Alternate-day Therapy Research Articles

健康人に発症した鼻脳型ムコール症例

Mucormycosis usually occurs in patients with diabetic acidosis or in immunosuppressive conditions such as malignant disease, steroid therapy or cytotoxic therapy. This paper describes our experience with rhinocerebral mucormycosis (RCM) in an apparently normal host, and an accompanying literature survey. A 68-year-old man was admitted because of pain in the right buccal region. Computerized tomography and magnetic resonance imaging revealed a shadow in the right maxillary sinus, which was expanding into his right orbit, cavernous sinus and middle cranial f ossa, with signs of destruction of the ethmoidal and maxillary walls. His definite diagnosis was RCM, due to the detection of the genera Rhizopus by an open biopsy of his maxillary sinus. He was treated by debridement of the right pansinuses, and an intravascular administration of amphotericin B (AMPH). There was kidney dysfunction as a side effect of the AMPH, but a total dose of 899 mg of AMPH was administered by discontinuation for a month and alternate-day therapy. He did not undergo orbital exenteration; he had normal visual acuity and ocular movement. There was no recurrence 18 months after the treatment.RCM is a fatal disease, and the mortality rate is 38% even given a correct diagnosis and treatment. About 4.5% to 18% of RCM cases have no predisposing factors according to the literature. RCM in normal hosts has a lower mortality rate than in patients with diabetes, but early diagnosis and treatment are still imperative.

Safety of prolonged low-dose alternate-day adrenocortical steroid therapy in Crohn's disease

Safety of prolonged low-dose alternate-day adrenocortical steroid therapy in Crohn's disease

Safety of Prolonged Low-Dose Alternate-Day Adrenocortical Steroid Therapy in Crohnʼs Disease

Safety of Prolonged Low-Dose Alternate-Day Adrenocortical Steroid Therapy in Crohnʼs Disease

Beneficial effects of corticosteroids on ocular myasthenia gravis.

To determine if moderate-or low-dose corticosteroid therapy can reduce the diplopia and frequency of deterioration to generalized disease in ocular myasthenia gravis. Retrospective record review. Two university-based neuro-ophthalmology services. All 32 patients with ocular myasthenia gravis, treated with prednisone, followed up for a minimum of 2 years were included. Patients were treated with 1 or more courses of daily prednisone (highest initial dose, 40-80 mg) gradually withdrawn over 4 to 6 weeks. Subsequently, in 6 patients, 2.5 to 20 mg of prednisone was given on alternate day. Diplopia in the primary position or downgaze diplopia and generalized myasthenia gravis after 2 years of follow-up. Diplopia, which was initially found in the primary position in 29 patients and in the downgaze position in 26 patients, was absent in 21 patients at 2 years. Generalized myasthenia gravis occurred in 3 patients at 2 years. Elevated serum acetylcholine receptor antibody levels and abnormal electromyography findings were not predictive of worsening. No patient experienced a major steroid complication. Moderate-dose daily prednisone for 4 to 6 weeks, followed by low-dose alternate-day therapy as needed, can control the diplopia in patients with ocular myasthenia gravis. The frequency of deterioration to generalized myasthenia gravis at 2 years may be reduced; 9.4% in this study compared with more than 40% previously reported frequency. Corticosteroids may be useful even when ocular motor dysfunction is not normalized.

Effects of different treatment regimens of methylprednisolone on rat diaphragm contractility, immunohistochemistry and biochemistry.

