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Sample records for azathioprine

  1. Azathioprine

    Science.gov (United States)

    ... immediately if you notice any changes in your skin or any lumps or masses anywhere in your body.Some teenage and young adult males who took azathioprine alone or with another medication called a tumor necrosis factor (TNF) blocker to treat Crohn's disease (a ...

  2. Azathioprine induced cholestatic hepatitis

    OpenAIRE

    Viju Moses; Banumathi Ramakrishna; Kurien Thomas

    2011-01-01

    We report a case of cholestatic hepatitis developed one week after exposure to azathioprine. The subsequent prolonged cholestatic phase was followed by full clinical remission. Current knowledge on pathogenesis and epidemiology and the diagnostic challenges presented by this rare complication are discussed, followed by recommendations for monitoring and management.

  3. Azathioprine induced cholestatic hepatitis

    Directory of Open Access Journals (Sweden)

    Viju Moses

    2011-01-01

    Full Text Available We report a case of cholestatic hepatitis developed one week after exposure to azathioprine. The subsequent prolonged cholestatic phase was followed by full clinical remission. Current knowledge on pathogenesis and epidemiology and the diagnostic challenges presented by this rare complication are discussed, followed by recommendations for monitoring and management.

  4. Azathioprine treatment during lactation

    DEFF Research Database (Denmark)

    Christensen, L.A.; Dahlerup, J.F.; Nielsen, M.J.;

    2008-01-01

    BACKGROUND: Thiopurines are widely used to maintain remission in inflammatory bowel disease. Treatment during pregnancy is generally recommended to improve the chance of a normal birth outcome, but advice concerning breastfeeding is conflicting. Aim To estimate the exposure of breastfed infants to...... 6-mercaptopurine, as a metabolite of azathioprine, from maternal milk. METHODS: Eight lactating women with inflammatory bowel disease receiving maintenance therapy with azathioprine 75-200 mg daily were studied. Milk and plasma samples were obtained 30 and 60 min after drug administration and hourly...... maternal milk. After 6 h an average of 10% of the peak values were measured. CONCLUSIONS: The major part of 6-mercaptopurine in breast milk is excreted within the first 4 h after drug intake. On the basis of maximum concentration measured, the infant ingests mercaptopurine of <0.008 mg/kg bodyweight/24 h...

  5. Azathioprine for primary biliary cirrhosis

    DEFF Research Database (Denmark)

    Gong, Yanzhang; Christensen, E; Gluud, C

    Azathioprine is used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been conflicting.......Azathioprine is used for patients with primary biliary cirrhosis, but the therapeutic responses in randomised clinical trials have been conflicting....

  6. Hypersensitivity and jaundice due to azathioprine.

    OpenAIRE

    Davis, M.; Eddleston, A L; Williams, R.

    1980-01-01

    A patient is described who suffered hypersenitivity reactions (anorexia, nausea and vomiting) as well as cholestatic jaundice from therapy with azathioprine. Evidence is given that the 2 reactions were mediated by different portions of the azathioprine molecule.

  7. Compound list: azathioprine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available azathioprine AZP 00046 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human.../in_vitro/azathioprine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/i...n_vitro/azathioprine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...vo/Liver/Single/azathioprine.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates

  8. Chronic idiopathic polyneuropathy treated with azathioprine.

    OpenAIRE

    Pentland, B; Adams, G G; Mawdsley, C

    1982-01-01

    The results of azathioprine therapy in five patients with chronic progressive or relapsing idiopathic inflammatory polyneuropathy are described. In four patients a sustained improvement followed treatment and in the other patient azathioprine successfully replaced corticosteroid therapy. The improvement was often delayed for up to three months. The literature on the use of azathioprine in chronic polyneuropathy is reviewed. We suggest that there is a place for azathioprine treatment in patien...

  9. Multiple cutaneous neutropenic ulcers associated with azathioprine

    OpenAIRE

    Baisakhi Laha; Rajib Guha; Avijit Hazra

    2012-01-01

    We report a case of neutropenic ulceration in a 42-year-old woman receiving azathioprine for pemphigus vulgaris. She developed multiple indolent ulcers involving the nose, neck, and back, after about 6–8 weeks following commencement of azathioprine 50 mg daily. The ulcers were large, disfiguring, dry, and with basal necrotic slough. They were painless and did not discharge pus. The absolute neutrophil count was severely depressed initially, but normalized following azathioprine withdrawal. Sw...

  10. Pancytopenia related to azathioprine in rheumatoid arthritis.

    OpenAIRE

    Jeurissen, M E; Boerbooms, A M; van de Putte, L B

    1988-01-01

    Two patients with rheumatoid arthritis developed pancytopenia during treatment with azathioprine 100 mg daily. In one patient this side effect occurred after three weeks, in the other after eight weeks of treatment. Rapid fall of platelets in one patient necessitated platelet transfusion. In the other patient additional treatment with allopurinol was probably responsible for the toxic effect. Haematological side effects of azathioprine are discussed.

  11. Azathioprine favourably influences the course of malaria

    OpenAIRE

    Huber Stephan M; Föller Michael; Geiger Corinna; Koka Saisudha; Bobbala Diwakar; Lang Florian

    2009-01-01

    Abstract Background Azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may accelerate the clearance of Plasmodium-infected erythrocytes. The present study thus explored whether azathioprine influences eryptosis of Plasmodium-infected erythrocytes, development of parasitaemia and thus the course of malaria. Methods Human erythrocytes were infected in vitro with Plasmodium falcip...

  12. Severe megaloblastic anaemia associated with abnormal azathioprine metabolism.

    OpenAIRE

    Lennard, L; Murphy, M F; Maddocks, J L

    1984-01-01

    Severe anaemia is a rare, unexplained, side effect of azathioprine therapy. We report here such a case associated with a previously unreported abnormality in azathioprine metabolism. A 57 year old man on azathioprine therapy, for a presumed collagen vascular disease, developed severe megaloblastic anaemia. This resolved on cessation of azathioprine treatment. A very high concentration of an azathioprine metabolite, 6-thioguanine nucleotide, was found in the patient's red blood cells and this ...

  13. Leucocytoclastic vasculitis in a patient with azathioprine hypersensitivity.

    OpenAIRE

    Beckett, C. G.; Hill, P.; Hine, K R

    1996-01-01

    We report the case of a 77-year-old man admitted nine days after being commenced on azathioprine with symptoms initially thought to be secondary to sepsis but in fact due to azathioprine hypersensitivity. He developed histologically proven cutaneous leucocytoclastic vasculitis following the re-introduction of azathioprine. We review the literature concerning adverse reactions to azathioprine and the problems of making the diagnosis as well as highlighting azathioprine as a novel cause of leuc...

  14. Safety of azathioprine use during pregnancy

    OpenAIRE

    Natekar, Aniket; Pupco, Anna; Bozzo, Pina; Koren, Gideon

    2011-01-01

    Question Quite a few of my female patients with rheumatic diseases and inflammatory bowel disease are using azathioprine. They are afraid to take a “cancer drug” during pregnancy. What is known about the risks?

  15. Azathioprine in chronic relapsing idiopathic polyneuropathy.

    OpenAIRE

    Pentland, B

    1980-01-01

    A 33-year-old housewife with a 14-year history of relapsing polyneuropathy of unknown cause who has apparently responded to azathioprine therapy is described. The place of this form of treatment in idiopathic polyneuropathy is discussed.

  16. Hypersensitivity to azathioprine in myasthenia gravis.

    OpenAIRE

    Watts, G. F.; Corston, R.

    1984-01-01

    A patient with myasthenia gravis is described who exhibited hypersensitivity including an apparent acute exacerbation of the underlying disorder when treated with azathioprine. 6-mercaptoprine (6-MP) also produced hypersensitivity which, in contrast, did not manifest as a myasthenic exacerbation.

  17. Azathioprine-induced fever in autoimmune hepatitis

    OpenAIRE

    Tawfik Khoury; Ollech, Jacob E; Shmuel Chen; Meir Mizrahi; Meir Shalit

    2013-01-01

    Underdiagnosis of drug-induced fever leads to extensive investigation and prolongation of hospitalization, and may lead to multiple unnecessary invasive procedures and a wrong diagnosis. Azathioprine is a widely used immunosuppressive drug. We report a case of a 53-year-old female patient diagnosed with autoimmune hepatitis treated with azathioprine, who presented to the emergency room with a 6-wk history of fever and chills without other associated symptoms. Since the patient’s fever ...

  18. Association between azathioprine therapy and lymphoma in rheumatoid disease.

    OpenAIRE

    Pitt, P I; Sultan, A H; Malone, M; Andrews, V.; Hamilton, E. B.

    1987-01-01

    Three out of 41 patients treated with azathioprine and low-dose corticosteroids from 1976 to 1983 developed non-Hodgkin's lymphoma. This strikingly high incidence of lymphoma may be a reflection of long-term use of azathioprine.

  19. Infliximab, azathioprine, or combination therapy for Crohn's disease

    DEFF Research Database (Denmark)

    Colombel, Jean Frédéric; Sandborn, William J; Reinisch, Walter;

    2010-01-01

    The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown.......The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn's disease are unknown....

  20. Portal hypertension secondary to azathioprine in myasthenia gravis.

    OpenAIRE

    Fonseca, V.; Havard, C W

    1988-01-01

    A 52 year old man with myasthenia gravis and normal liver function was treated with neostigmine, prednisolone and azathioprine. Three years after starting azathioprine he developed clinical evidence of portal hypertension. A liver biopsy showed nodular regenerative hyperplasia (NRH). The development of NRH following azathioprine treatment in a patient with myasthenia gravis strengthens the case for a causal role of azathioprine in producing NRH and portal hypertension.

  1. Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study

    OpenAIRE

    Kaushal K Verma; G Sethuraman; M Kalavani

    2015-01-01

    Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly...

  2. Are we giving azathioprine too much time?

    Institute of Scientific and Technical Information of China (English)

    Fernando Gomollón; Santiago García López

    2008-01-01

    Azathioprine is Currently the key drug in the maintenance treatment of inflammatory bowel diseases. However, there are still some practical issues to be resolved: one is how long we must maintain the drug. Given that inflammatory bowel diseases are to date chronic, non-curable conditions, treatment should be indefinite and only the loss of efficacy or the appearance of serious side effects may cause withdrawal. As regards to efficacy and their maintenance over time, evidence supports the continuous usefulness of the drug in the long term: in fact its withdrawal very substantially increases the risk of relapse. About side effects, azathioprine is a relatively well tolerated drug and even indefinite use seems safe. The main theoretical risks of prolonged use would be the myelotoxicity, hepatotoxicity, and the development of cancer. In fact, serious bone marrow suppression or serious liver damage are uncommon, and can be minimized with proper use of the drug. Recent metanalysis suggests that the risk of lymphoma is real, but the individual risk is rather low, and decision analysis suggests a favorable benefit/risk ratio in the long term. Therefore, in patients with inflammatory bowel diseases in whom azathioprine is effective and well tolerated, the drug should not be stopped. This recommendation concerns the use of azathioprine as a single maintenance drug, and is not necessarily applicable to patients receiving concomitant biological therapy.

  3. Spectrophotometric determination of azathioprine in pharmaceutical formulations.

    Science.gov (United States)

    Lakshmi, C S; Reddy, M N

    1998-12-01

    Four simple and sensitive visible spectrophotometric methods (A-D) have been described for the assay of azathioprine (ATP) either in pure form or in pharmaceutical formulations. Methods A and B are based on the oxidation of ATP with excess N-bromosuccinimide (NBS) or chloramine-T (CAT) and determining the consumed NBS or CAT with a decrease in colour intensity of celestine blue (CB) (method A) or gallocyanine (GC) (method B), respectively. Methods C and D are based on the diazotisation of reduced azathioprine (RATP) with excess nitrous acid and estimating either the consumed nitrous acid (HNO(2)) with cresyl fast violet acetate (CFVA) (method C) or by coupling reaction of the diazonium salt formed with N-1-naphthyl ethylene diamine dihydrochloride (NED) (method D). All of the variables have been optimized and the reactions presented. The concentration measurements are reproducible within a relative standard deviation of 1.0%. Recoveries are 99.2-100.3%. PMID:18967434

  4. A placebo controlled, crossover study of azathioprine in Reiter's syndrome.

    OpenAIRE

    Calin, A

    1986-01-01

    Eight patients with intractable Reiter's disease were entered into a double blind, placebo controlled, crossover study of azathioprine versus placebo--each patient serving as his own control. Drug therapy was administered for 16 weeks, patients receiving azathioprine (eight weeks) or placebo (eight weeks) in random order. Azathioprine was given as 1 mg/kg body weight for the first month and 2 mg/kg body weight for the second month. Six individuals completed both arms of the crossover. One wit...

  5. Monitoring and Safety of Azathioprine Therapy in Inflammatory Bowel Disease

    OpenAIRE

    Kim, Mi Jin; Choe, Yon Ho

    2013-01-01

    Azathioprine is the most common drug used to maintain clinical remission in inflammatory bowel disease. This drug is also important as a steroid-sparing agent in steroid-dependent and chronically active inflammatory bowel disease. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine. The dose of azathioprine has to be reduced or the therapy has to be discontinued frequently because of drug-induced toxicity. In this review, we discuss monitoring of thio...

  6. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

    OpenAIRE

    Hawthorne, A. B.; Logan, R. F.; Hawkey, C. J.; Foster, P. N.; Axon, A T; Swarbrick, E T; Scott, B B; Lennard-Jones, J E

    1992-01-01

    OBJECTIVE--To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN--One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING--Outpatient clinics of five hospitals. SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separate...

  7. Pancytopenia due to the interaction of allopurinol with azathioprine or mercaptopurine.

    Science.gov (United States)

    2000-04-01

    (1) Allopurinol increases the haematological toxicity of azathioprine and mercaptopurine, with a risk of pancytopenia. (2) Combination of allopurinol with azathioprine or mercaptopurine should be avoided. PMID:11503788

  8. [Panzytopenia from combination therapy with azathioprin and allopurinol].

    Science.gov (United States)

    Seidel, W

    2004-10-01

    Azathioprine has been used in rheumatology for more than twenty years. Indications are collagen diseases with multiorgan involvement, where co-medications are frequently necessary. We describe a patient suffering from pancytopenia following a combination therapy of azathioprine and allopurinol because of lupus erythematodes and diabetic nephropathy with hyperuricemia. PMID:15517303

  9. Side effects of azathioprine in patients with Crohn's disease.

    NARCIS (Netherlands)

    Jong, Dirk de; Goullet, M.; Naber, A.H.J.

    2004-01-01

    OBJECTIVE: In clinical trials 0-15% of patients discontinued azathioprine due to side effects. The aim of this study was to assess the rate of side effects leading to discontinuation of azathioprine and to determine predictive factors for discontinuation. DESIGN: A retrospective cohort analysis of c

  10. Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study

    Directory of Open Access Journals (Sweden)

    Kaushal K Verma

    2015-01-01

    Full Text Available Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92% patients on WAP and 21 (96% on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically significant and comparable (P = 0.366. Patients on WAP had a higher incidence of adverse effects (P = 0.02. Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

  11. Azathioprine-induced Sweet's syndrome and published work review.

    Science.gov (United States)

    Choonhakarn, Charoen; Chaowattanapanit, Suteeraporn

    2013-04-01

    Hypersensitivity to azathioprine can manifest with a wide clinical spectrum. Azathioprine-induced Sweet's syndrome (SS) is rare and usually overlooked because it can mimic disease exacerbation and sepsis. This study aims to characterize the clinical findings of azathioprine-induced SS. A retrospective analysis of the records of three patients diagnosed with azathioprine-induced SS and a review of the relevant English-language published work was performed. Twelve (71%) of the 17 patients were male, ranging 9-89 years in age (mean, 47.2). The time of onset after starting azathioprine was 5-28 days (mean, 13.3). The most common associated disease was inflammatory bowel disease including ulcerative colitis and Crohn's disease (76%). The clinical features typically consisted of fever and classic rash of SS with pustules and vesicles. The lesions occurred most commonly on the face and trunk. Systemic involvement was rare and no hypotension or shock was reported as seen in azathioprine hypersensitivity syndrome. Thiopurine methyltransferase activity is not predictive of this type of adverse effect. Most patients dramatically responded to systemic corticosteroids. Azathioprine-induced SS may be underdiagnosed because it can be easily misinterpreted as inflammatory bowel disease-associated skin eruption. Patients with inflammatory bowel disease may be at higher risk of this condition. Early recognition and drug withdrawal can decrease morbidity of the patients. PMID:23294021

  12. PTCH mutations in basal cell carcinomas from azathioprine-treated organ transplant recipients

    OpenAIRE

    Harwood, C.A.; Attard, N R; O'Donovan, P.; Chambers, P; Perrett, C. M.; Proby, C M; McGregor, J. M.; Karran, P.

    2008-01-01

    The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the a...

  13. Histiocytoid Sweet syndrome treated with azathioprine: a case report.

    Science.gov (United States)

    Miller, Jonathan; Lee, Nicole; Sami, Naveed

    2015-01-01

    Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of neutrophils. We report a 22-year-old woman with HSS, who, after minimal improvement with colchicine and dapsone, had significant improvement of her cutaneous eruption and systemic symptoms following empiric treatment with azathioprine. Since azathioprine has historically been known to cause SS, this case highlights a previously unreported treatment response for the histiocytoid variant. PMID:26436977

  14. Histiocytoid Sweet syndrome treated with azathioprine: a case report

    OpenAIRE

    Miller, Jonathan; Lee, Nicole; Sami, Naveed

    2015-01-01

    Histiocytoid Sweet syndrome (HSS) is a rare histologic variation of Sweet syndrome (SS) predominantly exhibiting mononuclear histiocytoid cells instead of neutrophils. We report a 22-year-old woman with HSS, who, after minimal improvement with colchicine and dapsone, had significant improvement of her cutaneous eruption and systemic symptoms following empiric treatment with azathioprine. Since azathioprine has historically been known to cause SS, this case highlights a previously unreported t...

  15. Controlled trial of azathioprine in chronic ulcerative colitis.

    OpenAIRE

    Kirk, A P; Lennard-Jones, J E

    1982-01-01

    A double-blind controlled trial of azathioprine in a dose of 2-2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis. Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed. Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo; the reduction...

  16. Effect of interleukin-2 on the inhibition of the human mixed lymphocyte reaction (MLR) by azathioprine.

    OpenAIRE

    Szawlowski, P W; Maddocks, J L

    1985-01-01

    The effect of interleukin-2 on the response of the human MLR to azathioprine was studied. Azathioprine (36 microM) inhibited the MLR by 86% and interleukin-2 (25%) stimulated the MLR by 99%. Only partial relief (16%) of azathioprine (36 microM) inhibition was found in the interleukin-2 treated MLR compared with azathioprine treatment alone. However, [3H]-thymidine incorporation by azathioprine (36 microM) + interleukin-2 treated MLR was 4.3 times greater than that exposed to azathioprine alon...

  17. Early pregnancy azathioprine use and pregnancy outcomes.

    LENUS (Irish Health Repository)

    Cleary, Brian J

    2012-02-01

    BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular\\/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular\\/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

  18. An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions

    DEFF Research Database (Denmark)

    Vestergaard, T; Bygum, A

    2009-01-01

    Summary Background. Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression. Aim. To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this d...

  19. Azathioprine with prednisone for polymyositis. A controlled, clinical trial.

    Science.gov (United States)

    Bunch, T W; Worthington, J W; Combs, J J; Ilstrup, D M; Engel, A G

    1980-03-01

    A controlled, prospective, double-blind, therapeutic trial of azathioprine was conducted in the initial therapy of polymyositis. Sixteen patients received 60 mg prednisone per day plus either azathioprine (2 mg/kg of body weight per day) or placebo for a period of 3 months. Creatine phosphokinase (CPK) levels fell to normal slightly sooner in the placebo group, but not significantly so. The azathioprine group did not become significantly stronger (P = 0.58) and did not manifest significantly greater improvement of histopathologic features of muscle (P = 0.80) than the placebo group. Initial CPK elevations were significantly related to the degree of muscle inflammation (P = 0.037), but this was not the case at 3 months (P greater than 0.05). Normalization of the CPK could not be equated with disease control. Type II fiber atrophy, attributed to steroid therapy, was more marked in women than in men (P less than 0.03). PMID:6986827

  20. Treatment of Crohn's disease recurrence after ileoanal anastomosis by azathioprine.

    Science.gov (United States)

    Berrebi, W; Chaussade, S; Bruhl, A L; Pariente, A; Valleur, P; Hautefeuille, P; Couturier, D

    1993-08-01

    Ileoanal anastomosis is a surgical procedure performed in patients with ulcerative colitis. In a small number of patients operated on for ulcerative colitis, Crohn's disease occurs in the reservoir, mimicking pouchitis, and may lead to pouch excision and to a permanent terminal ileostomy. Two patients with recurrent Crohn's disease in the reservoir after ileoanal anastomosis were treated with azathioprine for 18 and 24 months, respectively. Azathioprine induced a complete clinical and endoscopic remission. These two observations suggested that immunosuppressive drugs were a good option for permanent ileostomy in cases of recurrence of Crohn's disease in the reservoir after ileoanal anastomosis. PMID:8344116

  1. Biochemical and morphological study on hepatotoxicity of azathioprine in rat.

    Directory of Open Access Journals (Sweden)

    Watanabe,Akiharu

    1979-02-01

    Full Text Available Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.

  2. Risk of non-melanoma skin cancer in myasthenia patients treated with azathioprine

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, A; Hallas, J;

    2014-01-01

    The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine...

  3. Attenuation of murine graft-versus-host reactivity by azathioprine

    Energy Technology Data Exchange (ETDEWEB)

    Shand, F.L.

    1980-07-01

    The therapeutic effects of azathioprine were evaluated in a murine graft-versus-host (GVH) model. A single high dose (200 mg/kg) of azathioprine, administered to FI recipients 2 to 3 days after the injection of parental spleen cells, abrogated the ensuing GVH reaction. Lower doses of the drug, even when injected over an extended period of time (14 days), were found to be ineffective. However, high doses of azathioprine failed to protect when FI recipients were sublethally irradiated or injected with cyclophosphamide before GVH induction, and even the transfer of syngeneic FI spleen cells immediately after irradiation failed to alter this outcome. Further analysis of the changes that occurred in sublethally irradiated recipients revealed that the protective effect of azathioprine on CBA leads to (CBA x C57BL)FI GVH reaction was totally abrogated by doses of irradiation as low as 200 rad. Further experiments in which death was used as an indicator of GVH disease showed that lethality could not be reversed in sublethally irradiated FI recipients by the transfer of syngeneic FI spleen cells unless approximately 10 days were allowed to elapse between syngeneic reconstitution and GVH induction. Since syngeneic FI cells from spleen, lymph node, or bone marrow all behaved similarly, it seems likely that the increased severity of GVH reaction induced by prior immunosuppression may not be attributable to a simple cell deletion event.

  4. Attenuation of murine graft-versus-host reactivity by azathioprine

    International Nuclear Information System (INIS)

    The therapeutic effects of azathioprine were evaluated in a murine graft-versus-host (GVH) model. A single high dose (200 mg/kg) of azathioprine, administered to FI recipients 2 to 3 days after the injection of parental spleen cells, abrogated the ensuing GVH reaction. Lower doses of the drug, even when injected over an extended period of time (14 days), were found to be ineffective. However, high doses of azathioprine failed to protect when FI recipients were sublethally irradiated or injected with cyclophosphamide before GVH induction, and even the transfer of syngeneic FI spleen cells immediately after irradiation failed to alter this outcome. Further analysis of the changes that occurred in sublethally irradiated recipients revealed that the protective effect of azathioprine on CBA leads to (CBA x C57BL)FI GVH reaction was totally abrogated by doses of irradiation as low as 200 rad. Further experiments in which death was used as an indicator of GVH disease showed that lethality could not be reversed in sublethally irradiated FI recipients by the transfer of syngeneic FI spleen cells unless approximately 10 days were allowed to elapse between syngeneic reconstitution and GVH induction. Since syngeneic FI cells from spleen, lymph node, or bone marrow all behaved similarly, it seems likely that the increased severity of GVH reaction induced by prior immunosuppression may not be attributable to a simple cell deletion event

  5. Primary CNS lymphoma in a patient treated with azathioprine

    DEFF Research Database (Denmark)

    Glesner, Matilde Kanstrup; Ocias, Lukas Frans; Larsen, Thomas Stauffer; Pedersen, Court

    2014-01-01

    A 33-year-old man treated with azathioprine for 12 years for Crohn's disease presented with headache, nausea and vomiting accompanied by difficulty in putting words together and slight mental confusion. Prednisolone and antibiotics were without effect. MRI of the brain showed multiple focal lesions...

  6. Azathioprine-induced bullous Sweet's syndrome: a rare association.

    Science.gov (United States)

    Biswas, Sugata Narayan; Chakraborty, Partha Pratim; Gantait, Kripasindhu; Bar, Chittaranjan

    2016-01-01

    A 52-year-old man presented with high-grade fever, headache and painful vesicular skin rash involving the upper trunk and upper extremities, 8 days after initiation of chemotherapy with azathioprine (50 mg/day), which had been prescribed for acral vitiligo. There was neither any history of preceding respiratory or gastrointestinal tract infection, nor was the patient known to have malignancy, drug hypersensitivity, inflammatory bowel disease, vasculitis or other autoimmune disease. Laboratory results revealed leucocytosis with neutrophilia and markedly elevated acute phase reactants. Antinuclear antibody, perinuclear and cytoplasmic antineutrophil cytoplasmic antibody were found negative. Punch biopsy from skin of the upper trunk revealed dense neutrophilic infiltration of dermis without signs of vasculitis, suggestive of Sweet's syndrome. In view of the temporal association with azathioprine and absence of an obvious alternative aetiology, provisional diagnosis of drug-induced bullous Sweet's syndrome was made. Azathioprine was discontinued and high-dose oral prednisolone initiated. The response was dramatic with resolution of skin lesions within 72 h without further recurrence at fourth week of follow-up. PMID:27090551

  7. Azathioprine Induced Pancreatitis in a Patient with Co-Existing Autoimmune Pancreatitis and Hepatitis

    Directory of Open Access Journals (Sweden)

    Preethi GK Venkatesh

    2011-05-01

    Full Text Available Context Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease of pancreas including autoimmune pancreatitis is unclear. Case report We report here a case of an African American patient with co-existing autoimmune pancreatitis and autoimmune hepatitis who developed azathioprine induced acute pancreatitis complicated by a large symptomatic pseudocyst compressing the duodenum requiring a cystoduodenostomy. Conclusions Future studies to investigate the risk of azathioprine induced pancreatitis in the presence of underlying disease of the pancreas including autoimmune pancreatitis are required to further understand the safety of azathioprine in this sub group of patients.

