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Improved results of cadaver renal transplantation with azathioprine, prednisone and antilymphoblast globulin.

From 1980 to 1982, 100 consecutive cadaver renal transplants were performed. All but 2 recipients received preoperative transfusion and all received an initial 2-week course of antilymphoblast globulin. A prospective controlled evaluation of high versus low maintenance prednisone, and antilymphoblast globulin versus intravenous methylprednisolone for first rejection therapy was done. Over-all 1-year graft and patient survivals were 77 and 96 per cent, respectively. Graft survival was equal in the high and low steroid groups. Antilymphoblast globulin was as effective as intravenous methylprednisolone in reversing first rejections. Graft survival was improved with better donor-recipient matched grafts. We conclude that excellent results can be obtained in transfused cadaver renal allograft recipients managed with azathioprine, prednisone and antilymphoblast globulin. The regimen of prophylactic antilymphoblast globulin, low maintenance prednisone and antilymphoblast globulin alone for first rejections is immunologically effective and steroid sparing.

Antilymphocyte Serum↗

Fetal survival after prednisone suppression of maternal lupus-anticoagulant.

The presence of the lupus anticoagulant was diagnosed in six pregnant women because they had prolonged activated partial thromboplastin and kaolin clotting times which could not be corrected by dilution of test samples with normal plasma. All previous pregnancies (14) had ended in intrauterine death in the five multigravidas. Three women had had thrombotic episodes during pregnancy. The diagnosis of SLE was established in four. Antinuclear antibody was identifiable in all 6. All were treated with prednisone 40-60 mg/day and aspirin 75 mg/day. Suppression of the lupus anticoagulant activity was achieved in five patients, all of whom gave birth to live infants. In the sixth patient suppression of the anticoagulant activity was demonstrated between pregnancies; a further pregnancy in this patient was lost before she had received sufficient prednisone to suppress the anticoagulant. Since treatment with prednisone and aspirin can lead to successful pregnancies, it is important to screen all women with SLE, thrombotic episodes, recurrent intrauterine deaths, or a biologically false-positive VDRL for the presence of the lupus anticoagulant.

Adult↗

Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy.

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.

AIDS-Associated Nephropathy↗

Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen.

Membranoproliferative glomerulonephritis (MPGN) is classified as type I, II, or III based on ultrastructural alterations in the glomerular basement membrane. Whereas type II has long been recognized as clinically and pathologically unique, types I and III are often difficult to distinguish and have not been separated in most clinical studies. We compared the course and long-term outcome of patients with types I and III MPGN followed up at this institution since 1960. During this period, 21 patients with type I and 25 patients with type III were followed up for a minimum of 5 years. Patients with types I and III MPGN did not differ in age at apparent onset, age at diagnosis, or interval from apparent onset of symptoms to diagnosis (biopsy). They had similar initial serum C3 and serum albumin levels. Patients with type I had a significantly lower initial mean estimated glomerular filtration rate (GFR(est)) compared with those with type III (99.1 +/- 35.9 versus 131.6 +/- 36. 1 mL/min/1.73 m(2); P < 0.01). Type and duration of therapy, length of follow-up, and frequency of complications of therapy did not differ between groups. There was, however, a significant difference in duration of hypocomplementemia. After 1 year of an alternate-day prednisone regimen, 90% of the type I patients normalized their serum C3 levels compared with less than 50% of type III patients (P < 0.01). After 3 years of therapy, only 5% of type I patients were hypocomplementemic compared with 33% of type III patients (P < 0.02). In addition, disease relapse occurred in six type III patients (24%) compared with no type I patients. At last follow-up, type I patients had a slight improvement in mean GFR(est) (+6.3 +/- 48.4 mL/min/1.73 m(2)), whereas type III patients had a 25% decrease in mean GFR(est) (-34.8 +/- 47.6 mL/min/1.73 m(2); P < 0.01). Residual urinary abnormalities were significantly more frequent in patients with type III than type I MPGN. Hematuria persisted in 72% versus 38% (P < 0.05) and proteinuria in 28% versus 0% (P < 0.01) of those with types III and I, respectively. These results give clear evidence of significant differences in the clinical progression of the two types and their response to the alternate-day prednisone regimen. Whereas the outcome of patients with type I MPGN treated with alternate-day prednisone was generally good, similarly treated patients with type III experienced significant reductions in renal function, slower improvement in serum C3 levels, more persistent urinary abnormalities, and more frequent relapses.

