treated groups compared with placebo. The number of muscle fibers focally invaded by lymphocytes was also significantly decreased in the two treated groups compared with controls. There were no differences between the low- and high-dose groups. The numbers of B cells, natural killer cells, CD4+ cells, macrophages, and necrotic muscle fibers were not significantly different in the treated and control groups. This study suggests that prednisone may improve strength in Duchenne muscular dystrophy through primarily immunologic mechanisms involving T lymphocytes.

Adolescent↗