Intermittent Prednisone Research Articles

Hepatic Abscess in Crohnʼs Disease: Does Certolizumab Increase the Risk?

Purpose: Hepatic abscess (HA) is more common in Crohn's disease (CD) patients with an incidence of 114-297/100,000 compared to 8-16/100,000 in general population. HA usually form in long standing and active CD. There are no documented cases of HA in patients treated with Certolizumab. We present a case of HA that developed in a CD patient using Certolizumab. A 14 year-old male with history of CD presented with RUQ pain and distension for 3 days. He denied any fever or chills or worsening diarrhea. Clinical course of his CD was significant for recurrent small bowel obstructive symptoms and joint involvement requiring intermittent prednisone use and lack of response to Infliximab. Two months prior, he was started on Certolizumab for persistent symptoms and his last dose was 3 weeks before this visit. In the ER, he had a fever of 102.6°F, mild tachycardia with hypotension. Abdominal exam revealed a firm mass on the right side. WBC was 14500 /mm3, Albumin of 2.1 and LFTs were normal. A CT scan of the abdomen showed a 5.5 × 7.9 × 4.4 cm low attenuation lesion in the inferior right lobe of the liver suspicious for an abscess. Ileum was dilated and thickened with enhancement. Ciprofloxacin and Metronidazole were started. Abscess was aspirated by IR and a drain was placed. The aspirate cultures were positive for streptococcus intermedius. He was discharged after symptomatic improvement. Despite antibiotics and mesalamine, he continued to have abdominal symptoms. A repeat CT scan showed reduction in abscess size but significantly dilated bowel with narrowing in the distal and proximal ileum. Segmental resection and two strictureplasties of the distal ileum were done with resolution of symptoms. The degree of ileal disease on CT and resolution of his symptoms after bowel resection suggested that HA is more likely a complication of CD than a side effect of Certolizumab. Hence, after completing a six week course of antibiotics, he was restarted on Certolizumab. Our case illustrates the importance of considering HA in the differential for sudden worsening of abdominal pain in CD patients. Literature review showed no cases of HA associated with Certolizumab use. Degree of bowel inflammation and the overall clinical picture must be considered before incriminating immunomodulators. Incidence of serious infection has not been shown to increase in the treatment of CD with biologic agents in recent studies. In the Precise II trial, there were reports of 6 patients with abscess formation in the Certolizumab treatment group as opposed to 3 such infections in the placebo group. Two recent meta-analyses did not demonstrate a difference in overall infection between patients treated with biologic agents.

Subperiosteal deep granuloma annulare of the orbital rim

FIGURE 3: Histologic findings A 52-year-old Caucasian male with rheumatoid arthritis presented with a five-week history of a 1 cm left upper lid central mass. He denied antecedent trauma, insect bites, recent viral illness, or other skin lesions or changes. He had no recent fevers, chills, weight loss, or night sweats. His past medical history was significant only for hypertension and rheumatoid arthritis, with a positive Rheumatoid factor and anti-CCP antibodies. His medications included methotrexate, sulfasalazine, intermittent Prednisone, and folate. On exam the mass was non-tender and appeared fixed to the lateral aspect of the left superior orbital rim. There was an additional flesh-colored plaque involving the skin overlying the medial aspect of the superior lid consistent with a xanthoma. He had no associated diplopia, vision changes, or ocular discharge. There was no change in his lid closure.

Treatment of Duchenne muscular dystrophy with cyclosporin A – A randomized, double-blind, placebo controlled trial

Treatment with steroids has shown to slow down progression of muscle weakness in patients with Duchenne muscular dystrophy (DMD) but its use is limited by side effects. In a randomized, multi-centre, double-blind placebo-controlled trial we investigated the effect of cyclosporin A (CSA) in DMD. 153 patients were randomized to receive either placebo or 4mg/kg CSA. After three months both groups received additional treatment with intermittent prednisone (0.75mg/kg, 10 days on/10 days off) for another 12 months. In each group 73 patients were available for intention to treat analysis. Baseline characteristics were comparable in both groups. There was no significant difference between the two groups concerning primary (manual muscle strength according to MRC) and secondary (myometry, loss of ambulation, side effects) outcome measures. Peak CSA values were measured blindly and ranged from 12–658ng/ml (mean 210ng/ml) in the verum group. In conclusion, CSA does not improve muscle strength as a monotherapy and does not improve the efficacy of intermittent prednisone in DMD. Networks of rare diseases such as the BMBF-funded MD-NET facilitate the conduction of meaningful multicentre trials even in rare diseases.