Child↗

Lack of objective improvement in ventricular systolic function in patients with myocarditis treated with azathioprine and prednisone.

Six patients with myocarditis documented by biopsy, after a baseline right heart catheterization and echocardiogram, underwent treatment with azathioprine and prednisone. After 3 months of treatment, biopsy, right heart catheterization and echocardiogram were repeated. In addition to the immunosuppressive therapy, most patients received additional conventional medications for heart failure between evaluation periods (mean number of cardiac drugs increased from 1.7 +/- 1.0 to 2.7 +/- 0.05, p = 0.041). Mean heart rate decreased (105 +/- 14 to 84 +/- 13 beats/min, p = 0.016), as did pulmonary wedge pressure (23 +/- 8 to 12 +/- 4 mm Hg, p = 0.012). There were no significant changes in cardiac index (3.1 +/- 0.8 to 2.9 +/- 1.0 liters/min), end-diastolic dimension (62 +/- 13 to 62 +/- 12 mm) or fractional shortening (11 +/- 6 to 12 +/- 3%) with treatment. Complications from immunosuppressive therapy included severe soft tissue infection, acute psychosis and adrenal insufficiency in one patient each. The benefits from prednisone and azathioprine in this group of patients have not been demonstrated. Although heart rate and pulmonary wedge pressure decreased, these changes could be ascribed to increases in the conventional therapy for heart failure. Finally, there is a high incidence of side effects from prednisone and azathioprine therapy. These findings suggest that this unproven therapy for myocarditis should be limited to experimental protocols.

Adult↗

Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma.

The purpose of this study was to determine the frequency with which magnetic resonance (MR) imaging detects avascular necrosis of the bone (AVNB) in children with acute lymphoblastic leukemia (ALL) or advanced-stage non-Hodgkin lymphoma (NHL) who receive prednisone during remission induction, reinduction, and maintenance chemotherapy; to assess the clinical significance of these findings; and to identify factors predictive of AVNB. We prospectively obtained MR imaging of the hips and knees of 116 children who had completed at least 1 year of treatment for ALL or advanced-stage NHL on identical prednisone-containing regimens between December 1991 and October 1994. MR imaging findings of AVNB were compared with clinical outcomes, and the effect of therapeutic and patient factors on the frequency of AVNB was analyzed. The MR imaging findings of 17 of the 116 participating patients were consistent with AVNB. The most common clinical manifestation was joint pain (11 patients). Only one patient had progressive joint deterioration that necessitated surgical replacement. Only age 10 years or more at the time of the primary diagnosis was significantly associated with the development of AVNB (P = 0.004). MR imaging showed changes consistent with AVNB in approximately 15% of this patient population. However, most patients in this study who had MR imaging signs of AVNB did not experience progressive joint destruction, even with continued prednisone therapy. Therefore, the clinical usefulness of MR imaging as a screening tool for AVNB in this set of patients remains uncertain.

Adolescent↗

The mechanisms of prednisone inhibition of inflammation in Crohn's disease involve changes in intestinal permeability, mucosal TNFalpha production and nuclear factor kappa B expression.

BACKGROUND: The clinical course of Crohn's disease after the induction of remission with medical therapy is characterized by unpredictable relapse. AIM: To evaluate three surrogate markers, intestinal permeability, mucosal TNFalpha and nuclear factor (NF)-kappaB/IkappaBalpha expression, in order to determine the relationship of these parameters to clinical relapse. METHODS: Thirty patients with active Crohn's disease were treated with a 10 week course of prednisone using a tapering dosing regimen. Intestinal permeability (lactulose/mannitol [L/M ratio]) was determined at baseline and at the end of prednisone tapering. TNFalpha production and the levels of expression of NF-kappaB/IkappaBalpha were measured in colonic mucosal biopsies obtained after the induction of remission. RESULTS: Twenty-two patients (73%) achieved remission and 50% of patients experienced a clinical relapse during the ensuing 12 months. Treatment with prednisone resulted in a significant decrease in the L/M ratio. Of the patients that relapsed, 75% had a raised L/M ratio at the time of remission compared with 20% of patients with a normal L/M ratio (P < 0.008; hazard ratio = 6.094; CI 1.55, 17.43). Mucosal TNFalpha production was greater in relapsers compared with those who remained in remission. The levels of NF-kappaB in relapsers were significantly greater and levels of cytosolic IkappaBalpha were significantly lower compared with those measured in patients who remained in remission. CONCLUSIONS: These findings underscore the importance of incorporating biological parameters of inflammation in determining the clinical course of Crohn's disease.