  8. Azathioprine pharmacokinetics after intravenous, oral, delayed release oral and rectal foam administration.

    OpenAIRE

    Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J

    1996-01-01

    BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 m...

  9. Azathioprine-induced accelerated cutaneous and pulmonary nodulosis in a patient with rheumatoid arthritis*

    OpenAIRE

    Kellet, Cristian Vera; Navarrete, Romina Andino; Bombardieri, Sergio González; Manriquez, Juan

    2015-01-01

    We report the case of a 42-year-old female with a 5-year history of rheumatoid arthritis treated with Rituximab and Azathioprine. Three months after the initiation of Azathioprine, the patient started with dry cough and noted the rapid development of multiple subcutaneous nodules on her right leg. CT scan of the chest demonstrates pulmonary nodulosis. Skin biopsy was compatible with rheumatoid nodule. A diagnosis of "accelerated cutaneous and pulmonary nodulosis" was considered. Azathioprine ...

  10. Azathioprine Induced Pancreatitis in a Patient with Co-Existing Autoimmune Pancreatitis and Hepatitis

    OpenAIRE

    Preethi GK Venkatesh; Udayakumar Navaneethan

    2011-01-01

    Context Azathioprine induced pancreatitis usually runs a benign self limited course with rapid disappearance of signs and symptoms upon with drawl of the drug. Azathioprine is used in treating relapses in patients with autoimmune pancreatitis and maintenance of remission in autoimmune hepatitis. Acute pancreatitis complicated by symptomatic pseudocysts requiring drainage is not usually associated with drug induced pancreatitis. The risk of azathioprine use in patients with underlying disease ...

  11. A study of the utility of azathioprine metabolite testing in myasthenia gravis.

    Science.gov (United States)

    Rae, William; Burke, Georgina; Pinto, Ashwin

    2016-04-15

    Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterised by fatigable voluntary skeletal muscle weakness. The underlying pathogenesis is complex involving adaptive autoimmune responses. Azathioprine remains a first line broad acting immunosuppressant for MG. Due to varied clinical responses to azathioprine we aimed to investigate the relationship between azathioprine metabolites and symptom control. Mild correlations between Quantitative Myasthenia Gravis Score (QMG) vs. 6-thioguanine nucleotides (R=-0.317 p=0.186) and QMG vs. lymphocyte count (R=0.402 p=0.08) were found. Azathioprine metabolite measurement should be considered in MG patients with; pancytopenia, deranged liver function or recurrent infections. PMID:27049566

  12. Azathioprine suppresses the mixed lymphocyte reaction of patients with Lesch-Nyhan syndrome.

    OpenAIRE

    Szawlowski, P W; Al-Safi, S A; Dooley, T.; Maddocks, J L

    1985-01-01

    The mixed lymphocyte reaction of Lesch-Nyhan patients (HGPRT deficient) was used to study the immunosuppressive effects of azathioprine and 6-mercaptopurine (6-MP). Mitogen stimulated lymphocytes of these patients are highly resistant to azathioprine and 6-MP. When both stimulator and responder lymphocytes in the MLR were HGPRT deficient, azathioprine (36 microM) was much more inhibitory than 6-MP (100 microM). Azathioprine produced inhibition of 98.2% and 78.5% compared with the values of 63...

  13. Use of azathioprine and the risk of cancer in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Pasternak, Björn; Svanström, Henrik; Schmiegelow, Kjeld;

    2013-01-01

    %) used azathioprine) in Denmark from 1997 to 2008. We linked registry data on filled drug prescriptions, cancer diagnoses, and covariates and compared rates of overall incident cancer and cancer subgroups between users and nonusers of azathioprine, adjusting for propensity scores. During a median 7...

  14. Treatment of progressive renal failure and nephrotic syndrome with azathioprine and prednisolone.

    OpenAIRE

    Baker, L R; Tucker, B; Macdougall, I C; Oommen, R

    1997-01-01

    Four patients with idiopathic membranous glomerulonephritis, heavy proteinuria and progressive renal failure received azathioprine and prednisolone. Renal function improved in all four and proteinuria declined sharply in three. We suggest that treatment with azathioprine and prednisolone may be of benefit in this form of idiopathic membranous glomerulonephritis.

  15. Azathioprine therapy for acquired myasthenia gravis in five dogs.

    Science.gov (United States)

    Dewey, C W; Coates, J R; Ducoté, J M; Meeks, J C; Fradkin, J M

    1999-01-01

    Five dogs with acquired myasthenia gravis (MG), verified via positive serum acetylcholine (ACh) receptor antibody concentrations, were treated with a drug protocol including azathioprine (AZA). Four of the five dogs were concurrently treated with pyridostigmine. Azathioprine was used as the sole immunosuppressive agent in four dogs. One dog was temporarily treated with a combination of an immunosuppressive dose of prednisone and AZA, then maintained on AZA as the sole immunosuppressive drug. Three patients experienced complete remission of clinical signs within three months of therapy. In the four dogs for which follow-up serum ACh receptor antibody concentrations were available, initial versus final concentrations decreased substantially (81%), coincident with clinical improvement. One dog died suddenly due to a suspected myasthenic crisis before attaining the target dose of AZA. Two of the four surviving dogs were euthanized approximately one and seven years after diagnosis. One of these two dogs was euthanized because of a rib osteosarcoma, and the other dog was euthanized because of paraparesis of undetermined cause. The remaining two dogs were alive and doing well at the time of final follow-up evaluation, approximately six months and one year after diagnosis. The use of AZA as a therapeutic agent for acquired canine MG has not been investigated. The cases presented in this report suggest a potentially important role for AZA in the treatment of acquired MG in dogs. PMID:10493415

  16. Low-dose allopurinol plus azathioprine/cyclosporin/prednisolone, a novel immunosuppressive regimen.

    Science.gov (United States)

    Chocair, P; Duley, J; Simmonds, H A; Cameron, J S; Ianhez, L; Arap, S; Sabbaga, E

    1993-07-10

    Early rejection can still complicate renal transplantation even with cyclosporin. We added low-dose allopurinol (25 mg on alternative days) to "triple" immunosuppression with cyclosporin, prednisolone, and azathioprine for twelve recipients of cadaver renal grafts. The controls were fifteen patients on triple therapy alone. Only one rejection episode occurred among the allopurinol-treated patients, whereas eleven controls had rejections (seven with more than one episode). Allopurinol may be toxic when combined with azathioprine, yet the bone marrow tolerated the new regimen well. As expected, reduction of the azathioprine dose was necessary in the treated group. PMID:8100914

  17. Azathioprine as a corticosteroid-sparing agent in air-borne contact dermatitis

    Directory of Open Access Journals (Sweden)

    Verma Kaushal

    1996-01-01

    Full Text Available Two patients having air-borne contact dermatitis (ABCD caused by Parthenium hysterophorus.for 10 and 15 years respectively and without having had complete remissions in spite of oral betamethasone in a dose of 2-3 mg per day, experienced complete relief while taking 50-100 mg azathioprine for 5 and 12 weeks without having to take systemic corticosteroids. There were no side effects of azathioprine. With further experience and standardization of the treatment schedule, it may be possible to use azathioprine as a corticosteroid-sparing agent to reduce the side effects of corticosteroids in patients having ABCD.

  18. Azathioprine and mercaptopurine in the management of patients with chronic, active microscopic colitis

    DEFF Research Database (Denmark)

    Münch, A; Fernandez-Banares, F; Munck, L K

    2013-01-01

    BACKGROUND: Microscopic colitis (MC) is a common chronic diarrhoeal disease, and remission can be induced with budesonide. However, diarrhoea relapses frequently when budesonide is tapered and a few patients become budesonide intolerant. AIM: To examine retrospectively the effect of azathioprine...

  19. Haemolytic anaemia complicating the concurrent use of allopurinol & azathioprine after kidney transplantation

    OpenAIRE

    Neeraj Dhaun; Catherine Hanna; Maria Squires; Simon Watson

    2013-01-01

    Gout is a common problem in renal transplant recipients but often difficult to treat. Allopurinol can be combined with azathioprine but clinicians should be aware of the need for dose reduction, the potential to measure azathioprine breakdown products and the possible side effects of this combination. Leucopenia is a known side effect but this case report shows that haemolytic anaemia can also occur. [Int J Basic Clin Pharmacol 2013; 2(3.000): 330-332

  20. Haemolytic anaemia complicating the concurrent use of allopurinol & azathioprine after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Neeraj Dhaun

    2013-06-01

    Full Text Available Gout is a common problem in renal transplant recipients but often difficult to treat. Allopurinol can be combined with azathioprine but clinicians should be aware of the need for dose reduction, the potential to measure azathioprine breakdown products and the possible side effects of this combination. Leucopenia is a known side effect but this case report shows that haemolytic anaemia can also occur. [Int J Basic Clin Pharmacol 2013; 2(3.000: 330-332

  1. Alopecia totalis in a patient with Crohn's disease and its treatment with azathioprine.

    OpenAIRE

    Goddard, C. J.; August, P. J.; Whorwell, P J

    1989-01-01

    A patient with Crohn's disease and alopecia totalis is described. Despite relative inactivity of the Crohn's disease, treatment with azathioprine was commenced. This led to complete regrowth of hair which was lost when the drug was discontinued. Re-institution of azathioprine restored hair to normal again and the patient has since declined to try stopping the drug despite the knowledge of potential side effects.

  2. Long-term azathioprine in rheumatoid arthritis: a double-blind study.

    OpenAIRE

    M. Silva; Hazleman, B L

    1981-01-01

    Several studies have demonstrated the beneficial effect of azathioprine in rheumatoid arthritis. But fears have been expressed about the possible mutagenic and teratogenic effects of prolonged use. If the drug could be withdrawn once remission is achieved, and this remission be then maintained with other agents, the possible complications of long-term therapy might be avoided. A double-blind controlled study was carried out over 8 months in 32 patients receiving long-term azathioprine therap...

  3. Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn's disease

    OpenAIRE

    Neurath, M; Wanitschke, R; Peters, M.; Krummenauer, F; zum, B; Schlaak, J.

    1999-01-01

    BACKGROUND—Crohn's disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn's disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients. 
AIMS—To compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients wit...

  4. The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

    OpenAIRE

    Rinkardt, N E; Kruth, S.A.; A Kaushik

    1999-01-01

    This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radia...

  5. Are Pancreatic Autoantibodies Associated with Azathioprine-Induced Pancreatitis in Crohns Disease?

    OpenAIRE

    Weersma, Rinse K; Manou R Batstra; Kleibeuker, Jan H; van Dullemen, Hendrik M.

    2008-01-01

    Context Azathioprine is frequently used in the treatment of Crohn’s disease. A severe side effect is acute pancreatitis, which is specific for Crohn’s disease. Autoantibodies against exocrine pancreas occur in about 30% of Crohn’s disease cases but not in other inflammatory diseases. Pancreatic autoantibody positive Crohn’s disease patients might have a low grade inflammation of the pancreas which may be aggravated by the introduction of azathioprine, resulting in clinically overt acute pancr...

  6. Determination of azathioprine in bulk and pharmaceutical dosage form by HPTLC

    OpenAIRE

    Jain, Pritam S.; Pradip Thakre; Chaudhari, Amar J.; Chavhan, Manish L.; Surana, Sanjay J.

    2012-01-01

    Introduction: An HPTLC method for analysis of Azathioprine in bulk and pharmaceutical formulation has been established and validated. Materials and Methods: The analyte was separated on aluminium plates precoated with silica gel 60 F254. The mobile phase was Ethyl acetate: Methanol: Triethylamine (4:1:0.5v/v). Quantification was done by densitometric scanning at 300nm. Results: Response was a linear function of Azathioprine concentration in the range of 200-1200 ng/band. The limit of detectio...

  7. The effects of prednisone and azathioprine on circulating immunoglobulin levels and lymphocyte subpopulations in normal dogs.

    Science.gov (United States)

    Rinkardt, N E; Kruth, S A; Kaushik, A

    1999-01-01

    This study investigates serum immunoglobulin (SIg) levels and lymphocyte subpopulations in normal dogs in response to putative immunosuppressive doses of prednisone and/or azathioprine. The objectives were to quantify SIg levels and lymphocyte subpopulations, including Thy-1+, CD4+, CD8+ and B cells, in normal dogs both before and after the administration of prednisone and/or azathioprine at 2 mg/kg, PO, each. Eighteen beagles were divided into 3 groups of 6 dogs each. Blood samples for radial immunodiffusion assay of IgG, IgM and IgA, complete blood count (CBC)and flow cytometry were collected prior to the administration of any drugs and again after 14 d of azathioprine, prednisone or azathioprine and prednisone. Peripheral blood mononuclear cells were isolated using density centrifugation and were incubated with monoclonal antibodies reacting with CD4+, CD8+, Thy-1+ and membrane immunoglobulin. Lymphocyte subsets were quantified using flow cytometry. Azathioprine-treated dogs had no significant changes in SIg levels or lymphocyte subpopulations. Prednisone-treated dogs had significant (P azathioprine-treated dogs had significant (P dogs also had a significant decrease in erythrocyte number and a significant increase in the monocyte count. These findings suggest that azathioprine and prednisone in combination or prednisone alone may be useful for the treatment of T cell-mediated diseases since decreased circulating T cell levels were demonstrated following treatment. The combination of drugs or azathioprine alone may not be appropriate for treatment of acute or autoantibody-mediated immune disease, because SIg levels were minimally affected by treatment. PMID:9918329

  8. Tautomerism and spectroscopic properties of the immunosuppressant azathioprine

    Science.gov (United States)

    Makhyoun, Mohamed A.; Massoud, Raghdaa A.; Soliman, Saied M.

    2013-10-01

    The molecular structure and the relative stabilities of the four possible tautomers of the immunosuppressant azathioprine (AZA) are calculated by DFT/B3LYP method using different basis sets. The results of the energy analysis and thermodynamic treatment of the obtained data are used to predict the relative stabilities of the AZA tautomers. The effect of solvents such as DMSO and water on the stability of the AZA tautomers was studied using the polarized continuum method (PCM) at the same level of theory. The calculation predicted that, the total energies of all tautomers are decreased indicating that all tautomers are more or less stabilized by the solvent effect. The vibrational spectra of AZA are calculated using the same level of theory and the results are compared with the experimentally measured FTIR spectra. Good correlation is obtained between the experimental and calculated vibrational frequencies (R2 = 0.997). The electronic spectra of AZA in gas phase and in methanol as solvent are calculated using the TD-DFT method. The calculations predicted bathochromic shift in all the spectral bands in presence of solvent compared to the gas phase. Also the NMR spectra of all tautomers are calculated and the results are correlated with the experimental NMR chemical shifts where the most stable tautomer gives the best correlation coefficient (R2 = 0.996).

  9. Role of Rosemary Leaves Extract as A Protective Agent Against Azathioprine-Induced Toxicity in Rats

    Directory of Open Access Journals (Sweden)

    Hala M T El-Mougy*, Gehan A Youssef

    2011-04-01

    Full Text Available Background: Rosemary is widely found along the coasts of the Mediterranean Sea. Its leaves or extract were found to have a high antioxidant and anti-inflammatory activity. It is also used as an antispasmodic, analgesic, anti-rheumatic and expectorant. These actions are mainly due to its content of essential oils. Azathioprine (AZA is an immunosuppressive drug. It is widely used in many diseases. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Aim of the work: This work was done to study the effect of dietary supplement of rosemary leaves as a strategy for amelioration of the side-effects of azathioprine. Material and Methods: Thirty-two adult male albino rats were used in this study. They were equally divided into four groups. Group I: control group, group II: rosemary group, the animals were given a daily oral dose of rosemary leaves extract. Group III: azathioprine group, the animals were given a single dose of AZA intraperitoneally. Group IV: rosemary azathioprine group: the rats were given daily doses of rosemary leaves extract then azathioprine in the last day of the experiment as in the previous regimen. The experiment continued for ten days. Blood samples were taken from all groups and examined for tumour necrosis factor alpha, serum amylase enzyme, C-reactive protein and renal function tests (serum urea and creatinine. Results: Rosemary significantly decreased the levels of tumour necrosis factor alpha, serum amylase enzyme and serum urea and C-reactive protein in rosemary AZA group compared to AZA group . Conclusion: The aqueous rosemary leaves extract has the ability to ameliorate the biochemical pathways of the side-effects of azathioprine, so it is advisable to give it concomitantly to patients treated by azathioprine.

  10. Relationship between red blood cell thiopurine methyltransferase activity and myelotoxicity in dogs receiving azathioprine.

    Science.gov (United States)

    Rodriguez, Damon B; Mackin, Andrew; Easley, Roger; Boyle, Carolyn R; Hou, Weiying; Langston, Cory; Walsh, Amy M; Province, Michael A; McLeod, Howard L

    2004-01-01

    Thiopurine methyltransferase (TPMT) produces inactive metabolites of azathioprine and, in humans, has a variable amount of activity. Humans with low TPMT activity commonly develop myelotoxicity when receiving azathioprine. Our study sought to characterize the distribution of TPMT activity in a population of dogs and to determine whether the pretreatment knowledge of red blood cell (RBC) TPMT activity could predict myelotoxicity in dogs receiving azathioprine. RBC TPMT activity was measured in 299 healthy dogs, and 9 dogs that represented a wide range of enzyme activity received azathioprine at a standard therapeutic dose for 30 days. TPMT activity in healthy dogs was log normally distributed and varied over an approximately 7-fold range. Geometric mean, minimum, and maximum RBC TPMT activities were 37.1, 16.3, and 115 nmol per gram of hemoglobin (gHb) per hour, respectively. TPMT deficiency was not identified. Two populations of TPMT activity in dogs were detected by statistical modeling (commingling analysis). Dogs with intermediate TPMT activity (14-38 nmol/gHb/h) receiving azathioprine had significantly lower neutrophil counts during week 4 than during weeks 0-3, whereas those with high activity (>39 nmol/gHb/h) did not have a significant change in neutrophil count. An analysis of TPMT activity in 6 dogs with a history of azathioprine-associated myelotoxicity in a clinical setting revealed either intermediate or high TPMT enzyme activity in all dogs, suggesting that TPMT activity, as measured in RBCs, is not the sole cause of severe azathioprine-associated myelosuppression in dogs. PMID:15188821

  11. Myelosuppression associated with azathioprine-allopurinol interaction after heart and lung transplantation.

    Science.gov (United States)

    Cummins, D; Sekar, M; Halil, O; Banner, N

    1996-06-15

    It is widely recommended that, during concurrent therapy with allopurinol, the azathioprine dosage should be decreased by at least two thirds. We retrospectively studied compliance with this guideline in 24 patients who had commenced allopurinol at a median of 33 months (range, 2-145 months) after heart and/or lung transplantation. The median reduction in azathioprine dose at initiation of allopurinol was 73.3% but ranged from 0% to 90% (>67% in 14 patients). Within 3 months, 11 (46%) of the patients became leukopenic (white blood cell count azathioprine by two thirds or greater reduced but did not abolish the risk of myelotoxicity. These data highlight the need for close hematological monitoring of patients treated with this drug combination. Agents other than allopurinol should be considered for treating hyperuricemia after thoracic organ transplantation. PMID:8669118

  12. Epstein-Barr-virus-associeret lymfom hos en patient med colitis ulcerosa i behandling med azathioprin

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Kiszka-Kanowitz, Marianne; Albrectsen, Jens Mørch; Andersen, Ove

    2008-01-01

    A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV-associat......A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV...

  13. Azathioprine and 6-mercaptopurine (6-MP) suppress the human mixed lymphocyte reaction (MLR) by different mechanisms.

    OpenAIRE

    Al-Safi, S A; Maddocks, J L

    1984-01-01

    6-MP inhibitory effects on the MLR were reversed by AIC (46%), adenine (32%), hypoxanthine (89%), adenosine (86%) and inosine (93%). AIC, adenine, hypoxanthine and inosine had no effect on azathioprine inhibition of the MLR. Adenosine at 10 microM caused 29% reversal and had no effect at 100-400 microM on azathioprine inhibition of the MLR. Reversal of 6-MP suppression of the MLR was decreased with the delay of adenosine addition. Guanine, xanthine and guanosine caused no reversal of 6-MP or ...

  14. The effect of azathioprine on anastomotic healing: an experimental study in rats

    DEFF Research Database (Denmark)

    Stolzenburg, Tilo; Ljungmann, Ken; Christensen, Henrik

    2007-01-01

    healing was tested. METHODS: In an experimental study, rats were randomly given one oral dose of azathioprine (5 mg or 20 mg/kg body weight per day) or placebo. After 28 days of treatment, a left colonic anastomosis was performed. After three days of healing, the breaking strengths of the anastomoses were...... tested, along with measurements of azathioprine major metabolite concentrations: 6-thioguanine and 6-methyl-mercaptopurine. RESULTS: There were no significant differences in the anastomotic breaking strength between the three groups. CONCLUSIONS: Daily treatment for four weeks with high or low...

  15. Mycophenolate mofetil versus azathioprine for maintenance treatment of lupus nephritis.

    Science.gov (United States)

    Kaballo, Babikir G; Ahmed, Ahmed Elias; Nur, Musa Mohammed; Khalid, Ismail Osman; Abu-Aisha, Hasan

    2016-01-01

    To compare the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) drugs in the maintenance therapy of lupus nephritis (LN) patients, we studied 81 Sudanese patients with LN (32 in Class III, 34 in Class IV, and 15 in combined Class V + IV of the ISN/RPS 2003 Classification). All patients received induction therapy consisting of monthly intravenous pulse doses of cyclophosphamide (CYC) (500 mg/m 2 of body-surface area) for six months, plus three consecutive pulses of intravenous methylprednisolone 15 mg/kg/day of body weight (maximum 500 mg). Subsequently, 41 (50.6%) patients were randomized into a group that received oral MMF (22 mg/kg/day), and 40 (49.4%) patients randomized to a group that received oral AZA (2 mg/kg/day). All patients initially received oral prednisone (1 mg/kg of body weight daily) for four weeks. The baseline characteristics of the two groups were similar. Total remission rate was 75.3% (80.5% in MMF and 70% in AZA), complete remission rate of 54.3% (56.1% with MMF and 52.5% with AZA), and a partial remission rate of 21% (24.4% with MMF and 17.5% with AZA) over 29 months. During maintenance therapy, six patients died (four in the AZA group and two in the MMF group), and end-stage renal disease (ESRD) developed in five patients (three in the AZA group and two in the MMF group). During the 36-months of the study, both groups had comparable event-free survival rate for the composite end point of death or ESRD and rate of relapse-free survival. Furthermore, both groups had no significant differences in terms of frequency of hospitalization, amenorrhea, infection, nausea, and vomiting. We conclude that our study showed that short-term therapy with intravenous CYC followed by maintenance therapy with oral MMF or AZA had similar efficacy and safety for the treatment of patients with moderate to severe LN. PMID:27424688

  16. A Rare Case of Azathioprine-Induced Sweet's Syndrome in a Patient with Crohn's Disease.

    Science.gov (United States)

    Ben Salem, Chaker; Salem, Chaker B; Larif, Sofiene; Fathallah, Neila; Slim, Raoudha; Aounallah, Amina; Sakhri, Jaballah; Hmouda, Houssem

    2015-01-01

    Sweet's syndrome has been reported in association with inflammatory diseases such as Crohn's disease. It has also been reported in association with several drugs. Here, we report a rare case of Sweet's syndrome induced by azathioprine in a patient with Crohn's disease. PMID:26219289

  17. Comparative study of azathioprine-interferon g dispensing to patients with idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Fotios Drakopanagiotakis

    2009-01-01

    Full Text Available SUMMARY. Introduction: Idiopathic pulmonary fibrosis (IPF is characterized by progressive deterioration of lung function, leading ultimately to death. No pharmacological treatment has been found to stabilize the evolution of the disease, but interferon-g and azathioprine have been used as therapeutic options. Aim: To compare the effectiveness of treatment with interferon-g plus low dose prednisone or azathioprine plus low dose prednisone in patients with IPF. Materials and methods: Patients newly diagnosed with IPF were recruited, 22 in total, of whom 10 received azathioprine plus prednisone and 12 patients received interferon-g plus prednisone for six months. Clinical evaluation, lung function tests, HRCT, bronchoscopy and bronchoalveolar lavage (BAL were performed at baseline and after six months of treatment. Results: All patients were alive after six months of treatment. No statistically significant difference between the two groups was detected regarding clinical deterioration, inflammatory biomarkers such as erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, and BAL cell sub-populations. There was a trend, not statistically significant, towards a greater reduction in forced vital capacity and diffusing capacity for carbon monoxide in the interferon-g group. Conclusion: Interferon-g does not offer any therapeutic advantage over azathioprine as regards the clinical course, lung function tests and BAL cell counts of patients with IPF. Pneumon 2009, 22(3:240-253.

