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Listeriosis in patients with chronic lymphocytic leukemia who were treated with fludarabine and prednisone.

OBJECTIVE: To determine whether therapy with fludarabine plus prednisone in patients with chronic lymphocytic leukemia increases the risk for developing listeriosis. DESIGN: Retrospective cohort study based on hospital surveillance data. SETTING: Referral cancer center. PARTICIPANTS: A total of 795 patients with chronic lymphocytic leukemia who received care at The University of Texas M. D. Anderson Cancer Center between 1980 and 1990. INTERVENTIONS: Patients were treated with fludarabine alone or fludarabine and prednisone. MEASUREMENTS: The listeriosis attack rate was analyzed according to the type of treatment received. RESULTS: Seven of 408 patients in the fludarabine group developed listeriosis (1.7%; 95% Cl, 0.2% to 6%) compared with 0 of 387 patients who received conventional chemotherapy alone (0% to 0.9%; P = 0.015). The 7 patients were among 248 patients who were treated with both fludarabine and prednisone; none of 160 patients treated with fludarabine alone developed listeriosis (P = 0.045 by the Fisher exact test). A dramatic reduction in CD4 counts occurred in patients after fludarabine and prednisone treatment and coincided with the development of listeriosis. CONCLUSION: The administration of fludarabine plus prednisone is associated with an increased incidence of listeriosis in patients with chronic lymphocytic leukemia. The depletion of CD4 cells may underlie the pathogenesis.

Aged↗

Low-dose prednisone induces rapid reversible axial bone loss in patients with rheumatoid arthritis. A randomized, controlled study.

OBJECTIVE: To determine the effects of a short course of a low dose of a glucocorticoid agent on bone mass. DESIGN: Double-blind, placebo-controlled, randomized study. SETTING: Outpatient clinic of a university hospital. PATIENTS: Forty patients with active rheumatoid arthritis. INTERVENTION: All patients started receiving intramuscular gold salts. In addition, they were randomly allocated to receive either prednisone or placebo. The initial dose was 10 mg/d, which was tapered between weeks 12 and 20. Thereafter, patients were followed for an additional 24 weeks. MEASUREMENTS: Lumbar bone mineral density was measured with dual-energy, quantitative computed tomography in a trabecular and a cortical region of interest. RESULTS: Despite favorable effects on disease activity and functional capacity, trabecular bone mineral density decreased in the prednisone-treated patients between baseline and week 20 (mean change, -8.2%; 95% CI, -12.7% to -3.7%; P = 0.001). Little change was found in the placebo-treated patients (P > 0.2), and the prednisone group had a greater mean bone loss than the placebo group (9.5%; CI, 3.4% to 15.6%; P = 0.003). After discontinuation of prednisone, an increase was found in trabecular bone mineral density between weeks 20 and 44 (mean change, 5.3%; CI, 0.7% to 9.9%; P = 0.03). Little change was found after withdrawal of placebo (P > 0.2). The mean improvement in the prednisone group was 6.8% (CI, 0.8% to 12.8%; P = 0.03) greater than for placebo. In both treatment groups, cortical bone mineral density did not change markedly in either period (P > or = 0.2). CONCLUSIONS: Low doses of glucocorticoid agents cause marked vertebral trabecular bone loss in the initial months of therapy in patients with active rheumatoid arthritis. After discontinuation of treatment, this bone loss seems to be (partially) reversible.

Analysis of Variance↗

Oral prednisone in guarded filtration procedures supplemented with antimetabolites.

