Total Dose Of Prednisolone Research Articles

P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: Clinical implications and influence of glucocorticoid administration

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with a chronic clinical course that requires long-term glucocorticoid (GC) therapy. A drug efflux pump, P-glycoprotein (P-gp), actively transports GC out of target cells, thereby reducing its efficacy. We evaluated the P-gp function of peripheral-blood mononuclear cells in 59 MG patients. P-gp function was estimated from a decrease in fluorescent P-gp substrate Rhodamine 123 and its inhibition by the conformation-sensitive UIC2 monoclonal antibody. P-gp function on CD8 + T cells in 21 MG patients having experienced GC therapy was higher than that in 19 MG patients having no history of GC therapy ( p = 0.026). There was a significant correlation between P-gp function in CD3 + ( r = 0.55, p = 0.014) or CD4 + ( r = 0.48, p = 0.034) T cells and the total dose of prednisolone for treatment. P-gp function on CD4 + T cells in MG patients who showed low responses to prednisolone therapy ( n = 8) was higher than that in patients who showed relatively high responses to prednisolone therapy ( n = 10) ( p = 0.045). These results suggest that higher P-glycoprotein activity on CD3 + or CD4 + cells necessitated treatment with higher steroid doses in order to achieve a clinical response. The measurement of P-gp function on CD4 + T cells is useful in the assessment of clinical response to GC therapy.

Osteonecrosis of the lateral femoral condyle in a patient with ulcerative colitis: report of a case

Osteonecrosis is a major complication in patients with ulcerative colitis (UC). It appears most commonly in the femoral head, but sometimes occurs in the proximal humerus or femoral condyle. A 27-year-old Japanese woman presented with severe pain in the left knee in 2006. Osteonecrosis was found in the left lateral femoral condyle, and osteochondral autografting was performed. Ten and a half years prior to this episode, at the age of 17years, she had been diagnosed as having UC, and after 18months of medication, she had undergone total colectomy. A total prednisolone dose of 3020mg had been administered before the operation, but the true pathogenesis-i.e. idiopathic or steroid-associated osteonecrosis-had not been determined at that time. The osteonecrosis occurred long after prednisolone therapy had been discontinued, and the total dose of prednisolone was not considered to be unusually high. In this case, osteochondral autografting was ultimately required for treatment of the osteonecrosis. However, conservative therapy is indicated for early-stage cases and should result in a good course. We report this case to draw attention to this relatively rare complication of UC and to facilitate early detection of similar lesions.

Mycophenolate mofetil therapy for children with intractable nephrotic syndrome

Cyclosporin A (CyA) can suppress relapses and reduce proteinuria in frequent-relapse nephrotic syndrome (FRNS) and steroid-resistant nephrotic syndrome (SRNS). However, some patients remain resistant to CyA therapy. The purpose of the present paper was to evaluate mycophenolate mofetil (MMF) treatment in pediatric patients with CyA-resistant intractable nephrotic syndrome. MMF therapy was given to 11 patients with FRNS who had relapse despite CyA therapy, and one patient with SRNS who had been receiving combined therapy using steroid and CyA until immediately before the start of MMF. MMF was administered at a daily dose of 750-1000 mg/m(2) in two divided doses. Ten of the 11 patients with FRNS were able to maintain remission. Among them, seven patients remained relapse free for 1 year, and two patients had a decrease in the frequency of relapse after initiation of MMF therapy. One patient, however, had repeated cycles of remission and relapse, and was considered resistant to MMF therapy. The total prednisolone dose during the period from month 6 to month 12 after the start of MMF therapy was significantly lower than that during the 6 month period before the start of MMF therapy. The patient with SRNS, who had not achieved remission despite CyA administration, had complete remission on MMF. No serious adverse effects were seen in any of the present patients. MMF could be useful in CyA-treatment-refractory FRNS and CyA-resistant SRNS.

Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris

Pemphigus is a severe autoimmune blistering disease affecting the skin and mucosa. Mortality is high in the absence of treatment. Nowadays, treatment is based mainly on corticosteroids and cytotoxic drugs; however, because of the rarity of the disease worldwide, there is not yet a standard treatment based on randomized controlled trials, and the treatment used is based mainly on the experience of experts. The aim of this study was to compare the efficacy and safety of 4 treatment regimens for pemphigus vulgaris: prednisolone alone, prednisolone plus azathioprine, prednisolone plus mycophenolate mofetil, and prednisolone plus intravenous cyclophosphamide pulse therapy. One hundred twenty new cases of pemphigus vulgaris were enrolled. These patients were randomly allocated into 1 of 4 treatment groups (each comprising 30 patients) and received prednisolone (P), prednisolone and azathioprine (P/A), prednisolone and mycophenolate mofetil (P/MM), and prednisolone and intravenous cyclophosphamide pulse therapy (P/PC). They were followed up for 1 year at the Pemphigus Research Unit. In groups P, P/A, P/MM, and P/PC, 23 (76.5%), 24 (80%), 21 (70%), and 22 (73.3%) of the patients, respectively, followed the regimen for the full 1-year period. The mean total dose of prednisolone administered in groups P, P/A, P/MM, and P/PC was 11631 mg (standard deviation [SD] = 7742), 7712 mg (SD = 955), 9798 mg (SD = 3995), and 8276 mg (SD = 810), respectively. The mean total dose of prednisolone in group P (prednisolone alone) was 11,631 mg, The mean total dose of prednisolone in the 3 cytotoxic groups was 8652 mg. By using analysis of variance, the difference was statistically significant (P = .047). In the cytotoxic groups, there was a significant difference between the P/A and P/MM groups (P = .007), but not between P/A and P/PC (P = .971), and P/MM and P/PC (P = .670). Side effects were not significantly different among the 4 groups. Larger sample sizes and blind design are suggested for future studies. The efficacy of prednisolone is enhanced when it is combined with a cytotoxic drug. The most efficacious cytotoxic drug to reduce steroid was found to be azathioprine, followed by cyclophosphamide (pulse therapy), and mycophenolate mofetil.

Bell麻痺完全麻痺症例に対するステロイド大量療法の検討

The purpose of this study was to investigate the existence of any relationship between the initial or total prednisolone dose and the degree of facial nerve recovery in patients with complete idiopathic facial nerve palsy (Bell's palsy). This study was carried out on 102 patients with unilateral complete Bell's palsy of no more than 14 days duration. The patients were divided into four study groups: one receiving a single tapering course of steroids after an initial hydrocortisone (HC) dose of 600 mg, one receiving a second tapering course of steroids after an initial HC dose of 600 mg, one receiving a single tapering course of steroids after an initial HC dose of 1200 mg, and one receiving a second tapering course of steroids after an initial HC dose of 1200 mg. The following variables were analyzed among the groups: the cure rate, the average time needed to achieve maximum recovery, and the rate of side effects. The total cure rate of the patients was 77%. No significant differences were detected among the groups in terms of the cure rate, average time to achieve maximum recovery, or the side effects rate (P > 0.05). High-dose steroid therapy was considered to be somewhat effective in curing complete Bell's palsy. However, there were no correlations between the initial or total steroid dose and the prognosis if a prednisolone equivalent dose of more than 150 mg initially, or a total dose of more than 880 mg was used. These findings show no significant benefits of treating complete Bell's palsy with a second course of steroids.

Intestinal Behcet’s disease with esophageal ulcers and colonic longitudinal ulcers

Intestinal Behcet's disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and ileocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet's disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.

Glucocorticoid receptor α expression in the intrahepatic biliary epithelium and adjuvant steroid therapy in infants with biliary atresia

Background/Purpose In patients with cirrhosis, proinflammatory cytokines increase progressively in relation to the severity of liver dysfunction. Proinflammatory cytokines regulate the expression of glucocorticoid receptors (GcRs). On the other hand, GcRs mediate the effects of glucocorticoid steroids on bile excretion in the biliary epithelium. Glucocorticoid receptors have 2 isoforms: a cytoplasmic glucocorticoid receptor α (GcR α) mediates thier physiological effects, whereas a nuclear localized glucocorticoid receptor β (GcR β) acts as a dominant negative inhibitor of GcR α activity. We examined the histology features of liver biopsy and the expression of GcR α in the intrahepatic biliary epithelium in infants with biliary atresia. Patients/Methods The patients were divided into 2 groups: patients in group 1 (n = 17) had a total bilirubin level below 1.0 mg/dL at least once after surgery, whereas patients in group 2 (n = 14) has never had bilirubin level below 1.0 mg/dL postoperatively. Liver biopsies taken from 31 infants with biliary atresia at the time of hepatic portoenterostomy between 1988 and 2002 were examined for immunohistochemistry and histology with H&E staining. The degree of GcR α expression in the biliary epithelium was semiquantitatively analyzed using staining scores. The histology features of the liver biopsy were also semiquantitatively analyzed by using the same scores to evaluate the liver injury. Intravenous prednisolone dosage was started with 4 mg/kg per day and tapered by a half dose every 2 days. The protocol was orally repeated during admission until the stool became constantly cholic. Statistical analysis was performed using Mann-Whitney U test and Spearman correlation coefficient by rank. Significance is set at a 95% confidence interval ( P < .05). Results There was a significant positive correlation between the liver histology and the GcR α scores in all patients with biliary atresia ( P = .0128; r = 0.429). In group 1, there was a significant positive correlation between the GcR α expression scores and the total dose of prednisolone administered ( P = .0063; r = 0.767). Conclusions The increase and degree of GcR α expression were associated with the severity of liver injury and may correlate with the dose of prednisolone required to sustain bile flow after successful hepatic portoenterostomy.