Adult↗

VAD or VMBCP in multiple myeloma refractory to or relapsing after cyclophosphamide-prednisone therapy (protocol MY 85).

263 patients (median age 65+/-10 years) with multiple myeloma were treated with cyclophosphamide-prednisone. Out of this cohort, 103 patients had progressive disease and were randomly assigned to either VAD (vincristine, doxorubicin, dexamethasone; 50 cases) or VMBCP (vincristine, BCNU, cyclophosphamide, melphalan and prednisone; 53 cases). There were no statistical differences between the two groups with the respect to clinical, biological and radiological parameters. There was no difference in survival between the VAD and VMBCP groups. The 4 months response rate was similar in the two groups (50% VAD, 56% VMBCP). With multivariate analysis for survival (Cox model), two factors had a statistically significant impact: Karnofsky index (> 60) and albuminaemia (< 34 g/l). With both Karnofsky index > 60 and albuminaemia > or = 34 g/l, the median survival was 29 months v 2 months with a Karnofsky index < or = 60 and albuminaemia < 34 g/l (P<0.05). In conclusion, VAD or VMBCP had similar activity for salvage treatment in MM refractory or relapsing to first-line treatment with cyclophosphamide-prednisone.

Adult↗

Recurrent aphthous stomatitis unresponsive to topical corticosteroids: a study of the comparative therapeutic effects of systemic prednisone and systemic sulodexide.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is a common oral condition, the etiology of which remains largely unclear. Numerous therapeutic protocols have been tried. Apart from immunomodulators, no therapy is unequivocally effective, and many systemic therapies have potential adverse effects. OBJECTIVE: To compare, in patients with frequent RAS unresponsive to conventional therapies, the therapeutic effectiveness of systemic prednisone with that of systemic sulodexide, a low-molecular-weight heparin with immunosuppressive activity but few adverse effects. METHODS: The study involved a group of 30 patients suffering from frequent minor RAS over >or= 4 months unresponsive to topical corticosteroids. Patients were randomly assigned to one of three study groups: blind therapy with systemic sulodexide or systemic prednisone and control (no treatment). The outcomes were assessed blind on the basis of the days to recovery from pain and days to recovery from ulceration (epithelialization) during the first month of therapy; the number of aphthae appearing during the second month of therapy; and the number of aphthae appearing in the 2 months after the end of the 2-month treatment cycle. RESULTS AND CONCLUSIONS: The effectiveness of systemic sulodexide was almost comparable with that of systemic prednisone in patients with frequent RAS, without significant adverse effects.

Administration, Topical↗

Prednisone as initial treatment of analgesic-induced daily headache.

The majority of the patients who seek medical care in tertiary headache centres present with transformed migraine, and convert to daily headache, as a result of excessive intake of symptomatic medications (SM). This study aimed to analyse the possibility of using a short course of oral prednisone for detoxifying patients with chronic daily headache due to medication overuse in an out-patient setting. Four hundred patients with headache occurring more than 28 days per month for longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic medications were stopped suddenly and prednisone was initiated in tapering doses during 6 days, followed by the introduction of preventive treatment. Withdrawal symptoms and the frequency, intensity and duration of the headache, as well as the consumption of rescue medications, were analysed during the first 16 and 30 days of withdrawal. Eighty-five percent of the patients experienced a reduction in headache frequency and no patients presented severe attacks during the first 6 days. With regard to the following 10 days, 46% of the patients experienced at least 2 days without headache and 58% less intense attacks. Most of the patients noticed attacks with longer duration. After the 30-day period there was a significant decrease in headache frequency (mean 0.83, P<0.001), and no patients returned to overuse of SM. This study demonstrates that it is possible to detoxify patients suffering from rebound headaches, using oral prednisone during the first days of withdrawal, in an out-patient setting.

Adult↗

Hydroxyethyl starch and prednisone as adjuncts to granulocyte collection.