BACKGROUND AND OBJECTIVE: To evaluate whether a three-day course of oral prednisone perioperatively improves the surgical outcome of guarded filtering procedures supplemented with antifibrosis agents. DESIGN, MATERIALS AND METHODS: A prospective, randomized, double-masked, placebo-controlled, clinical trial was designed. Adult patients with non-inflammatory glaucoma undergoing a guarded filtration procedure supplemented with antimetabolite were enrolled. Patients received a three-day course of prednisone (50 mg BID) or placebo perioperatively. The main outcome measures were intraocular pressure (IOP) and number of antiglaucoma medications. Surgical success was defined before data collection according to two different criteria: "success-I": IOP level < or = 15 mmHg with no more than one anti-glaucoma medication, and "success-II": IOP reduction of at least 20% of baseline level with no more than one antiglaucoma medication. RESULTS: Thirty-five subjects were enrolled. Seventeen patients were treated with prednisone and eighteen with placebo. Mean follow-up was 9.2 months +/-6.2 months. The probability of success-I at 9 months was 63.0% in the study group and 65.6% in the control groups (p>0.05). The probability of success-II at 9 months was 60.2% in the study group and 55.0% in the control groups, (p>0.05). The difference in frequency of postoperative complications between groups was not statistically significant. The most common complication was choroidal detachment (n=2) in the prednisone-treated group and bleb leak (n=2) in the control group. CONCLUSION: The perioperative use of oral prednisone did not alter the surgical outcome of filtering procedures associated with antifibrosis agents in this population of glaucoma patients.

Administration, Oral↗

Studies of the effects of cyclophosphamide, vincristine, and prednisone on some hepatic oxidations and conjugations.

The effects of low and high doses of three anticancer agents, cyclophosphamide, vincristine, and prednisone (given individually or in various combinations), on oxidative and conjugation pathways were studied in Sprague-Dawley male rats. Cyclophosphamide used alone at low doses decreased aniline hydroxylase and ethylmorphine demethylase activities by about 20% and at high doses produced a 30%-50% decrease in the specific activities of several microsomal mixed-function oxygenase activities, in the contents of cytochromes P-450 and b5, and in the magnitudes of type I and II drug-binding spectrum. The levels of microsomal glucouronidase, glucuronyl transferase, and sulfatase per gram of liver were also decreased (30%-50%) by the high dose of cyclophosphamide. The high dose of cyclophosphamide in conjunction with either vincristine or prednisone also produced a noticeable decrease in several activities tested; however, when cyclophosphamide was given at either low or high doses in combination with vincristine and prednisone, the activities tested were comparable to those seen in untreated controls. The mechanism of this protection is presently unknown. Vincristine, at both low and high doses, produced little effect on oxidative pathways; however, at low doses it caused a significant increase (80%) in the specific activity of hepatic microsomal sulfatase. This effect was also discernible when vincristine was given in combination with cyclophosphamide and prednisone. Other than producing a 15% decrease in liver weight and a 40% decrease in the specific activity of microsomal glucuronidase, the high dose of prednisone used had no effect on various activities tested. Results of these studies indicate a potential for drug interaction among anticancer agents and supportive drugs used in combination cancer chemotherapy.

Animals↗

Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia.

To define prognostic factors in infant acute lymphoblastic leukemia (ALL), the outcome of 106 infants (age </=12 months) during 3 consecutive multicenter trials of the Berlin-Frankfurt-Münster group (ALL-BFM 83, 86, and 90) was retrospectively analyzed according to presenting features and early in vivo response to prednisone. The prednisone response was defined as the cytoreduction (number of blood blasts per microliter at day 8) to a 7-day prednisone prephase and 1 intrathecal dose of methotrexate on day 1. Prednisone good responder (PGR; <1,000 blasts/microL) received conventional therapy and prednisone poor responder (PPR; >/=1,000 blasts/microL) received intensified therapy. Infant ALL was characterized by a high incidence of a white blood cell count greater than 100 x 10(3)/microL (57%), central nervous system leukemia (24%), lack of CD10 expression (59%), 11q23 rearrangement (49%) including the translocation t(4;11) (29%), and a comparatively high proportion of PPR (26%), which were all significantly associated with inferior outcome by univariate analysis. The estimated probability for an event-free survival at 6 years (pEFS) was by far better for PGR compared with PPR, who had a dismal prognosis despite intensified treatment (pEFS, 53% +/- 6% v 15% +/- 7%, P =.0001). Infant PGR, who were less than 6 months of age (n = 40), lacked CD10 expression (n = 43), and/or had an 11q23 rearrangement (n = 17) fared significantly better compared with corresponding PPR, as indicated by a pEFS of 44% +/- 8%, 49% +/- 8%, and 41% +/- 12%, respectively. In multivariate analysis, PPR was the strongest adverse prognostic factor (relative risk, 3.3; 95% confidence interval, 1.9 to 5.8; P <.0001). Infants with PGR, comprising a major subgroup (74%) among infants, might successfully be treated with conventional therapy, whereas PPR require new therapeutic strategies, including early treatment intensification or bone marrow transplantation in first remission.