Systemic corticosteroid therapy may affect diaphragm structure and function. We postulated that functional, immunohistochemical and biochemical characteristics of rat diaphragm were less affected by alternate-day methylprednisolone (MP) administration, and more by repeated bursts of MP, in comparison to daily s.c MP. Sixty adult rats were randomized into four groups: saline s.c.; MP continuously (MP-C), 1 mg.kg-1 daily, MP alternate-day therapy (MP-A), 2 mg.kg-1 every other day; or MP in bursts (MP-B), MP 2 mg.kg-1 daily for 2 weeks, saline for 4 weeks, MP 2 mg.kg-1 daily for 2 weeks. The total treatment period was 8 weeks. Contractile properties of isolated diaphragm strips were measured. Antibodies reactive with type I, IIa, IIx and IIb myosin heavy chains were used for immunohistochemical analysis. Biochemical evaluation included markers of fast energy supply, glycogenolytic activity, beta-oxidation capacity and oxidative capacity. The force-frequency curve was depressed in all MP groups. Fibre type I, IIx and IIb cross-sectional area (CSA) decreased in all MP groups. Burst therapy decreased the contribution of type IIb fibres to total diaphragm muscle area. MP-A affected glycogenolytic activity less than MP-C. Burst MP therapy reduced creatine kinase (CK) activity and beta-oxidation capacity compared to MP-C. Oxidative capacity was increased in all MP groups. In conclusion, although the methylprednisolone treatment regimens affected diaphragm muscle morphology and bioenergetic enzyme activities in different ways, force generation decreased in all methylprednisolone treated groups to the same extent.

Growth and height in children after liver transplantation.

To assess the linear growth after liver transplantation, height curves were constructed for 45 children who underwent liver transplantation at the Children's Hospital "La Paz", Madrid, and were followed for more than 2 years. The prednisolone dose was progressively tapered and switched to alternate-day administration at 12 months. Growth was severely impaired during daily steroid therapy but the mean growth rate normalized in the second year and a significant improvement was observed in successive years. Observations over a long period revealed fluctuating growth rates under stable or decreasing doses of prednisolone on alternate-day administration. Beyond the first year, some annual periods of abnormal growth rate occurred in 57% of the children. Marginally better posttransplantation growth was observed in children transplanted for intrahepatic cholestatic diseases. The prednisolone dose did not correlate with growth rate. In the long term, short stature was highly prevalent due to an accumulation of factors: previous disease, daily prednisolone period, inconstant growth rate under alternate-day steroid therapy, and pubertal delay.

Glucocorticoids and growth in asthmatic children.

The effects of asthma and oral and inhaled glucocorticoid therapy on growth in children are reviewed. Previous reports have shown that asthma itself may delay the onset of puberty, an effect which may masquerade as growth suppression. Oral glucocorticoids appear to impair growth; however, lower doses and alternate-day therapy may have less risk of this effect. While a controversial topic, inhaled glucocorticoids in lower doses appear to be associated with a small risk of adverse effects on growth. Minimal data are available for higher doses. Knemometry, a relatively new technique used for measuring small changes in growth, has detected short-term effects with both oral and inhaled glucocorticoids therapy. However, a number of limitations are associated with short-term growth studies. Clinicians should be aware of the potential for growth impairment with glucocorticoid therapy so adequate monitoring can be undertaken and appropriate intervention introduced when deemed necessary.

Deflazacort in Duchenne dystrophy: Study of long‐term effect

A randomized double-blind controlled trial of deflazacort was conducted in 28 Duchenne muscular dystrophy patients either treated with deflazacort 2.0 mg/kg alternate-day therapy or placebo. The deflazacort group showed significant improvement in climbing stairs (P < 0.01), in rising from a chair, Gower's maneuver, and walking (P < 0.0025) after 6 months of treatment. After 1 year, all the above changes remained significantly improved and the MRC index was significantly better (P < 0.05) in the treated group. After 2 years, a significant change was found in the MRC index: higher scores in walking, chair rising (P < 0.02), and grade and time of Gower's maneuver (P < 0.05) were found. The mean time for loss of ambulation for the treated group after we started the trial was 33.2 +/- 9 months; for the placebo group it was 20.5 +/- 11 months (deflazacort vs. placebo group, P < 0.05) [corrected]. Our treated patients lost their ambulation at a median age of 11.8 years vs. 10.5 years in the placebo group. Side effects were mild, consisting of moderate weight gain and slight behavioral changes.

Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone

purpose: To assess the status of the hypothalamic-pituitary-adrenal (HPA) axis in corticosteroid-treated patients whose prednisone dose had been tapered to physiologic doses. patients and methods: The design of the study was a retrospective chart review of 50 consecutive patients receiving 10 mg or less of prednisone daily at a university teaching hospital rheumatology clinic. Patients were given a rapid adrenocorticotropic hormone stimulation test, with cortisol levels obtained at baseline and after intravenous administration of cosyntropin. Charts were reviewed for duration of therapy, highest, current, and total cumulative steroid dose, and average daily steroid dose in each month of the preceding 2 years. results: Current steroid dose was the only significant indicator of HPA axis function. Patients receiving less than 5 mg of prednisone daily had a normal HPA axis response, whereas those receiving 5 mg or more had widely varied responses. Neither the total, the highest prednisone dose, nor the duration of therapy was a significant indicator of HPA axis recovery. conclusions: Spontaneous recovery of the HPA axis is usual for patients who are taking prednisone at daily doses of 5 mg or less. Return of normal HPA axis function can be achieved without alternate-day therapy in patients whose disease allows tapering to daily prednisone doses of 5 mg or less.

Growth rate in children receiving alternate-day corticosteroid treatment after kidney transplantation

A controlled study of growth in children receiving alternate-day versus daily corticosteroid regimens was performed with 60 children and adolescents with kidney grafts. The study started 14 to 27 months after transplantation in patients with normal graft function, after a graft biopsy. Thirty-five patients were available for the growth study; 17 were randomly allocated to receive alternate-day therapy and 18 remained on a daily regimen. The cumulative dose was similar in the two groups, as were bone age and renal function. After 1 year of follow-up, the mean statural growth, expressed as change in SD score, was significantly better in those on the alternate-day regimen (+0.49 +/- 0.42 SD/yr) than in those on the daily regimen (-0.12 +/- 0.53 SD/yr; p less than 0.005). The difference was also significant when prepubertal and pubertal children were analyzed separately. During the second year of the study most children who were receiving daily treatment were given alternate-day therapy; their mean growth velocity increased to +0.29 +/- 0.35 SD/yr (p less than 0.05 vs the first year); children who had been on the alternate-day regimen since the outset of the study continued to have similar positive SD scores (0.52 +/- 0.37 SD/yr). Renal function remained stable throughout the study regardless of corticosteroid regimen, except in the case of one patient undergoing daily therapy who had a rejection crisis. We conclude that in children with a kidney graft a given cumulative dose of corticosteroid has a significantly lesser inhibitory effect on growth velocity when given on alternate days.

Growth rate in children receiving alternate-day corticosteroid treatment after kidney transplantation

A controlled study of growth in children receiving alternate-day versus daily corticosteroid regimens was performed with 60 children and adolescents with kidney grafts. The study started 14 to 27 months after transplantation in patients with normal graft function, after a graft biopsy. Thirty-five patients were available for the growth study; 17 were randomly allocated to receive alternate-day therapy and 18 remained on a daily regimen. The cumulative dose was similar in the two groups, as were bone age and renal function. After 1 year of follow-up, the mean statural growth, expressed as change in SD score, was significantly better in those on the alternate-day regimen (+0.49 +/- 0.42 SD/yr) than in those on the daily regimen (-0.12 +/- 0.53 SD/yr; p less than 0.005). The difference was also significant when prepubertal and pubertal children were analyzed separately. During the second year of the study most children who were receiving daily treatment were given alternate-day therapy; their mean growth velocity increased to +0.29 +/- 0.35 SD/yr (p less than 0.05 vs the first year); children who had been on the alternate-day regimen since the outset of the study continued to have similar positive SD scores (0.52 +/- 0.37 SD/yr). Renal function remained stable throughout the study regardless of corticosteroid regimen, except in the case of one patient undergoing daily therapy who had a rejection crisis. We conclude that in children with a kidney graft a given cumulative dose of corticosteroid has a significantly lesser inhibitory effect on growth velocity when given on alternate days.

