Conventional Steroid Research Articles

Cohort Study of Advanced IgA Nephropathy: Efficacy and Limitations of Corticosteroids with Tonsillectomy

Background: Elevated serum creatinine is associated with poor outcome in IgA nephropathy (IgAN). The efficacy and limitations of corticosteroids in advanced IgAN (Cr ≧1.5 mg/dl), however, remains controversial. Methods: We retrospectively investigated 70 patients with advanced IgAN (Cr ≧1.5 mg/dl) classified into three groups according to their treatment regimens, that is, steroid pulse with tonsillectomy, conventional steroid, and supportive therapy. We evaluated the three groups to elucidate predictors for the endpoints ESRF and doubled serum creatinine from baseline. Results: Steroid pulse with tonsillectomy, conventional steroid and supportive therapy were performed in 30, 25 and 15 patients, respectively. During the mean follow-up period of 70.3 (12–137) months, 41.4% of patients reached ESRF (13.3 vs. 56.0 vs. 73.3%, p < 0.001) and 45.7% doubled serum creatinine from baseline (16.7 vs. 64.0 vs. 73.3%, p < 0.001). The incidence of ESRF in the patients treated by steroid pulse with tonsillectomy was significantly lower than the incidences in the patients treated by conventional steroid and supportive therapy at a baseline creatinine level of 1.5–2 mg/dl, but no statistical difference was observed at a level of >2 mg/dl. The Kaplan-Meier estimated probability of renal survival without ESRF was 89.2, 74.1 and 72.2% at 5 years and 82.8, 51.0 and 45.1% at 8 years, respectively (p = 0.017). The predictors for ESRF, identified in a Cox proportional hazards model, were baseline serum creatinine (p < 0.001) and interstitial infiltrate (p = 0.003). Steroid pulse with tonsillectomy also had a protective effect on the risk of reaching ESRF (p = 0.013). By target cross-stratification, the patients with baseline creatinine of 1.5–2 mg/dl who underwent steroid pulse with tonsillectomy showed a better renal survival rate than the others (p < 0.001). Conclusion: Steroid pulse therapy combined with tonsillectomy may be more effective than conventional steroid therapy in patients with a baseline creatinine level of ≤2 mg/dl.

Consensus and controversy in the management of pediatric Crohn disease: an international survey.

Treatment options for patients with Crohn disease (CD) have expanded, but the use of some of these options in pediatric patients remains controversial. The authors evaluate current trends in treatment and areas of consensus or controversy. An international survey of certified pediatric gastroenterologists was conducted using an e-mail questionnaire in an attempt to evaluate management of active Crohn disease, attitudes toward four types of therapy, and prevalence of testing for osteopenia and 6-thioguanine levels. One hundred sixty-seven physicians from the United States, Canada, Western Europe, and Israel were included. The majority of North American physicians (71%) prefer to use conventional steroids and azathioprine (AZA) before nutritional therapy or budesonide for patients with mild to moderately active disease, versus 21% of Western Europeans (P < 0.001). Western Europeans prefer nutritional therapy followed by budesonide or steroids for those with mild or moderate disease. Only 4% of North American gastroenterologists use nutritional therapy frequently versus 62% of their Western European colleagues (P < 0.001). Infliximab was thought to be effective for steroid-unresponsive disease by almost all physicians surveyed, although its efficacy as a maintenance therapy was rated higher by North American physicians than by their Western European and Israeli colleagues (P < 0.01). Bone mineral density is routinely evaluated by about 45% of physicians in Western Europe and North America. Attitudes toward current therapies vary significantly by region, with North Americans strongly favoring corticosteroids followed by immunomodulatory therapy, and Western Europeans favoring nutritional therapy or budesonide and the avoidance of conventional corticosteroids.

Efficacy and safety of repeated intrathecal triamcinolone acetonide application in progressive multiple sclerosis patients

Available immunomodulatory and conventional steroid treatment options for patients with progressive multiple sclerosis (MS) only provide limited symptomatic benefit. We performed an open trial on the short-term and long-term efficacy and safety of repeated intrathecal application of the sustained release steroid triamcinolone acetonide (TCA) in 36 progressive MS patients. Six TCA administrations, performed every third day, reduced the EDSS score (initial: 5.6±0.93 [mean±S.D.]; end: 4.9±1.0; p<0.001) and increased the walking distance (WD) (initial: 294±314 m; end: 604±540 m; p<0.001). Twenty MS patients continued intrathecal TCA treatment with one TCA injection performed with a variable frequency ranging from 6 to 12 weeks. Both EDSS and walking distance remained stable in these patients until the end of the follow-up investigation period. No serious side effects occurred. We conclude that repeated intrathecal TCA injection provides substantial benefit for progressive MS patients with predominantly spinal symptoms.