Substance P containing nerve fibers in rectal mucosa of ulcerative colitis.

The intestine is rich in peptidergic innervation, which modulates mucosal immune responses. Among neuropeptides, substance P (SubP) has received considerable attention for stimulatory effects on various immunocytes in inflammatory diseases. In our prior study, we demonstrated increased innervation of SubP containing nerve fibers (SubP fibers) in ulcerative colitis (UC) surgically resected colonic specimens. In the present study, we examined the alterations of SubP fibers among various subgroups of UC, divided according to clinicopathologic features. Distribution of SubP fibers were examined immunohistochemically in the rectal biopsy specimens of UC. The UC group was further divided into subgroups according to six clinicopathologic parameters. The linear density of SubP fibers was measured by digitalized morphometry for quantitative analysis. Multivariate analysis revealed significant correlations between linear density of SubP fibers vs. activity of diseases and total dose of prednisolone. Linear density was significantly increased in active cases of UC (active UC, 22.6 +/- 1.6 microm/1,000 microm2; vs. inactive UC, 12.2 +/- 0.8 microm/1,000 microm2; P < 0.01). Furthermore, the increase was pronounced in cases that showed persistent inflammation and, accordingly, needed a high dose or continuous administration of prednisolone. Alterations in SubP fibers appear to play an important role in the pathogenesis of UC.

Treatment of ulcerative colitis with high doses of oral prednisolone. The rate of remission, the need for surgery, and the effect of prolonging the treatment.

Treatment of acute attacks of ulcerative colitis in 89 patients with doses of prednisolone above or equal to 40 mg resulted in an overall remission in 67%. Remission rate and colectomy rate were 47% and 42%, respectively, when the disease was severe, 80% and 13% when moderate, and 84% and 3% when mild. The need for surgery was 28% in pancolitis, 11% in left-sided colitis, and 5% in proctitis. After subsequent treatment episodes colectomy was performed in 35% of patients with pancolitis, in 37% with left-sided colitis, and in 5% with proctitis. The median total duration of therapy in patients who went into clinical remission was 4 months, and the median dose just above 3 g prednisolone. Patients who stayed in remission during the follow-up received a significantly higher start dose and total dose of prednisolone in the treatment episode than patients who had a relapse. In 25 patients treatment with doses equal to or above 75 mg of prednisolone was continued beyond 10 days, and 11 patients experienced remission whereas 14 patients had surgery performed. Orally administered corticosteroids produce results comparable to those obtained after the previously suggested intravenous regimen.

Immunoglobulins (IgG, IgA, IgM, IgE) and complement components (C3, C4) in nephrotic syndrome due to minimal change and other forms of glomerulonephritis, a clue for steroid therapy?

Serum IgG, IgA, IgM, IgE, C3 and C4 were measured in 13 patients with minimal change (MC) glomerulonephritis and 10 with the nephrotic syndrome (NS) due to other forms of glomerulonephritis. The tests were repeated in all patients with MC glomerulonephritis when they went into remission. Serum IgG was reduced, IgM, IgE and C3 were raised while serum IgA was within the normal range when the patients were nephrotic. Changes in serum immunoglobulins and complement components were not specific to MC glomerulonephritis and these parameters reverted towards normal when the NS went into remission. Elevated C3 levels probably reflected increased hepatic protein synthesis since C3 correlated significantly with serum cholesterol. There was a tendency for serum IgE concentrations to positively correlate with the total dose of prednisolone required to bring the NS to remission.

Single daily dose corticosteroid treatment.

Thirteen patients with rheumatoid or psoriatic arthritis who had not previously received corticosteroids were treated with prednisolone in a single-dose each morning. Insulin-hypoglycaemia tests were performed before starting steroids in each patient, and again at the conclusion of the study in twelve of the thirteen (duration of steroid treatment 8-40 m). There was no difference in the mean basal or peak levels of corticosteroids, or the mean peak of growth hormone (GH) in the tests done before or during treatment, although one patient lost GH responsiveness. There was thus no evidence of hypothalamo-pituitary-adrenal (HPA) suppression in any of the twelve patients, and there was a good therapeutic response in twelve out of thirteen. One patient was dropped from the trial because treatment failed. In contrast, of seven patients who had received a similar total dose of prednisolone twice daily, three showed HPA suppression and two had lost GH responsiveness.