A Comparison of Daily and Alternate-Day Prednisone Therapy in the Treatment of Duchenne Muscular Dystrophy

We previously reported the results of a randomized, double-blind 6-month trial of prednisone therapy in which 102 boys aged 5 to 15 years with Duchenne muscular dystrophy received daily doses of 1.5 and 0.75 mg/kg per day and were compared with those receiving placebo. The strength and function in both prednisone-treated groups improved equally and were significantly better than in the placebo group. To compare alternate-day and daily dosing of prednisone with respect to benefits and adverse side effects, the placebo group was started on alternate-day prednisone therapy, and the treatment group regimens were changed to equivalent doses of alternate-day prednisone without breaking the double-blind nature. At the end of 6 months, the group that was changed from daily to alternate-day therapy had declined in strength back to levels observed 12 months previously, at the start of daily therapy. The group in which alternate-day therapy was started showed a significant improvement in strength at 3 months, similar in magnitude to the response of boys treated with daily therapy. However, their strength declined significantly in the subsequent 3 months compared with boys who received daily therapy. The frequency of side effects was not significantly different for alternate-day therapy compared with daily therapy. We conclude that alternate-day prednisone therapy effectively increases strength but does not sustain the improvement to the same extent as daily therapy or mitigate side effects.

Risk-Benefit Assessment of Drugs Used in the Treatment of Inflammatory Bowel Disease

Although the aetiology of inflammatory bowel disease remains elusive, many agents are available for the control of symptoms and inflammation. Knowledge of drug pharmacology, indications and side effects is essential to ensure the best possible clinical care while minimising toxicity and inappropriate use. Sulfasalazine consists of sulfapyridine linked to mesalazine (5-aminosalicylic acid) via an azobond. Its use is indicated in the treatment of mild to moderately active ulcerative colitis and in the prevention of relapse in patients with quiescent disease. Patients with mild to moderate colonic or ileocolonic Crohn's disease also benefit from this drug, as do a proportion of patients with isolated small bowel disease. Sulfasalazine has not been uniformly effective in preventing relapse in Crohn's disease, although many clinicians continue its use in patients who respond initially. A high incidence of side effects which limit therapy include intolerance, hypersensitivity reactions and impairment of male infertility. The newer aminosalicylates offer targeted delivery of mesalazine to the bowel, with fewer side effects. Topical mesalazine has proved extremely effective in patients with distal ulcerative colitis; oral forms are effective in the treatment of mild to moderately active ulcerative colitis and in relapse. Both types appear to be effective in the treatment of Crohn's disease, and possibly in preventing relapse. There is no current clinical advantage of one mesalazine preparation over another, nor is there an indication for their use in sulfasalazine-treated patients who have satisfactory response without adverse effects. Corticosteroids are indicated for more severe disease activity where the aminosalicylates have limited efficacy-specifically to induce remission in patients with severe or refractory ulcerative colitis or Crohn's disease. They should not be used to maintain disease remission or in the prevention of postoperative recurrence. Topical corticosteroids allow their local use in distal colitis with minimal systemic side effects. Long term use is limited by side effects, many of which are dose related, although alternate-day therapy may lessen the incidence. Immunosuppressive agents are beneficial for the treatment of refractory inflammatory bowel disease unresponsive to other medications, and may also facilitate the withdrawal of steroids in refractory patients. Mercaptopurine has an added benefit in the treatment of Crohn's disease fistulae; the role of cyclosporin in bowel disease has not been established and its use cannot currently be recommended. The potential toxicity of immunosuppressive agents warrants careful consideration of their use by both physician and patient. Metronidazole is indicated for the treatment of mild to moderate Crohn's disease, including perineal disease. Common side effects include peripheral neuropathy and nausea.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphotericin B has an elimination half-life suitable for alternate-day therapy

Amphotericin B has an elimination half-life suitable for alternate-day therapy

Comparison of Different Regimens of Prednisone Therapy in Frequently Relapsing Nephrotic Syndrome

The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was administered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received 19 mg/m2/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75d); however, they were significantly shorter with short-term prednisone therapy (median 33d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.

Corticosteroids and adrenal suppression. Characterising and avoiding the problem.