Antineoplastic Agents, Hormonal↗

Effect of indomethacin and phenylbutazone-prednisone combination of gastric mucosa: gastroscopic and histological study.

The effect of a phenylbutazone-prednisone combination and indomethacin on the anatomical state of the gastric mucosa were studied by gastroscopy, gastrophotography, and gastrobiopsy. All four patients examined had redness of the antral mucosa after administration of either drug. Intramucosal gastric haemorrhage was present in two patients after both phenylbutazone-prednisone combination and indomethacin. Mucosal erosions occurred in three cases after the phenylbutazone-prednisone combination, one of them slight, and in two cases after indomethacin. On histological examination, increased intramucosal haemorrhage could be seen in the specimens from all four patients after indomethacin, and in the specimens from three patients after the phenylbutazone-prednisone combination. There was considerable mucosal vasodilatation in one patient on the phenylbutazone-prednisone combination and in two patients on indomethacin. The effects of both drugs on the gastric mucosa were similar. None of the subjects suffered from abdominal symptoms during the drug administration.

Biopsy↗

[Withdrawal of prednisone from a triple combination of immunosuppressive agents after kidney transplantation].

BACKGROUND: Triple-drug immunosuppression may not be necessary in a majority of stabilized patients over 1 year after kidney transplantation. In contrary steroid withdrawal may be beneficial for the patient by elimination of side-effects. The primary aim of this study was assessment of the risk of rejection after the prednisone withdrawal. METHODS AND RESULTS: 88 patients 1 year after the first renal transplantation with stable graft function and serum creatinine < 160 mumol/l treated with cyclosporine-A, azathioprine and prednisone were randomized into group A (n = 46) with a prednisone withdrawal and group B (n = 42) on triple-drug therapy without change. At the time of randomization, fine-needle biopsy was carried out in all of the patients. In group A, the dose of prednisone was gradually reduced to zero in the course of six months and the patients were followed up for the next 12 months. In the group B, patients on triple-drug therapy were followed for the corresponding period of time. 3 patients (6.6%) in group A, and 2 (4.8%) in group B experienced rejection (NS). Mean values of serum creatinine were in the course of follow-up in both groups without any statistical difference. Suspect immunological activity or proved immunological activity in aspiration biopsy was present in 4 patients in each group, but one of them rejected the graft. In comparison with group B, a significant decrease of cholesterol and leukocytes was observed in group A. Prednisone withdrawal had no influence on hypertension and triglyceride. CONCLUSIONS: Gradual withdrawal of steroids is not associated with higher risks of rejection and has a beneficial effect on cholesterol levels. Aspiration biopsy was of no use for the prediction of rejection.

Azathioprine↗

[Clinical effect of Tripterygiitotorum combined with prednisone and its effect on serum IL-6 level in treating patients with myasthenia gravis].

