Short Course Of Methylprednisolone Research Articles

Covid-19-stembandparalyse en -parese bij een patiënte met stridor

COVID-19 vocal cord paralysis and paresis in a patient with stridor COVID-19 can affect several organs, giving various disease presentations. The authors describe a case of a 42-year-old patient who presented with stridor. A bronchoscopy and flexible endoscopy revealed vocal cord paralysis on the left and vocal cord paresis on the right. With additional imaging, no other aetiology for the vocal cord impairment could be found, upon which the diagnosis of COVID-19-related vocal cord paralysis and paresis was made. The patient was successfully treated with short-term CPAP and a short course of methylprednisolone in tapering schedule. Hereafter, clinically and visually by means of a flexible endoscopy, there was rapid improvement of the vocal cord dysfunction. With this case, the authors suspect that corticosteroids may have a beneficial effect on the recovery of vocal cord deterioration caused by COVID-19.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BackgroundSteroid use for COVID-19 is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by SARS-CoV-2. This study aimed at evaluating at evaluating the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19.MethodsParallel, double-blind, placebo-controlled, randomized, phase IIb clinical trial was performed with hospitalized patients aged ≥ 18 years with clinical, epidemiological and/or radiological suspected COVID-19, at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution), twice daily, for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. ClinicalTrials Identifier NCT04343729.FindingsFrom April 18 to June 16, 2020, 647 patients were screened, 416 randomized, and 393 analyzed as mITT, MP in 194 and placebo in 199 individuals. SARS-CoV-2 infection was confirmed by RT-PCR in 81.3%. Mortality at day 28 was not different between groups. A subgroup analysis showed that patients over 60 years in the MP group had a lower mortality rate at day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until day 7.ConclusionThe findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population.

Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19.

BackgroundThere is no proven antiviral or immunomodulatory therapy for coronavirus disease 2019 (COVID-19). The disease progression associated with the proinflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19.MethodsWe conducted a single pretest, single posttest quasi-experiment in a multicenter health system in Michigan from 12 March to 27 March 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on 20 March 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to intensive care unit (ICU), new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up.ResultsWe analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs 54.3%, P = .005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (5 vs 8 days, P < .001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (adjusted odds ratio: 0.41; 95% confidence interval, .22 – .77). ConclusionsAn early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes.Clinical Trials RegistrationNCT04374071.

Enhanced Steroid Therapy in Adult Minimal Change Nephrotic Syndrome: A Systematic Review and Meta-analysis.

The best regimen for adult minimal change nephrotic syndrome (MCNS) is still unknown. Due to an excessive number of adverse events caused by oral steroid monotherapy, enhanced steroid therapy (low dose of prednisolone with a short course of methylprednisolone or with another immunosuppressant) has been studied extensively for years. In this study, the PubMed, Embase, EBSCO and Cochrane Library databases were searched for clinical trials which compared enhanced steroid therapy with oral steroid monotherapy in adult MCNS and a meta-analysis was performed. Seven studies involving 357 patients were included. We found that patients treated with enhanced steroid therapy responded more quickly to complete remission (CR) [mean difference = -9.52, 95% confidence interval (CI): -12.66--6.39, p<0.00001] and showed fewer adverse events [risk radio (RR) = 0.72, 95% CI: 0.54-0.97, p=0.03] than patients receiving oral steroid monotherapy. The CR rate (RR= 0.96, 95% CI: 0.83-1.10, p=0.53) and relapse rate (RR=0.87, 95% CI: 0.57-1.34, p=0.53) were similar in both groups.

Incidence of engraftment fever post autologous transplant for lymphomas and analysis of risk factors.