  18. Use of azathioprine for non-thymoma myasthenia and risk of cancer

    DEFF Research Database (Denmark)

    Pedersen, E G; Pottegård, Anton; Hallas, J; Friis, S; Hansen, K; Jensen, P E H; Gaist, D

    2013-01-01

    BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time...

  19. Effect of levamisole and azathioprine on the human mixed lymphocyte reaction (MLR).

    OpenAIRE

    Al-Safi, S A; Maddocks, J L

    1984-01-01

    Levamisole (1.25-4.15 microM) had no effect on tritiated thymidine incorporation into DNA of mixed lymphocyte cultures. Moreover, it did not cause any reversal of azathioprine (18-36 microM) inhibitory effects on the MLR.

  20. Alcohol binging causes peliosis hepatis during azathioprine therapy in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Christoph Elsing; Joerg Placke; Thomas Herrmann

    2007-01-01

    Patients with inflammatory bowel disease have normal life expectancy and, due to modern immunosuppressive therapies, also a normal quality of life. Since mostly young people are affected, their social behaviour suits this environment. Alcohol binging is an increasingly disturbing factor among young people. We describe a patient with Crohn's disease, treated with azathioprine,who developed peliosis hepatis after three epsiodes of alcohol binging. Liver toxicity was not observed previously during the course of the treatment.Azathioprine-induced peliosis hepatis is thought to be idiosyncratic in humans. From animal studies, however,it is clear that hepatic depletion of glutathione leads to azathioprine toxicity to the sinusoidal endothelial cells. Damage of these cells causes peliosis hepatis.Since alcohol binging leads to hepatic glutathione depletion, we conclude that in our patient the episodes of binging have reduced liver gluathione content and therefore this has increased azathioprine toxicity causing peliosis hepatis. The problem of alcohol binging has not yet been addressed in IBD patients undertaking immunosuppressive therapy. This should be reviewed in future considerations regarding patients advice.

  1. Long-term follow-up of cyclophosphamide compared with azathioprine for initial maintenance therapy in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Walsh, M.; Faurschou, M.; Berden, A.;

    2014-01-01

    BACKGROUND AND OBJECTIVES: Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine...... after 3-6 months or after 12 months of cyclophosphamide treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of...... diagnosis, participants were randomly allocated to convert to azathioprine after 3-6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death...

  2. Le cas clinique du mois. Sclérose hepato-portale chez un patient traité par azathioprine

    OpenAIRE

    Roland, S.; Delwaide, Jean; Cornet, G.; Mahieu, Ph; Jacquet, N.; Belaiche, Jacques

    1998-01-01

    We report a case of hepatoportal sclerosis in a renal transplant patient treated with azathioprine. The initial symptom was ascites. On the biochemical level, there were cholestasis without cytolysis or hepatocellular insufficiency. A presinusoidal portal hypertension was found on haemodynamic studies, without portal thrombosis at CT-scan. A diagnosis of hepatoportal sclerosis was evoked on histology and attributed to azathioprine. This case gives an illustration of a classical albeit rare co...

  3. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study.

    OpenAIRE

    Silman, A.J.; Petrie, J.; Hazleman, B; Evans, S. J.

    1988-01-01

    Two hundred and two patients with rheumatoid arthritis (RA) starting treatment with large doses of azathioprine (median 300 mg/day) between 1964 and 1974 were followed up until March 1984. All but one patient (99.5%) were traced from either hospital or general practice records; and death certificates, where relevant, were obtained. A comparison group of 202 patients with RA not treated with azathioprine was selected from the diagnostic index of another rheumatology unit and followed up in 198...

  4. [Bone marrow depression after azathioprine. New discoveries on an old drug].

    Science.gov (United States)

    Löwhagen, G B; Lindstedt, G

    2000-02-01

    Azathioprine, a cytostatic and immunosuppressive drug in use for some 30 years, can give rise to life-threatening neutropenia and thrombocytopenia. This may be caused by unexpectedly high concentrations of cytotoxic metabolites due to abnormally slow inactivation of 6-mercaptopurine (6-MP) by thiopurine S-methyltransferase (TPMT) and/or xanthine oxidase. Low TPMT activity may be due to genetic polymorphism or interaction with drugs such as salicylic acid derivatives, while xanthine oxidase may be inhibited by allopurinol. High TPMT activity, on the other hand, may hamper cytostatic treatment. Safer and more effective treatment with azathioprine and its metabolite 6-MP becomes possible with new laboratory methods for pharmacotherapy monitoring. PMID:10707497

  5. Role of Rosemary Leaves Extract as A Protective Agent Against Azathioprine-Induced Toxicity in Rats

    OpenAIRE

    Hala M T El-Mougy*, Gehan A Youssef

    2011-01-01

    Background: Rosemary is widely found along the coasts of the Mediterranean Sea. Its leaves or extract were found to have a high antioxidant and anti-inflammatory activity. It is also used as an antispasmodic, analgesic, anti-rheumatic and expectorant. These actions are mainly due to its content of essential oils. Azathioprine (AZA) is an immunosuppressive drug. It is widely used in many diseases. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Aim of the wor...

  6. Corticosteroids and Azathioprine Do Not Prevent Radiation-Induced Lung Injury

    OpenAIRE

    Eva Kwok; Chan, Charles K.

    1998-01-01

    The case of a man who presented with dyspnea and a dry cough six weeks after mediastinal radiotherapy for malignant thymoma is described. The patient was on prednisone (30 mg/day) and azathioprine (100 mg/day) throughout the course of radiation. The respiratory difficulties developed as the dose of prednisone was gradually decreased to 20 mg/day postradiation. Chest x-ray showed bilateral pulmonary infiltrates. Computed tomography scan of the thorax confirmed bilateral ground glass opacities,...

  7. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System

    OpenAIRE

    Abdullah Al Maruf; Luke Wan; O’Brien, Peter J

    2014-01-01

    Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using “Accelerated Cytotoxicity Mechanism Screening” techniques. The concentration of AZA required to cause 50% cytotoxicity in 2 hrs at 37°C was found to be 400 μM. A sig...

  8. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

    OpenAIRE

    Bradford, Kara; Shih, David Q

    2011-01-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as we...

  9. Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?

    OpenAIRE

    Stocco, Gabriele; Pelin, Marco; Franca, Raffaella; De Iudicibus, Sara; Cuzzoni, Eva; Favretto, Diego; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2014-01-01

    Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease (IBD). In vivo it is active after reaction with reduced glutathione (GSH) and conversion to mercaptopurine. Although this reaction may occur spontaneously, the presence of isoforms M and A of the enzyme glutathione-S-transferase (GST) may increase its speed. Indeed, in pediatric patients with IBD, deletion of GST-M1, which determines reduced enzymatic activity, was recently associated with reduced s...

  10. Generation of radical anions from metronidazole, misonidazole and azathioprine by photoreduction in the presence of EDTA

    International Nuclear Information System (INIS)

    Ultraviolet irradiation of the nitroimidazole derivatives metronidazole, misonidazole, azathioprine and 1-methyl-4-nitroimidazole in aqueous solution with various reductants produced the respective nitro radical anions, as detected by electron spin resonance spectroscopy. The most effective reductant, yielding high concentrations of the radical anions, was EDTA at pH 10. NADH, NADPH, formaldehyde glutathione and methanol were also tested but were less efficient as reductants. (author)

  11. Generation of radical anions from metronidazole, misonidazole and azathioprine by photoreduction in the presence of EDTA

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.E.; Chignell, C.F.; Sik, R.H.; Motten, A.G.

    1986-11-01

    Ultraviolet irradiation of the nitroimidazole derivatives metronidazole, misonidazole, azathioprine and 1-methyl-4-nitroimidazole in aqueous solution with various reductants produced the respective nitro radical anions, as detected by electron spin resonance spectroscopy. The most effective reductant, yielding high concentrations of the radical anions, was EDTA at pH 10. NADH, NADPH, formaldehyde glutathione and methanol were also tested but were less efficient as reductants.

  12. Azathioprine associated acute respiratory distress syndrome: case report and literature review

    OpenAIRE

    Scherbak D; Wyckoff R; Singarajah C

    2014-01-01

    A 58-year-old Caucasian man treated with azathioprine to prevent rejection of an orthotopic liver transplant, presented to the Carl Hayden VA Medical Center with rapid respiratory decline and appeared septic. He required urgent intubation, mechanical ventilator support and empiric antibiotics. His clinical picture and imaging studies were consistent with acute respiratory distress syndrome; however, extensive infectious work up failed to reveal an offending organism. Review of his current med...

  13. Evaluation of azathioprine on lesion severity and lymphocyte blastogenesis in dogs with perianal fistulas.

    Science.gov (United States)

    Harkin, Kenneth R; Phillips, Dianne; Wilkerson, Melinda

    2007-01-01

    Fourteen dogs with perianal fistulas were entered into a prospective clinical study to investigate the effects of long-term azathioprine on clinical outcome and to determine if the clinical results correlated with lymphocyte blastogenesis tests. Complete remission of perianal fistulas was seen in eight (57%) of 14 dogs; partial remission occurred in one (7%) dog; and no response was detected in five (36%) dogs. The results of lymphocyte blastogenesis assays did not correlate with therapeutic response. PMID:17209081

  14. Sweet syndrome on a patient with autoimmune hepatitis on azathioprine and CMV infection.

    Science.gov (United States)

    Xenophontos, Eleni; Ioannou, Antreas; Constantinides, Thrasos; Papanicolaou, Eleni

    2016-02-01

    Sweet syndrome (SS) is a rare inflammatory process presenting with painful erythematous skin eruptions, accompanied by fever and neutrophilia. It is associated with upper respiratory infection in fertile women (classic form), malignancy, infections, drugs and autoimmune diseases. Its pathogenesis remains to be determined. Nevertheless, cytokines may have a prominent role, due to a rapid response after corticosteroid administration. We describe a 32-year-old female with autoimmune hepatitis on azathioprine and prednisone, presenting with fever and inflammatory skin eruptions. Histologic examination of the skin lesions showed neutrophilic infiltrations of the dermis, confirming the diagnosis of SS. Concurrently, she tested borderline positive for recent CMV infection. PMID:26913201

  15. Erythema nodosum as azathioprine hypersensitivity reaction in a patient with bullous pemphigoid

    Directory of Open Access Journals (Sweden)

    Jose Antonio Vargas-Hitos

    2013-01-01

    Full Text Available A 65-year-old woman with bullous pemphigoid presented with fever and several red-purple nodular subcutaneous lesions on both lower legs 1 week after starting treatment with azathioprine (AZA. Biopsy of a skin nodule was compatible with erythema nodosum (EN and hypersensitivity reaction to AZA was suspected. AZA was subsequently discontinued, observing complete remission of fever and EN within 2 weeks. This case highlights the importance of recognizing EN as a possible manifestation of hypersensitivity reaction to AZA.

  16. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study.

    OpenAIRE

    M. Silva; Hazleman, B L

    1986-01-01

    The ability of azathioprine to reduce the maintenance prednisolone requirement of 31 patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA), or both, was tested in a double-blind placebo controlled study over one year. Clinical and laboratory assessments were made at four-weekly intervals over a period of 52 weeks. A statistically significant difference (p less than 0.05) in mean prednisolone dose was noted between the two groups at the end of 52 weeks, there being a fall in...

  17. Pure red cell aplasia due to azathioprine therapy for Crohn′s disease

    Directory of Open Access Journals (Sweden)

    Nagesh Kamath

    2016-01-01

    Full Text Available Various mechanisms contribute to anemia in inflammatory bowel diseases (IBD, drug-related causes being less frequent. The hematological and other adverse events of azathioprine (AZA therapy are well documented, but drug-associated pure red cell aplasia (PRCA is an uncommon event. We hereby describe two cases of AZA-associated PRCA in patients with Crohn′s disease. The diagnosis was supported by pathological reports, and prompt hematological recovery was seen with discontinuation of the offending drug. This report highlights the need to consider this rare entity in IBD patients in appropriate settings and for adopting adequate precautionary measures.

  18. Fatal Epstein-Barr Virus Primo Infection in a 25-Year-Old Man Treated with Azathioprine for Crohn's Disease ▿

    OpenAIRE

    N'Guyen, Y.; Andreoletti, L; Patey, M; Lecoq-Lafon, C.; Cornillet, P; Léon, A.; Jaussaud, R.; Fieschi, C; Strady, C.

    2009-01-01

    We report a case of Epstein-Barr virus (EBV) primo infection with the development of successive infectious mononucleosis, hemophagocytic lymphohistiocytosis, and B-cell lymphoproliferative disorder in a patient treated with azathioprine for Crohn's disease. This case report suggests that specific EBV-related clinical and virological management should be considered when treating a patient with inflammatory bowel disease with azathioprine.

  19. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease.

    Science.gov (United States)

    Bradford, Kara; Shih, David Q

    2011-10-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor α; 6-TGN administration; desensitization trials; and split dosing of 6-MP. PMID:22072847

  20. Stability of acetazolamide, allopurinol, azathioprine, clonazepam, and flucytosine in extemporaneously compounded oral liquids.

    Science.gov (United States)

    Allen, L V; Erickson, M A

    1996-08-15

    The stability of drugs commonly prescribed for use in oral liquid dosage forms but not commercially available as such was studied. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were prepared in 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus (Paddock Laboratories), and cherry syrup and placed in polyethylene terephthalate bottles. The sources of the drugs were capsules and tablets. Six bottles were prepared per liquid; three were stored at 5 degrees C and three at 25 degrees C, all in the dark. A sample was removed from each bottle initially and at intervals up to 60 days and analyzed for drug concentration by stability-indicating high-performance liquid chromatography. At least 94% of the initial drug concentration was retained in all the oral liquids for up to 60 days. There were no substantial changes in the appearance or odor of the liquids, or in the pH. Acetazolamide 25 mg/mL, allopurinol 20 mg/mL, azathioprine 50 mg/mL, clonazepam 0.1 mg/mL, and flucytosine 10 mg/mL were stable for up to 60 days at 5 and 25 degrees C in three extemporaneously compounded oral liquids. PMID:8862208

  1. Optimizing 6-mercaptopurine and azathioprine therapy in the management of inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Kara Bradford; David Q Shih

    2011-01-01

    The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine, are efficacious in the arsenal of inflammatory bowel disease (IBD) therapy. Previous reports indicate that 6-thioguanine nucleotide (6-TGN) levels correlate with therapeutic efficacy, whereas high 6-methylmercaptopurine (6-MMP) levels are associated with hepatotoxicity and myelotoxicity. Due to their complex metabolism, there is wide individual variation in patient response therein, both in achieving therapeutic drug levels as well as in developing adverse reactions. Several strategies to optimize 6-TGN while minimizing 6-MMP levels have been adopted to administer the thiopurine class of drugs to patients who otherwise would not tolerate these drugs due to side-effects. In this report, we will review different approaches to administer the thiopurine medications, including the administration of 6-mercaptopurine in those unsuccessfully treated with azathioprine; co-administration of thiopurine with allopurinol; co-administration of thiopurine with anti-tumor necrosis factor a; 6-TGN administration; desensitization trials; and split dosing of 6-MP.

  2. Svær interstitiel lungesygdom på grund af infliximab og azathioprin hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Hansen, L. K.; Cecere, Stefano; Thøgersen, Thøger

    A 41-year-old man developed severe interstitial lung disease (ILD) after treatment with infliximab (IFX) and azathioprine (AZA). A relapse of ulcerative colitis was treated with corticosteroids (CS) and IFX as rescue therapy. Following remission AZA was given as prophylaxis. AZA was initiated the...

  3. Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency

    DEFF Research Database (Denmark)

    Yenson, P.R.; Forrest, D.; Schmiegelow, K.;

    2008-01-01

    risk of hematologic toxicity and leukemogenesis. We present such a patient who was a slow metabolizer for azathioprine, and developed a rapidly lethal form acute myeloid leukemia after relatively low dose exposure to the drug. There was prominent hemophagocytic activity in the bone marrow, and...

  4. Lack of evidence of a beneficial effect of azathioprine immune-mediated hemolytic anemia: a retrospective cohort study

    NARCIS (Netherlands)

    Piek, C.J.; Spil, Van W.E.; Junius, G.; Dekker, A.

    2011-01-01

    Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA

  5. Clinical and magnetic resonance imaging (MRI) findings of idiopathic aplastic pancytopenia in a dog treated with cyclosporine and azathioprine

    OpenAIRE

    Kim, Jung-Hyun; Kim, Ju-Won; Lim, Chae-Young; Park, Hee-Myung

    2012-01-01

    A dog was referred for pancytopenia. Bone marrow biopsy showed hypocellular fatty marrow. Magnetic resonance imaging had a high signal on T1-weighted image in the metaphyseal region of the femur. We suggest that MRI could be a valuable supportive diagnostic method and introduce a strategy of treatment with cyclosporine and azathioprine in canine aplastic pancytopenia.

  6. Clinical and magnetic resonance imaging (MRI) findings of idiopathic aplastic pancytopenia in a dog treated with cyclosporine and azathioprine.

    Science.gov (United States)

    Kim, Jung-Hyun; Kim, Ju-Won; Lim, Chae-Young; Park, Hee-Myung

    2012-04-01

    A dog was referred for pancytopenia. Bone marrow biopsy showed hypocellular fatty marrow. Magnetic resonance imaging had a high signal on T1-weighted image in the metaphyseal region of the femur. We suggest that MRI could be a valuable supportive diagnostic method and introduce a strategy of treatment with cyclosporine and azathioprine in canine aplastic pancytopenia. PMID:23024391

  7. EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis

    OpenAIRE

    Yee, C; Gordon, C.; Dostal, C.; Petera, P; Dadoniene, J; Griffiths, B; Rozman, B; Isenberg, D; Sturfelt, G; NIVED, O.; Turney, J.; Venalis, A; Adu, D.; Smolen, J.; Emery, P.

    2004-01-01

    Objective: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE).

  8. Eudragit-S, Eudragit-L and cellulose acetate phthalate coated polysaccharide tablets for colonic targeted delivery of azathioprine.

    Science.gov (United States)

    Kotagale, Nandkishor; Maniyar, Mithun; Somvanshi, Sachin; Umekar, Milind; Patel, Chirag J

    2010-01-01

    The present work deals with the formulation and evaluation of polymer-coated polysaccharide tablets of azathioprine prepared by direct compression method using different ratios of avicel (MCC), inulin and triacetin. The tablets formulations containing 25 mg of azathioprine were prepared and evaluated for thickness, hardness, friability, weight variation, content uniformity and in vitro dissolution test. Hardness and percentage friability were in the range of 7.23-7.43 kg/cm(2) and 0.21-0.41%, respectively, and showed 99-100% uniformity in drug content. The coated tablets exploiting different polymer combinations were evaluated for drug release under different pH conditions. The formulation containing Eudragit-S, Eudragit-L and cellulose acetate phthalate (ES, EL and CAP) (1:1:1) displayed desired release pattern with only 9.75% drug release in first 5 h (lag phase) and satisfactory release in lowered pH conditions. Drug release increased with the plasticizer (triacetin) concentration. Increase in the concentration of inulin and citric acid above 5% w/w increases the drug release. The addition of inulin in the formulation with coating level 28% w/w demonstrated increased drug release in presence of rat cecal content. Thus inulin containing ES, EL and CAP (1:1:1) polymer-coated formulation system can be used for the targeted delivery of azathioprine with desired release pattern. PMID:20236031

  9. Successful low-dose azathioprine for myasthenia gravis despite hepatopathy from primary sclerosing cholangitis: a case report

    Directory of Open Access Journals (Sweden)

    Höflich Sonja

    2010-11-01

    Full Text Available Abstract Introduction Although myasthenia gravis is frequently associated with other disorders, it has not been reported together with primary sclerosing cholangitis, complicating the administration of liver-toxic immunosuppressive therapy. Case presentation A 73-year-old Caucasian woman with a history of arterial hypertension, thyroid dysfunction, glaucoma, right-sided ptosis and later generalized weakness, was diagnosed with myasthenia gravis. Additionally, primary sclerosing cholangitis was detected, initially prohibiting the administration of immunosuppressants. Despite treatment with steroids and pyridostigmine she repeatedly experienced myasthenic crises. After the fifth crisis and after antibody titers had reached levels > 100 nmol/L during two years of follow-up, it was decided to restart azathioprine. Interestingly, low-dose azathioprine (1.5 mg/kg/day was well tolerated, had a positive clinical and immunological effect and did not worsen primary sclerosing cholangitis. Conclusion Myasthenia gravis may occur together with primary sclerosing cholangitis in the same patient. Mild immunosuppression with azathioprine is feasible and effective in such a patient, without worsening myasthenia gravis or primary sclerosing cholangitis.

  10. Evaluation of Azathioprine-Induced Cytotoxicity in an In Vitro Rat Hepatocyte System

    Directory of Open Access Journals (Sweden)

    Abdullah Al Maruf

    2014-01-01

    Full Text Available Azathioprine (AZA is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using “Accelerated Cytotoxicity Mechanism Screening” techniques. The concentration of AZA required to cause 50% cytotoxicity in 2 hrs at 37°C was found to be 400 μM. A significant increase in AZA-induced cytotoxicity and reactive oxygen species (ROS formation was observed when glutathione- (GSH- depleted hepatocytes were used. The addition of N-acetylcysteine decreased cytotoxicity and ROS formation. Xanthine oxidase inhibition by allopurinol decreased AZA-induced cytotoxicity, ROS, and hydrogen peroxide (H2O2 formation and increased % mitochondrial membrane potential (MMP. Addition of N-acetylcysteine and allopurinol together caused nearly complete cytoprotection against AZA-induced hepatocyte death. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, a known ROS scavenger and a superoxide dismutase mimic, and antioxidants, like DPPD (N,N′-diphenyl-p-phenylenediamine, Trolox (a water soluble vitamin E analogue, and mesna (2-mercaptoethanesulfonate, also decreased hepatocyte death and ROS formation. Results from this study suggest that AZA-induced cytotoxicity in isolated rat hepatocytes may be partly due to ROS formation and GSH depletion that resulted in oxidative stress and mitochondrial injury.

  11. Should 6-thioguanine nucleotides be monitored in heart transplant recipients given azathioprine?

    Science.gov (United States)

    Schütz, E; Gummert, J; Mohr, F W; Armstrong, V W; Oellerich, M

    1996-06-01

    The commonly used immunosuppressive regimen after orthotopic heart transplantation consists of cyclosporine (CsA), azathioprine (AZA), and steroids. Although AZA therapy is generally regarded as unproblematic, its use can be associated with severe side effects, particularly myelosuppression. Since AZA is a prodrug, which must first be metabolized to its active metabolites, AZA therapy, in contrast to CsA therapy, cannot be controlled by measuring blood levels of this drug. Because of the myelosuppressive properties of the AZA metabolites, the 6-thioguanine nucleotides (6-TGN), the white blood cell count is usually monitored in patients on AZA therapy, and AZA is discontinued if neutropenia appears. In a group of 20 consecutive heart recipients, 6-TGN concentrations ranged from allopurinol, an inhibitor of xanthine oxidase, the other major detoxifying enzyme for AZA. In this patient AZA therapy could be individually adapted by RBC 6-TGN monitoring. Based on our experience, we suggest that RBC 6-TGN monitoring allows for better individualization of treatment with AZA and may help avoid fatal complications. PMID:8738760

  12. Evaluation of azathioprine-induced cytotoxicity in an in vitro rat hepatocyte system.

    Science.gov (United States)

    Al Maruf, Abdullah; Wan, Luke; O'Brien, Peter J

    2014-01-01

    Azathioprine (AZA) is widely used in clinical practice for preventing graft rejection in organ transplantations and various autoimmune and dermatological diseases with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of AZA towards isolated rat hepatocytes were investigated in this study using "Accelerated Cytotoxicity Mechanism Screening" techniques. The concentration of AZA required to cause 50% cytotoxicity in 2 hrs at 37°C was found to be 400 μM. A significant increase in AZA-induced cytotoxicity and reactive oxygen species (ROS) formation was observed when glutathione- (GSH-) depleted hepatocytes were used. The addition of N-acetylcysteine decreased cytotoxicity and ROS formation. Xanthine oxidase inhibition by allopurinol decreased AZA-induced cytotoxicity, ROS, and hydrogen peroxide (H2O2) formation and increased % mitochondrial membrane potential (MMP). Addition of N-acetylcysteine and allopurinol together caused nearly complete cytoprotection against AZA-induced hepatocyte death. TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl), a known ROS scavenger and a superoxide dismutase mimic, and antioxidants, like DPPD (N,N'-diphenyl-p-phenylenediamine), Trolox (a water soluble vitamin E analogue), and mesna (2-mercaptoethanesulfonate), also decreased hepatocyte death and ROS formation. Results from this study suggest that AZA-induced cytotoxicity in isolated rat hepatocytes may be partly due to ROS formation and GSH depletion that resulted in oxidative stress and mitochondrial injury. PMID:25101277

  13. Pulmonary infection in patients with cyclosporine, azathioprine, and corticosteroids after cardiac transplantation; Clinical and radiographic assessment

    Energy Technology Data Exchange (ETDEWEB)

    Murayama, Sadayuki; Ikezoe, Junpei; Godwin, J.D.; Marglin, S.I.; Allen, M.D. (University of Washington Medical Center, Seattle, WA (United States))

    1991-07-01

    Between November 1985 and November 1989, 54 patients have undergone 55 cardiac transplants, 5 of whom died during operation or one week after transplantation. The remaining 49 patients with a minimum follow-up of 5 months were studied to examine pulmonary infection clinically and radiologically while receiving triple drug immunosuppression consisting of cyclosporine, azathioprine, and prednisolone. Pulmonary infection occurred in 14 patients (29%) with a total of 21 occasions. Causative organisms were identified in 9 occasions, with the most common organism being Cytomegalovirus (CMV). One patient died of pulmonary infection with Aspergillus. Causative organisms occurring in the remaining 12 occasions of pulmonary infection were unknown, which did not lead to death. Because pulmonary infection of unknown organisms rapidly responded to convensional antibiotics, it seemed to have been caused by bacteria. Pulmonary infection of unknown organism occurred 13.2{+-}3.2 months after transplantation, as compared with 3.3{+-}1.0 months in pulmonary infection of known organisms. Chest plain radiographic features fell into four types: (1) interstitial shadow seen in pulmonary infection of CMV, Pneumocystis carinii, or Hemophilia influenza, (2) patchy, and basilar and lobular consolidation shadows in bacterial pneumonia, (3) localized nodular shadow in aspergillosis, and (4) multiple patchy and confluent opacity patterns occurring in herpes simplex viral infection. Pulmonary infection of influenza bacteria for one patient and pulmonary infection of unknown organisms for 4 patients were difficult to identify from pulmonary infection of CMV. (N.K.).