Spontaneous Tumoural Regression in a Patient with t(4;14) Translocation Multiple Myeloma. A Case Report.

INTRODUCTION Despite recent advances, multiple myeloma continues to be an incurable malignancy, with a median overall survival (OS) of 29–62 months. A shortened survival is seen in myeloma patients having a t(4;14) translocation either with standard or high-dose chemotherapy (median OS 26 and 33 months, respectively). CASE REPORT A 60 year-old female was found to have a high ESR (121mm/h) and low hemoglobin (113g/L) in December 2005. Further work-up led to the diagnosis of stage 1A (Durie-Salmon) multiple myeloma on the basis of the following investigations:1.a protein electrophoresis showed IgG 12.2g/L, IgA 23.4g/L and IgM 0.33g/L with an IgA-kappa paraprotein;2.a bone marrow biopsy revealed 20–30% infiltration with atypical plasma cells, kappa restricted; IGH-MMSET fusion transcripts were detected by RT-PCR, consistent with the presence of t(4;14) positive cells in the specimen;3.a metastatic survey showed generalized osteopenia throughout the axial skeleton and multiple subtle permeative lucencies in the proximal humeral diaphyses bilaterally.A 24-hour urine collection showed 0.05g/L proteinuria with no Bence-Jones proteins detected. Her peripheral blood counts were as follows: hemoglobin 118g/L (MCV 91fL), platelets 275 bil/L and white blood cells 6.6 bil/L with 3.9 neutrophils and 1.8 lymphocytes. Her electrolytes and calcium were within normal limits but she had a slightly elevated creatinine at 107umol/L (normal <99). Her b2-microglobulin, C-reactive protein and albumin were all normal at 219nmol/L (normal ≤219), 4mg/L (normal ≤12) and 36g/L (36–50) respectively. No active therapy was recommended apart from monthly PAMIDRONATE for permeative lucencies. Her past medical history was significant for an IgA cryoglobulinemia diagnosed in 1985 when she presented with arthritis, purpura and Raynaud's phenomenon. Her cryocrit has been ranging from 0–25% over the years; most recently still at 5%. She did not require any treatment until 1989 when she was started on low dose-steroids. Her flares consist mainly of lower limbs arthritis and purpura and they have been treated with intermittent PREDNISONE 5–7.5mg per day. A progressive drop in her M-protein has been documented since June 2006 with her most recent protein electrophoresis revealing no paraprotein, quantitative IgG is 7.7g/L, IgA 2.23g/L and IgM 0.63g/L. A bone marrow biopsy has shown less than 5% plasma cells. Her peripheral blood counts and biochemistry remained within normal limits and her skeletal survey is unchanged. A 24-hour urine collection shows no significant proteinuria (0.07g/L). Her free light chains assay revealed kappa 13.8mg/L and lambda 11.0mg/L with a ratio kappa/lambda 1.3.CONCLUSIONS We have documented tumoural regression in a patient with IgA-kappa multiple myeloma and t(4;14) only receiving intermittent low dose PREDNISONE and monthly PAMIDRONATE. This exceptional phenomenon has been well described with other malignancies such as testicular germ cell tumours, hepatocellular carcinomas and neuroblastomas; however, to the best of our knowledge, only in 2 cases of multiple myeloma. The unusual nature of this finding is highlighted by the presence of the t(4;14) in the plasma cells, known to be associated with more aggressive disease. The underlying mechanisms, speculated to be immunological for most of the other cancers, remain completely unknown in this case.