7043 Background: Engraftment fever (EF) is a phenomenon observed in some patients undergoing autologous transplant (ASCT). We analyzed our data to evaluate the incidence and risk factors associated with EF. Methods: Seventy-nine patients underwent ASCT (53-Hodgkin’s and 26- Non Hodgkin’s) from August 2007 – January 2013. All except 5 received LACE (Lomustine, Ara-C, Cyclophosphamide and Etoposide) conditioning regimen. EF was defined as onset of fever with rising white cell count for which no infectious cause was ascertained. Patients of EF and non-EF groups were compared for the following variables to determine risk factors. These included histology, number of lines of chemotherapy regimens pre-transplant, complete remission (CR) at transplant, peripheral blood CD 34 count on day 1 of collection (PBCD34-D1), CD 34 cell dose collected and infused and number of days of stem cell collection. Results: The median age at transplant was 23.5 years with 57 males and 22 females. Time to neutrophil and platelet engraftment was 10 and 13 days respectively. EF was seen in 35 patients (44 %) at a median of 9 days. Short course of methylprednisolone (n=28) or hydrocortisone (n=3) was given to which all responded. On univariate analysis, PBCD34-D1 &gt; 50/uL (P = 0.037), CD 34 cell dose infused &gt;5.9x106/kg (P=0.012),CD34 cell dose collected &gt; 7.2 x 10 6 /kg (P=0.032) , those receiving ≤ 2 lines of chemotherapy regimens before transplant (P=0.04), those who had ≤ 2 days of stem cell collection (P=0.002) and patients in CR at transplant (P = 0.015) were associated with risk of developing EF. On multivariate analysis, patients in CR at transplant and those who had ≤ 2 days of collection had higher risk of EF. Conclusions: The incidence of EF is high. Patients with lesser days of stem collection and those in CR at transplant have significant risk of developing EF.

Transplantation With Pathologic Kidneys to Improve the Pool of Donors

Kidney transplantation is the best treatment for patients with end-stage renal disease (1), but donors are lacking and waiting lists are increasing in many countries. Living donors, expanded criteria donors, and donations after cardiac death are three ways currently used to increase the pool of donors. Another possibility is to use pathologic organs. Indeed, kidneys with diseases induced by extrarenal mechanisms could recover after transplantation in a new environment. Here, we report an example of this potential strategy. Fourteen months after beginning hemodialysis, a 19-year-old man with Alport syndrome was admitted for a potential transplantation. The donor was a 17-year-old man with a history of a ventriculoperitoneal shunt for hydrocephalus caused by an aqueduct stenosis. He had no underlying renal disease. The cause of death was recurrent hydrocephalus. A kidney biopsy was performed at the time of kidney removal because of a proteinuria (9.2 g/L; estimated glomerular filtration rate [eGFR]=94 mL/min/1.73 m2 using the modification of diet in renal disease formula). Mild and focal glomerular basement membrane duplication was observed in 14 of 17 glomeruli (see Fig. 1). An immunofluorescence study revealed C3 and IgM deposition. This was compatible with an early stage of shunt nephritis (2). At the time of transplantation, no donor-specific antibodies were identified in the recipient using Luminex technology. The flow cytometric crossmatch on T and B lymphocytes for IgG antibodies was negative. We hypothesized that the renal lesions would resolve in a new environment, and transplantation was performed. The recipient received basiliximab and a short course of methylprednisolone for induction and then tacrolimus and mycophenolate mofetil for maintenance therapy. The renal outcome was favorable with immediate output of urine and restoration of graft function. Fifteen days after transplantation, the eGFR was 57 mL/min/1.73 m2 and the proteinuria/creatininuria ratio was 145 mg/mmol. Six weeks after transplantation, the serum creatinine level increased by 20% compared with baseline, and a kidney biopsy was performed (proteinuria=0 g/L). Histopathologic analysis showed mild tubulitis and mild interstitial inflammation (i1, t1, g0, v0, cpt0, ci0, ct0, cg0, mm0, cv0, and ah0), and an immunofluorescence study was negative for C4d, IgM, and C3 deposits, leading to the diagnosis of borderline rejection. None of the nine glomeruli had lesions of membranoproliferative glomerulonephritis. The patient received three pulses of methylprednisolone (500 mg/day). Three months posttransplantation, a protocol kidney biopsy was performed. It contained 14 glomeruli and showed mild interstitial fibrosis and tubular atrophy (i0, t0, g0, v0, cpt0, ci1, ct1, cg0, mm0, cv0, and ah0). An immunofluorescence study was negative for C4d, IgM, and C3 deposits. Six months posttransplantation, the eGFR was 62 mL/min/1.73 m2 and the proteinuria/creatininuria ratio was 17 mg/mmol.FIGURE 1: Histopathologic analysis (PAS). (A) Preimplantation biopsy, showing mild and focal glomerular basement membrane duplication, with normal degree of mesangial cellularity. Taken together with clinical history and IgM and C3 deposition found on immunofluorescence study, these lesions were compatible with an early stage of shunt nephritis. (B, C). Day 40 and day 90 biopsies, showing normal degree of mesangial cellularity (mm0) and no glomerular basement membrane duplication (cg0).This is the first reported case of kidney transplantation from a donor with shunt nephritis. As we had hypothesized, the glomerular lesions were reversible and the graft outcome was good, likely because the kidney was extracted from a deleterious immunologic environment of the donor (3). We cannot rule out the potential role of immunosuppressive treatment on this outcome (4). In conclusion, kidneys with diseases induced by immune-mediated extrarenal mechanisms may be considered for transplantation, after histological evaluation in emergency. This strategy could increase the pool of donors. Florent Guerville Sebastien Lepreux Delphine Morel Thomas Bachelet Karine Moreau Pierre Merville Lionel Couzi Department of Nephrology CHU Bordeaux Hôpital Pellegrin Bordeaux, France Université de Bordeaux CNRS UMR 5164 Bordeaux, France Department of Pathology CHU Bordeaux, Hôpital Pellegrin Bordeaux, France