  14. Radioactive Iodo-azathioprine as a possible model for cancer imaging and therapy

    International Nuclear Information System (INIS)

    Azathioprine (Aza) is antimetabolite drug, could be labeled with the auger emitters iodine-125. Aza could be used an ideal vehicle to deliver radioactive decay energy to DNA of tumor cells causing DNA double strand break, thus stop DNA synthesis. In this study, the process of labeling was done via direct labeling technique using chloramine-T as an oxidizing agent and heating to 75 degree C, for 30 minutes at ph using 0.5 M phosphate buffer. The radiochemical purity of the labeled compound, at the above conditions, was determined using electrophoresis technique and was above 90%. About 2.5x106 of enrich ascites carcinoma (EAC) was injected intraperitoneally(i.p) to produce ascites and intramuscularly (i.m) in the right thigh to produce solid tumor in female mice. Biodistribution studies were carried out by injecting solution of 125I-aza in normal and tumor bearing mice. The uptake in ascites was over 40 % of the injected dose at 12 h post injection and above 20 % in solid tumor . These data revealed localization of the tracer in the tumor tissues with high percentage sufficient to give radiotherapeutic effect as well as promising tool for diagnosis.

  15. Non-TPMT determinants of azathioprine toxicity in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    K. Katsanos

    2010-04-01

    Full Text Available Azathioprine (AZA follows three metabolic routes: the first is the route to 6-thioguanine (TGN catalyzed by thiopurine methyltransferase (TPMT and the other two routes are S-methylation to methylmercaptopurine catalyzed also by TPMT or oxidation to thiouric acid via the enzyme xanthine oxidase. Bone marrow toxicity (BMT mainly in the form of leucopenia represents a major adverse event during AZA therapy in inflammatory bowel disease (IBD. Single nucleotide polymorphisms (SNPs in the TPMT gene locus affecting 6-TGN intracellular accumulation play a significant role in the occurrence of side effects including BMT. Conflicting data exist regarding the role of TPMT genotyping or TPMT enzyme activity in predicting AZA toxicity. Although some BMT cases can be explained by TPMT genotyping or enzyme activity in the majority of cases BMT remains unexplained. These limitations in TPMT testing pointed out to other genes involved in AZA metabolization. Many non-TPMT genes were investigated but their clinical importance is controversial. To explore the applicability of TPMT and non-TPMT genotyping for AZA toxicity monitoring, large prospective studies are needed. Until the results of such studies are available, the dose adjustments of AZA should be guided primarily by clinical response and peripheral blood counts.

  16. Pulmonary infection in patients with cyclosporine, azathioprine, and corticosteroids after cardiac transplantation

    International Nuclear Information System (INIS)

    Between November 1985 and November 1989, 54 patients have undergone 55 cardiac transplants, 5 of whom died during operation or one week after transplantation. The remaining 49 patients with a minimum follow-up of 5 months were studied to examine pulmonary infection clinically and radiologically while receiving triple drug immunosuppression consisting of cyclosporine, azathioprine, and prednisolone. Pulmonary infection occurred in 14 patients (29%) with a total of 21 occasions. Causative organisms were identified in 9 occasions, with the most common organism being Cytomegalovirus (CMV). One patient died of pulmonary infection with Aspergillus. Causative organisms occurring in the remaining 12 occasions of pulmonary infection were unknown, which did not lead to death. Because pulmonary infection of unknown organisms rapidly responded to convensional antibiotics, it seemed to have been caused by bacteria. Pulmonary infection of unknown organism occurred 13.2±3.2 months after transplantation, as compared with 3.3±1.0 months in pulmonary infection of known organisms. Chest plain radiographic features fell into four types: (1) interstitial shadow seen in pulmonary infection of CMV, Pneumocystis carinii, or Hemophilia influenza, (2) patchy, and basilar and lobular consolidation shadows in bacterial pneumonia, (3) localized nodular shadow in aspergillosis, and (4) multiple patchy and confluent opacity patterns occurring in herpes simplex viral infection. Pulmonary infection of influenza bacteria for one patient and pulmonary infection of unknown organisms for 4 patients were difficult to identify from pulmonary infection of CMV. (N.K.)

  17. Azathioprine as a single immunosuppressive drug in the treatment of myasthenia gravis.

    Science.gov (United States)

    Cosi, V; Lombardi, M; Erbetta, A; Piccolo, G

    1993-04-01

    We retrospectively evaluated results obtained from azathioprine (AZA) treatment on a selected sample of 40 patients affected by autoimmune myasthenia gravis (MG). Patients received AZA as a single immunosuppressive drug for at least 2 years. Twenty out of 40 patients received also a one-month course of cyclophosphamide (CP) before starting AZA. All patients started immunosuppressive treatment out of myasthenic crisis. After 3, 12 and 24 months of AZA treatment, 82.5%, 92.5% and 97.5% of the patients respectively showed improvement in functional state, disappearance of bulbar involvement, or both. The impressive percentage of short-term positive results did not seem influenced by pre-treatment by CP. Side effects included only minor and transitory gastrointestinal symptoms and reversible cytopenia. Although the patient population was either particularly suitable for AZA treatment or candidate to a better response, our data suggest that AZA might also have good short term effects in a subgroup of MG patients. PMID:8328322

  18. Alterations in rat pulmonary macrophage function by the immunosuppressive agents cyclosporine, azathioprine, and prednisolone.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1983-06-01

    Disturbances of the immune response of the lung induced by the action of immunosuppressive agents on the functional abilities of rat pulmonary alveolar macrophages (PAM) were analyzed following in vitro incubation or in vivo administration (for 30 days) of cyclosporinea, (CsA) azathioprine (Az) or prednisolone (Pr). Two major parameters were analyzed: oxygen consumption and superoxide release as indices of the overall state of oxygen metabolism of these cells reflecting the integrity of PAM oxidative mechanisms of microbicidal activity, and chemotaxis, an event clinically important for normal defense to infection. In vitro incubation with cyclosporine at concentrations as low as 10(-9) M caused a 52% inhibition of PAM superoxide release, but Az had no effect at concentrations up to 10(-6) M. Prednisolone caused a 38% inhibition of superoxide release; comparable levels of inhibition with Pr required concentrations at least 10-fold greater than with cyclosporine. Further experiments indicated that cyclosporine induced a 40% inhibition after contact with PAM for only 30 min. In vivo experiments indicated that cyclosporine (5 mg/kg), Az (20 mg/kg), or Pr (2 or 0.5 mg/kg) administered intraperitoneally had no effect on the number of PAM available for host defense, PAM oxygen consumption, or PAM superoxide release. However, PAM from cyclosporine-treated animals demonstrated complete inhibition of active migration or chemotaxis in modified Boyden chambers upon incubation with formylmethionyl-leucyl-phenylalanine (FMLP). The effect was apparently dampened by simultaneous administration of Pr with cyclosporine. These experiments suggest that with the exception of a marked effect on chemotaxis the in vivo effects of physiologic amounts of cyclosporine on PAM function are modest compared with the marked depression after in vitro addition. PMID:6306880

  19. Generalized Pyoderma Gangrenosum Associated with Ulcerative Colitis: Successful Treatment with Infliximab and Azathioprine.

    Science.gov (United States)

    Chatzinasiou, Foteini; Polymeros, Dimitrios; Panagiotou, Maro; Theodoropoulos, Konstadinos; Rigopoulos, Dimitrios

    2016-04-01

    Pyoderma gangrenosum (PG) is a rare ulcerative skin disease, part of the spectrum of neutrophilic and auto-inflammatory dermatoses. Its pathogenesis is unknown, although immune pathways have been implicated. Lesion biopsies show a predominantly neutrophilic infiltrate. The incidence of PG is uncertain, but it is estimated to be 3-10 per million per year, occurring at any age but most commonly between 20 and 50 years with a possible slightly higher incidence in women. Approximately 50% of patients with PG also have another disease associated with PG. The most common is inflammatory bowel disease (IBD), particularly Crohn's and ulcerative colitis (UC). Local treatment may be sufficient for mild cases, while for severe cases systemic immunosuppressants are the mainstay (1,2). We report the case of a patient with bullous PG and UC successfully treated with infliximab and azathioprine. A 32-year-old male Caucasian patient presented with painful violaceous vesicles and enlarging bullae of various sizes and with acute onset, located on the trunk and bilaterally on both the lower and the upper extremities. Lesions on the trunk were composed of hemorrhagic pustules with a surrounding erythematous overhanging border. Some of the lesions had undergone central necrosis and ulceration (Figure 1, a-d). The patient reported of the lesions had appeared one week ago, simultaneously with the exacerbation of a known inflammatory bowel disease with hemorrhagic mucoid diarrhea and fever of up to 38.5°C. The patient's medical history included UC affecting the whole colon (pancolitis), diagnosed 5 months prior to the onset of the epidermal lesions, for which the patient was receiving treatment with oral prednisolone 10 mg/day and mesalazine granules. Blood tests showed severe anemia, leukocytosis, and increased inflammatory markers (C-reactive protein, erythrocyte sedimentation rate). Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) andtibodies, antineutrophil

  20. Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

    Science.gov (United States)

    McCarthy, Neil E.; Hedin, Charlotte R.; Sanders, Theodore J.; Amon, Protima; Hoti, Inva; Ayada, Ibrahim; Baji, Vidya; Giles, Edward M.; Wildemann, Martha; Bashir, Zora; Whelan, Kevin; Sanderson, Ian; Lindsay, James O.; Stagg, Andrew J.

    2015-01-01

    Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn’s disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7–expressing Vδ2 T cells, while “Th1-committed” CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27+ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance. PMID:26168223

  1. Azathioprine therapy selectively ablates human Vδ2⁺ T cells in Crohn's disease.

    Science.gov (United States)

    McCarthy, Neil E; Hedin, Charlotte R; Sanders, Theodore J; Amon, Protima; Hoti, Inva; Ayada, Ibrahim; Baji, Vidya; Giles, Edward M; Wildemann, Martha; Bashir, Zora; Whelan, Kevin; Sanderson, Ian; Lindsay, James O; Stagg, Andrew J

    2015-08-01

    Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn's disease patients (CD patients) and healthy controls. Blood from CD patients included an increased percentage of gut-tropic integrin β7-expressing Vδ2 T cells, while "Th1-committed" CD27-expressing Vδ2 T cells were selectively depleted. A corresponding population of CD27+ Vδ2 T cells was present in mucosal biopsies from CD patients and produced elevated levels of TNFα compared with controls. In colonic mucosa from CD patients, Vδ2 T cell production of TNFα was reduced by pharmacological blockade of retinoic acid receptor-α (RARα) signaling, indicating that dietary vitamin metabolites can influence Vδ2 T cell function in inflamed intestine. Vδ2 T cells were ablated in blood and tissue from CD patients receiving azathioprine (AZA) therapy, and posttreatment Vδ2 T cell recovery correlated with time since drug withdrawal and inversely correlated with patient age. These results indicate that human Vδ2 T cells exert proinflammatory effects in CD that are modified by dietary vitamin metabolites and ablated by AZA therapy, which may help resolve intestinal inflammation but could increase malignancy risk by impairing systemic tumor surveillance. PMID:26168223

  2. Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn’s disease patients

    Directory of Open Access Journals (Sweden)

    Kumi Ishida

    2013-01-01

    Full Text Available AIM: To assess adalimumab’s efficacy with concomitant azathioprine (AZA for induction and maintenance of clinical remission in Japanese Crohn’s disease (CD patients. METHODS: This retrospective, observational, single-center study enrolled 28 consecutive CD patients treated with adalimumab (ADA. Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn’s disease activity index (CDAI and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered: 160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS: The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION: Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn’s disease patients.

  3. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study

    DEFF Research Database (Denmark)

    Sørensen, P.S.; Wanscher, B; Szpirt, W; Jensen, C.V.; Ravnborg, M; Christiansen, P; Schreiber, K; Nordenbo, Annette Mosbæk

    1996-01-01

    We enrolled 11 patients with secondary progressive MS in a randomized single-masked cross-over study of plasma exchange (PE) in combination with azathioprine 2 mg/kg. PE was performed once a week for 4 weeks and thereafter every second week for 20 weeks (14 treatments). Eight patients completed the...... whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3...

  4. Preclinical evaluation of azathioprine plus buthionine sulfoximine in the treatment of human hepatocarcinoma and colon carcinoma

    Directory of Open Access Journals (Sweden)

    Borja Hernández-Breijo

    2011-01-01

    Full Text Available AIM: To evaluate the efficacy and the safety of azathioprine (AZA and buthionine sulfoximine (BSO by localized application into HepG2 tumor in vivo. METHODS: Different hepatoma and colon carcinoma cell lines (HepG2, HuH7, Chang liver, LoVo, RKO, SW-48, SW-480 were grown in minimal essencial medium supplemented with 10% fetal bovine serum and 1% antibiotic/antimycotic solution and maintained in a humidified 37 °C incubator with 5% CO2. These cells were pretreated with BSO for 24 h and then with AZA for different times. We examined the effects of this combination on some proteins and on cellular death. We also studied the efficacy and the safety of AZA (6 mg/kg per day and BSO (90 mg/kg per day in HepG2 tumor growth in vivo using athymic mice. We measured safety by serological markers such as aminotransferases and creatine kinase. RESULTS: The in vitro studies revealed a new mechanism of action for the AZA plus BSO combination in the cancer cells compared with other thiopurines (6-mercaptopurine, 6-methylmercaptopurine, 6-thioguanine and 6-methylthioguanine in combination with BSO. The cytotoxic effect of AZA plus BSO in HepG2 cells resulted from necroptosis induction in a mitochondrial-dependent manner. From kinetic studies we suggest that glutathione (GSH depletion stimulates c-Jun amino-terminal kinase and Bax translocation in HepG2 cells with subsequent deregulation of mitochondria (cytochrome c release, loss of membrane potential, and proteolysis activation leading to loss of membrane integrity, release of lactate dehydrogenase and DNA degradation. Some of this biochemical and cellular changes could be reversed by N-acetylcysteine (a GSH replenisher. In vivo studies showed that HepG2 tumor growth was inhibited when AZA was combined with BSO. CONCLUSION: Our studies suggest that a combination of AZA plus BSO could be useful for localized treatment of hepatocellular carcinoma as in the currently used transarterial chemoembolization method.

  5. Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Junius Greet

    2011-04-01

    Full Text Available Abstract Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA, but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. Results The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149 and dogs treated according to the prednisolone protocol (P protocol; n = 73. At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77% in the P protocol group and 69% (95% CI 59-80% in the AP protocol group, respectively. Conclusions Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

  6. Plasma exchange combined with azathioprine in multiple sclerosis using serial gadolinium-enhanced MRI to monitor disease activity: a randomized single-masked cross-over pilot study

    DEFF Research Database (Denmark)

    Sørensen, P.S.; Wanscher, B; Szpirt, W; Jensen, C.V.; Ravnborg, M; Christiansen, P; Schreiber, K; Nordenbo, Annette Mosbæk

    1996-01-01

    whole trial, and three patients discontinued the trial, two during the run-in period of azathioprine treatment and one at the introduction of PE. The primary efficacy variables were the number of gadolinium-enhancing lesions and the occurrence of new enhancing lesions on serial MRI performed every 3...

  7. Azathioprine desensitizes liver cancer cells to insulin-like growth factor 1 and causes apoptosis when it is combined with bafilomycin A1

    International Nuclear Information System (INIS)

    Hepatoblastoma is a primary liver cancer that affects children, due to the sensitivity of this tumor to insulin-like growth factor 1 (IGF-1). In this paper we show that azathioprine (AZA) is capable of inhibiting IGF1-mediated signaling cascade in HepG2 cells. The efficiency of AZA on inhibition of proliferation differs in the evaluated cell lines as follows: HepG2 (an experimental model of hepatoblastoma) > Hep3B (derived from a hepatocellular carcinoma) > HuH6 (derived from a hepatoblastoma) ≫ HuH7 (derived from a hepatocellular carcinoma) = Chang Liver cells (a non-malignant cellular model). The effect of AZA in HepG2 cells has been proven to derive from activation of Ras/ERK/TSC2, leading to activation of mTOR/p70S6K in a sustained manner. p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1. As a consequence, proliferation induced by IGF-1 is inhibited by AZA and autophagy increases leading to senescence of HepG2 cells. Our results suggest that AZA induces the autophagic process in HepG2 activating senescence, and driving to deceleration of cell cycle but not to apoptosis. However, when simultaneous to AZA treatment the autophagy was inhibited by bafilomycin A1 and the degradation of regulatory proteins of cell cycle (e.g. Rb, E2F, and cyclin D1) provoked apoptosis. In conclusion, AZA induces resistance in hepatoblastoma cells to IGF-1, which leads to autophagy activation, and causes apoptosis when it is combined with bafilomycin A1. We are presenting here a novel mechanism of action of azathioprine, which could be useful in treatment of IGF-1 dependent tumors, especially in its combination with other drugs. - Highlights: • Azathioprine activated Ras/ERK/TSC-2/mTOR/p70S6K signaling pathway in HepG2 cells. • Azathioprine inhibited IGF-1-mediated signaling cascade. • Azathioprine induced autophagy leading to cell cycle

  8. Azathioprine desensitizes liver cancer cells to insulin-like growth factor 1 and causes apoptosis when it is combined with bafilomycin A1

    Energy Technology Data Exchange (ETDEWEB)

    Hernández-Breijo, Borja [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Monserrat, Jorge [Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Román, Irene D. [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); González-Rodríguez, Águeda [Departamento de Biomedicina y Biotecnología, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); Fernández-Moreno, M. Dolores [Departamento de Biología de Sistemas, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Universidad de Alcalá, 28871 Alcalá de Henares (Spain); and others

    2013-11-01

    Hepatoblastoma is a primary liver cancer that affects children, due to the sensitivity of this tumor to insulin-like growth factor 1 (IGF-1). In this paper we show that azathioprine (AZA) is capable of inhibiting IGF1-mediated signaling cascade in HepG2 cells. The efficiency of AZA on inhibition of proliferation differs in the evaluated cell lines as follows: HepG2 (an experimental model of hepatoblastoma) > Hep3B (derived from a hepatocellular carcinoma) > HuH6 (derived from a hepatoblastoma) ≫ HuH7 (derived from a hepatocellular carcinoma) = Chang Liver cells (a non-malignant cellular model). The effect of AZA in HepG2 cells has been proven to derive from activation of Ras/ERK/TSC2, leading to activation of mTOR/p70S6K in a sustained manner. p70S6K phosphorylates IRS-1 in serine 307 which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of PI3K) and therefore causing the lack of response of HepG2 to IGF-1. As a consequence, proliferation induced by IGF-1 is inhibited by AZA and autophagy increases leading to senescence of HepG2 cells. Our results suggest that AZA induces the autophagic process in HepG2 activating senescence, and driving to deceleration of cell cycle but not to apoptosis. However, when simultaneous to AZA treatment the autophagy was inhibited by bafilomycin A1 and the degradation of regulatory proteins of cell cycle (e.g. Rb, E2F, and cyclin D1) provoked apoptosis. In conclusion, AZA induces resistance in hepatoblastoma cells to IGF-1, which leads to autophagy activation, and causes apoptosis when it is combined with bafilomycin A1. We are presenting here a novel mechanism of action of azathioprine, which could be useful in treatment of IGF-1 dependent tumors, especially in its combination with other drugs. - Highlights: • Azathioprine activated Ras/ERK/TSC-2/mTOR/p70S6K signaling pathway in HepG2 cells. • Azathioprine inhibited IGF-1-mediated signaling cascade. • Azathioprine induced autophagy leading to cell cycle

  9. Acute Pancreatitis Induced by Azathioprine and 6-mercaptopurine Proven by Single and Low Dose Challenge Testing in a Child with Crohn Disease.

    Science.gov (United States)

    Yi, Geum-Chae-Won; Yoon, Ka-Hyun; Hwang, Jin-Bok

    2012-12-01

    We report here a case of drug-induced acute pancreatitis proved by elimination and single, low dose challenge test in a child with Crohn disease. A 14-year-old boy with moderate/severe Crohn disease was admitted due to high fever and severe epigastric pain during administration of mesalazine and azathioprine. Blood test and abdominal ultrasonography revealed acute pancreatitis. After discontinuance of the medication and supportive care, the symptoms and laboratory findings improved. A single, low dose challenge test was done to confirm the relationship of the adverse drug reaction and acute pancreatitis, and to discriminate the responsible drug. Azathioprine and 6-mercaptopurine showed positive responses, and mesalazine showed a negative response. We introduce the method of single, low dose challenge test and its interpretation for drug-induced pancreatitis. PMID:24010098

  10. Disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under azathioprine and steroids: First case report and literature review.

    Science.gov (United States)

    Santos-Antunes, João; Abreu, Cândida; Magro, Fernando; Coelho, Rosa; Vilas-Boas, Filipe; Andrade, Patrícia; Lopes, Susana; Macedo, Guilherme

    2014-04-01

    Immunosuppressive treatments used in the management of Inflammatory Bowel Disease, namely steroids, thiopurines and anti-TNF drugs, raise the risk of acquiring opportunistic infections. However, most of these infections are mild and self-limited, not requiring specific therapy or suspension of the immunosuppressors. We report a case of disseminated cutaneous herpes simplex infection in a patient with Crohn's disease under steroids and azathioprine. PMID:24257435

  11. Effects of carbon tetrachloride and azathioprine on diethylnitrosamine and N-2-fluorenylacetamide-induced hyperplastic liver nodule and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sakata,Tatsuro

    1984-12-01

    Full Text Available Effects of carbon tetrachloride (CCl4 and azathioprine (AZP on the evolution of hyperplastic liver nodules and foci and hepatocellular carcinoma (HCC were tested in short- and long-term in vivo experiments. In diethylnitrosamine (DEN-treated rats, which were fed a N-2-fluorenylacetamide (FAA-containing diet and additionally treated with repeated CCl4 injections, gamma-glutamyl transpeptidase (gamma-GTP-positive hyperplastic nodules were markedly developed in the 8th week of the experiment. However, their number and area in liver sections were remarkably small in DEN-treated rats fed a diet containing both FAA and AZP. Increased area of gamma-GTP-positive foci was also observed in the 12th week in DEN-injected rats fed a choline-devoid died alone or treated with repeated doses of CCl4 alone. Hepatocellular carcinoma in DEN-injected rats treated with both FAA and CCl4 was first detected in the 21st week, and the incidence up to the 36th week was very high. However, no hepatocellular carcinoma developed in DEN-injected rats treated with both FAA and AZP. The increased activity of liver aniline hydroxylase observed 12 h after the administration of FAA, AZP or DEN alone was not observed when AZP was administered simultaneously with FAA to DEN-injected rats. The mechanisms of the effects of CCl4 and AZP on hepatocarcinogenesis are discussed with special reference to drug interaction.

  12. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    International Nuclear Information System (INIS)

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage IEA disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.)

  13. Determination of 6-thioguanine and 6-methylmercaptopurine metabolites in renal transplantation recipients and patients with glomerulonephritis treated with azathioprine.

    Science.gov (United States)

    Chrzanowska, M; Krzymański, M

    1999-04-01

    The metabolism of azathioprine (AZA) was studied by monitoring the concentrations of red blood cell (RBC) 6-thioguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-mMP) in 27 renal transplantation recipients and in 10 patient subjects with glomerulonephritis (GN). Concentrations of 6-TGNs and 6-mMP metabolites were measured using high-performance liquid chromatography (HPLC). Six patients from the group of renal transplantation recipients were also administered allopurinol. Median values of RBC 6-TGN and of 6-mMP metabolites concentrations in 21 renal transplantation recipients (without allopurinol) were 122 pmol/8x10(8) RBCs (range, allopurinol were significantly higher, despite AZA dose reduction, compared with the group without allopurinol and were equal to 363 and 122 pmol/8x10(8) RBC, p < 0.004, respectively. No significant differences were found between the concentrations of 6-mMP metabolites in either group. In the group of renal transplantation recipients, a significant correlation between white blood cell (WBC) count and 6-TGN concentration was established (r(s) = -0.59, p < 0.005). In the group of GN patients, the median values of 6-TGN and of 6-mMP metabolites concentrations were 108 pmol/8x10(8) RBCs (range, 0-297) and 420 pmol/8x10(8) RBC (range, 0-1440), respectively. There were no significant correlations between either the WBC count and 6-TGN concentrations or between 6-TGN concentrations and 6-mMP metabolites. We expect the results of our study to provide indications for better individualization of AZA therapy. PMID:10217345

  14. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    Energy Technology Data Exchange (ETDEWEB)

    Baadsgaard, O.

    1986-04-01

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared.

  15. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    International Nuclear Information System (INIS)

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared

  16. Prospective Evaluation of Pharmacogenomics and Metabolite Measurements upon Azathioprine Therapy in Inflammatory Bowel Disease: An Observational Study.