Infliximab in Pediatric Crohn Disease Patients With Enterovesicular Fistulas

Infliximab in Pediatric Crohn Disease Patients With Enterovesicular Fistulas

Renal Allograft Histopathology in Dog Leukocyte Antigen Mismatched Dogs After Renal Transplantation

To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. Prospective study. Ten healthy adult mongrel dogs. Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.

Report on the 124th ENMC International Workshop. Treatment of Duchenne muscular dystrophy; defining the gold standards of management in the use of corticosteroids 2–4 April 2004, Naarden, The Netherlands

Thirty-two participants representing parents, funding agencies and clinicians involved in the care of children with Duchenne Muscular Dystrophy (DMD) from Belgium, Canada, Denmark, Finland, France, Germany, Italy, the Netherlands, Spain, Sweden, the UK and the USA met in Naarden on 2–4th April 2004. The meeting was held under the auspices of the ENMC Clinical Trials Network, and with the additional support of the United Parent Project. The aims of the workshop were to define the need for clinical trials in DMD and develop a protocol for such trials, relating primarily to the use of steroids (prednisolone, prednisone and deflazacort) in DMD. The first part of the meeting summarised the current state of practice on the use of steroids in DMD. Elizabeth Vroom (Netherlands) and Pat Furlong (USA) presented the views of parents surveyed by questionnaire by the United Parent Project. A major worry for parents was the lack of use of steroids at all in some countries, the multiplicity of steroid regimes used and the problems of getting firm information about which type of steroid or which regime for using steroids was best. This was reflected in the variation in practice amongst the participants at the Workshop, who between them used at least seven different regimes for giving steroids, and some did not use steroids at all. Adnan Manzur (UK), co-author of the Cochrane report on the use of glucocorticosteroids in DMD described the major findings of this systematic review [1]. Only five randomised controlled trials of the use of steroids in DMD were published in sufficient detail to be able to be included in the review. These trials did, however, present evidence that use of daily prednisolone (0.75 mg/kg per day) or deflazacort (0.9 mg/kg per day) increased strength in DMD. Robert Griggs, Richard Moxley (USA) and Doug Biggar (Canada) were able to confirm that long-term follow up of cohorts of patients treated under one or other of these regimes and who mostly continued using steroids beyond the loss of independent ambulation shows that this increase in strength is mirrored by improvement in function (with age at loss of ambulation in the mid teens, preservation of respiratory function, lack of need for scoliosis surgery and possibly preservation of cardiac function) [2–4]. With longterm use of steroids, the per kilogram dose of corticosteroid tended to reduce with time. In some cases, this was in response to side effects such as weight gain or behaviour changes, but in the majority represented a tendency not to keep up strictly with change in weight over time. Many different regimes for giving steroids in DMD have been suggested as a way to reduce the risk of the well-known side effects associated with the long-term use of daily steroids. The dose of 0.75 mg/kg per day was shown to be Neuromuscular Disorders 14 (2004) 526–534 www.elsevier.com/locate/nmd

Intermittent prednisone adequate for arthritis and lupus?

Intermittent prednisone adequate for arthritis and lupus?

Treatment of the idiopathic nephrotic syndrome: regimens and outcomes in children and adults.