The risk of fracture in incident multiple sclerosis patients: The Danish National Health Registers

Background: Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling. Objective: To evaluate the risk of fracture in incident MS patients drawn from a dedicated MS registry compared with population-based controls. Methods: We conducted a population-based cohort study (1996–2007) utilising the Danish National Health Registers that were linked to the Danish MS Registry and the Danish MS Treatment Registry. Incident MS patients (2963 cases) were 1:6 matched by year of birth, gender, calendar time and region to persons without MS (controls). Cox proportional hazards models and logistic regression were used to estimate the risk of fracture in MS. Time-dependent adjustments were made for age, history of diseases and drug use. Results: Compared with controls, patients with MS had no overall increased risk of fracture (adjusted hazard ratio (adj. HR): 1.0, 95% CI: 0.9–1.2). However, the risk of femur/hip fracture (adj. HR: 1.9, 95% CI: 1.1–3.4) was significantly increased compared to controls. As compared with unexposed patients, MS patients who had been exposed to a short course of methylprednisolone in the prior year had no significantly increased risk of osteoporotic fracture (adj. HR: 1.2, 95% CI: 0.5–2.9). Disabled MS patients with Expanded Disability Status Scale [EDSS] scores between 6 and 10, had a 2.6-fold increased risk of osteoporotic fracture (adjusted odds ratio (adj. OR): 2.6, 95% CI: 1.0–6.6) compared to patients with an EDSS score between 0 and 3. Conclusion: Patients with MS had a higher risk of femur/hip fracture than controls. Disability status is probably more important than glucocorticoid use in the aetiology of MS and osteoporotic fracture.

Genital Ulcers Associated with Epstein-Barr Virus Infection (Ulcus Vulvae Acutum)

Epstein-Barr virus (EBV) infection may rarely be associated with genital ulcers (ulcus vulvae acutum), a very painful manifestation. The aetiopathogenesis of the disease is not fully understood. We describe here a case of an adolescent virgin with multiple, deep genital ulcers associated with acute infectious mononucleosis. The diagnosis was supported by the clinical symptoms, atypical lymphocytosis, elevated circulating levels of liver enzymes, positive EBV serology, and the detection of EBV in a swab sample and a biopsy specimen by PCR. The virus could not be detected by immunohistochemistry or in situ hybridization. After a short course of methylprednisolone as a supportive treatment, the ulcers healed within one month. No relapse occurred during the 2-year follow-up. Available data relating to the aetiopathogenesis of this condition are reviewed, and we speculate that it may have been caused by percutaneous autoinoculation through cervicovaginal fluid.

Mega-dose methylprednisolone in hematologic and non-hematological disorders.