    Science.gov (United States)

    Fangbin, Zhang; Xiang, Gao; Liang, Ding; Hui, Liu; Xueding, Wang; Baili, Chen; Huichang, Bi; Yinglian, Xiao; Peng, Cheng; Lizi, Zhao; Yanjun, Chu; Feng, Xu; Minhu, Chen; Min, Huang; Pinjin, Hu

    2016-04-01

    Up to approximately 40% to 50% of patients discontinue thiopurine therapy during the course of inflammatory bowel disease (IBD). We investigated the role of the metabolite thiopurine in IBD treatment. This was a prospective study.IBD patients receiving azathioprine (AZA) were prospectively included. Thiopurine methyltransferase (TPMT) genotypes were examined before therapy, and thiopurine metabolite levels were examined at weeks 2, 4, 8, 12, 24, and 48. In total, 132 patients were included. The frequency of leucopenia increased at 6-thioguanine nucleotide (6-TGN) levels ≥420 pmol/8 × 10 RBC (odds ratio [OR] = 7.9; 95% confidence interval (95%CI): 3.5-18.0; P < 0.001) and increased more during the initial 12 weeks of thiopurine therapy (OR = 16.0; 95%CI: 5.7-44.9; P < 0.001). The patients with 6-TGN levels ≥420 pmol/8 × 10 RBC at weeks 4, 8, and 12 had an increased likelihood of leucopenia. Clinical response increased at 6-TGN levels ≥225 pmol/8 × 10 RBC (OR = 13.5; 95% CI: 3.7-48.9; P < 0.001) in Crohn disease (CD) patients. The CD patients with 6-TGN levels ≥225 pmol/8 × 10 RBC at weeks 8, 12, and 24 had an increased likelihood of successful clinical response. TPMT*3C had a specificity of 100%, but a sensitivity of 8% for predicting leucopenia.A 6-TGN level between 225 and 420 pmol/8 × 10 RBC could be a therapeutic window in patients receiving AZA therapy, and it could likely predict leucopenia in the initial 12 weeks of AZA therapy and a reasonable chance of successful clinical response in CD patients. The value of TPMT genotyping before thiopurine therapy is limited in Chinese patients with IBD, considering the low sensitivity of predicting leucopenia. PMID:27082580

  17. Effects of inhibitors of DNA, RNA, and protein synthesis on frequencies and types of premature chromosome condensation from x-ray induced micronuclei. [Cytosine arabinoside, azathioprine, thymidine, trenimon

    Energy Technology Data Exchange (ETDEWEB)

    Madle, S.; Nowak, J.; Obe, G.

    1976-10-28

    Cells containing x-ray induced micronuclei were treated for a few hours before fixation with inhibitors of DNA synthesis (cytosine arabinoside; azathioprine; thymidine; trenimon), of RNA synthesis (actinomycin D; ethidium bromide), and of protein synthesis (puromycin). Only the inhibitors of DNA synthesis lead to a significant suppression of the frequencies of mitoses with micronucleus derived premature chromosome condensation (PCC). We tend to interpret the result as follows: Micronuclei that are in the G1 phase of their cell cycles are accumulated at the G1/S border or in the early S phase of their cell cycles under the influence of the inhibitors of the DNA synthesis. Micronuclei blocked in this way cannot be induced to undergo PCC and seem to disappear from the cells.

  18. Hemossiderose pulmonar idiopática tratada com azatioprina: relato de caso em criança Idiopathic pulmonary hemosiderosis treated with azathioprine in a child

    Directory of Open Access Journals (Sweden)

    Clemax Couto Sant`Anna

    2007-12-01

    Full Text Available A hemossiderose pulmonar idiopática (HPI, principal causa de hemossiderose pulmonar em crianças, cursa com sangramento alveolar intermitente e presença de hemossiderófagos no escarro ou no lavado gástrico. O tratamento é baseado nos corticoesteróides e citostáticos, em condições especiais. Descreve-se o caso de uma menina de sete anos com HPI, que conseguiu controle parcial da doença mediante altas doses de corticoesteróide. O tratamento, no entanto, necessitou ser suspenso gradualmente visto a paciente ter desenvolvido fácies cushingóide. Foi iniciada a associação da azatioprina ao corticóide até a substituição total por azatioprina isolada, cujo uso foi mantido por quatro anos, com ótimo resultado.Idiopathic pulmonary hemosiderosis (IPH, the main cause of pulmonary hemosiderosis in children, is characterized by intermittent alveolar bleeding and hemosiderin-laden macrophages in sputum and in gastric lavage. The treatment is based on corticosteroids and cytotoxic drugs, under special conditions. We describe the case of a 7-year-old girl with IPH who achieved partial clinical remission with high doses of corticosteroids. However, the treatment had to be discontinued because the patient developed Cushing's syndrome. Treatment was started with an azathioprine-corticosteroid combination and then changed to azathioprine alone, which was maintained for four years, with excellent results.

  19. The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

    Science.gov (United States)

    Liu, Hui; Ding, Liang; Zhang, Fangbin; Zhang, Yu; Gao, Xiang; Hu, Pinjin; Bi, Huichang; Huang, Min

    2015-10-01

    Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs. PMID:26432087

  20. The effect of methotrexate and azathioprine on the serum levels of IgA-a1-antitrypsin complex in juvenile chronic arthritis

    Directory of Open Access Journals (Sweden)

    J.K. Lacki

    1997-06-01

    Full Text Available In the present study we investigated the influence of methotrexate (MTX and azathioprine (AZA on the serum levels of the IgA-a1-antitrypsin (IgA-AT complex in patients with the systemic form of juvenile chronic arthritis (JCA. Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months whereas AZA for 11 months (SD = 6 months. The average value of the complex was higher in JCA patients than in both control groups (0.74 ± 0.73 U vs 0.37 ± 0.13 U (control children, Pa1-acid-glycoprotein (r = 0.45, Pa1-antichymotrypsin (r = 0.52, Pa1-antitrypsin (r = 0.40, P<0.01 and IgA (r = 0.56, P<0.01 was established

  1. Glassy carbon electrodes modified with a film of nanodiamond-graphite/chitosan: Application to the highly sensitive electrochemical determination of Azathioprine

    International Nuclear Information System (INIS)

    A novel modified glassy carbon electrode with a film of nanodiamond-graphite/chitosan is constructed and used for the sensitive voltammetric determination of azathioprine (Aza). The surface morphology and thickness of the film modifier are characterized using atomic force microscopy. The electrochemical response characteristics of the electrode toward Aza are investigated by means of cyclic voltammetry. The modified electrode showed an efficient catalytic role for the electrochemical reduction of Aza, leading to a remarkable decrease in reduction overpotential and enhancement of the kinetics of the electrode reaction with a significant increase of peak current. The effects of experimental variables, such as the deposited amount of modifier suspension, the pH of the supporting electrolyte, the accumulation potential and time were investigated. Under optimal conditions, the modified electrode showed a wide linear response to the concentration of Aza in the range of 0.2-100 μM with a detection limit of 65 nM. The prepared modified electrode showed several advantages: simple preparation method, high stability and uniformity in the composite film, high sensitivity, excellent catalytic activity in physiological conditions and good reproducibility. The modified electrode can be successfully applied to the accurate determination of trace amounts of Aza in pharmaceutical and clinical preparations.

  2. Glassy carbon electrodes modified with a film of nanodiamond-graphite/chitosan: Application to the highly sensitive electrochemical determination of Azathioprine

    Energy Technology Data Exchange (ETDEWEB)

    Shahrokhian, Saeed, E-mail: shahrokhian@sharif.ed [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of); Institute for Nanoscience and Technology, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Ghalkhani, Masoumeh [Department of Chemistry, Sharif University of Technology, Tehran 11155-9516 (Iran, Islamic Republic of)

    2010-04-15

    A novel modified glassy carbon electrode with a film of nanodiamond-graphite/chitosan is constructed and used for the sensitive voltammetric determination of azathioprine (Aza). The surface morphology and thickness of the film modifier are characterized using atomic force microscopy. The electrochemical response characteristics of the electrode toward Aza are investigated by means of cyclic voltammetry. The modified electrode showed an efficient catalytic role for the electrochemical reduction of Aza, leading to a remarkable decrease in reduction overpotential and enhancement of the kinetics of the electrode reaction with a significant increase of peak current. The effects of experimental variables, such as the deposited amount of modifier suspension, the pH of the supporting electrolyte, the accumulation potential and time were investigated. Under optimal conditions, the modified electrode showed a wide linear response to the concentration of Aza in the range of 0.2-100 muM with a detection limit of 65 nM. The prepared modified electrode showed several advantages: simple preparation method, high stability and uniformity in the composite film, high sensitivity, excellent catalytic activity in physiological conditions and good reproducibility. The modified electrode can be successfully applied to the accurate determination of trace amounts of Aza in pharmaceutical and clinical preparations.

  3. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Henkenberens, Christoph; Christiansen, Hans [Medizinische Hochschule Hannover, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Franzke, Anke [Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation, Hannover (Germany); Raab, Peter [Medizinische Hochschule Hannover, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Hannover (Germany); Oschlies, Ilske; Klapper, Wolfram [Universitaetsklinikum Schleswig-Holstein, Institut fuer Pathologie, Sektion Haematopathologie, Kiel (Germany)

    2014-09-15

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I{sub E}A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [German] Retrospektive und prospektive Kohortenstudien deuten daraufhin, dass eine Beteiligung des zentralen Nervensystems (ZNS) in etwa bei 0,5 % der Patienten mit fortgeschrittenem Hodgkin-Lymphom auftritt. Die isoliert primaer intrakranielle Manifestation des Hodgkin-Lymphoms ist extrem selten, mit wenigen bisher bekannten Faellen. Wenig ist auch ueber die optimale

  4. In-vitro immunosuppression of canine T-lymphocyte-specific proliferation with dexamethasone, cyclosporine, and the active metabolites of azathioprine and leflunomide in a flow-cytometric assay.

    Science.gov (United States)

    Nafe, Laura A; Dodam, John R; Reinero, Carol R

    2014-07-01

    A high rate of mortality, expense, and complications of immunosuppressive therapy in dogs underscores the need for optimization of drug dosing. The purpose of this study was to determine, using a flow-cytometric assay, the 50% T-cell inhibitory concentration (IC50) of dexamethasone, cyclosporine, and the active metabolites of azathioprine (6-mercaptopurine) and leflunomide (A77 1726) in canine lymphocytes stimulated with concanavalin A (Con A). Whole blood was collected from 5 privately owned, healthy dogs of various ages, genders, and breeds. Peripheral blood mononuclear cells, obtained by density-gradient separation, were cultured for 72 h with Con A, a fluorochrome-tagged cell proliferation dye, and various concentrations of dexamethasone (0.1, 1, 10, 100, 1000, and 10 000 μM), cyclosporine (0.2, 2, 10, 20, 30, 40, 80, and 200 ng/mL), 6-mercaptopurine (0.5, 2.5, 50, 100, 250, and 500 μM), and A77 1726 (1, 5, 10, 25, 50, and 200 μM). After incubation, the lymphocytes were labeled with propidium iodide and an antibody against canine CD5, a pan T-cell surface marker. Flow cytometry determined the percentage of live, proliferating T-lymphocytes incubated with or without immunosuppressants. The mean (± standard error) IC50 was 3460 ± 1900 μM for dexamethasone, 15.8 ± 2.3 ng/mL for cyclosporine, 1.3 ± 0.4 μM for 6-mercaptopurine, and 55.6 ± 22.0 μM for A77 1722. Inhibition of T-cell proliferation by the 4 immunosuppressants was demonstrated in a concentration-dependent manner, with variability between the dogs. These results represent the initial steps to tailor this assay for individual immunosuppressant protocols for dogs with immune-mediated disease. PMID:24982547

  5. Patterns of 6-mercaptopurine and azathioprine maintenance therapy among a cohort of commercially insured individuals diagnosed with Crohn's disease in the United States

    Directory of Open Access Journals (Sweden)

    Lund JL

    2013-12-01

    Full Text Available Jennifer L Lund,1 Suzanne F Cook,2 Jeffery K Allen,2 Charlotte F Carroll,2 Michael D Kappelman3 1Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark; 2Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background and aims: Thiopurines, including 6-mercaptopurine (6-MP and azathioprine (AZA, are the mainstay of maintenance therapy for Crohn's disease (CD. However, studies examining their effectiveness in routine practice among diverse patient populations are lacking. Among a cohort of new users of 6MP/AZA, we described treatment patterns and changes in subsequent therapy. Methods: Using the Truven Health Analytics databases, we identified all individuals diagnosed with CD and initiating 6-MP/AZA monotherapy from 2001–2008 (n=3,657. We estimated the proportion of CD patients remaining on 6-MP/AZA monotherapy, using Kaplan–Meier methods, and identified predictors of treatment noncontinuation, using multivariable Cox regression. Among the “noncontinuers,” we described subsequent patterns of maintenance therapy and summarized the diagnosis and procedure codes and prescription drug claims preceding treatment discontinuation. Results: The 1-year 6-MP/AZA treatment continuation rate was 42%. Children (age ≤18 years and individuals with no prior anti-tumor necrosis factor (TNF use were more likely to continue 6-MP/AZA, while those dispensed more (>4 outpatient prescriptions for any drug before initiation of 6-MP/AZA were less likely to continue maintenance treatment. Overall, 1,128 (39% and 105 (4% individuals experienced a clinical event potentially indicating active disease or 6-MP/AZA-intolerance prior to discontinuation, respectively. Most patients discontinued therapy; among the remaining patients who failed to continue 6-MP/AZA, most augmented with an anti-TNF. Conclusion: Most patients initiating 6-MP

  6. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    International Nuclear Information System (INIS)

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 x 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished

  7. Effects of gamma radiation and azathioprine on Brucella abortus infection in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Elzer, P.H.; Rowe, G.E.; Enright, F.M.; Winter, A.J. (Department of Veterinary Microbiology, Immunology and Parasitology, College of Veterinary Medicine, Cornell University, Ithaca, NY (United States))

    1991-06-01

    Sublethal irradiation of BALB/c mice 4 hours prior to inoculation with 5 {times} 10(4) virulent Brucella abortus, caused significant (P less than 0.01) reductions in bacterial numbers in comparison with numbers in unirradiated controls. Numbers of brucellae in the spleen were significantly lower by 5 days after inoculation and decreased thereafter, so that at 2 and 3 weeks after inoculation, there were up to 1,000-fold fewer organisms in the spleen of irradiated mice. The number of brucellae in the spleen increased in irradiated mice thereafter. The course of events in the liver was similar, but developed more slowly, and peak differences in bacterial numbers were about 1 log less. These phenomena were not attributable to differences in implantation of brucellae in the liver or spleen, nor to an abnormal distribution of organisms in other organs of irradiated mice. Irradiation of mice during the plateau phase of infection also resulted in significant (P less than 0.05) reductions in bacterial counts in the spleen during the succeeding 4 weeks. Macrophage activation in the spleen, measured by a Listeria monocytogenes-killing assay, was significantly (P less than 0.01) increased by irradiation alone at 1 week after inoculation and at that time was significantly (P less than 0.01) greater in B abortus-infected, irradiated mice than in B abortus-infected controls. Histologic, cytologic, and immunologic studies revealed that the decrease in numbers of organisms between 1 and 2 weeks after inoculation in irradiated mice occurred at a time when their immune response to B abortus was suppressed and when numbers of neutrophils and monocytes infiltrating the spleen were significantly (P less than 0.01) diminished.

  8. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    Directory of Open Access Journals (Sweden)

    Sadaf A Karbelkar

    2016-01-01

    Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also.

  9. Use of azathioprine during pregnancy and in the postoperative setting in Crohn's disease: A worldwide survey of experts

    OpenAIRE

    Peyrin-Biroulet, Laurent; Oussalah, Abderrahim; Roblin, Xavier; Sparrow, Miles,

    2011-01-01

    Abstract Background: While thiopurines are considered safe in humans, they are still pregnancy FDA category D drugs. Prevention of postoperative recurrence is a challenge in clinical practice in Crohn?s disease. The ECCO consensus states that thiopurines should be considered in high-risk patients. Aim: To perform a worldwide survey for evaluating the extent to which gastroenterologists who are experts in the field of IBD are utilizing thiopurines during pregnancy and in ...

  10. Determination of the orientation of azathioprine adsorbed on a silver electrode by SERS and ab initio calculations

    Science.gov (United States)

    Chen, Shi-Ping; Qiao, Zhuahong; Vivoni, Alberto; Hosten, Charles M.

    2003-10-01

    We report the SERS spectrum of azthioprine (AZA) on a silver electrode surface and the results of normal mode calculations using empirical and ab initio calculations of the 6-mercaptopurione (6-MP) component of AZA. The empirical calculations were done with a Urey-Bradley force field (UBFF) and the ab initio calculations with the STO-3G basis set using the UHF, MP2 and BLYP methods. From the difference between the SERS and solid spectra, we determined that AZA attaches edge-on to the surface through the N3 site on the 6-MP component of the molecule. The UBFF calculation on an Ag adatom-molecule model reproduced most of the main observed frequency shifts in the SERS spectrum. With a similar model, the ab initio calculations yielded frequency shifts in the same direction as the one observed for the in-plane normal modes, but they yielded opposite shifts for the out-of-plane normal modes. This phenomenon may be attributed to a face-on interaction of the 6-MP component with a neighboring adatom made possible by an inclination of the molecule on the surface.

  11. Hemossiderose pulmonar idiopática tratada com azatioprina: relato de caso em criança Idiopathic pulmonary hemosiderosis treated with azathioprine in a child

    OpenAIRE

    Clemax Couto Sant`Anna; Angélica Almada Horta; Mônica Tessinari Rangel Tura; Maria de Fatima Bazhuni Pombo March; Sidnei Ferreira; Rafaela Baroni Aurilio; Débora Brandão Vieira

    2007-01-01

    A hemossiderose pulmonar idiopática (HPI), principal causa de hemossiderose pulmonar em crianças, cursa com sangramento alveolar intermitente e presença de hemossiderófagos no escarro ou no lavado gástrico. O tratamento é baseado nos corticoesteróides e citostáticos, em condições especiais. Descreve-se o caso de uma menina de sete anos com HPI, que conseguiu controle parcial da doença mediante altas doses de corticoesteróide. O tratamento, no entanto, necessitou ser suspenso gradualmente vist...

  12. Comparative Analysis of Azathioprine versus Cyclosporine-based Therapy in Primary Haplo-identical Live-Donor Kidney Transplantation: A 20-Year Experience

    OpenAIRE

    Gheith Osama; Bakr Mohamed; Fouda Mohamed; Shokeir Ahmed; Sobh Mohamed; Ghoneim Mohamed

    2008-01-01

    Chronic allograft nephropathy (CAN) remains a major cause of graft failure over the long term, second only to patient mortality. The main adverse effects of cyclosporine A (CsA) include nephrotoxicity, hypertension, symptomatic hyperuricemia, hirsutism, and gum hyperplasia. Available studies among live related donor renal transplants lack adequate information regarding the long-term efficacy and safety of primary CsA-based immunosuppressive regimens. This prospective randomized study is aimed...

  13. The immunosuppressive drug azathioprine inhibits biosynthesis of the bacterial signal molecule cyclic-di-GMP by interfering with intracellular nucleotide pool availability.

    OpenAIRE

    Antoniani, Davide; Rossi, Elio; Rinaldo, Serena; BOCCI, PAOLA; Lolicato, Marco; Paiardini, Alessandro; Raffaelli, Nadia; Cutruzzolà, Francesca; Landini, Paolo

    2013-01-01

    In Gram-negative bacteria, production of the signal molecule c-di-GMP by diguanylate cyclases (DGCs) is a key trigger for biofilm formation, which, in turn, is often required for the development of chronic bacterial infections. Thus, DGCs represent interesting targets for new chemotherapeutic drugs with anti-biofilm activity. We searched for inhibitors of the WspR protein, a Pseudomonas aeruginosa DGC involved in biofilm formation and production of virulence factors, using a set of microbiolo...

  14. Drug: D03033 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03033 Drug Azathioprine ... sodium (USP); Imuran (TN) C9H7N7O2S. Na 300.028 300.2523 D03033.gif Imm ... UPPRESSANTS L04AX Other immunosuppressants L04AX01 Azathioprine ... D03033 Azathioprine ... sodium (USP) USP drug classifi ... :br08302] Immunological Agents Immune Suppressants Azathioprine ... D03033 Azathioprine ... sodium (USP) CAS: 55774-33-9 P ...

  15. Polyarteritis nodosa

    Science.gov (United States)

    ... steroids, such as prednisone. Similar medicines, such as azathioprine, methotrexate or mycophenolate that allow for reducing the ... drugs that suppress the immune system (such as azathioprine or cyclophosphamide) can improve symptoms and the chance ...

  16. Enkeltcenteropgorelse af nyretransplanterede patienters nyrefunktion og immunsuppressive behandling

    DEFF Research Database (Denmark)

    Frederiksen, A.M.; Ewers, B.; Gasbjerg, A.; Marckmann, P.; Hansen, Jesper Melchior

    2008-01-01

    (74%) were treated with triple-drug immunosuppression, in most cases (46%) with the combination prednisolone-ciclosporine-azathioprine. During recent years, azathioprine has been increasingly replaced by mycophenolate mofetil. CONCLUSIONS: The majority of kidney-transplanted patients with a...

  17. Oseltamivir

    Science.gov (United States)

    ... system such as azathioprine (Imuran); cyclosporine (Neoral, Sandimmune); cancer chemotherapy medications; methotrexate (Rheumatrex); sirolimus (Rapamune); oral steroids such as dexamethasone ( ...

  18. Thiopurines and inhibition of Rac1 in vascular disease

    OpenAIRE

    Marinković, G.

    2015-01-01

    The mechanism of immunosuppressive drug azathioprine is not clear, while azathioprine has been used for 60 years in clinical practice in patients undergoing transplantation surgery or to combat autoimmune disease. Part of the function of azathioprine became evident in specific immune cells, namely T cells, demonstrating that small GTPase Rac1 was inhibited by azathioprine and thereby reduced their inflammatory response. We show that 6-mercaptopurine and thiopurines 6-thio-GDP and 6-thio-GTP, ...

  19. Drug: D00238 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D00238 Drug Azathioprine ... (JP16/USP/INN); Azasan (TN); Imuran (TN) C9H7N7O2S 277.0382 277.2626 D0 ... ng metabolism 399 Miscellaneous 3999 Others D00238 Azathioprine ... (JP16/USP/INN) Anatomical Therapeutic Chemical (AT ... UPPRESSANTS L04AX Other immunosuppressants L04AX01 Azathioprine ... D00238 Azathioprine ... (JP16/USP/INN) USP drug classi ...

  20. L’azathioprine dans les maladies inflammatoires chroniques intestinales : impact de son métabolisme sur l’efficacité et la sécurité thérapeutique

    OpenAIRE

    Dewit, Olivier

    2012-01-01

    Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side effects and inefficacy are a major concern as they lead to withdrawal of the drug. Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyl transferase is the only one routinely measured by pheno- or genotyping. A decreased TPMT activity results in a potential overdosing of TP drugs leadin...

  1. Disease Modifying Antirheumatic Drugs (DMARDs) (Beyond the Basics)

    Science.gov (United States)

    ... medications include gold salts, azathioprine , and cyclosporine . Methotrexate — Methotrexate was originally used as a chemotherapy treatment for cancer. When used in much lower doses for rheumatoid ...

  2. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.9.2. Haematological complications. Leukopenia.

    Science.gov (United States)

    2002-01-01

    GUIDELINE: Because leukopenia is relatively common after kidney transplantation, regular screening and careful evaluation of its causes are recommended. Azathioprine and mycophenolate mofetil may lead to leukopenia. The combination of allopurinol and azathioprine should be avoided. Leukopenia is often associated with viral infections. PMID:12091648

  3. Cyanocobalamin Nasal Gel

    Science.gov (United States)

    ... absorbed from food; or a vegan diet (strict vegetarian diet that does not allow any animal products ... of the following: azathioprine; antibiotics such as chloramphenicol; cancer chemotherapy; colchicine; folic acid; iron supplements; medications for ...

  4. Primaer cerebral vaskulitis hos børn

    DEFF Research Database (Denmark)

    Pradsgaard, Dan Østergaard; Stausbøl-Grøn, Brian; Østergaard, John Rosendahl;

    2010-01-01

    successful in most of the patients. In two patients with progressive CNS vasculitis, the treatment was supplemented by intravenous cyclophosphamide and azathioprin, respectively. CONCLUSION: Primary CNS vasculitis is an acutely acquired inflammatory disease with severe neurological deficits and sequelae...

  5. Use of thiopurines in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen;

    2013-01-01

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine ...

  6. Immune mediated neutropenia and thrombocytopenia in 3 giant schnauzers.

    Science.gov (United States)

    Vargo, Cheryl L; Taylor, Susan M; Haines, Deborah M

    2007-11-01

    Neutropenia, thrombocytopenia, and splenomegaly were recognized in 3 adult female giant schnauzers. Antineutrophil antibodies were demonstrated in 2 dogs. Following splenectomy, administration of prednisone and azathioprine resulted in normalization of neutrophil and platelet numbers in all dogs. PMID:18050797

  7. Ulcerative colitis and Sweet’s syndrome: A case report and review of the literature

    OpenAIRE

    Ali, Massud; Duerksen, Donald R

    2008-01-01

    A 47-year-old man with a history of ulcerative colitis on prednisone and azathioprine was admitted to the hospital with a four-day history of fever, skin rash, arthralgias and leukocytosis. A skin biopsy demonstrated neutrophilic infiltration of the dermis that was consistent with Sweet’s syndrome. He improved after several days with an increase in his prednisone and azathioprine. Sweet’s syndrome is a rare cutaneous manifestation of inflammatory bowel disease, with approximately 40 cases rep...