This review compares the biopsy patterns, complications, responses to therapy, and long-term outcomes of idiopathic NS in children and adults. On first examination, distinctions between the pediatric and adult diseases seem more quantitative than absolute. However, underlying determinants of outcome, including immunocompetence, growth, maturity, and senescence, can present very different challenges for pediatricians and internists. The major biopsy patterns in pediatric NS include MCD, FSGS, and DMP. MCD is overwhelmingly the most frequent and most steroid-responsive of the three but commonly presents problems of massive edema, serious bacterial infections, and multiple relapses. Because of the prompt response of pediatric MCD to corticosteroids, steroid resistance in children has generally been defined as persistence of proteinuria after 1 month of daily followed by 1 month of intermittent prednisone administration. By this criterion, nephrotic FSGS is usually steroid-resistant and, if not controlled by more aggressive therapy, typically progresses to ESRD. DMP is commonly steroid-resistant but may slowly resolve. It is not clear to what extent remissions of DMP represent a delayed response to steroids or would have occurred without treatment. Biopsies showing a few globally obsolescent glomeruli or mild mesangial hypercellularity may be associated with greater difficulty in management but have been included in the broad category of MCD. Moreover, evolution of patterns in serial biopsies, variable steroid-responsiveness of FSGS and DMP, and progression of some cases of MCD to ESRD suggest common features in the three major categories. Among adults with idiopathic NS, FSGS is the most frequent biopsy pattern, followed by MN (which is rare in children) and then by MCD. In contrast to its pediatric counterpart, MCD in adults is less regularly and more slowly responsive to corticosteroids and in the elderly is more commonly associated with hypertension and renal failure. MCD in adults is less likely to relapse once remission is achieved. Adults with FSGS present less commonly with severe edema than do children with this lesion. Although children and adults with FSGS present similar challenges of resistance to therapy and loss of renal function, the more aggressive oral steroid regimens used by internists preclude strict comparisons between pediatric and adult series. There is insufficient information to support a systematic analysis of DMP in adults. Cytotoxic agents and cyclosporine have been used with varying success in children and adults with difficult cases of NS. In MCD, an alkylating agent can increase the likelihood and duration of remission. Cyclosporine can also improve control in MCD, but continued treatment is often needed to maintain remission. Significant control of steroid-resistant FSGS has not been achieved with limited courses of an alkylating agent or cyclosporine. Longer courses of either of these immunosuppressants, especially when combined with intermittent steroid administration, can produce more complete and/or more sustained remissions. However, cyclosporine nephrotoxicity is more severe in FSGS than in MCD and in steroid-resistant than in steroid-dependent NS, regardless of biopsy pattern. A protocol combining iv M-P pulses, alternate-day prednisone, and an alkylating agent in steroid-resistant pediatric FSGS has produced the highest percentage of sustained remissions with normal renal function, of all reported regimens. Controlled trials of this and other combined drug protocols are needed in children and adults.

Teratogenicity and carcinogenicity in a twin exposed in utero to cyclophosphamide

A 29-year-old pregnant woman diagnosed with acute lymphocytic leukemia maintained remission with daily cyclophosphamide and intermittent prednisone treatment. She delivered a male twin with multiple congenital abnormalities who was diagnosed with papillary thyroid cancer at 11 years of age and stage III neuroblastoma at 14 years of age. The female twin was unaffected and has exhibited normal development to date. First trimester exposure to cyclophosphamide has been associated with major malformations. Metabolites of cyclophosphamide have been demonstrated to be teratogens and carcinogens in animals. Differences in placental or fetal hepatic cytochrome P-450 may account for the variability in response between the twins. In addition, disparity between the twins may be the result of differences in metabolite inactivating enzymes present either in fetal liver or placenta. The risk of second malignancies caused by alkylating agents such as cyclophosphamide has been well documented in adults and children but to the best of our knowledge this is the first description of transplacental second cancer.

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.

Gonadal function in women treated with cyclophosphamide for childhood nephrotic syndrome: a long-term follow-up study

The gonadal function of 18 women who were treated for childhood nephrotic syndrome at a mean age of 10.7 years with cyclophosphamide (mean dosage, 28 gm; mean duration of therapy, 354 days) was evaluated at a mean of 14.5 years after treatment by means of detailed questionnaires. Menstrual patterns were normal in all except two, who were still receiving intermittent prednisone therapy. Eight healthy children had been born to five mothers. Compared with males, there is little current evidence of gonadal toxicity in this patient group. Further follow-up is required to determine whether these women will undergo premature menopause.

Prednisone pulse therapy for refractory myeloma

The utility of vindesine and a frequent prednisone schedule was evaluated in 70 patients with refractory myeloma. No patient responded to vindesine alone, but about one-fourth achieved significant tumor reductions from intermittent high-dose prednisone, either alone or in combination with vindesine. Forty-seven percent responded when prednisone pulses were combined with vincristine and doxorubicin, providing the best results yet achieved in our patients with refractory myeloma. In responding patients, remissions were of excellent quality and survival was prolonged significantly. These results supported the utility of a more frequent corticosteroid schedule with increased doxorubicin dose in patients with advanced and resistant multiple myeloma.