OBJECTIVE: To explore the clinical effect of Tripterygiitotorum (T II) combined with prednisone in treating patients with myasthenia gravis (MG) and the changes of immune function after treatment. METHODS: Sixty-eight patients with MG were randomly divided into two groups, the 36 patients in the treated group were treated with T II plus prednisone and the 32 in the control group were treated with prednisone alone. The therapeutic effect, serum interleukin-6 (IL-6) and peripheral B lymphocyte levels were observed. RESULTS: The therapeutic effect in the treated group was significantly higher than that in the control group (P < 0.05). There were significant decrease in serum IL-6 and peripheral B lymphocyte in both groups after treatment (P < 0.05), with the decrements more significant in the treated group (P < 0.05). CONCLUSION: The therapy of T II plus prednisone is superior to that of prednisone alone in treating MG, it has a more potent effect of immunosuppression.

Adolescent↗

Duration of pituitary and adrenocortical suppression after long-term administration of anti-inflammatory doses of prednisone in dogs.

Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P less than 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P less than 0.05) reduced and reserve function was markedly (P less than 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Administration, Oral↗

Effectiveness of antacids in reducing digestive disturbances in patients treated with prednisone and prednisolone.

To appraise the efficiency of complemental antacid administration in preventing and reducing digestive disturbances during prolonged treatment with prednisone and prednisolone, 100 patients with active rheumatoid arthritis who were maintained on combined antacid and prednisone or prednisolone therapy for periods of one year or longer, were studied clinically and roentgenographically. Antacid therapy consisted of 300 mg. of dried aluminum hydroxide gel and 50 mg. of magnesium trisilicate taken with each 2.5 mg. dose of the steroids. Digestive symptoms, such as indigestion, heartburn, sour eructations, gnawing epigastric distress and the like, were experienced by 18 per cent of patients during treatment with prednisone or prednisolone combined with antacids. Among patients who had been maintained on the steroids without antacids beforehand, the incidence of digestive complaints was reduced from 38 per cent to 17 per cent by the addition of alkali therapy, and the severity of the distress decreased in others. Active peptic ulcers were detected roentgenographically in three of the 100 patients. In two instances the ulcers were asymptomatic and in two instances they were considered as reactivations of previously healed lesions. The incidence of active ulcers in this series was substantially lower than that reported by several investigators among patients treated with prednisone and prednisolone without the concomitant administration of alkalis. The size of dosage and individual susceptibility appeared to be important factors in the development of digestive disturbances from steroids. Results of the study indicated that the complemental use of antacids with each divided dose of steroid is highly effective in reducing the frequency and severity of digestive symptoms during prednisone and prednisolone administration. The low incidence (3 per cent) for roentgenographically demonstrable active lesions in the series suggests that the addition of acid-neutralizing agents during prolonged treatment with these steroids may afford at least partial protection against the development and reactivation of peptic ulcers.

Aluminum Hydroxide↗

[Effects of jingui shenqi pill combined prednisone on expression of glucocorticoid receptor and its clinical effect in treating bullous pemphigoid patients].

OBJECTIVE: To investigate the effect of Jingui Shenqi Pill (JSP) on the expression of glucocorticoid receptor (GR) in the skin lesion and its clinical effect in treating bullous pemphigoid (BP) patients. METHODS: Thirty BP patients were randomly divided into the treatment group (n=15) treated with JSP plus prednisone and the prednisone group (n=15) with prednisone alone both for 4 weeks. And a normal control group was set up also. Expressions of GR-alpha and GR-beta in the skin lesion of BP patients and the normal skin of the normal control were detected by immunohistochemical assay. Results The total effective rate was 93.33% in the treatment group, significantly higher than that in the prednisone group which was 73.33% (P < 0.05); GR-alpha expression was higher in the treatment group than that in other two groups (P < 0.01), while GR-beta expression in the treatment group was lower than that in the prednisone group (P < 0.01). CONCLUSION: JSP could increase GR-alpha expression and decrease GR-beta expression in the skin lesion of BP patients, so as to improve sensitivity of skin to glucocorticoid.

Aged↗

Spermatic cord torsion: effects of cyclosporine and prednisone on fertility and the contralateral testis in the rat.