The comprehensive, basic and stimulating review article entitled “A novel approach to treatment in childhood acute myeloblastic leukemia and myelodysplastic syndrome with high-dose methylprednisolone as a differentiation and apoptosis–inducing agent of myeloid leukemia cells” by Prof. Hicsonmez in the recent issue of the Journal gives me an opportunity to clarify this mode of treatment [1]. Although high-dose corticosteroid administration (up to 1000 mg) was used prior to our recommended method of methylprednisolone (MP) treatment, the drug was infused any time of the day intravenously over a 4-hour period, which is generally called “pulse MP treatment” although this term was not used before 1960. The term “high-dose methylprednisolone” (HDMP) was used for our method of MP administration initially [2-6], following the dose recommendation by Bacigalupo et al. [7], but we changed the term to mega-dose methylprednisolone (MDMP), since HDMP was also used in the literature for 4-10 mg/kg doses. I would also like to emphasize that MDMP treatment differs from conventional corticosteroid (2 mg/kg in divided doses) HDMP and pulse and bolus MP (1000 mg infused by Bacigalupo et al. in 4 hours) administration, not only by dose (which is increased up to 100 mg/ kg, if required for 3 days initially and then tapered gradually) but also the time of administration [8]. Each MDMP dose (in 10-15 iv or at once orally, covered by honey) is given around 6 am (originally stated as before 9 am) when the corticosteroid level is highest physiologically in the body, which seems to be important for adrenocorticotropic hormone (ACTH) and corticosteroid homeostasis (highest dose of 4950 mg was given to a patient with acquired aplastic anemia). We gave a short course of MP (30 mg/kg for 3 days followed by 20 mg/kg for 4 days) to patients with acute idiopathic thrombocytopenic purpura, in which the disease prognosis was good; the duration of treatment usually extended to months or even years, according to the severity of the disease. It seems that longer usage of MDMP treatment is better for the prevention of recurrences and relapses [9]. Thus far, more than 500 patients with different hematological (acquired aplastic anemia, DiamondBlackfan anemia, idiopathic myelofibrosis, idiopathic thrombocytopenic purpura, severe pure red cell hypoplasia, acquired thrombotic thrombocytopenic purpura, severe Coombs (+) hemolytic anemia, hypereosinophilic syndrome, paroxysmal nocturnal hemoglobinuria, Evans syndrome, idiopathic pulmonary hemosiderosis, Kasabach-Merritt syndrome, different acute leukemias, thalassemia intermedia) and non-hematological (steroid-resistant nephrotic syndrome, systemic lupus erythematosus, dermatomyositis, Kawasaki disease, mixed collagen disease, polyarteritis nodosa, rheumatic fever, rheumatoid arthritis, diaphyseal dysplasia, lymphocytic infiltration of the lung, alopecia universalis, sarcoidosis, osteopetrosis, hemangiomatosis) diseases have been treated with MDMP [10-13]. Corticosteroid side effects (hypertension, hyperglycemia, growth retardation, cushingoid appearance, etc.) were practically non-existent as reported by others [14], inasi Ozsoylu

Bolus Methylprednisolone Efficacy for Uncontrolled Exacerbation of Cystic Fibrosis in Children

We present here the clinical course of 4 children with cystic fibrosis, deltaF508/deltaF508, who were admitted with severe respiratory distress and in whom no improvement was obtained by intensive antibiotic therapy and systemic corticosteroids. Chest computed-tomography scans showed hyperinflation and atelectasis. The severity of these exacerbations was explained neither by visible mucus plugging nor by allergic bronchopulmonary aspergillosis. We hypothesized that these clinical features were related to a severe inflammatory process in small airways. Therefore, a high-dose short course of methylprednisolone (1 g/1.73 m(2) per day for 3 days) was given; all the patients' conditions were dramatically improved, and the therapy was safe. To our knowledge, this is the first reported use of bolus methylprednisolone in the treatment of uncontrolled pulmonary exacerbation in children with cystic fibrosis.