Prognosis for nonoperative management of small-bowel obstruction in Crohn's disease.

Small-bowel obstruction has been the most common indication for surgical intervention in Crohn's disease. If, however, obstruction relents without surgery, new programs of management may reduce or eliminate the need for resection. Over 7 years, 25 of 26 patients were relieved of an index episode of ileal obstruction--in most cases aided by a small-bowel tube and intravenous ACTH. They were then maintained on medical therapy, sulfasalazine (SASZ) alone in seven, SASZ and intermittent prednisone in 18, and then 6-mercaptopurine with or without SASZ in 14 of those 18. Seven patients have had no recurrence of obstruction after an average follow-up of 52 months. Recurrent obstruction occurred 52 times in 18 patients over the next 16-106 months; in all the obstruction was again relieved nonoperatively. Twelve patients underwent elective surgery, for recurrent obstruction in nine. Eight months seemed to offer a useful cutoff criterion for the likelihood of recurrence. When recurrence of obstruction took place within 8 months, surgery was ultimately required in six of seven patients. In contrast, patients who weathered the first 8 months without obstruction did well; only three of 11 ultimately required resection. Of 18 patients without recurrent obstruction for 8 months, only five were eventually operated upon, two for other indications; in 11 of the 13 patients who underwent no operation, the quality of life was excellent or good. We conclude that if the initial episode of small-bowel obstruction can be reversed, subsequent maintenance therapy including SASZ, and/or 6-mercaptopurine with an intermittent liquid diet in some patients eliminates or postpones the need for resection without compromise of the quality of life.

Delayed pressure urticaria

Delayed pressure urticaria (DPU) is a poorly understood syndrome. We describe 17 patients with DPU. Chronic urticaria was present in 94%. All had negative challenges for immediate dermographism and cold urticaria. DPU was induced with a pressure challenge on the shoulder of 15 pounds for 15 min. Average onset of pressure lesions after challenge was 6.5. Lesions were painful, not pruritic, peaked at 9 hr, and disappeared by 24 to 48 hr. Fever, chills, and/or arthralgias occurred in 78%. Positive laboratory abnormalities included leukocytosis in 20% and elevated erythrocyte sedimentation rate in 37.5%. Skin biopsies of lesions showed perivascular round cell infiltrates and negative immunofluorescence. Urticaria responded to antihistamines, but not aspirin, in 100% of patients, while pressure lesions improved with nonsteroidal anti-inflammatory drugs (NSAID), but not antihistamines, in 80% of patients. Both urticaria and DPU were controlled with prednisone, which was necessary in 87.5% of patients A severe nonremitting course was noted in 7%, 40% had a moderate remitting course requiring intermittent prednisone, and 53% had a mild remitting disease requiring no medication or antihistamines and/or NSAID only. We conclude that DPU is more common than previously appreciated and likely involves mediators other than histamine, possibly the prostaglandin system.

ALTERNATE-DAY VERSUS INTERMITTENT PREDNISONE IN FREQUENTLY RELAPSING NEPHROTIC SYNDROME: A Report of "Arbeitsgemeinschaft fur Pädiatrische Nephrologie"

23 children with frequently relapsing minimal-change nephrotic syndrome were treated with alternate-day prednisone (35 mg/m 2/48 h) and 25 other patients were treated with intermittent prednisone (40 mg/m 2 on three consecutive days out of seven) for six months. This was followed by six months without any maintenance steroid treatment except when relapse required a short period of prednisone therapy until remission. The number of relapsers was significantly lower on alternate-day than on intermittent treatment. In the alternate-day group, the number of relapsers and the rate of relapse was significantly less before treatment withdrawal; in the intermittent group, only the number of relapsers was reduced. An alternate-day regimen is therefore preferable to the intermittent regimen in the interrupted steroid treatment of children with nephrotic syndrome.