A total of 232 leukaphereses were performed with a continuous flow (CFC) of 89 donors related to recipients to obtain granulocytes for infected granulocytopenic recipients. One hundred fifteen runs were done without pretreatment of the donors and were used as controls. Pharmacological pretreatment of the remaining one hundred seventeen donors included Prednisone, given in an oral dose (50 mg) the evening prior to the run, and/or 250ml of 6 per cent hydroxyethyl starch added to the input line of the CFC throughout the run. A median of 9.2 liters of donor blood was processed with each run. The pretreatment of the donors with Prednisone plus the addition of HES to the input line significantly increased the number of granulocytes collected. Donors tolerated the leukapheresis procedure well, and no significant side effects were associated with Prednisone or HES administration. Early and frequent use of such granulocytes was effective in the short-term control of fever in the granulocytopenic recipients who failed to respond to 48 hours of broad spectrum antibiotic coverage.

ABO Blood-Group System↗

A combined low-density lipoprotein apheresis and prednisone therapy for steroid-resistant primary focal segmental glomerulosclerosis in children.

BACKGROUND: Treatment of steroid-resistant (SR) primary focal segmental glomerulosclerosis (FSGS) remains a major challenge in nephrology. A prospective study was conducted to clarify the therapeutic role of low-density lipoprotein apheresis (LDL-A) in 11 nephrotic children with SR and cyclosporine A (CsA)-resistant primary FSGS. METHODS: Based on entry criteria, all 11 eligible patients had biopsy-proven primary FSGS presenting with nephrotic syndrome (NS) and were resistant to steroid and conventional-dose CsA therapy. LDL-A was performed twice a week for 3 weeks (first course), then weekly for 6 weeks (second course). Beginning from the second LDL-A course, a dosage of 1 mg/kg/d of prednisone was administered for 6 weeks, then tapered. RESULTS: Seven patients experienced remission of NS, 5 of whom achieved complete remission within 4 weeks after initiating prednisone therapy with LDL-A. These 5 patients maintained normal renal function during follow-up (median, 4.4 years). Of 2 patients with partial remission, 1 patient maintained stable renal function during follow-up (4.5 years), whereas the other patient showed a gradual decline in renal function and progressed to end-stage renal failure (ESRF) 7.8 years after LDL-A therapy. Four patients who were considered to experience treatment failure had persistent NS and progressed to ESRF in 1.3 years (median) after LDL-A therapy. Complete remission (n = 5) was associated with significantly more highly selective proteinuria compared with treatment failure (n = 4). CONCLUSION: This study suggests that combined LDL-A and prednisone therapy can be a valuable addition to therapeutic options for treating patients with SR-FSGS. The role of LDL-A in treating these patients deserves to be assessed further in larger randomized controlled trials.

Adolescent↗

Effect of prednison therapy on serum levels of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3), T3-binding capacity, basal TSH level and TSH response to thyreoliberin (TRH) in children.

Effects of Prednison therapy on serum levels of T4, T3, rT3, TBC, basal TSH and TSH response to TRH in 10 children (7 with nephrotic syndrome, 3 with trombocytopenia) were studied. It has been found out that corticotherapy (Prednison 1--2 mg/kg/24 h; 2--4 weeks) causes a significant decrease of total T3 concentration together with a considerable rise of reverse T3 and lower T3-binding capacity. Basal TSH level was increased about twice; TSH response to TRH between both groups (without and with Prednison therapy) did not differ significantly. The observations suggest the presence of hypothyroidism during chronic corticotherapy in children.

Child↗

[Prevention of nausea and emesis during cytostatic therapy. Antiemetic efficacy of high-dosage oral metoclopramide without and with prednisone].

In a randomized trial of 58 cancer patients receiving strongly emetogenic cytostatic drugs (cisplatin or comparable cytostatic agents, alone or in combination), the anti-emetic action of oral metoclopramide was tested, alone or combined with prednisone. Patients of group A (33 during 46 treatment cycles) received three times 50 mg metoclopramide and three times 25 mg prednisone. Those of group B (25 patients during 35 cycles) received three times 50 mg metoclopramide. The drug was given two hours before as well as two hours and six hours after administration of the cytostatic drugs. Good or satisfactory prophylaxis of nausea and vomiting (no or at most three vomits) was achieved during 37 cycles (80.5%) of group A patients and 30 (85.7%) of group B patients. Complete absence of vomiting was obtained in 52% of cycles in group A, 46% of cycles in group B; complete absence of nausea in 39% and 32%, respectively. There was no statistically significant difference between the two treatments in their preventive action. Three times 50 mg metoclopramide (with or without prednisone) four hours apart during one cytostatic-drug cycle was well tolerated by patients in both groups and can be recommended as a simple, practical prophylaxis of nausea and vomiting in the course of strongly emetogenic treatment of cancer.