Second transplant with two unrelated cord blood units for early graft failure after cord blood transplantation for thalassemia

Early GF is a frequent complication following hematopoietic stem cell transplantation for patients with thalassemia. We report the outcome of double-unit CBT in three patients who developed early GF after CBT. The initial conditioning regimen consisted of i.v. Bu 14 mg/kg (day -9 to -6), i.v. Cy 200 mg/kg (day -5 to -2) and ATG at 120 mg/kg (day -4 to -1). They received GVHD prophylaxis with cyclosporine-A from day -3 and a short course of methylprednisolone (1 mg/kg i.v., every 12 h on days 5-19 with a taper, thereafter 25% decrease every other day). The interval between two transplants was seven and 10 months. The retransplant recipients were preconditioned with i.v. Bu 14 mg/kg (day -7 to -4), i.v. Cy 120 mg/kg (day -3 to -2) and ATG at 150 mg/kg (day -5 to -1 and +1 to +5). GVHD prophylaxis regimen was the same as the first transplant. Neutrophil engraftment were observed in all patients between day +15 and +26. All are alive, between nine and 11 months after retransplant. Our group reported successful utilization of double umblical cord blood grafts in thalassemia patients with early GF.

Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone

Hepatic veno-occlusive disease (VOD) is one of the most common and important regimen-related toxicities observed after hematopoietic stem cell transplantation (HSCT). There are no universally accepted preventative or therapeutic approaches for VOD. We prospectively evaluated the safety and efficacy of a short course of methylprednisolone (MP) in 48 patients undergoing allogeneic HSCT who were diagnosed with hepatic VOD. MP was administered at a dose of 0.5 mg/kg i.v. every 12 h for a total of 14 doses, and then discontinued without taper. Thirty (63%) patients responded with a reduction in total serum bilirubin of 50% or more after 10 days of treatment. In univariate analysis, non-responders had a higher total bilirubin at the start of MP therapy, more weight gain, evidence of fungal infection and platelet refractoriness. High SGPT and early engraftment were significant factors among responders. Twenty-five of the 30 responders survived up to day +100, whereas all but three non-responders died within 100 days post-HSCT, for a probability of survival of 58% among responders and 10% for non-responders. Prospective comparative studies are needed to confirm the observed encouraging outcome of MP therapy for VOD.

Successful treatment of hepatic veno-occlusive disease(VOD) after allogeneic bone marrow transplantation by early administration of a short course of methylprednisolone

Successful treatment of hepatic veno-occlusive disease(VOD) after allogeneic bone marrow transplantation by early administration of a short course of methylprednisolone

Muscle weakness after short course of steroids

To the Editor: Nava et al. 1 have shown acute weakness of respiratory and skeletal muscles after a short course of methylprednisolone given for acute lung rejection after transplantation. As many chest physicians commonly use …

The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: a randomized double-blind controlled study

Objectives: To evaluate the efficacy of methylprednisolone (MPS) versus placebo (PCO) in pregnant women with hyperemesis gravidarum (HG). Methods: All pregnant women admitted with a diagnosis of HG were candidates for the study. Twenty-five patients were randomized by the pharmacy, 14 to the MPS group and 11 to the look-alike PCO group. Both groups received 12 tablets daily for 3 days, then a 10-day taper, decreasing 1 tablet daily. MPS patients received 4-mg MPS tablets. Recurrence of emesis during tapering was treated by restarting the 12 tablets daily, with a new taper. Results: All demographics and clinical variables for the 25 patients were similar. Median weight loss at enrollment was 6 and 10 pounds (MPS and PCO, respectively, P = NS). In both groups the mean weeks when vomiting started and mean weeks at enrollment were 7 and 10, respectively. Recurrence of vomiting after randomization occurred in 4 (29%) and 8 (73%), MPS and PCO, respectively, P = 0.05. Readmission for repeat treatment occurred in 1 (7%) and 4 (36%), MPS and PCO, respectively, P = 0.07. Thirteen MPS patients (93%) and 10 PCO patients (91%) tolerated the medication, P = NS. Other outcome variables were similar. Conclusions: A short course of MPS in patients with hyperemesis gravidarum decreases the likelihood of a recurrence of vomiting.