Idiopathic catastrophic epileptic encephalopathy presenting with acute onset intractable status

Purpose: To delineate a catastrophic childhood epileptic syndrome of unknown cause presenting with persistent intractable multifocal status. Methods: Case note review. Results: Six children aged 5 months to 6 years presented with focal seizures that progressed within days to intractable multifocal seizures with or without secondary generalisation, which recurred every few minutes and persisted for weeks. One developed impaired consciousness shortly before seizures started. The two younger children showed mild developmental delay before onset but the others were normal. The seizures were unresponsive to all conventional anticonvulsants, steroids or pyridoxine and could only be controlled with doses of thiopentone sufficient to cause electrical suppression. MRI scans were initially normal but later showed focal cortical swelling followed by generalised atrophy. Two developed hepatomegaly, with a normal liver biopsy in one and steatosis in the other. No cause has been found even after neuropathological investigation. Three have died, two within 3 months of onset, while the three survivors have very severe neurological impairment and continued seizures. Conclusion: The similarity of the clinical features suggests that this is a consistent clinical syndrome.

The effects of high dose methylprednisolone on apoptosis in children with acute lymphoblastic leukemia.

Rapid leukemic cell kill at initial diagnosis of patients with acute lymphoblastic leukemia (ALL) has been shown to be associated with a favorable outcome. The aim of the present study was to investigate the effect of high dose methylprednisolone (HDMP) on in vivo blast cell apoptosis in children with ALL. Annexin V-binding and Fas (CD95), Fas ligand (FasL; CD95L), and Bcl-2 expression in PB blasts were determined in newly diagnosed children with ALL before and 4, 24, 96 h after initiation of HDMP treatment (n=20) or conventional dose steroids (CDS) (n=10) as the control group. A decrease in absolute blast count (from 40.8 x 09 to 21.4 x 109/l) associated with an increase in apoptosis (14.2 to 26.9%) (P < 0.05) was detected 4 h after initiation of HDMP. A significant increase in Fas and FasL expression was detected 96 h after HDMP. There was no significant change in apoptosis, Fas and FasL expression from baseline in the control group treated with CDS. The changes in Bcl-2 expression after treatment was not significant in both groups. The results of this preliminary study have shown that HDMP treatment was effective in inducing immediate (within 4 h) blast cell apoptosis. The contribution of Fas/FasL interaction in the rapid component of cell kill remains to be determined, as the increase in the expression of these molecules was evident later.

The Dose Related Effect of Steroids on Blast Reduction Rate and Event Free Survival in Children with Acute Lymphoblastic Leukemia

We examined the effect of high-dose methylprednisolone (HDMP) on blast reduction rate and compared it to conventional dose steroid treatment, administered during the first 7+ days of the induction remission period in patients with acute lymphoblastic leukemia (ALL). In our previous randomized study, the event free survival (EFS) was found to be higher in patients treated with HDMP (Group B) than in patients treated with a conventional dose of steroids (Group A). We used the chemotherapy protocol for ALL patients according to the St Jude Total XI study group. Medical records of all 194 patients who achieved complete remission were reviewed to determine the absolute blast count (ABC) in peripheral blood smears from day 0 of treatment until day 8. A target response of 1000 blast/mm 3 was employed. The time in which ABC remained ≥ 1000/mm 3 and the EFS rates were assessed in group A (n =44) and B (n =51) of high risk patients. Group A and B patients were branched to chemotherapy schedules (A1, B1: steroid+vincristine+daunorubicine+intrathecal+ 3 doses l -asparaginase; A2, B2: steroid+vincristine+daunorubicine+intrathecal; A3, B3: only steroid monotherapy). Number of patients from whom the ABC remained ≥ 1000/mm 3 during all 7 days of induction treatment and the median number of days for blasts to reach the target level were significantly lower in group B1 than A1 (p <0.05), concordantly the 8-year EFS was higher in group B1 (p =0.01). In comparison of the subgroups, results of A2 and A3 were worse than of group B2 and B3. These findings strongly suggest that the effects of HDMP on blast cytoreduction and EFS are more potent than conventional dose steroids.