  8. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  9. Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs

    DEFF Research Database (Denmark)

    Olsen, N; Halberg, P; Halskov, O; Bentzon, M W

    1988-01-01

    In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed...... joints decreased in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease....

  10. Nonmelanoma skin cancer risk awareness in azathioprine‐treated myasthenia gravis patients

    OpenAIRE

    McGurgan, Iain J.; McGuigan, Christopher

    2015-01-01

    Abstract Objectives Increased rates of NMSC (nonmelanoma skin cancer) have recently been reported in people with MG (myasthenia gravis) receiving azathioprine treatment. Guidelines on azathioprine for patients with dermatological and gastrointestinal disorders stress the importance of NMSC risk awareness and prevention. The aim of this study is to assess whether MG patients are being informed of this risk. Methods Clinical records of patients with MG attending a university hospital neurology ...

  11. Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

    OpenAIRE

    Elisa Liverani; Filippo Leonardi; Lucia Castellani; Carla Cardamone; Andrea Belluzzi

    2013-01-01

    Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis...

  12. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing.

    Science.gov (United States)

    Teml, Alexander; Schaeffeler, Elke; Herrlinger, Klaus R; Klotz, Ulrich; Schwab, Matthias

    2007-01-01

    This review summarises clinical pharmacological aspects of thiopurines in the treatment of chronic inflammatory bowel disease (IBD). Current knowledge of pharmacogenetically guided dosing is discussed for individualisation of thiopurine therapy, particularly to avoid severe adverse effects. Both azathioprine and mercaptopurine are pro-drugs that undergo extensive metabolism. The catabolic enzyme thiopurine S-methyltransferase (TPMT) is polymorphically expressed, and currently 23 genetic variants have been described. On the basis of an excellent phenotype-genotype correlation for TPMT, genotyping has become a safe and reliable tool for determination of a patient's individual phenotype. Thiopurine-related adverse drug reactions are frequent, ranging from 5% up to 40%, in both a dose-dependent and -independent manner. IBD patients with low TPMT activity are at high risk of developing severe haematotoxicity if pharmacogenetically guided dosing is not performed. Based on several cost-benefit analyses, assessment of TPMT activity is recommended prior to thiopurine therapy in patients with IBD. The underlying mechanisms of azathioprine/mercaptopurine-related hepatotoxicity, pancreatitis and azathioprine intolerance are still unknown. Although the therapeutic response appears to be related to 6-thioguanine nucleotide (6-TGN) concentrations above a threshold of 230-260 pmol per 8 x 10(8) red blood cells, at present therapeutic drug monitoring of 6-TGN can be recommended only to estimate patients' compliance.Drug-drug interactions between azathioprine/mercaptopurine and aminosalicylates, diuretics, NSAIDs, warfarin and infliximab are discussed. The concomitant use of allopurinol without dosage adjustment of azathioprine/mercaptopurine leads to clinically relevant severe haematotoxicity due to elevated thiopurine levels. Several studies indicate that thiopurine therapy in IBD during pregnancy is safe. Thus, azathioprine/mercaptopurine should not be withdrawn in strictly

  13. Use of thiopurines in inflammatory bowel disease.

    Science.gov (United States)

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen; Rogler, Gerhard

    2013-02-21

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine and thioguanine. We will briefly summarize dose recommendations, indications for thiopurine therapy and side effects which are relevant in clinical practice. We discuss some currently debated topics, including the combination of azathioprine and allopurinol, switching of thiopurine therapy in case of side effects, the use of azathioprine in pregnancy, the infection risk using thiopurines and the evidence when to stop thiopurines. Excellent reviews have been published on the thiopurine metabolic pathway which will not be discussed here in detail. PMID:23467510

  14. Bird's Nest View from a Dermatologist's Eye

    Science.gov (United States)

    Anisha, Sethi; Sukhjot, Kaur; Sunil, Gupta Kumar; Sandeep, Puri

    2016-01-01

    Plica neuropathica also known as “birds nest” is irreversible matting of hair seen in otherwise healthy individuals and is usually associated with use of ionic/herbal soaps, shampoos, parasitic infestations, psychiatric alterations, or neglect. Anagen effluvium is a known side effect of many immunosuppressive drugs. Rarely matting of hair has been reported following azathioprine. We report plica neuropathica in two chronically ill patients on immunosuppressive drugs, that is, azathioprine and methotrexate along with a review of literature of its etiological factors and pathogenesis.

  15. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E;

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time of transplanta......A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time of...

  16. Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

    2012-01-01

    We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activation...

  17. Endoscopic case: Crohn’s disease with pyloric stenosis

    OpenAIRE

    Pereira, F

    2012-01-01

    ABSTRACT We present a case of pyloric stenosis that occurred in a patient with ileocolic Crohn’s disease without significant gastric inflammation, and treated with azathioprine and messalamine. Balloon dilatation, steroid therapy, omeprazol and polymeric enteral nutrition were successful to resolve the stenosis. Later the patient was put on infliximab with good clinical response.

  18. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    OpenAIRE

    O. N. Egorova; B S Belov; S G Radenska-Lopovok; Ye. G. Sazhina

    2014-01-01

    Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  19. Two Brothers with Skewed Thiopurine Metabolism in Ulcerative Colitis Treated Successfully with Allopurinol and Mercaptopurine Dose Reduction

    OpenAIRE

    Hoentjen, Frank; Hanauer, Stephen B.; de Boer, Nanne K; Rubin, David T.

    2011-01-01

    Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism....

  20. Drug hypersensitivity syndrome

    OpenAIRE

    Rashmi Kumari; Dependra K Timshina; Devinder Mohan Thappa

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalit...

  1. Fatal hæmofagocytisk lymfohistiocytose og mononukleose hos en patient med colitis ulcerosa

    DEFF Research Database (Denmark)

    Juul Ingvardsen, Charlotte; Ballegaard, Vibe Cecilie; Homøe, Preben

    2012-01-01

    We report a case of Epstein-Barr virus primo infection with the development of lethal haemophagocytic lymphohistiocytosis (HLH) in a 22 year-old man, who was being treated with azathioprin for colitis ulcerosa. HLH is a rare, life-threatening disease, which is caused by an inappropriate activatio...

  2. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    Directory of Open Access Journals (Sweden)

    O. N. Egorova

    2012-01-01

    Full Text Available Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  3. Combination therapy of the plaque form of Weber–Christian idiopathic panniculitis

    Directory of Open Access Journals (Sweden)

    O. N. Egorova

    2014-07-01

    Full Text Available Panniculitides are a group of heterogenic inflammatory diseases that involve the subcutaneous fat. Treatment for panniculitides, idiopathic ones in particular, has not been conclusively developed and is generally performed empirically. The paper describes a case successfully treated with glucocorticosteroids in combination with azathioprine for the plaque form of Weber–Christian panniculitis.

  4. Pharmacokinetic optimization of immunosuppressive therapy in thoracic transplantation: part I.

    OpenAIRE

    Monchaud, Caroline; Marquet, Pierre

    2009-01-01

    International audience Although immunosuppressive treatments and therapeutic drug monitoring (TDM) have significantly contributed to the increased success of thoracic transplantation, there is currently no consensus on the best immunosuppressive strategies. Maintenance therapy typically consists of a triple-drug regimen including corticosteroids, a calcineurin inhibitor (ciclosporin or tacrolimus) and either a purine synthesis antagonist (mycophenolate mofetil or azathioprine) or a mammali...

  5. Interactions of Prednisolone and Other Immunosuppressants Used in Dual Treatment of Systemic Lupus Erythematosus in Lymphocyte Proliferation Assays

    OpenAIRE

    Kamal, Mohamed A.; Jusko, William J.

    2004-01-01

    Systemic lupus erythematosus is an autoimmune disease primarily affecting women. Currently, systemic lupus erythematosus therapy is suboptimal due to adverse effects of immunosuppressants, particularly corticosteroids. This study determines the single effects of prednisolone, dehydroepiandrosterone, bromocriptine, tamoxifen, mycophenolic acid, 2-chloro-2′-deoxyadenosine, azathioprine, and chloroquine on lectin-stimulated proliferation of human T lymphocytes, as well as determining whether the...

  6. Liver transplantation

    OpenAIRE

    Rodríguez-Perálvarez, M; De La Mata, M; Burroughs, A K

    2014-01-01

    Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients sh...

  7. Budesonide in previously untreated autoimmune hepatitis

    NARCIS (Netherlands)

    Wiegand, J; Schuler, A; Kanzler, S; Lohse, A; Beuers, U; Kreisel, W; Spengler, U; Koletzko, S; Jansen, PLM; Hochhaus, G; Mollmann, HW; Prols, M; Manns, MP

    2005-01-01

    Background: Autoimmune hepatitis (AIH) is a chronic liver disease that is effectively treated with immunosuppressive therapy. Predniso(lo)ne, often in combination with azathioprine, is the basic therapeutic option to induce remission. However, this regimen can cause numerous side effects. The aim of

  8. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing

    DEFF Research Database (Denmark)

    Relling, M V; Gardner, E E; Sandborn, W J; Schmiegelow, K; Pui, C-H; Yee, S W; Stein, Paul C.; Carrillo, Maria Berrocal; Evans, W E; Klein, T E

    2011-01-01

    Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TP...... recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype....

  9. Eosinofil enteritis

    DEFF Research Database (Denmark)

    Gjersøe, P; Rasmussen, S N; Hansen, B F

    2000-01-01

    examination revealed the diagnosis of eosinophilic enteritis primarily localized to the tunica muscularis. One year postoperatively he relapsed and small bowel X-ray demonstrated 1 m narrow and irregular ileum. He was treated with mesalamine, azathioprine, and cromoglicate, went into remission and fares well...

  10. Deoxyspergualin in relapsing and refractory Wegener's granulomatosis

    DEFF Research Database (Denmark)

    Flossmann, O; Baslund, B; Bruchfeld, A; Cohen Tervaert, J W; Hall, C; Heinzel, P; Hellmich, B; Luqmani, R A; Nemoto, K; Tesar, V; Jayne, D R W

    2008-01-01

    primary endpoint was complete remission (BVAS 0 for at least 2 months) or partial remission (BVAS <50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for 6 months. RESULTS: 42/44 patients (95%) achieved at least partial remission and 20/44 (45%) achieved complete...

  11. Dramatic improvement of severe acne pustolosa after adalimumab in a patient with ulcerative colitis.

    Science.gov (United States)

    Rispo, Antonio; Musto, Dario; Imperatore, Nicola; Testa, Anna; Rea, Matilde; Castiglione, Fabiana

    2016-04-01

    A 22-year-old male with extensive steroid-dependent/azathioprine-refractory ulcerative colitis and preexistent severe refractory acne pustolosa (AP) was successfully treated with adalimumab for both conditions. Severe AP could be considered a further indication, instead of a relative restriction, to anti-TNFα in steroid-dependent IBD patients needing therapy with this class of drugs. PMID:27099725

  12. Is amyloid A (AA) amyloidosis always secondary?

    OpenAIRE

    Maury, C P; Törnroth, T; Wegelius, O

    1985-01-01

    The case is reported of a patient with systemic AA amyloidosis associated with non-specific mesenteric lymphadenitis and chronic sideropenia. Renal, small bowel, and rectal biopsies showed amyloid deposits containing AA protein, as defined by potassium permanganate sensitivity and by reactivity with AA antiserum. Reversal of the nephrotic syndrome occurred during steroid-azathioprine therapy.

  13. Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

    Directory of Open Access Journals (Sweden)

    Elisa Liverani

    2013-01-01

    Full Text Available Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullo’s syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?

  14. Clinical Outcomes of Remission Induction Therapy for Severe Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    NARCIS (Netherlands)

    Miloslavsky, E. M.; Specks, U.; Merkel, P. A.; Seo, P.; Spiera, R.; Langford, C. A.; Hoffman, G. S.; Kallenberg, C. G. M.; St Clair, E. W.; Tchao, N. K.; Viviano, L.; Ding, L.; Sejismundo, L. P.; Mieras, K.; Ikle, D.; Jepson, B.; Mueller, M.; Brunetta, P.; Allen, N. B.; Fervenza, F. C.; Geetha, D.; Keogh, K.; Kissin, E. Y.; Monach, P. A.; Peikert, T.; Stegeman, C.; Ytterberg, S. R.; Stone, J. H.

    2013-01-01

    Objective. To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). Methods. The Rit

  15. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  16. Hematologic toxicity of immunosuppressive treatment.

    Science.gov (United States)

    Danesi, R; Del Tacca, M

    2004-04-01

    The administration of immunosuppressive agents may be associated with the occurrence of hematologic toxicity, such as anemia, due to bone marrow suppression or hemolysis, leukopenia, and thrombocytopenia. The administration of azathioprine and mycophenolate mofetil is more frequently associated with bone marrow suppression, while hemolytic-uremic syndrome may occur after administration of cyclosporine, tacrolimus, or muromonab (OKT3) and may be associated with the loss of the allograft. Moreover, microangiopathic hemolytic anemia and thrombocytopenia are rare, but potentially severe, complications of immunosuppressive treatment with tacrolimus and cyclosporine; they are characterized by intravascular hemolysis due to mechanical destruction of red cells as a result of pathological changes in small blood vessels. Viral infections (cytomegalovirus), administration of antiviral agents (gancyclovir), inhibitors of angiotensin-converting enzyme and angiotensin II receptor antagonists, antibacterial agents (sulfamethoxazole and trimethoprim), and allopurinol may aggravate bone marrow suppression, particularly when administered with agents that interfere with purine biosynthesis, including azathioprine and mycophenolate mofetil. PMID:15110637

  17. [Drug-drug interactions in antirheumatic treatment].

    Science.gov (United States)

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  18. Absence of osteoporosis in an adult population undergoing combined immunosuppressive therapy for chronic active hepatitis

    International Nuclear Information System (INIS)

    Thirty adult patients who had received 1-20 years of combined immunosuppressive therapy (CIT) for chronic active hepatitis (CAH) underwent dual-photon absorptiometry (DPA) of L-2 through L-4 CIT consisted of azathioprine and prednisone supplemented and calcium and vitamin D. Osteoporosis is known to occur in patients with CAH, and in other clinical settings prednisone therapy has been shown to induce osteoporosis. For these 30 adult CAH patients undergoing CIT, absorptiometric measurements did not differ significantly from those in age- and sex-matched normal controls. CIT therapy for CAH may have arrested the long-term loss of bone mineral often produced by CAH. The authors' hypothesize that a combined azathioprine and prednisone regimen with reduced corticosteroid requirements was responsible for this favorable outcome

  19. Infliximab for inflammatory bowel disease in Denmark 1999-2005: clinical outcome and follow-up evaluation of malignancy and mortality

    DEFF Research Database (Denmark)

    Caspersen, Sarah; Elkjaer, Margarita; Riis, Lene;

    2008-01-01

    .4%). Significantly fewer infusion reactions were seen in patients also receiving azathioprine or methotrexate (63 of 2079; 3.0%), compared with patients not receiving azathioprine or methotrexate (83 of 1272; 6.5%) (P < .0001). Severe adverse events were observed after 112 of 3351 infusions (3.3%) in a total of 95...... patients (14.6%). Four patients developed cancer versus 5.9 expected (standardized incidence ratio, 0.7; 95 confidence interval, 0.2-1.7) and 13 patients died versus 6.9 expected (standardized mortality ratio, 1.9; 95% confidence interval, 1.0-3.2). Two deaths caused by infections were possibly related to...... infliximab. CONCLUSIONS: Infliximab seemed effective in IBD and generally was well tolerated. However, rare but severe adverse events occurred, and patients receiving infliximab therefore should be selected carefully and monitored closely. No lymphomas and no increased risk of cancer were observed....

  20. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

  1. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Foegh, M.L.; Khirabadi, B.S.; Ramwell, P.W.

    1986-07-01

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day.

  2. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    International Nuclear Information System (INIS)

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day

  3. Púrpura trombocitopénico inmune asociado a infección por virus hepatitis C en paciente hemofílico: Caso clínico Immune thrombocytopenic purpura associated to hepatitis C virus infection: Report of one case

    Directory of Open Access Journals (Sweden)

    LILIAN PILLEUX C

    2010-09-01

    Full Text Available Hepatitis C Virus (HCV is a cause of secondary chronic immune thrombocytopenic purpura (ITP. We report a 43 year old man with mild Hemophilia A, who received blood transfusions during childhood, that consulted for epistaxis and ecchymoses. The laboratory showed a platelet count of 23.000/mm³, positive HCV serology and elevated transaminases. Steroids administered in pulses followed by oral doses resulted in a partial response requiring a second pulse and association of azathioprine. A steroidal diabetes appeared. Given his refractoriness, splenectomy and liver biopsy were performed. He continued on azathioprine maintaining a platelet count near 50.000/mm³ but continued with bleeding episodes. Liver biopsy showed a chronic active hepatitis.

  4. A case of cutaneous sterile pyogranuloma/granuloma syndrome in a maltese.

    Science.gov (United States)

    Kawarai, Shinpei; Matsuura, Shinobu; Yamamoto, Saburo; Kiuchi, Akio; Kanemaki, Nobuyuki; Madarame, Hiroo; Shirota, Kinji

    2014-01-01

    Cutaneous sterile pyogranuloma/granuloma syndrome (SPGS) is a locally restricted multinodular dermatitis. Affected dogs are typically healthy, but a few show systemic signs. Herein, a case of a dog presenting with generalized ulcerative dermatitis with systemic signs of mild anemia and an increased C-reactive protein level is described. Cutaneous SPGS was diagnosed by histopathology, negative staining causative organisms, and polymerase chain reaction for Mycobacterium spp. Successful treatment was achieved by immunosuppressive drugs, including prednisolone and azathioprine, administered for at least 20 mo. Recurrences of skin lesions were observed when prednisolone and/or azathioprine were discontinued. Long-term management with immunosuppressive agents may be required if the affected dog exhibits severe symptoms of cutaneous SPGS. PMID:24855086

  5. Cardiac sarcoidosis &hypen; the value of magnetic resonance imaging.

    Science.gov (United States)

    Smedema, J. P.; Doubell, A. F.

    2000-08-01

    This report describes the management of a 40-year-old woman presenting with recurrent monomorphic ventricular tachycardias secondary to cardiac sarcoidosis. She was managed with a combination of steroids, azathioprine and mexiletine. Magnetic resonance imaging proved to be of great help in diagnosing this condition as well as in following up the response to therapy. A brief review on the management of this condition is presented. PMID:11447482

  6. New properties of immunotropic preparation from porcine skin.

    Science.gov (United States)

    Belova, O V; Arion, V Y; Zimina, I V; Lukandina, T A; Krotova, S B; Sysoeva, O B; Tret'yakov, V A

    2007-09-01

    We studied new immunological and physicochemical properties of K-activin, immunotropic preparation from porcine skin isolated by the acetone method. The preparation restored the sensitivity of background rosette-forming cells in the spleen of thymectomized mice to the inhibitory effect of azathioprine in vivo and practically normalized serum thymic activity reduced in thymectomized mice. The molecular weight of proteins present in K-activin and previously detected by SDS-PAAG electrophoresis was determined by MALDI mass spectrometry PMID:18457058

  7. Post-transplantation diabetes mellitus

    OpenAIRE

    N Zbiti; K Souly; Z Errami; L Guendouz; L Benamar; F Ezaitouni; N Ouzeddoun; R Bayahia; A Chabraoui; H Rhou

    2012-01-01

    To determine the prevalence of post-kidney transplantation diabetes (PTDM) and to assess its risk factors, we retrospectively studied 92 non-diabetic kidney transplant patients. The immunosuppressive drugs used to prevent rejection included prednisone, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antimetabolite (azathioprine or mycofenolate mofetil). Diabetes was defined according to the WHO criteria and the American Diabetes Association. The mean age of our patients was 35.8 ±...

  8. Sweet syndrome associated with interferon

    OpenAIRE

    Rodriguez-Lojo, Romina; Castineiras, Iria; Juarez, Yolanda; Lueiro, Mercedes; Armesto, Ana; Fernandez-Diaz, M. Luisa

    2015-01-01

    Although still very rare, drug-related cases of Sweet’s syndrome have been reported. The more frequent associated medications with drug induced Sweet´s syndrome was: tetracyclines, trimethoprim-sulphamethaxazol, azatioprine, all trans retinoic acid, nitrofurantoin, granulocyte colony-stimulating factor, hydralazine, tripharil, lithium, oral contraceptives, furosemide, celecoxib and azathioprine. We only found one case of drug-induced Sweet´s syndrome secondary to pegylated interferon...

  9. Subcutaneous Histiocytoid Sweet Syndrome Associated with Crohn Disease in an Adolescent

    OpenAIRE

    Rosa María Fernández-Torres; Susana Castro; Ana Moreno; Roberto Álvarez; Eduardo Fonseca

    2014-01-01

    We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C) from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, ...

  10. Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

    OpenAIRE

    G.A. Spinelli; C.R. Felipe; P.G. Machado; Garcia, R.; D.E. Casarini; S.R. Moreira; Park, S. I.; H. Tedesco-Silva Jr.; J.O. Medina-Pestana

    2006-01-01

    The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttrans...

  11. Severe Refractory Immune Thrombocytopenia Successfully Treated with High-Dose Pulse Cyclophosphamide and Eltrombopag

    Directory of Open Access Journals (Sweden)

    Faiz Anwer

    2015-01-01

    Full Text Available Severe refractory ITP is clinically challenging and a variety of single or combination chemotherapies have been tried with limited outcome. We report a case of ITP that was unresponsive to multiple agents including high-dose steroid, IVIG, Rho(D immune globulin, rituximab, cyclosporine, azathioprine, vincristine, mycophenolate mofetil, romiplostim, and eltrombopag; however, it achieved complete remission with combination treatment of cyclophosphamide and eltrombopag.

  12. Use of a xanthine oxidase inhibitor in autoimmune hepatitis.

    Science.gov (United States)

    Al-Shamma, Safa; Eross, Balint; Mclaughlin, Simon

    2013-03-01

    A 62-year-old woman with type 1 autoimmune hepatitis (AIH) failed to sustain remission when steroids were withdrawn from a regimen of steroids and azathioprine (AZA). Thiopurine metabolites revealed elevated 6-MMP (6-methyl mercaptopurine) and low 6-TGN (6-thioguanine nucleotide) consistent with AZA-induced hepatotoxicity. Introducing the xanthine oxidase inhibitor allopurinol led to rapid normalization of alanine aminotransferase (ALT) and discontinuation of steroids. PMID:23238820

  13. Acute thiopurine overdose: analysis of reports to a national poison centre 1995-2013

    OpenAIRE

    Gregoriano, Claudia; Ceschi, Alessandro; Rauber-Lüthy, Christine; Kupferschmidt, Hugo; Banner, Nicholas R.; Krähenbühl, Stephan; Taegtmeyer, Anne B

    2014-01-01

    Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were w...

  14. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS)

    OpenAIRE

    Shaman Gill; Amitabh Sagar; Shankar, S.; Velu Nair

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, ...

  15. Use of Allopurinol to Optimize Thiopurine Immunomodulator Efficacy in Inflammatory Bowel Disease

    OpenAIRE

    Sparrow, Miles P.

    2008-01-01

    The thiopurine immunomodulators azathioprine and 6-mercaptopurine are integral to the management of inflammatory bowel disease (IBD), particularly as corticosteroid-sparing and maintenance agents; however, up to 50% of patients do not adequately respond to these agents. Advances in pharmacogenomics and an increased understanding of thiopurine metabolism have led to the practice of measuring the thiopurine metabolites 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP) to help achieve opt...

  16. Use of thiopurines in inflammatory bowel disease

    OpenAIRE

    Frei, Pascal; Biedermann, Luc; Nielsen, Ole Haagen; Rogler, Gerhard

    2013-01-01

    The use of thiopurines as immunosuppression for the treatment of refractory or chronic active inflammatory bowel disease is established for both Crohn's disease and ulcerative colitis. Nevertheless, many questions remain concerning the optimal treatment regimens of azathioprine, 6-mercaptopurine and thioguanine. We will briefly summarize dose recommendations, indications for thiopurine therapy and side effects which are relevant in clinical practice. We discuss some currently debated topics, ...

  17. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  18. Immunomodulators and Immunosuppressants for Japanese Patients with Ulcerative Colitis

    OpenAIRE

    Shigeki Bamba; Tomoyuki Tsujikawa; Masaya Sasaki; Yoshihide Fujiyama; Akira Andoh

    2011-01-01

    Ulcerative colitis (UC) is characterized by a long-standing chronic course with remissions and exacerbations. Previously, patients do not respond to 5-aminosalicylic acid compounds and corticosteroids are considered for colectomies, however, in recent years, alternative treatments emerged for steroid-refractory or steroid-dependent UC. In this review article, we focus on immunomodulators (such as azathioprine [AZA] and 6-mercaptopurine [6-MP]) and immunosuppressants (such as cyclosporine A [C...

  19. Liver transplantation: immunosuppression and oncology

    OpenAIRE

    Rodríguez-Perálvarez, Manuel; de la Mata, Manuel; Burroughs, Andrew K.

    2014-01-01

    Purpose of review Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed t...

  20. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    OpenAIRE

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication...

  1. 免疫抑制剂及其临床应用进展

    Institute of Scientific and Technical Information of China (English)

    刘汝臣

    2001-01-01

    @@ 临床应用已久的免疫抑制剂,如环磷酰胺(cyclophosphamide,CTX)、甲氨蝶呤(methotrexate,MTX)、硫唑嘌呤(azathioprine,Aza)等在器官移植抗排斥、自身免疫性疾病及肿瘤的治疗上起了重要作用.