The efficacy of methylprednisolone in the treatment of hyperemesis gravidarum: A randomized, double-blind, controlled study

Objective: The study compared the efficacy of methylprednisolone with that of promethazine for the treatment of hyperemesis gravidarum. Study Design: Patients with a normal-appearing intrauterine pregnancy of ≤16 weeks’ gestation with hyperemesis gravidarum (persistent vomiting and large ketonuria despite outpatient therapy) were admitted to the hospital for continuous intravenous hydration and offered participation in the study. Patients meeting study criteria were randomly assigned to receive (from identical-appearing dispensers packaged in advance with a 2-week supply) oral methylprednisolone, 16 mg 3 times daily, or oral promethazine, 25 mg 3 times daily. After 3 days the methylprednisolone was tapered completely during the course of 2 weeks whereas the promethazine was continued without change for 2 weeks. For patients who continued to vomit after 2 days the study medication was discontinued. Patients receiving study medication at discharge continued to take the remainder of the assigned medication from the packaged pill dispensers. Patients were followed up weekly. The study outcomes, as established in advance, were (1) improvement of symptoms within 2 days of starting therapy and (2) readmission for hyperemesis within 2 weeks of starting the study. Results: Forty patients were enrolled in the course of 11 months (20 per group). There were no significant differences between the groups with respect to maternal age, gravidity, parity, gestational age at entry, number of previous admissions, or >5% body weight loss. Three patients in the methylprednisolone group and 2 in the promethazine group failed to stop vomiting within 2 days. One patient from the promethazine group was unavailable for follow-up. No patient from the methylprednisolone group but 5 of the 17 patients receiving promethazine were readmitted for hyperemesis within 2 weeks of discharge (P = .0001). There were no adverse effects noted for either drug. Conclusion: A short course of methylprednisolone is more effective than promethazine for the treatment of hyperemesis. (Am J Obstet Gynecol 1998;179:921-4.)

Tolerance to rat liver allografts. III. Donor cell migration and tolerance-associated cytokine production in peripheral lymphoid tissues.

The aim of this work was to investigate the mechanism of spontaneous rat liver allograft tolerance. Liver allografts from a LEW donor into DA recipient (LEW-->DA) or of PVG-->DA were spontaneously tolerated (TOL) across a complete MHC mismatch. In contrast, DA-->LEW or PVG-->LEW liver allografts were rejected in 10 to 15 days (REJ). We examined whether donor cell migration to recipient lymphoid tissues might be associated with TOL. Many donor cells were observed in draining (celiac) lymph nodes (LN) and spleen, reaching a peak on day 1 and then decreasing rapidly thereafter. Irradiation of liver donors, which we have previously shown to delete tolerance, significantly reduced the number of donor leukocytes in recipient lymphoid tissues. While this suggested an association between donor cell migration and tolerance, the number, distribution, and type of donor cells in recipient lymphoid tissues of REJ was similar to those of TOL. Expression of cytokine mRNA in LN and spleen showed an early increase in the expression of IL-2 and IFN-gamma mRNA on day 1 and then a rapid decrease to constitutive levels. Spleen and LN levels of IL-6, IL-10, TNF-alpha, or TGF-beta mRNA showed much less up-regulation than IL-2 or IFN-gamma. Paradoxically, there was greater expression of IL-2 and IFN-gamma mRNA in TOL lymphoid tissues than in REJ, and this superinduction was partially prevented by donor irradiation. Superinduction of IL-2 and IFN-gamma was, therefore, more closely associated with TOL than was donor cell migration. This was confirmed by treatment of TOL recipients with a short course of methylprednisolone, which reduced survival of subsequent donor strain skin grafts. This finding has implications for treatment of human liver transplants and is evidence for a novel pathway of transplant tolerance.

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<h3>PATHOLOGIC QUIZ CASE 1</h3> Susan E. Dozier, MD; Catherine C. Newman; Dayna G. Diven, MD; Stephen K. Tyring, MD, PhD, Galveston, Tex A 59-year-old Hispanic woman presented with a 3-year history of recurring ulcerations over her mouth and tongue and occasionally on her vaginal and nasal mucosa. The ulcers were described as painful and slow to heal, with frequent development of new ulcerations. Before presenting to the dermatology clinic at the University of Texas Medical Branch, Galveston, the patient had been treated first with a short course of methylprednisolone, with some healing of the oral ulcers, and second with colchicine for 2 years, with no improvement in healing or decrease in the incidence of new lesions. The patient denied any complaints of fever, gastrointestinal symptoms, visual changes, or neurologic symptoms. Nikolsky's sign was absent on initial presentation of the lesions. The ophthalmologic examination performed at that time revealed no ocular changes. An autoimmune panel performed 6 months after the onset of the patient's lesions showed no evidence of anti-DNA, anti-Smith, anti-ribonucleoprotein, antinuclear,