Delayed optic nerve decompression for indirect optic nerve injury.

To test the efficacy of delayed optic nerve decompression in traumatic optic nerve injury. Critical analysis of Proforma-based, prospectively accrued data of all cases with injury to surgery interval of greater than 2 weeks. Thirty-five cases with a median injury to surgery interval of 56 days (range, 16-374 d). Surgical decompression was undertaken only in cases that continued to have poor vision after treatment with steroids in conventional doses (1 mg/kg prednisolone). Pre- and postoperative visual acuity measurements were converted to the logMAR scale of visual acuity and the percentage of visual improvement was calculated. Surgery was universally unrewarding in all 9 cases with persistent and complete blindness of greater than 2 weeks and no response to steroid therapy. Of the cases with some residual vision, 20 of 26 cases improved (mean percentage improvement, 41.0 +/- 5.7%). Cases were categorized on the basis of the injury to surgery interval into groups of 2 weeks to 2 months, 2 months to 4 months, and greater than 4 months. No significant difference was demonstrated in the probability or quantum of improvement in these groups (P =.97). Optic nerve decompression remains useful as a salvage procedure for conventional dose steroid failed cases of traumatic optic neuropathy. In cases that are not completely blind, vision can be improved even when surgery is undertaken a few months after the injury.

Treatment of relapsing polychondritis

Relapsing polychondritis (RP) manifests as an inflammation of cartilaginous structures throughout the body. Since RP affects cartilage tissues and proteoglycan-rich structures, symptoms appear in the ear, nose, eye, joints, and respiratory system. Otolaryngologists are frequently involved in RP's initial diagnosis, since it is likely to affect the head and neck regions. The etiology of RP remains unknown and it is relatively uncommon, so appropriate treatment remains to be determined. We studied the clinical course and treatment response. We studied clinical courses in 12 cases of RP treated at our hospital in the 11 years from 1991 to 2001. In 11 of the 12 cases, conventional steroid therapy was implemented. Five required steroid pulse therapy, and 7 immunosuppressive drugs to control the disease. Strong initial therapy such as steroid pulse therapy plus immunosuppressive drugs suppressed inflammation and decreased its relapse in severe RP patients. One patient could be controlled only with nonsteroidal antiinflammatory drugs. Side effects such as cataracts and diabetes from steroid therapy or pancytopenia from Dapson were found in some patients. All 12 are alive at present. Six were subsequently released from steroid therapy. Anti-type II collagen antibody was not useful as an indicator for treatment but helpful as one of a complementary factors for diagnosis. Manifestations of RP are sometimes self-limited, but in most cases, inflammation is recurrent, gradually worsening and finally becoming life-threatening. It is difficult to determine the severity of RP and choose appropriate treatment in its initial stage. Because severe RP cannot be controlled with conventional steroid therapy, strong therapy is indicated in initial treatment if patients have serious symptoms.

Gemcitabine and docetaxel every 2 weeks in advanced non-small cell lung cancer: a phase II study of the Gruppo Oncologico Italia Meridionale

Introduction: Platinum-based chemotherapy is the gold standard in advanced non-small cell lung cancer (NSCLC), although with relevant toxic effects. Both docetaxel (DCT) and gemcitabine (GEM) have shown activity as single agent in advanced NSCLC with a different toxicity profile and a lack of cross-resistance. Materials and methods: From April 2000 to May 2001, 47 consecutive patients were enrolled in a multicenter phase II trial. Main inclusion criteria included untreated patients with histologically confirmed NSCLC, age⩽70 years, stage IIIB/IV, Eastern Cooperative Oncology Group performance status (PS) 0–2, measurable disease, adequate hematologic, cardiac, hepatic and renal functions, and written informed consent. Treatment schedule consisted of DCT at the dosage of 50 mg/m 2 with conventional steroid premedication and GEM at the dosage of 2000 mg/m 2. Both drugs were administered every 2 weeks without prophylactic use of growth factors. Results: Enrolled patients included 40 males and seven females with a median age of 65 years, and a median PS 1. There were 26 squamous carcinomas, 13 adenocarcinomas, and eight others, 13 stage IIIB and 34 stage IV. A total of 371 cycles were administered. Overall 18 partial responses were observed (38.3%); 14 patients were considered as stable disease and 13 showed progressive disease. Two treatment-not related deaths occurred before the first disease evaluation was performed. Median duration of response was 6 months (range 2–10) and median duration of survival was 10.5 months (range 1–25+). One year survival probability was 38% (95% CI 25–54%). In a statistical analysis responses were independent to histology or stage. Grade 3–4 toxicity, according NCI criteria, was mild with neutropenia in eight patients (17%), anemia in two patients (4%). Asthenia affected two patients and mucositis occurred in one patient. Conclusions: In our experience the biweekly combination of DCT and GEM is active and well tolerated and can be administered without G-CSF primary prophylaxis reducing treatment costs. It should be considered as a promising alternative to more toxic platinum-based regimens.