  2. Accelerated induction of skin cancers by ultraviolet radiation in hairless mice treated with immunosuppressive agents

    International Nuclear Information System (INIS)

    An increased incidence of cancer is well recognized in organ transplant recipients treated with immunosuppressive agents. Skin cancers are the most common lesions encountered. To investigate a possible relationship between the immunosuppressive agents and ultraviolet radiation (UVR), several groups of hairless mice were treated with ultraviolet light, azathioprine, or prednisone, or the three in various combination. The two latter drugs are the immunosuppressive agents most frequently used in organ transplant recipients

  3. Increased cartilagenous uptake on bone scintigraphy in a patient with relapsing polychondritis

    Energy Technology Data Exchange (ETDEWEB)

    Borg, E.J. ter; Piers, A.; Thijn, C.J.P.

    1988-09-01

    A patient with relapsing polychondritis and increased uptake on bone scintigraphy (using /sup 99m/Tc-MDP) in the cartilagenous parts of the ribs, the sternum and in the larynx region is described. A biopsy of a costochondral junction (where uptake on the bone scan was increased) was compatible with relapsing polychondritis. After treatment with prednisolone and azathioprine the patient improved and a repeated bone scan (after six years) showed less intensive uptake.

  4. Increased cartilagenous uptake on bone scintigraphy in a patient with relapsing polychondritis

    International Nuclear Information System (INIS)

    A patient with relapsing polychondritis and increased uptake on bone scintigraphy (using 99mTc-MDP) in the cartilagenous parts of the ribs, the sternum and in the larynx region is described. A biopsy of a costochondral junction (where uptake on the bone scan was increased) was compatible with relapsing polychondritis. After treatment with prednisolone and azathioprine the patient improved and a repeated bone scan (after six years) showed less intensive uptake. (orig.)

  5. Accelerated induction of skin cancers by ultraviolet radiation in hairless mice treated with immunosuppressive agents

    Energy Technology Data Exchange (ETDEWEB)

    Koranda, F.C.; Loeffler, R.T.; Koranda, D.M.; Penn, I.

    1975-01-01

    An increased incidence of cancer is well recognized in organ transplant recipients treated with immunosuppressive agents. Skin cancers are the most common lesions encountered. To investigate a possible relationship between the immunosuppressive agents and ultraviolet radiation (UVR), several groups of hairless mice were treated with ultraviolet light, azathioprine, or prednisone, or the three in various combination. The two latter drugs are the immunosuppressive agents most frequently used in organ transplant recipients.

  6. Case report of cheilitis granulomatosa and joint complaints as presentation of Crohn's disease.

    Science.gov (United States)

    Hoekman, Daniël R; Roelofs, Joris J T H; van Schuppen, Joost; Schonenberg-Meinema, Dieneke; D'Haens, Geert R; Benninga, Marc A

    2016-04-01

    Cheilitis granulomatosa is characterized by granulomatous lip swelling. We report a case of a 13-year-old girl who presented with orofacial swelling and arthralgia, who eventually was diagnosed with Crohn's disease, which was successfully treated with infliximab and azathioprine combination therapy. Recurrent or persistent orofacial swelling should prompt consideration of cheilitis granulomatosa, and further diagnostic evaluation to exclude the presence of Crohn's disease seems warranted. PMID:27017505

  7. Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases.

    Science.gov (United States)

    Palmeiro, Brian S; Morris, Daniel O; Goldschmidt, Michael H; Mauldin, Elizabeth A

    2007-10-01

    Thirty-two cases of canine cutaneous histiocytosis were retrospectively evaluated. Median age at onset was 4 years. Lesions included nodules and plaques affecting the head/face, trunk and limbs, and erythema, swelling and depigmentation of the nasal planum/nares. Systemic involvement was not ruled out in all cases. All dogs had complete resolution of dermatological lesions after initial treatment (median 45 days). Initial treatment included prednisone +/- antibiotics (12 of 32 dogs), prednisone and tetracycline/niacinamide (four of 32), prednisone and azathioprine (three of 32), tetracycline/niacinamide +/- vitamin E/essential fatty acids (six of 32), antibiotics +/- antihistamines (three of 32), cyclosporine and ketoconazole (one of 32), topical therapy (two of 32), and no treatment (one of 32). Seventeen dogs received maintenance therapy which consisted of tetracycline/niacinamide +/- vitamin E/essential fatty acids (12 of 17), cyclosporine/ketoconazole (two to three times a week) (two of 17), azathioprine daily (one of 17), prednisone/azathioprine (two times a week) (one of 17), and prednisone daily (one of 17). Median follow up was 25 months. Nine dogs had a recurrence of cutaneous histiocytosis (median days to recurrence 130 days), with seven of nine having more than one recurrence. At study completion, six dogs were deceased (no lesions at the time of death) and 26 of 32 were alive with no lesions. Ten of 26 dogs were on maintenance treatment (eight tetracycline/niacinamide, one azathioprine, one vitamin E). Previous dermatological disease and season had no detectable influence on recurrence. Recurrence was significantly more likely in dogs with nasal planum/nares lesions than dogs without these lesions. Tetracycline/niacinamide was an effective treatment option for dogs in this study population. PMID:17845621

  8. Are we giving biologics too late? The case for early versus late use

    OpenAIRE

    Ricart, Elena; García-Bosch, Orlando; Ordás, Ingrid; Panés, Julián

    2008-01-01

    Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short-term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their on...

  9. Pancreatic mass as an initial presentation of severe Wegener's granulomatosis

    OpenAIRE

    Valerieva, Yana; Golemanov, Branimir; Tzolova, Nadezhda; Mitova, Rumiana

    2013-01-01

    Acute pancreatitis or a pancreatic mass is a very rare initial presentation of Wegener's granu-lomatosis. A 62-year-old woman presented with tumor-like pancreatitis and otitis media Abdominal ultrasound and magnetic resonance suggested the presence of pancreatic tumor. Ultrasound-guided fine needle aspiration was negative. Distal pancreatic resection and splenectomy were performed and histopathology proved Wegener's vasculitis of the pancreas and spleen. Azathioprine and steroids were subsequ...

  10. Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

    OpenAIRE

    Bipul Nath; Lila Kanta Nath

    2013-01-01

    The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microfl...

  11. Brain Abscess following Rituximab Infusion in a Patient with Pemphigus Vulgaris

    OpenAIRE

    Al-Harbi, Talal M.; Muammer, Shahad A.; Ellis, Ronald J.

    2015-01-01

    Patient: Female, 52 Final Diagnosis: Brain abscess Symptoms: Fever • headache • weakness, left sided Medication: Prednisolone • Azathioprine • Rituximab Clinical Procedure: Stereotactic brain biopsy and LP Specialty: Neurology Objective: Rare disease Background: Immunocompromised patients are at increased risk for developing meningitis or, rarely, brain abscess with opportunistic organisms like Listeria monocytogenes. Case Report: A 52 year-old Saudi Arabian woman who was diagnosed with pemph...

  12. Pulmonary Mycobacterium szulgai infection and treatment in a patient receiving anti-tumor necrosis factor therapy.

    OpenAIRE

    Van Ingen, J.; Boeree, M. J.; Janssen, M.; Ullmann, E.F.; Lange, W; P. HAAS; Dekhuijzen, P N R; van Soolingen, D.

    2007-01-01

    BACKGROUND: A 54-year-old man with a 22-year history of rheumatoid arthritis and an 8-year history of chronic obstructive pulmonary disease presented with dyspnea on exertion, nonproductive cough and fatigue of 1 month's duration. His medication at presentation consisted of etanercept, azathioprine, naproxen and inhaled fluticasone and salbutamol. INVESTIGATIONS: At presentation, the patient underwent physical examination, chest X-ray and high-resolution CT, blood tests, and bronchoalveolar l...

  13. Behçet's pulmonary artery aneurysms treated with infliximab and monitored with the 6-min walk test

    OpenAIRE

    Kotecha, Jalpa; Kamath, Ajay V.; Mukhtyar, Chetan

    2016-01-01

    Pulmonary involvement in Behçet's disease (BD) is uncommon; however, it is potentially fatal due to the risk of massive haemoptysis. We describe the case of a 36-year-old male presenting with a 2-month history of worsening dyspnoea, weight loss, haemoptysis, oral ulceration, erythema nodosum and superficial thrombophlebitis. He was diagnosed with pulmonary vasculitis secondary to BD; however, his symptoms were refractory to initial treatment with cyclophosphamide, azathioprine and prednisolon...

  14. Eosinophilic fasciitis associated with L-tryptophan ingestion.

    OpenAIRE

    Hamilton, M. E.

    1991-01-01

    A 62 year old woman taking L-tryptophan developed eosinophilic fasciitis shortly after starting an exercise class. She received prednisone without benefit but improved after azathioprine treatment was started and L-tryptophan was discontinued. As products containing L-tryptophan have recently been implicated in development of the eosinophilia-myalgia syndrome it is suggested that the use of L-tryptophan might have contributed to the development of eosinophilic fasciitis in this patient. Simil...

  15. Phagocytic cell function in response to immunosuppressive therapy.

    Science.gov (United States)

    Drath, D B; Kahan, B D

    1984-02-01

    The increased incidence of pulmonary infection in human renal allograft recipients is presumably related to antirejection immunosuppressive therapy. To assess immunosuppressive-related disturbances of the immune responses of the lung, we evaluated the functional abilities of the pulmonary alveolar macrophage (PAM) and polymorphonuclear leukocyte (PMN) of rats in chemotaxis, phagocytosis, and superoxide-release assays following 30 days of intraperitoneal administration of cyclosporine, azathioprine, and/or prednisolone sodium succinate. None of these drugs affected superoxide release by stimulated PAMs or PMNs. Except for a transient inhibition by azathioprine, the drugs had no effect on phagocytosis of Staphylococcus aureus by either cell type. On the other hand, cyclosporine inhibited formyl-methionyl-leucyl-phenylalanine (FMLP)-directed chemotaxis by PAMs, and both FMLP and C5a stimulated chemotaxis by PMNs. Azathioprine had more dramatic effects on PAMs than on PMNs and prednisolone at 2 mg/kg inhibited PAMs. The results indicated that, with the exception of chemotaxis, the immunosuppressive agents largely spare nonspecific elements of host defense. PMID:6320765

  16. June 2012 pulmonary journal club

    Directory of Open Access Journals (Sweden)

    Mathew M

    2012-06-01

    Full Text Available No abstract available. Article truncated at 150 words. Idiopathic Pulmonary Fibrosis (IPF continues to be a devastating disease with no clinically significant treatment options. For years the treatment of IPF centered on a trial of prednisone followed by the addition of either cyclophosphamide or azathioprine as a ‘lets see if this helps’ approach. The 2011 ATS Consensus statement on IPF declared that the use of prednisone as monotherapy was not recommended. The consensus statement also yielded a weak recommendation for N-acetylcysteine (NAC as monotherapy, and a weak recommendation of prednisone, azathioprine and NAC as combination therapy. This study is the first large multicenter, double-blind, placebo controlled trial looking at lung function in groups of patients treated with NAC monotherapy verses combination therapy (prednisone + azathioprine + NAC versus placebo. The study was performed throughout 25 centers from 2009-2011. Inclusion criteria were a diagnosis of IPF, age 35-85, FVC > 50% and DLC0 > 30%. A total of 236 …

  17. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, H.S.; Nielsen, S.L.; Larsen, S.; Lokkegaard, H.

    1987-01-01

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug.

  18. Renography and biopsy-verified acute rejection in renal allotransplanted patients receiving cyclosporin A

    International Nuclear Information System (INIS)

    Acute impairment of renal function caused by cyclosporin A can be hard to differentiate from acute rejection. Therefore, kidney function after cadaveric allograft transplantation was repeatedly determined by renography in 42 patients receiving either high dose cyclosporin A (32 patients) or azathioprine and prednisone (10 patients) until a graft biopsy showed either acute rejection or no rejection within the first 5 postoperative weeks. The graft function as judged from the renograms was significantly poorer when cyclosporin A was used than when azathioprine and prednisone were the immunosuppressants. In the azathioprine and prednisone group a biopsy showing acute rejection was always preceded by a deterioration in the renogram. In cyclosporin A treated patients a graft biopsy following an early deterioration in the renogram showed acute rejection in only 56% of the biopsies. It was not possible to identify a time course or a function level of the renogram that could predict rejection in these patients. It is concluded that graft biopsies should be used liberally to diagnose rejection during cyclosporin A treatment if surgical complications after transplantations have been ruled out. Radionuclide studies may offer an invaluable aid in determining a nonnephrotoxic initial dose of the drug. (orig.)

  19. Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort.

    Science.gov (United States)

    Coghill, A E; Johnson, L G; Berg, D; Resler, A J; Leca, N; Madeleine, M M

    2016-02-01

    Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus. PMID:26824445

  20. Complicated Crohn's-like colitis, associated with Hermansky-Pudlak syndrome, treated with Infliximab: a case report and brief review of the literature

    Directory of Open Access Journals (Sweden)

    Kouklakis George

    2007-12-01

    Full Text Available Abstract Introduction Hermansky-Pudlak syndrome (HPS is a rare autosomal recessive inherited disorder consisting of a triad of albinism, increased bleeding tendency secondary to platelet dysfunction, and systemic complications associated with ceroid depositions within the reticuloendothelial system. HPS has been associated with gastrointestinal (GI complications related to chronic granulomatous colitis with pathologic features suggestive of Crohn's disease. This colitis can be severe and has been reported to be poorly responsive to medical therapies including antibiotics, corticosteroids, sulfasalazine, mesalamine and azathioprine. Case presentation We report a patient with HPS which was complicated by inflammatory bowel disease with clinical and pathologic features of Crohn's disease, refractory to antibiotics, corticosteroids and azathioprine. A trial of infliximab was attempted and repeated infusions produced a complete response. Conclusion The occurrence of ileitis and perianal lesions and also the histopathological findings in our case suggest that HPS and Crohn's disease may truly be associated. Given this similarity and the failure of the standard medical therapy of corticosteroids and azathioprine, our patient received infliximab with marked clinical improvement.

  1. Thiopurine methyltransferase in red blood cells of dogs, cats, and horses.

    Science.gov (United States)

    White, S D; Rosychuk, R A; Outerbridge, C A; Fieseler, K V; Spier, S; Ihrke, P J; Chapman, P L

    2000-01-01

    Our objective was to determine if thiopurine methyltransferase (TPMT), the enzyme important in the metabolism of azathioprine in human beings, is detectable in red blood cell lysates (RBCL) of healthy dogs, cats, and horses. Values for TPMT activity were determined from blood collected from 20 healthy dogs, cats, and horses. The TPMT activity in each animal's RBCL was determined using a radioenzymatic end point involving TPMT-facilitated metabolism of 6-mercaptopurine to 6-methylmercaptopurine (6-MMP). One unit of TPMT activity represents the formation of 1 nmol of 6-MMP per milliliter of packed red blood cells per hour of incubation at 37 degrees C. TPMT activity in RBCL was detectable in all species, with mean RBC values +/- standard deviation of 17.9 +/- 3.79 U/mL in dogs; 2.76 +/- 0.70 U/mL in cats; and 2.185 +/- 0.36 U/mL in horses. Values for TPMT in the 3 species were significantly (P dogs were significantly higher than the other species, and TPMT values for cats were significantly higher than those for horses. We conclude that RBCL TPMT values are measurable in dogs. cats, and horses and that dogs have higher values than cats or horses. These findings are consistent with the lower tolerance for azathioprine in cats as compared with dogs. It remains to be determined whether RBCL TPMT values in these species correlate with TPMT activity in the liver, where most of the metabolization of azathioprine is believed to occur. PMID:11012112

  2. Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Ainsworth, Mark Andrew

    2013-01-01

    A 35-year-old man presents with an exacerbation of Crohn's ileocolitis. He received a diagnosis of Crohn's disease 8 years ago and has been treated on three previous occasions with prednisone. Because of a recurrent need for glucocorticoids, treatment with azathioprine (150 mg per day) was started...... resonance enterography shows inflammation localized to the distal ileum and colon. The patient is referred to a gastroenterologist. An ileocolonoscopy reveals patchy erythema and ulcerations near the hepatic flexure as well as similar lesions in the terminal ileum. Biopsy specimens obtained during...

  3. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS).

    Science.gov (United States)

    Gill, Shaman; Sagar, Amitabh; Shankar, S; Nair, Velu

    2013-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids. PMID:24014920

  4. Gout in pediatric renal transplant recipients.

    Science.gov (United States)

    Trück, Johannes; Laube, Guido F; von Vigier, Rodo O; Goetschel, Philippe

    2010-12-01

    Clinical gout has rarely been described after pediatric renal transplantation (RTx), although asymptomatic hyperuricemia is common in these patients. We describe three male pediatric patients who presented with gouty arthritis 7-8.5 years following RTx. Since receiving allopurinol, all patients had been free of gouty symptoms. To prevent severe bone marrow depletion, the dosage of azathioprine, an immunosupressant drug, was reduced by 50% to prevent interaction with allopurinol. Because atypical presentation of gout can occur, a high index of suspicion is needed to allow appropriate diagnosis of this disease in patients with skeletal pain after RTx. PMID:20640905

  5. Response to intravenous gammaglobulin in refractory Takayasu arteritis

    International Nuclear Information System (INIS)

    Takayasu arteritis (TA ) is a large-vessel vasculitis which affects the aorta and its major branches. Steroids are the cornerstone of treatment; however, more than half of the patients relapse, requiring additional immunosuppressive agents. Open studies have suggested that methotrexate, cyclophosphamide, azathioprine, mycophenolate mofetil and anti-TNF therapy may be useful in such cases. We conducted a case report of a patient with TA with multiple relapses despite methotrexate,steroids, rituximab, cyclophosphamide, infliximab, percutaneous, and surgical revascularization. Intravenous immunoglobulin (IVIg) was employed, obtaining total and sustained control of vasculitic manifestations, achieving tapering and suspension of steroids as well as diminution of acute phase reactants

  6. Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS

    Directory of Open Access Journals (Sweden)

    Shaman Gill

    2013-01-01

    Full Text Available Drug rash with eosinophilia and systemic symptoms (DRESS syndrome is an adverse reaction commonly occurring with antiepileptic agents. It was earlier referred to by various names such as dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome. It is characterized by the triad of fever, skin eruption, and systemic involvement. DRESS syndrome has also been reported with a number of other drugs including allopurinol, minocycline, terbinafine, sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity syndrome that was successfully treated with oral steroids.

  7. Treatment of Subepidermal Autoimmune Bullous Diseases

    Directory of Open Access Journals (Sweden)

    Ekin Şavk

    2011-06-01

    Full Text Available The common therapeutic goal for all subepidermal bullous diseases is to prevent inflammation and production of pathogenic autoantibodies and/or to facilitate the elimination of these antibodies. Diseases included in this group are the pemphigoids, linear IgA dermatosis, epidermolysis bullosa acquisita, dermatitis herpetiformis and bullous systemic erythematosus. Corticosteroids are the most commonly used systemic medication. Other alternatives include dapsone, various antibiotics and nicotinamide, azathioprine, cyclophosphamide, methotrexate, cycloporine, mycophenolate mofetil, IV immunoglobulins and plasmapheresis. Rapid reepithelialization and prevention of secondary infections are provided by local hygenic measures including antiseptic baths and wound care.

  8. Treatment of Subepidermal Autoimmune Bullous Diseases Sürekli Eğitim

    Directory of Open Access Journals (Sweden)

    Ekin Şavk

    2011-06-01

    Full Text Available The common therapeutic goal for all subepidermal bullous diseases is to prevent inflammation and production of pathogenic autoantibodies and/or to facilitate the elimination of these antibodies. Diseases included in this group are the pemphigoids, linear IgA dermatosis, epidermolysis bullosa acquisita, dermatitis herpetiformis and bullous systemic erythematosus. Corticosteroids are the most commonly used systemic medication. Other alternatives include dapsone, various antibiotics and nicotinamide, azathioprine, cyclophosphamide, methotrexate, cycloporine, mycophenolate mofetil, IV immunoglobulins and plasmapheresis. Rapid reepithelialization and prevention of secondary infections are provided by local hygenic measures including antiseptic baths and wound care. (Turkderm 2011; 45 Suppl 1: 54-8

  9. Successful treatment of postoperative pyoderma gangrenosum with cyclosporin.

    Science.gov (United States)

    Schöfer, H; Baur, S

    2002-03-01

    Postoperative pyoderma gangrenosum (PPG), also known as postoperative progressive gangrene of Cullen, is a rare and rapidly evolving complication of surgical procedures. Since the first description by Cullen in 1924 (Surg Gynecol Obstet 1924; 38: 579-582) various case reports have been published. Even in typical cases PPG is often misdiagnosed and therefore wrongly treated; the unknown aetiology makes treatment difficult. The therapies used for pyoderma gangrenosum include systemic corticosteroids, azathioprine, dapsone, mercaptopurine, sulphasalazine, sulphapyridine, thalidomide, cyclophosphamide, clofazimine, isotretinoin, immunoglobulins and cyclosporin. We report on two patients with PPG following breast surgery who were successfully treated with low-dose cyclosporin (2.5-5 mg/kg per day). PMID:12046819

  10. [Multiple abscesses after a cruise along the Latin American coast].

    Science.gov (United States)

    Reynolds, C; Schofer, N; Zengin, E; Lohse, A W; Faiss, S; Schmiedel, S

    2016-03-01

    We report a case of an extracutaneus involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneus involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved. PMID:26782091

  11. Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum.

    Science.gov (United States)

    Wan, Joy; Imadojemu, Sotonye; Werth, Victoria P

    2016-01-01

    The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus. PMID:27265072

  12. Use of 99Tcm radionuclides to show nephrotoxicity of cyclosporin A in transplanted kidneys

    International Nuclear Information System (INIS)

    In 60 patients, 99Tcm pertechnetate or 99Tcm methylene diphosphonate was injected through an arm vein within 36 h after renal transplantation and repeated 24 or 48 h later. Thirty-one were treated with azathioprine and prednisone, 27 of the grafts had a well-defined peak on the histograms similar to that from the iliac artery histograms at both examinations. In contrast, of the 29 patients treated with cyclosporin A, only 5 of the grafts had a well-defined peak at both examinations. The difference is highly significant. Treatment with cyclosporin A causes a decrease in renal blood flow in the days immediately after transplantation. (orig.)

  13. In vitro assessment of the immunosuppressive effect of fractionated total lymphoid irradiation in renal allotransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Ferguson, R.M.; Sutherland, D.E.R.; Kim, T.; Simmons, R.L.; Najarian, J.S.

    1981-09-01

    Ten uremic patients at high risk for rejection (nine patients with previous rapid rejection of a first transplant and one recipient of a two-haplotype mismatch primary graft) were treated with total lymphoid irradiation (TLI) prior to transplantation. TLI was delivered to mantle and inverted-Y fields simultaneously. Patients received either 125 or 100 rads daily for no more than 5 doses per week. Total dose ranged from 1800 to 3200 rads given over 29-67 days prior to transplantation. All patients received maintenance azathioprine and prednisone after the transplantation, but antilymphocyte globulin was not given.

  14. Magnetic resonance imaging in the evaluation of treatment in multiple sclerosis

    International Nuclear Information System (INIS)

    Magnetic resonance scans of 74 patients with multiple sclerosis participating in a controlled trial were compared 6 months before and at the end of a 24-32 months-treatment period with either Cyclosporin A (n=31) or Azathioprine (n=43). Both qualitative rating and computation of lesion volume showed deterioration in more than 40% of the patients, while by clinical criteria only 10-30% were worse. No significant difference was noted when the two treatment groups were compared. If careful repositioning and standardized image parameters are used, MRI is an indispensable tool for the objective determination of disease progression in MS although it cannot replace clinical examination. (orig.)

  15. In vitro assessment of the immunosuppressive effect of fractionated total lymphoid irradiation in renal allotransplantation

    International Nuclear Information System (INIS)

    Ten uremic patients at high risk for rejection (nine patients with previous rapid rejection of a first transplant and one recipient of a two-haplotype mismatch primary graft) were treated with total lymphoid irradiation (TLI) prior to transplantation. TLI was delivered to mantle and inverted-Y fields simultaneously. Patients received either 125 or 100 rads daily for no more than 5 doses per week. Total dose ranged from 1800 to 3200 rads given over 29-67 days prior to transplantation. All patients received maintenance azathioprine and prednisone after the transplantation, but antilymphocyte globulin was not given

  16. Successful treatment of severe refractory lupus hepatitis with mycophenolate mofetil.

    Science.gov (United States)

    Tagawa, Y; Saito, T; Takada, K; Kawahata, K; Kohsaka, H

    2016-04-01

    Systemic lupus erythematosus-related hepatitis, known as lupus hepatitis, is a rare manifestation of systemic lupus erythematosus, and is usually subclinical with mild abnormalities of serum liver enzymes. While cases with clinically significant and refractory lupus hepatitis are uncommon, treatment options for lupus hepatitis are to be established. Here, we report the case of a 45-year-old man with progressive lupus hepatitis accompanied by autoimmune haemolytic anaemia. Lupus hepatitis of this patient was refractory to tacrolimus, azathioprine and cyclophosphamide, but was successfully treated by mycophenolate mofetil. Mycophenolate mofetil might be an effective therapeutic option for refractory lupus hepatitis. PMID:26762472

  17. Thymic hormones

    Energy Technology Data Exchange (ETDEWEB)

    Davies, A.J.S.

    1975-02-28

    RResults of experiments by various investigators attempting to demonstrate the existence of thymic hormones are reported. In most cases irradiated, thymectomized mice injected with bone marrow cells were used; some experiments were carried out on various extracts of thymuses. Results of most experiments were negative. In one experiment using mice with thymus transplants, sera were evaluated for their capacity to restore azathioprine sensitivity in relation to the rosette forming capacity to spleen cells of thymectomized mice in vitro. In all instances the thymus-grafted mice had a higher titer of serum factor than did normal mice. (HLW)

  18. Magnetic resonance imaging in the evaluation of treatment in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kappos, L.; Staedt, D.; Schneiderbanger-Grygier, S.; Heitzer, T.; Ratzka, M.; Nadjmi, M.; Poser, S.; Keil, W.