Adult↗

T-lymphocyte--mediated granulopoietic failure. In vitro identification of prednisone-responsive patients.

To identify patients with T-lymphocyte--mediated granulopoietic failure, we compared clonal growth of unfractionated bone-marrow cells with that of autologous marrow cells from which T lymphocytes had been removed, in a group of 234 patients. We also attempted to identify prednisone-responsive patients by culturing both unfractionated and T-depleted cells with and without glucocorticoids in vitro. Ninety-three patients were treated with prednisone for two to four weeks. Neutropenia resolved in 24 of 25 patients whose colony growth was enhanced by glucocorticoids in vitro, but in none of 68 whose cultures showed no response (P = 10(-10). Hemopoietic inhibitory T cells were found in 21 of the 24 prednisone-responsive patients. When these 21 patients were restudied during steroid treatment, the hemopoietic inhibitory cells were undetectable in steroid-responsive patients but were present in steroid-resistant patients. T lymphocytes can mediate granulopoietic failure in a variety of conditions, and in vitro studies identify most of the patients with these conditions. Hemopoietic inhibitory T cells are often steroid-sensitive, and in vitro study accurately predicts responses to steroid therapy.

Agranulocytosis↗

Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss.

BACKGROUND: Recurrent fetal loss has been well described in women with antiphospholipid antibodies. Such women also often have other autoantibodies commonly found in patients with systemic lupus erythematosus. Treating them with prednisone and aspirin may reduce the risk of fetal loss. METHODS: We screened 773 nonpregnant women who had the unexplained loss of at least two fetuses for antinuclear, anti-DNA, antilymphocyte, and anticardiolipin antibodies and for the lupus anticoagulant. Of 385 women with at least one autoantibody, 202 who later became pregnant were randomly assigned in equal numbers to receive either prednisone (0.5 to 0.8 mg per kilogram of body weight per day) and aspirin (100 mg per day) or placebo for the duration of the pregnancy. The women were stratified according to age (18 to 34 years or 35 to 39 years) and the week of gestation at which the previous fetal losses had occurred (< or = 12 or > 12 weeks). The primary outcome measure was a successful pregnancy. RESULTS: Live infants were born to 66 women in the treatment group (65 percent) and 57 women in the placebo group (56 percent, P=0.19). More infants were born prematurely in the treatment group than in the placebo group (62 percent vs. 12 percent, P<0.001). The major side effects of therapy in the mothers were hypertension (treatment group, 13 percent; placebo group, 5 percent; P=0.05) and diabetes mellitus (15 percent and 5 percent, P=0.02). CONCLUSIONS: Treating women who have autoantibodies and recurrent fetal loss with prednisone and aspirin is not effective in promoting live birth, and it increases the risk of prematurity.

Abortion, Habitual↗

The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment.

OBJECTIVE: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). STUDY DESIGN: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. RESULTS: In 37 of 55 patients the initial platelet count was <10,000/microL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/microL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. CONCLUSION: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective.

Acute Disease↗

Normal growth of prepubertal nephrotic children during long-term treatment with repeated courses of prednisone.

The growth of 21 prepubertal children with steroid-dependent frequently relapsing nephrotic syndrome was studied before and during treatment with repeated courses of oral prednisone for 4 y. The height and height velocity standard deviation scores (HSDS and HVSDS) of the nephrotic children were -0.11 and -0.06, respectively, at the onset of the disease and -0.12 and +0.05, +0.14 and +1.02, +0.21 and +0.78 and +0.17 and +0.66, respectively, thereafter yearly during the treatment. The mean yearly cumulative dose of prednisone was 6300, 3459, 2677 and 2081 mg/body area (m2) at the first, second, third and fourth year, respectively. The nephrotic children grew normally for their age before onset of the disease and growth remained normal despite prednisone treatment.

Child↗