Review article: treatment of mild to moderate ulcerative colitis and pouchitis.

The meta-analyses of published trials have shown topical therapy with 5-aminosalicylic acid (5-ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5-ASA therapy. An alternative to 5-ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5-ASA or new steroids should be treated with oral steroids. Azathioprine or 6-mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried-out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.

PULSED HIGH-DOSE DEXAMETHASONE THERAPY IN CHILDREN WITH CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 2 10 9 /L, while mean platelet count at day 4 was 158 2 10 9 /L. At the end of 6 cycles 3 patients maintained a platelet count of >150 2 10 9 /L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.

The Desktop Guide to Complementary and Alternative Medicine: an Evidence-based Approach

The past twenty years have seen a remarkable paradox in popular attitudes to medicine. While regulations for licensing drugs and appraising doctors have become increasingly stringent, more and more patients have turned to untested therapies supplied by unregulated practitioners. An increased demand for evidence-based medicine has been paralleled by a steady rise in therapies based on tradition and opinion. This divergence cannot be explained by two populations of patients: the evidence is that the same patients use both approaches. Patients considering any new treatment want to know if it works and if it is safe, but seem to have two different sets of rules. The divide is both linguistic and philosophical: terms such as ‘natural’, ‘traditional’ and ‘holistic’ are difficult to compare with confidence intervals and P values. So what happens if we judge both types of medicine by the same standards? Does complementary and alternative medicine (CAM) have a valid place alongside orthodox medicine? The Desktop Guide, originating edited from the University of Exeter Department of Complementary Medicine, takes a serious look at the evidence for efficacy and safety of CAM. The opening section on investigative methods sets the tone of clarity, transparency and depth that characterize the book. Section 2, which summarizes diagnostic methods from bioresonance to the Vega-test, is informative and helpful. For each technique, published studies are systematically reviewed with verdicts ranging from ‘the method is not valid’ (iridology), through ‘its value as a diagnostic tool seems limited’ (Kirlian photography), to ‘some but not all diagnostic methods are valid’ (chiropractic). Section 3 takes us through therapies from acupuncture to yoga, and section 4 herbal and non-herbal medicine from aloe vera to yohimbe. Information including constituents, rationale, pharmacological properties, clinical evidence, risks, and quality issues is clearly presented and well referenced. Phytoestrogen comes out rather well (reducing bone resorption in postmenopausal women) as does garlic, which at least in high dose reduces the frequency of tick bites. Red clover is safe but ineffective while shark cartilage is probably not even safe. A valuable series of tables summarizes herbs with adverse effects and interactions with antidiabetic and cardiac drugs, anticoagulants and oral contraceptives. Section 5 considers 38 conditions commonly treated with CAM (other conditions are indexed and discussed under individual therapies). The conclusions regarding atopic eczema—that conventional steroid treatments cannot be matched by CAM, and that therapies with the most promising evidence for efficacy are those with a psychological component—confirm my own impressions from the skin clinic. For migraine, biofeedback and possibly feverfew are effective and safer than conventional drug therapy. Similarly gingko is promising for tinnitus. Acupuncture and ginger are helpful for motion sickness and postoperative nausea. For many therapies there is insufficient evidence to recommend them, but this deficiency must not be confused with lack of effect. What about the wisdom of centuries of sages? Surely years of experience reflected in ‘expert opinion’ must be valuable? The authors actually tested this hypothesis, by comparing CAM recommendations with evidence from their systematic reviews. Not only was there lack of agreement between seven general CAM textbooks, but in some cases a therapy was recommended when there was conclusive trial evidence that it was ineffective or even contraindicated. The final section deals with general topics including legal, ethical and safety issues. Users of CAMs perceive them to be safer than conventional treatments, but must understand that ‘natural’ is not necessarily safe, unregulated preparations may be impure, and CAM providers sometimes delay or hinder access to potentially life-saving treatment if they cannot diagnose medical disorders. These concerns could all be addressed by better training and regulation of CAM providers. The bottom line is that CAM is amenable to rigorous testing and some forms of CAM are supported by evidence and do have a role in modern healthcare. The information in this book is balanced, authoritative and accessible. The enclosure of a CD-rom, with Medline links to all references as well as the whole text of the book, makes it astonishingly good value. The index might be improved in the next edition, but terms not listed (e.g. acne and psoriasis) can easily be found by searching the disc. This is a work which I will refer to every time a patient asks me about an alternative treatment.

Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy

We conducted a retrospective investigation of renal outcome in 329 patients with immunoglobulin A (IgA) nephropathy with an observation period longer than 36 months (82.3 ± 38.2 months) in our renal unit between 1977 and 1995. Clinical remission, renal progression, and the impact of covariates were estimated by Kaplan-Meier analysis and a Cox regression model. In 157 of 329 patients (48%), disappearance of urinary abnormalities (clinical remission) was obtained. None of these 157 patients showed progressive deterioration, defined as a 50% increase in serum creatinine (Scr) level from baseline, during the observation period. Conversely, in patients without clinical remission, the Kaplan-Meier estimate of probability of progressive deterioration was 21% ± 5% at 10 years. In the multivariate Cox regression model with 13 independent covariates, initial Scr level, histological score, tonsillectomy, and high-dose methylprednisolone therapy had a significant impact on clinical remission, whereas proteinuria, age, sex, levels of hematuria, blood pressure, conventional steroid therapy, angiotensin-converting enzyme inhibitor therapy, and cyclophosphamide therapy had no significant effect. These findings indicate that interventions aimed at achieving clinical remission have provided encouraging results applicable to managing patients with IgA nephropathy. © 2001 by the National Kidney Foundation, Inc.

Making the Switch from Systemic Steroids to Budesonide in Inactive Crohn's

Budesonide is a systemic glucocorticosteroid with topical anti-inflammatory effects and low systemic activity compared with conventional steroids. It

Surface Steroid Sensors

The brassinosteroid insensitive gene ( BRI1 ) encodes a plasma membrane-localized, transmembrane serine/threonine kinase of the leucine-rich repeat (LRR) family. Genetic studies suggest that BRI1 participates in the response to the plant steroid hormone brassinosteroid. Wang et al. provide evidence from binding assays with BRI1-overexpressing plants and immunoprecipitation of BRI1 that BRI1 is in fact the brassinosteroid receptor. Furthermore, treatment of seedlings with brassinosteroid induced phosphorylation of BRI1, which was dependent on the cytoplasmic kinase domain of BRI1, suggesting that BRI1 autophosphorylates in response to brassinosteroid binding. Genomic analysis indicates that plants lack conventional nuclear steroid hormone receptors. These studies confirm that steroid signaling is initiated at the plasma membrane in plants and suggest that steroid signaling initiates a phosphorylation cascade beginning with the steroid receptor itself. Z.-Y. Wang, H. Seto, S. Fujioka, S. Yoshida, J. Chory, BRI1 is a critical component of a plasma-membrane receptor for plant steroids. Nature 410 , 380-383 (2001). [Online Journal]

Mesalazine plus adjunctive oligopeptide diet improve health related quality of life as efficiacous as conventional steroids in the treatment of mild to moderate acute Crohn's disease

Mesalazine plus adjunctive oligopeptide diet improve health related quality of life as efficiacous as conventional steroids in the treatment of mild to moderate acute Crohn's disease

A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm

Myofascial pain syndrome (MPS) is a common illness, characterised by acute or chronic focal pain, muscle stiffness and fatigue. The pathophysiology of MPS remains unclear. Previous preliminary studies have demonstrated therapeutic efficacy of the muscle relaxant botulinum toxin type A (BTX-A) in the treatment of MPS. A single-centre, randomised trial compared the effects of BTX-A with the steroid methylprednisolone (both administered intramuscularly with 0.5% bupivacaine), in 40 patients suffering from chronic myofascial pain in the piriformis, iliopsoas or scalenus anterior muscles. Thirty days after receiving an injection of either BTX-A or steroid followed by post-injection physiotherapy, pain severity had decreased significantly from baseline in both treatment groups, with no significant difference between the two treatment groups. However, the baseline pain score was significantly higher in the BTX-A treatment group compared with the steroid group (7.9 vs. 7.3), and the reduction in pain score between baseline and 30 days post-injection was greater in the BTX-A group compared with the steroid group (−3.9 vs. −3.5; P=0.06). At 60 days post-injection, the pain severity score for the BTX-A-treated patients was statistically significantly lower than the pain score for the steroid-treated population (2.3 vs. 4.9). Furthermore, the reduction in pain score in the BTX-A group at 60 days post-injection was greater than at 30 days (−5.5 vs. −3.9), whereas the effect of the steroid had begun to wane. These results indicate the superior efficacy of BTX-A over conventional steroid treatment in patients suffering from MPS, when combined with appropriate physiotherapy.