Unilateral spermatic cord torsion results in contralateral degeneration and reduced fertility in the prepubertal male rat. This study was conducted to investigate the use of immunosuppression with cyclosporine and prednisone to prevent these untoward effects. Thirty-five-day-old male rats were subjected to 720 degrees unilateral spermatic cord torsion of 9 hours duration. At the time of detorsion, animals were given a subcutaneous injection of i) cyclosporine, ii) prednisone, or iii) cyclosporine combined with prednisone. Control groups included: i) animals undergoing orchiectomy of the ipsilateral testis following the torsion period, ii) hemicastration in the absence of torsion and iii) sham surgery. Orchiectomy at the end of the torsion period prevented the torsion induced reduction of fertility, contralateral seminiferous tubule diameter and testis weight. Treatment with cyclosporine combined with prednisone significantly increased these parameters above detorsion alone. These data indicate that short term immunosuppression with cyclosporine alone or in combination with prednisone limits the adverse effects of unilateral spermatic cord torsion as does removal of the damaged organ at the end of the torsion period.

Animals↗

[Pharmacokinetic parameters of prednisone and prednisolone in healthy volunteers].

A cross-over, double-blind, randomized trial with 8 healthy volunteers was undertaken to compare prednisolone and prednisone pharmacokinetics after a single oral dose (1 mg/kg) of prednisone (Cortancyl) and prednisolone sodium metasulfobenzoate (Solupred). Maximum prednisolone concentrations measured after ingestion of prednisone are higher (535 +/- 32 ng/ml) and occur earlier than after taking prednisolone sodium metasulfobenzoate (198 +/- 114 ng/ml) (p less than 0.001). The areas under the curve are significantly larger after prednisone than after prednisolone sodium metasulfobenzoate (p less than 0.02). These findings suggest a decreased systemic availability of prednisolone after prednisolone sodium metasulfobenzoate (Solupred) administration and show, from a strictly pharmacokinetic point of view, that equimolar doses of prednisone and prednisolone sodium metasulfobenzoate are not equivalent therapies.

Adult↗

Prednisone when used as treatment for rejection correlates with poor outcome.

Since January 1974, 195 of 202 (95%) renal transplants have been performed on blacks at the Howard University Hospital Transplant Center. Hypertension is the most common cause of end-stage renal disease (ESRD) at this center (57%). The immunosuppressive regimens utilized were divided into four eras. The first era (1974-1980) consisted of the prophylactic administration of prednisone, Imuran (AZA), and Minnesota antilymphocyte globulin (MAG) with high prednisone dosage used to treat rejection. One-year, two-year, and five-year patient survival rates were 59% 54%, and 41%, respectively. Graft survival rates for the same period were 53%, 47%, and 36%. In the second era (1980-1983), the same immunoprophylaxis was used but only MAG was used to reverse rejection. One-year and two-year patient survival rates were 90% and 84%. Graft survival rates for the same period were 72% and 64%. When era 1 is compared with era 2, statistically significant improvement in patient survival is evident (P less than 0.005). Graft survival rates are statistically significant for one-year graft survival (P less than 0.05). In the third era (1983-1986), cyclosporine was the principal immunosuppressive agent used along with prednisone. Rejection in this era was treated by adjusting the cyclosporine dose to keep the level between 100 ng to 150 ng per mL and in addition to high prednisone. One-year patient survival and graft survival rates were 83% and 55%, respectively. The fourth era began April 1986 and was initiated because of previous bad experiences with high doses of prednisone to treat rejection in era 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[The effect of prednisone in the development of nephropathy in Schoenlein-Henoch purpura].