Two-hour Adrenocorticotropic Hormone Test: Accuracy in the Evaluation of the Hypothalamic- Pituitary-Adrenocortical Axis

Summary: The inter- and intraindividual variations of response to an iv bolus of tetracosactide (0.25 mg/1.73 m2) were studied, and a definitive diagnostic 2-hr test was established. The test was given to 179 subjects: hypopituitary, prednisone-treated ne-phrotics, patients with the autoimmune polyendocrinopathy-candidiasis syndrome (APECS), and reference subjects. It was repeated in 62 cases and the total of 84 test pairs was analyzed. The test was started either at 8–9 AM or at 10–11 AM, 2 hr after the injection of insulin for an insulin test. Thirty subjects had both the ACTH test and the insulin-ACTH test. Capillary blood samples for fluorometric determination of plasma cortisol were taken 1, 2, and 3 hr after the injection.The distributions of the basal and stimulated levels were positively skewed, and log transformation of the data gave clearly more appropriate statistics. In most subjects the cortisol level was highest 2 hr after the injection. There was no significant difference in the response to ACTH whether it was given alone or in the insulin-ACTH test. All the poststimulation cortisol levels showed a positive interindividual correlation with the basal levels, and all the increments a negative interindividual correlation with the basal levels.In repeated tests, the intraindividual variation in the responses was directly correlated with the level of the response, and this correlation could be removed by dividing the intrapair difference in the values of the parameters by the sum of the values for percentage of intrapair difference (PIPD). The SD of the distribution of PIPDs was used for an index of precision. The 2-hr cortisol level was substantially more precise than either the basal level or the increment. In analysis of correlation between PIPDs, variation of the 2-hr level showed no significant dependence on the variation of the basal level, but the variation of the 2-hr increment was highly dependent on the variations of both the basal level and the 2-hr level. Thus the 2-hr plasma cortisol level is the best single index of the response. A better definition of normal result is given by a reference area on a plot of 2-hr level versus basal level (Fig. 2.).Of 31 tests given to hypopituitary subjects with deficient cortisol responses to insulin, all but 7 gave subnormal basal and/ or 2-hr levels. In 8 the increment was also subnormal. In the nephrotic subjects, all but one of 36 tests given at the end of continuous prednisone medication gave subnormal basal and/or 2-hr levels; the increment was subnormal in 26. At the end of the following period of intermittent prednisone, 12/36 tests gave normal results and none failed to elicit a response. The increment remained subnormal in 6 despite normal basal levels.A high normal response to ACTH was constantly associated with a normal response to insulin, and was thus indicative of normal ACTH secretion. In the reference subjects, there was a highly significant correlation between the responses to insulin and ACTH. The mean ± SD of PIPDs between these responses was −9.2 ± 13.2%. Of the APECS patients, seven with incipient adrenocortical failure had a normal increment despite subnormal basal and stimulated levels. Thus the ACTH test did not differentiate this state from ACTH deficiency.Speculation: When the criteria for a normal finding in the 2-hr iv ACTH test have been carefully established, this test will serve as a definitive procedure for the diagnosis and follow-up of states associated with ACTH deficiency, as well as in primary diseases of the adrenal cortex. Like the other ACTH tests, however, it will not differentiate with certainty between primary and secondary adrenocortical failure.

Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL)

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

Sequential Therapy Compared With Combination Therapy in Multiple Myeloma

A timed sequential chemotherapeutic regimen for multiple myeloma was desinged, based on plasma cell kinetics. A randomized study comparing this regimen with the combination of intermittent melphalan and prednisone was started after an adequate pilot study. Studies with tritiated thymidine labeling and mitotic indexes were performed on patients treated with sequential therapy. Of 13 patients treated with the combination therapy, the responses were as follows: two, objective improvement; nine, subjective improvement; and two, no responses. Of nine patients treated with sequential therapy, the responses in six patients who could have evaluations were as follows: one, objective improvement; two, subjective improvement; one, no response; one, with progressive disease; and one, cardiac death. The two studies showed differences in pertubation of cell kinetics of myeloma that may be related to exponential growth and immunoblobulin types.