Glucocorticoids are used for a variety of illnesses. One of their major complications is suppression of the hypothalamic-pituitary-adrenal axis, rendering a patient unable to respond to stress. The risk of this suppression may be minimised by the use of short-acting glucocorticoid preparations, administration of the entire daily dose in the early morning, use of topical and intra-articular preparations where appropriate, and the use of alternate-day therapy where appropriate. Most importantly, glucocorticoids should be used cautiously when indicated, and the duration of therapy limited as much as possible.

Human corticotropin-releasing factor plus lysine vasopressin test during glucocorticoid therapy.

1.0 micrograms/kg body wt human corticotropin-releasing factor (hCRF) and 0.005 IU/kg body wt lysine vasopressin (LVP) were administered in a bolus dose to patients receiving daily or alternate-day glucocorticoid therapy. In normal subjects with this hCRF-LVP test, the plasma ACTH increment was significantly greater (approximately 2.5-fold) 15 min after injection than under the CRF test. In patients receiving daily glucocorticoid therapy (greater than 15 mg prednisolone or an equivalent daily dose), the plasma ACTH and cortisol responses to hCRF-LVP were suppressed 2 wk to 1 mo after the beginning of glucocorticoid administration but partially improved at 2-10 mo, and was markedly suppressed several years later. On the other hand, in patients receiving alternate-day glucocorticoid therapy, the plasma ACTH response was normal at 2 wk, normal or higher at 1-3 mo, and normal after 4 mo. A normal plasma cortisol response was observed throughout the test period in patients receiving alternate-day therapy after pulse therapy, whereas plasma cortisol response was gradually improved in patients receiving alternate-day therapy after several months of daily therapy.

The treatment of glomerulonephritis in children.

The results of treatment of glomerulonephritis (GN) in childhood with oral corticosteroids, immunosuppressive drugs, anticoagulants and the newer regimens of pulsed, high-dose intravenous methylprednisolone and plasma exchange are reviewed and compared with the natural history of the untreated condition. Poststreptococcal GN and the nephritis of Schönlein-Henoch purpura need no specific treatment unless extensive glomerular crescents are present. The progression of mesangiocapillary GN can probably be slowed or even reversed with long-term, alternate-day steroid therapy. As in adults, recovery of renal function in GN due to antibody to glomerular basement membrane can be achieved in some patients using plasma exchange, but only those in whom some renal function is still present when treatment is started. In rapidly progressive (extracapillary) GN with crescents, "traditional" therapy with oral steroids, immunosuppressive drugs and anticoagulants reduces renal mortality from 85%-90% to about 50%, while pulsed methylprednisolone and plasma exchange improve the outcome further, mortality falling to about 25%. It is recommended that children with crescentic GN and deteriorating function be treated initially with pulsed methylprednisolone, followed by plasma exchange in those who fail to respond or who deteriorate following temporary response to pulse therapy. Treatment must be given early in the course of the illness if good results are to be obtained.

Erects of alternate-day therapy with prednisolone in idiopathic membranous nephropathy

Erects of alternate-day therapy with prednisolone in idiopathic membranous nephropathy

Growth and Sexual Maturation in Children After Kidney Transplantation

Linear growth and sexual maturation were assessed in 68 long-term pediatric renal allograft recipients (43 boys) receiving dally or alternate-day prednisone therapy. Growth was analyzed both during the prepubertal period and during pubertly. Height at transplantation was >2 SD below the mean in 34.2% of prepubertal children. After the first posttransplant year, 59.2% of the prepubertal children had a normal height increment (>4.8 cm/yr). Onset of pubertly was recorded at a chronologic age of 14.6±1.9 years in boys and 13.3±1.9 years In grils. Height at onset of puberty related to chronologic age was −2.4±1.3 SD. Height velocity during puberty was within normal limits in 62.5% of the children. No significant difference in pubertal growth was detected in patients who had received transplants before and after the onset of puberty. Duration of pubertal development was within normal limits. In grils,menarche was achieved at a mean chronologic age of 15.9 years and bone age 12.9 years. Adult height was attained at an average age of 20.3 years in boys and 18.7 years in girls. Overall, one third of the children attained anadult height >2 SD below the mean. Our data indicate that although poor growth before kidney transplantation has a great inffuence on adult height, the loss of growth potential during pubertal development seems even more important.