The authors hospitalized in 1976-1987 39 children with Schönlein-Henoch's purpura who on admission had a normal finding in urine. Of the above patients 28 were given prednisone already at the onset of hospitalization, to 11 prednisone was not administered. Patients with prednisone developed nephropathy in one instance (3.5%), patients without prednisone 6 times (54.5%) which is a significant difference. The average prednisone dose was 1.7 mg per kg body weight per day for an average period of 21 days. Usually for 6-10 days the same dose was administered and then it was gradually reduced.

Child↗

Effect of divided daily dose prednisone therapy on circulating T cell subsets.

Prednisone induced reductions in the circulating human T cell population follow a characteristic time curve which persists even after a single daily dose of oral prednisone has been administered many times. If prednisone doses are administered every 6 h, so that a dose occurs near the point of maximum response from a previous dose (4-6 h), the reduction in size of the circulating T cell population will persist so long as administration of prednisone continues. A chronically depressed ratio of OKT4+ to OKT8+ cells is observed in most patients when as little as 2.5 mg of prednisone is administered every 6 h.

Adult↗

Prednisone, indomethacin and airway responsiveness in toluene diisocyanate sensitized subjects.

We investigated whether late asthmatic reactions and the associated increase in airway responsiveness induced by toluene diisocyanate (TDI) in sensitized subjects are inhibited by indomethacin and/or prednisone. Four sets of experiments were conducted in five subjects sensitized to TDI. To assess late asthmatic reactions to TDI, FEV1 was measured immediately before and after exposure to TDI and then hourly for 8 h. To assess change in airway responsiveness, the provocative dose (mg) of methacholine that caused a decrease in FEV1 of 20% (PD20FEV1) before treatment, and then before and after exposure to TDI was measured. In the first set of experiments, each subject was given no treatment and was studied before and 8 h after exposure to TDI; in the other two sets, each subject was studied before treatment, then during treatment with indomethacin (50 mg q.i.d. for 3 days, orally) or prednisone (50 mg once a day, for 3 days, orally), both before and 8 h after TDI exposure. In a fourth series of experiments, each subject was again given no treatment and studied before and 8 h after TDI. When the subjects were given no treatment or indomethacin, TDI caused late asthmatic reactions and increased airway responsiveness to inhaled methacholine. In contrast, when the subjects were given prednisone, TDI caused neither late asthmatic reactions nor increased airway responsiveness. Treatment with indomethacin and prednisone did not change baseline FEV1 and airway responsiveness. These results suggest that release of prostaglandins does not contribute to late asthmatic reactions and the associated increase in airway responsiveness induced by TDI. Inflammatory mediators inhibited by prednisone but not by indomethacin may be involved.

Adult↗

Prednisone-responsive aplastic anemia: a mechanism of glucocorticoid action.

We performed serial agar cultures (CFU-C) using marrow cells from a patient with prednisone-responsive aplastic anemia and from five patients with prednisone-resistant aplasia. Colony growth was decreased in all patients. Cortisol (10(-7)-10(-4)M) significantly enhanced colony growth in the prednisone-responsive patient but fauled to enhance colony growth in the remaining five patients. Further studies in the responsive patient indicated that (1) colony growth was enhanced by depleting T lymphocytes from the marrow cells, (2) colon growth T-depleted marrow cells was inhibited by autologous peripheral blood lymphocytes (PBL), (3) cortisol failed to enhance colony growth of T-depleted marrow cells, (4) PBL and PBL-conditioned medium inhibited colony growth of both autologous and allogeneic marrow cells, but neither cortisol-treated PBL nor T-depleted PBL were inhibitory. Serial cultures in the responsive patient showed that colony growth normalized during remission when "suppressor" cells were absent and that colony growth was subnormal during a later relapse when cortisol-resistant "suppressor" cells were present. Therefore, in this prednisone-responsive patient, cortisol-sensitive T lymphocytes suppressed granulopoiesis in vitro. Our observations suggest that aplastic anemia in this patient is immunologically mediated and that prednisone therapy enhanced hemopoiesis in vivo by inhibiting the "suppressor" T lymphocytes.

Anemia, Aplastic↗