Polymyalgia rheumatica as a manifestation of a large hepatic cavernous hemangioma

A 59-year-old woman presented with polymyalgia rheumatica which was refractory to conventional anti-inflammatory and steroid therapy. A full investigation for an underlying occult malignancy showed only the presence of a giant cavernous hepatic hemangioma. To our knowledge, polymyalgia rheumatica has never been described in association with giant cavernous hepatic hemangioma; resection of the latter lesion resulted in complete and, to this date, definite resolution of rheumatologic complaints in our patient.

Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154.

Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and cyclosporin A, may all contribute to islet allograft loss. Furthermore, intraportal infusion of allogeneic islets results in the activation of intrahepatic macrophages and endothelial cells, followed by production of proinflammatory mediators that can contribute to islet primary nonfunction. We reasoned that the beneficial effects of anti-CD154 treatment on autoimmunity, alloreactivity, and proinflammatory events mediated by macrophages and endothelial cells made it an ideal agent for the prevention of islet allograft failure. In this study, a nonhuman primate model (Papio hamadryas) was used to assess the effect of humanized anti-CD154 (hu5c8) on allogeneic islet engraftment and function. Nonimmunosuppressed and tacrolimus-treated recipients were insulin independent posttransplant, but rejected their islet allografts in 8 days. Engraftment and insulin independence were achieved in seven of seven baboon recipients of anti-CD154 induction therapy administered on days -1, 3, and 10 relative to the islet transplant. Three of three baboons treated with 20 mg/kg anti-CD154 induction therapy experienced delayed rejection episodes, first detected by elevations in postprandial blood glucose levels, on postoperative day (POD) 31 for one and on POD 58 for the other two. Re-treatment with three doses of anti-CD154 resulted in reversal of rejection in all three animals and in a return to normoglycemia and insulin independence in two of three baboons. It was possible to reverse multiple episodes of rejection with this approach. A loss of functional islet mass, as detected by reduced first-phase insulin release in response to intravenous glucose tolerance testing, was observed after each episode of rejection. One of two baboons treated with 10 mg/kg induction therapy became insulin independent post-transplant but rejected the islet graft on POD 10; the other animal experienced a reversible rejection episode on POD 58 and remained insulin independent and normoglycemic until POD 264. Two additional baboon recipients of allogeneic islets and donor bone marrow (infused on PODs 5 and 11) were treated with induction therapy (PODs -1, 3, 10), followed by initiation of monthly maintenance therapy (for a period of 6 months) on POD 28. Rejection-free graft survival and insulin independence was maintained for 114 and 238 days, with preservation of functional islet mass observed in the absence of rejection. Prevention and reversal of rejection, in the absence of the deleterious effects associated with the use of conventional immunosuppressive drugs, make anti-CD154 a unique agent for further study in islet cell transplantation.

Late onset of autoimmune hepatitis in myasthenia gravis

A 35-year-old caucasian female presented with acute onset bilateral ptosis while driving, followed by weakness of the facial and upper limb muscles. A diagnosis of myasthenia gravis (MG) was made on the basis of clinical examination, and confirmed by electromyography, high titres of anti-acetylcholine receptor antibodies and a positive response to pyridostigmine. She underwent thymectomy and her symptoms resolved. She presented again 16 years later (age 51) with tiredness, jaundice and a biochemical hepatitis. Serological and histopathological investigations were in keeping with autoimmune chronic hepatitis and there was a satisfactory response to oral prednisolone. She was unable to tolerate the conventional high dose steroid induction due to a relapse of her MG but subsequently entered remission with intermediate dose regime of prednisolone. Despite a recognised association between both autoimmune hepatitis (AIH) and MG with other autoimmune diseases, a literature search showed the combination of these two conditions to be extremely rare with only one adequately documented previous report.