    1988-08-01

    Magnetic resonance scans of 74 patients with multiple sclerosis participating in a controlled trial were compared 6 months before and at the end of a 24-32 months-treatment period with either Cyclosporin A (n=31) or Azathioprine (n=43). Both qualitative rating and computation of lesion volume showed deterioration in more than 40% of the patients, while by clinical criteria only 10-30% were worse. No significant difference was noted when the two treatment groups were compared. If careful repositioning and standardized image parameters are used, MRI is an indispensable tool for the objective determination of disease progression in MS although it cannot replace clinical examination.

  19. Immunomodulatory drugs and their application to the management of canine immune-mediated disease.

    Science.gov (United States)

    Whitley, N T; Day, M J

    2011-02-01

    This review summarises the current understanding of immune response and T cell subsets in the context of development of autoimmunity in the dog. Mode of action and rational usage in immune-mediated disease in the dog are discussed for the following drugs: glucocorticoids, azathioprine, cyclophosphamide, ciclosporin, tacrolimus, human intravenous immunoglobulin, vincristine, danazol, leflunomide, mycophenolate mofetil and liposome-encapsulated clodronate. Disease mechanisms are discussed and published evidence for drug efficacy is scrutinised for five important immune-mediated diseases: immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, myasthenia gravis, glomerulonephritis and inflammatory bowel disease. Future strategies for more refined manipulation of adverse immune responses are presented. PMID:21265846

  20. Cutaneous manifestations of disseminated toxoplasmosis in an immunosuppressed dog.

    Science.gov (United States)

    Webb, Jinelle A; Keller, Sonya L; Southorn, Erin P; Armstrong, Julie; Allen, Dana G; Peregrine, Andrew S; Dubey, J P

    2005-01-01

    A 3.5-year-old, castrated male, giant schnauzer was presented with alopecic pustular dermatitis. Immune-mediated hemolytic anemia had been diagnosed 45 days previously. At the time of presentation, the dog was receiving prednisone, azathioprine, and cyclosporine. Cutaneous protozoosis was diagnosed, and postmortem examination revealed protozoa within cutaneous, cardiac, pancreatic, and pulmonary tissues. The protozoa divided by endodyogeny, had the morphology of Toxoplasma gondii (T. gondii) tachyzoites, and stained positively with T. gondii polyclonal antibodies but not with antibodies to Neospora caninum or Sarcocystis neurona. Immunosuppression may have predisposed this dog to disseminated toxoplasmosis. PMID:15870255

  1. A retrospective study regarding the treatment of lupoid onychodystrophy in 30 dogs and literature review.

    Science.gov (United States)

    Mueller, Ralf S; Rosychuk, Rodney A W; Jonas, Leonard D

    2003-01-01

    The treatment records of 30 dogs with lupoid onychodystrophy were evaluated retrospectively. Dogs were treated with fatty acid supplementation (n=18), doxycycline and niacinamide (n=12), tetracycline and niacinamide (n=10), pentoxifylline (n=6), prednisolone (n=5), azathioprine (n=1), clofazimine (n=1), or with combinations thereof. An excellent response was seen in almost half of the patients treated with tetra- or doxycycline in combination with niacinamide. Six of the dogs were maintained successfully on fatty acid supplementation. Spontaneous remissions and recurrences made evaluation of success rates difficult and emphasized the varied and often unclear etiology and natural course of the syndrome. PMID:12617542

  2. Kidney transplantation in dogs with naturally occurring end-stage renal disease.

    Science.gov (United States)

    Mathews, K A; Holmberg, D L; Miller, C W

    2000-01-01

    Renal allografts were performed between unrelated donors and 15 dogs with naturally occurring end-stage renal disease. Donor selection was based on compatible dog erythrocyte antigen typing and cross-matching. An immunosuppressive protocol consisting of rabbit antidog antithymocyte serum, cyclosporin-A, azathioprine, and prednisone was used to control postoperative rejection of the donated kidney. Although seven animals died because of technical failures or rejection episodes, a median survival time of eight months has been achieved, with two dogs living for longer than five years after surgery. Long-term survivors have died from a variety of problems not related to renal allograft rejection. PMID:10914526

  3. Pemphigus foliaceus in 91 dogs.

    Science.gov (United States)

    Mueller, Ralf S; Krebs, Ingar; Power, Helen T; Fieseler, Kathryn V

    2006-01-01

    A retrospective study of 91 dogs with pemphigus foliaceus was performed. Clinical signs of the disease included crusts (n=79), pustules (n=36), and alopecia (n=33). Lesions were most common on the trunk (n=53), inner pinnae (n=46), face (n=37), and foot pads (n=32). Cytological evaluation revealed acantholytic keratinocytes in 37 of 48 dogs. Results of combination treatment with prednisolone and azathioprine were comparable to results with prednisolone therapy alone. More than half of the dogs achieved remission with appropriate therapy, and another 25% significantly improved. PMID:16611930

  4. Lameness associated with tarsal haemarthrosis as the sole clinical sign of idiopathic immune-mediated thrombocytopenia in a dog.

    Science.gov (United States)

    Walton, M B; Mardell, E; Spoor, M; Innes, J

    2014-01-01

    A four-year-old, male Cocker Spaniel was presented for investigation of pelvic limb stiffness. There was palpable effusion of both tarsi, and analysis of synovial fluid from these joints indicated previous haemorrhage. After further investigation a diagnosis of idiopathic immune-mediated thrombocytopenia was made. The dog responded to treatment with prednisolone and azathioprine. To the authors' knowledge, this is the first reported case of confirmed haemarthrosis as the sole presenting clinical sign for canine idiopathic immune-mediated thrombocytopenia. PMID:25327981

  5. Acquired myasthenia gravis associated with a non-invasive thymic carcinoma in a dog.

    Science.gov (United States)

    Stenner, V J; Parry, B W; Holloway, S A

    2003-09-01

    An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma. PMID:15086092

  6. Cutaneous neosporosis during treatment of pemphigus foliaceus in a dog.

    Science.gov (United States)

    Ordeix, Laura; Lloret, Albert; Fondevila, Dolors; Dubey, J P; Ferrer, Lluis; Fondati, Alessandra

    2002-01-01

    A 4-year-old, intact male rottweiler was presented with a 10-day history of papulonodular dermatitis. At the time of presentation, the dog was receiving prednisone and azathioprine to treat pemphigus foliaceus. Cutaneous neosporosis was diagnosed by immunohistochemistry on skin biopsy specimens and a high serum antibody titer to Neospora caninum by Neospora agglutination test. Electron microscopy examination of skin specimens further supported the diagnosis. Clindamycin therapy, together with withdrawal of immunosuppressive medication, resulted in prolonged clinical remission. This report documents cutaneous neosporosis in an adult dog and suggests that immunosuppressive therapy might be a predisposing factor. PMID:12220024

  7. Diagnosis and therapeutic options for peripheral vasculitic neuropathy.

    Science.gov (United States)

    Blaes, Franz

    2015-04-01

    Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

  8. LC-MS/MS Coupled with Stable Isotope Dilution Method for the Quantification of 6-Thioguanine and S6-Methylthioguanine in Genomic DNA of Human Cancer Cells Treated with 6-Thioguanine

    OpenAIRE

    Wang, Hongxia; Wang, Yinsheng

    2010-01-01

    Thiopurines, including mercaptopurine (MP), 6-thioguanine (SG) and azathioprine, are widely used for the treatment of many human diseases including acute lymphoblastic leukemia (ALL). To exert their cytotoxic effect, these prodrugs need to be metabolically activated to SG nucleotides and incorporated into nucleic acids. SG in DNA can be methylated spontaneously to S6-methylthioguanine (S6mG) in the presence of S-adenosyl-L-methionine. It was proposed that S6mG, owing to its high miscoding pot...

  9. Thrombotic microangiopathy involving the gallbladder as an unusual manifestation of systemic lupus erythematosus and antiphospholipid syndrome: Case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    Beatriz De-Leon-Bojorge; Samuel Zaltzman-Girsevich; Arturo Ortega-Salgado; Adelina Prieto-Patron; Ruth Córdoba-Córdoba; Marco Yamazaki-Nakashimada

    2006-01-01

    Gallbladder disease is no more common in patients with systemic lupus erythematosus (SLE) than in the general population. We describe a 17-year-old patient with SLE, who developed nephritis that was well controlled with medications. Initial treatment consisted of azathioprine, aspirin and prednisone with stable control of her symptoms. Two years later she developed a right quadrant abdominal pain,and an abdominal ultrasound revealed microlithiasic cholecystitis. Open cholecystectomy was performed and the histopathological findings revealed vasculitis with thrombotic microangiopathy in the gallbladder. This case presentation illustrates that calculous or acalculous cholecystitis should be considered as a manifestation of active SLE and APS.

  10. Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients.

    Science.gov (United States)

    First, M R; Schroeder, T J; Weiskittel, P; Myre, S A; Alexander, J W; Pesce, A J

    1989-11-18

    18 renal transplant recipients receiving cyclosporin, prednisone, and azathioprine were given ketoconazole, a potent inhibitor of the cytochrome P-450 enzyme system. Within a month ketoconazole-induced blockade of cyclosporin metabolism allowed a significant reduction (451 vs 106 mg/day; 77%) of the mean dose of cyclosporin without altering cyclosporin whole blood trough levels, although maximum blood levels were almost halved. This dose reduction was maintained in patients followed up for up to 13 months. Renal and hepatic function were unchanged after the addition of ketoconazole. This drug interaction has the potential to reduce dramatically expenditure on cyclosporin in transplant recipients. PMID:2572912

  11. Erythema multiforme possibly triggered by food substances in a dog.

    Science.gov (United States)

    Itoh, Teruo; Nibe, Kazumi; Kojimoto, Atsuko; Mikawa, Mayumi; Mikawa, Kazuhiro; Uchida, Kazuyuki; Shii, Hiroki

    2006-08-01

    A 5-year-old female border collie presented with erythematous skin lesions at the axillae, groin, mucocutaneous junctions, and pinnae. Biopsy revealed lymphocytic interface dermatitis with hydropic degeneration of basal cells and keratinocyte apoptosis. Based on gross and histological features, diagnosis of erythema multiforme was made. The disease was resolved by treatment with azathioprine, prednisolone, and a hypoallergenic diet. Finally, the skin lesion was controlled without drug therapy but recurred easily every time commercial foods except the hypoallergenic diet were used, suggesting that food substances triggered this outbreak. PMID:16953090

  12. [Autoimmune hepatitis and overlap syndrome: therapy].

    Science.gov (United States)

    Löhr, H F

    2002-08-21

    Autoimmune Hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) represent acute and chronic inflammatory liver diseases in which immune reactions against host antigens are found to be the major pathological mechanism. Only for AIH there is evidence of an autoimmune etiology and humoral and cellular immune reactions are found directed against various liver cell antigens. By diverse autoantibodies several subgroups of autoimmune hepatitis can be distinguished. A very important disease promoting factor seems to be the genetically determined background for autoimmunity characterized by the HLA haplotype A1, B8 and DR3, respectively DR4. Although the histopathology of AIH shows no pathognomonic features distinguishing this type of hepatitis from virus induced chronic hepatitis there are some distinct characteristic morphological lesions. If untreated the prognosis of AIH is unfavourable but the benefit from immunosuppressive therapy with prednisolone and azathioprin is well established. In the last years there was increasing evidence for an overlap syndrome between AIH and PBC and rarely AIH and PSC. These patients are characterized by PBC characteristic bileduct lesions and oftenly antimitochondrial antibodies (AMA). They also show AIH typical inflammatory hepatic lesions in the periportal areas and portal tracts and oftenly the typical genetical background, the HLA haplotype A1, B8, DR3 or DR4. Most of these patients respond probably to a combination therapy containing prednisolon, azathioprine and ursodesoxycholic acid that leads to the reduction of the inflammatory activity. PMID:12233265

  13. [An infected necrosis of the chin].

    Science.gov (United States)

    Muller, B S; van Goor, H F; Rosenberg, A J W P

    2016-07-01

    A 51-year-old man was referred by his dentist to a maxillofacial surgeon with complaints of illness and pain in the mandible, associated with a rapidly expanding area of black gingiva and mucosa surrounding the lower front teeth. Clinically and radiographically there was evidence of an infected necrosis of the chin and floor of mouth. Following debridement at the operating room, the patient was treated at the intensive care unit for septic shock leading to prolonged hospitalisation. Investigation of the bone marrow did not provide an explanation for pancytopenia or the severity of the illness. In addition, genetic investigation of thiopurine S-methyltransferase gene showed no mutations. This gene codes for an identically named protein enzyme that contributes in the metabolising of the medicine azathioprine, used daily for an autoimmune disease. A combination of the use of azathioprine, a folic acid deficiency and sepsis led to this exceptional course of illness. Therapeutic intervention consisted of surgical debridement and treatment of the bacteraemia. Afterwards several corrective surgeries were necessary to restore oral functions. PMID:27430038

  14. Thiopurine methyltransferase activity in the erythrocytes of adults and children: and HPLC-linked assay.

    Science.gov (United States)

    Micheli, V; Jacomelli, G; Fioravanti, A; Morozzi, G; Marcolongo, R; Pompucci, G

    1997-03-18

    A non-radioactive method that uses reverse-phase high performance liquid chromatography is described for the determination of thiopurine methyltransferase (E.C. 2.1.1.67) activity in human erythrocytes. The method is based on the direct quantitation of 6-methyl-mercaptopurine produced from 6-mercaptopurine by crude erythrocyte lysates. The method is accurate and reliable and suitable for diagnostic use. Activity values in control adults ranged from 5 to 32 pmol/h/mg haemoglobin. The activity in the erythrocytes of adult males was significantly higher compared to females (21 +/- 5 and 15 +/- 8 pmol/h/mg haemoglobin, respectively). The activity measured in the erythrocytes of children (22 +/- 5 pmol/h/mg haemoglobin) did not show any significant difference compared to adults. Thiopurine methyltransferase activity was measured in a female patient with systemic sclerosis who developed severe bone marrow depression after treatment with azathioprine and allopurinol. Activity (6.3 +/- 0.5 pmol/h/mg haemoglobin) was found in the lowest range of controls thus supporting the hypothesis that it could be responsible for increased azathioprine cytotoxicity. PMID:9086303

  15. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Directory of Open Access Journals (Sweden)

    Claudia Gregoriano

    Full Text Available Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5. Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8 times the usual dose in adults. Twelve cases (30% had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

  16. Cyclosporine-associated leukoencephalopathy in organ transplant recipients: experience of three clinical cases.

    Science.gov (United States)

    Muñoz, R; Espinoza, M; Espinoza, O; Andrade, A; Bravo, E; González, F

    2006-04-01

    Leukoencephalopathy is a structural alteration of cerebral white matter mainly involving damage to myelin. Several reports have linked cyclosporine (CsA) with this alteration. The clinical features vary from qualitative alterations of consciousness to neurological deficits. Magnetic resonance imaging (MRI) of the brain demonstrates the damage to the white matter, which is essential for the differential diagnosis. We describe three clinical cases of leukoencephalopathy. The first case is a 43-year-old man received a cadaveric kidney transplant using immunosuppression with of mycophenolate mofetil, prednisone, and CsA. Four months later he developed meningism and bilateral sixth nerve palsy. The second case is a 50-year-old man with a cadaveric kidney transplant received immunosuppressive treatment with azathioprine and prednisone. As a result of gouty arthritis of the ankle, azathioprine was replaced with CsA to allow addition of allopurinol. Two weeks later he developed confusion and personality changes. The third case is a 16-year-old man received a orthotopic liver transplant. Postoperatively he suffered generalized tonic-clonic seizures. In all patients the CsA levels were toxic and signs of neurological alterations were present on MRI. All patients recovered rapidly after CsA withdrawal. PMID:16647511

  17. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Science.gov (United States)

    Gregoriano, Claudia; Ceschi, Alessandro; Rauber-Lüthy, Christine; Kupferschmidt, Hugo; Banner, Nicholas R; Krähenbühl, Stephan; Taegtmeyer, Anne B

    2014-01-01

    Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion. PMID:24489721

  18. Disease-modifying antirheumatic drugs in pregnancy: current status and implications for the future.

    Science.gov (United States)

    Vroom, Fokaline; de Walle, Hermien E K; van de Laar, Mart A J F; Brouwers, Jacobus R B J; de Jong-van den Berg, Lolkje T W

    2006-01-01

    Drug use during pregnancy is sometimes unavoidable, especially in chronic inflammatory diseases such as rheumatoid arthritis (RA). The use of disease-modifying antirheumatic drugs (DMARDs) often starts in the early stage of RA; therefore, women of reproductive age are at risk for exposure to a DMARD at time of conception as well as during pregnancy. The aim of this paper was to review recent literature about DMARDs used for rheumatic diseases in pregnancy and to describe the type of study designs and results reported.Twenty-nine studies; eight on hydroxychloroquine/chloroquine, thirteen on methotrexate, three on sulfasalazine and six on azathioprine were identified. With respect to hydroxychloroquine, most studies concluded that it could be safely used in systemic lupus erythematosus or RA. The same conclusions were drawn from the azathioprine studies, but the available evidence is scarce. Although the evidence regarding the safety of methotrexate during pregnancy is conflicting, a high rate of pregnancy losses indicates a risk to the fetus. For each individual case it must be decided whether the benefits outweigh the potential risks. No major teratogenic effects of sulfasalazine were seen although teratogenic effects still can not be excluded. For all other DMARDs, the information on their use in pregnancy was limited. This review underscores the gross absence of data on safety and risks of DMARD use during conception and pregnancy. While young women use these drugs in pregnancy, this review stresses the importance of good monitoring and further research. PMID:16970509

  19. Exome sequencing and array-based comparative genomic hybridisation analysis of preferential 6-methylmercaptopurine producers.

    Science.gov (United States)

    Chua, E W; Cree, S; Barclay, M L; Doudney, K; Lehnert, K; Aitchison, A; Kennedy, M A

    2015-10-01

    Preferential conversion of azathioprine or 6-mercaptopurine into methylated metabolites is a major cause of thiopurine resistance. To seek potentially Mendelian causes of thiopurine hypermethylation, we recruited 12 individuals who exhibited extreme therapeutic resistance while taking azathioprine or 6-mercaptopurine and performed whole-exome sequencing (WES) and copy-number variant analysis by array-based comparative genomic hybridisation (aCGH). Exome-wide variant filtering highlighted four genes potentially associated with thiopurine metabolism (ENOSF1 and NFS1), transport (SLC17A4) or therapeutic action (RCC2). However, variants of each gene were found only in two or three patients, and it is unclear whether these genes could influence thiopurine hypermethylation. Analysis by aCGH did not identify any unusual or pathogenic copy-number variants. This suggests that if causative mutations for the hypermethylation phenotype exist they may be heterogeneous, occurring in several different genes, or they may lie within regulatory regions not captured by WES. Alternatively, hypermethylation may arise from the involvement of multiple genes with small effects. To test this hypothesis would require recruitment of large patient samples and application of genome-wide association studies. PMID:25752523

  20. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet’s Disease

    Science.gov (United States)

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-01-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet’s disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  1. Acute liver failure caused by concurrent autoimmune hepatitis and hepatitis B in a 16-year old girl

    Directory of Open Access Journals (Sweden)

    Małgorzata Pawłowska, Waldemar Halota

    2010-10-01

    Full Text Available A 16 year-old girl was admitted to hospital because of fatigue and somnolence, nausea, epistaxis and jaundice. Physical examination revealed jaundice, an enlarged liver and tenderness of upper right abdomen. Laboratory tests revealed an increased level of acute liver failure, bilirubin, bile acids, GGTP and a decreased prothrombin ratio, with elevated gamma-globulin and IgG levels, and the presence of anti-mitochondrial M2 antibodies and HBV infection markers. The patient was diagnosed with liver failure resulting from chronic hepatitis B with an autoimmune component. The treatment consisted of steroids, azathioprine, vitamin K, low-protein diet and lactulose enemas. After undergoing a molecular test (HBV DNA 3.23 × 105 IU/mL and mutations I 204 and I 80, the treatment was modified by adding entecavir. After one month the patient was discharged in good clinical condition, with the recommendation of continued entecavir, prednisone and azathioprine. In subsequent months, no clinical deterioration or abnormal biochemical liver function test results were found, despite the discontinuation of immunosuppressive therapy after 10 mo. The patient continues entecavir therapy.

  2. Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: A population-based cohort study in Australia.

    Science.gov (United States)

    Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

    2016-08-01

    Iatrogenic immunosuppression is a strong risk factor for non-Hodgkin lymphoma (NHL) but the dose-related association between individual immunosuppressive agents and NHL risk is unknown. We conducted a population-based cohort study of 4131 adult Australian liver, heart and lung transplant recipients (1984-2006). We ascertained NHL incidence by probabilistic record linkage between transplant registries and the Australian Cancer Database, and abstracted risk factor data at transplantation and at regular intervals thereafter from medical records. We estimated adjusted hazard ratios (HR) for early (immunosuppression, the risk of both early and late NHL did not significantly differ by organ type. In final models, higher mean daily doses of azathioprine were associated with increased risk of both early [HR 2·20, 95% confidence interval (CI): 1·21-4·01] and late NHL (HR 1·78, 95% CI: 1·12-2·84). There was no association between any other maintenance immunosuppressive agent and NHL risk. This study provides evidence that differences in immunosuppression may explain variation in NHL incidence by organ type, and high doses of azathioprine may independently predict NHL risk. PMID:27136044

  3. Current and emerging treatment options in the management of lupus

    Directory of Open Access Journals (Sweden)

    Jordan N

    2016-03-01

    Full Text Available Natasha Jordan,1 David D’Cruz2 1Department of Rheumatology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, 2Louise Coote Lupus Unit, Guy’s and St Thomas’ Hospital NHS Foundation Trust, London, UK Abstract: Systemic lupus erythematosus (SLE is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. Keywords: hydroxychloroquine, mycophenolate mofetil, azathioprine, cyclophosphamide, rituximab, belimumab

  4. Immunosuppressive therapy in patients with congestive cardiomyopathy and myocardial uptake of gallium-67

    International Nuclear Information System (INIS)

    Thirty-nine patients with idiopathic congestive cardiomyopathy underwent gallium-67 scintigraphy. Twenty had no evidence of myocardial uptake (group I) and 19 had demonstrable myocardial gallium-67 activity (group II). There was no significant difference in age, sex, duration of symptoms, antecedent viral illness, left ventricular end-diastolic pressure, pulmonary artery systolic pressure, or ejection fraction between the two groups. Fifteen patients in group II were treated with prednisone and azathioprine for a minimum of 8 months. Nine of 15 patients were clinically unchanged and gallium-67 scans remained positive (group IIa). Six patients had significant improvement and resolution of myocardial gallium-67 uptake (group IIb). The mean change in ejection fraction was +0.2% in group I, -4.8% in Group IIa, and +13.8% in group IIb. There were five deaths in group I (25% mortality), three in group IIa (33% mortality), and no deaths in group IIb. The only significant difference between patients in group IIa and those in group IIb was a greater left ventricular posterior wall thickness in group IIa patients. Twenty control patients without cardiac disease had negative gallium-67 scans. We conclude that gallium-67 myocardial scintigraphy may be a useful test for predicting the response to prednisone and azathioprine therapy

  5. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    International Nuclear Information System (INIS)

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy

  6. Improved results in high risk cadaveric kidney transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Toledo-Pereyra, L.H.; Baskin, S.; McNichol, L.; Edford, G.; Whitten, J.; Allaben, R.

    1980-01-01

    In general, cadaver kidney transplantation survival remains at 40-50% for the first year after transplantation. To compare the beneficial effect of a new immunosuppressive protocol to standard therapy (azathioprine and prednisone), we have studied 30 high risk first cadaveric renal allograft recipients who were randomly selected before (Group A, n.15) and after (Group B, n.15) 10/79. At 12 mos, actuarial graft survival of Group B is 75% compared to 46% in Group A. Actuarial patient survival for Group B is 94% for one year compared to 60% in Group A. We feel that these improved results are related to basic changes in our immunosuppressive protocol. These changes consist of: 1. Low doses of azathioprine and prednisolone (less than 1 mg/kg) with rapid reduction to very low levels (less than 0.3 mg/kg); 2. ALG administration at 30 mg/kg/day for 14 times; 3. Rapid placement (one month) on alternate day steroid therapy; 4. Elimination of steroids for the treatment of rejection; 5. Use of ALG (20 mg/kg/day for 10 days) for the treatment of rejection; 6. Use of ALG combined with modified lymph node irradiation for third rejection episodes; and 7. Long-term intermittent ALG administration provided that kidney function continues to be normal. The best immunosuppressive protocol is clearly the one associated with less morbidity and improved quality of life after transplantation. Our current protocol (Group B) provides the best results.

  7. Immunosuppressive therapy in patients with congestive cardiomyopathy and myocardial uptake of Gallium-67

    Energy Technology Data Exchange (ETDEWEB)

    O' Connell, J.B.; Robinson, J.A.; Henkin, R.E.; Gunnar, R.M.

    1981-10-01

    Thirty-nine patients with idiopathic congestive cardiomyopathy underwent gallium-67 scintigraphy. Twenty had no evidence of myocardial uptake (group I) and 19 had demonstrable myocardial gallium-67 activity (group II). There was no significant difference in age, sex, duration of symptoms, antecedent viral illness, left ventricular end-diastolic pressure, pulmonary artery systolic pressure, or ejection fraction between the two groups. Fifteen patients in group II were treated with prednisone and azathioprine for a minimum of 8 months. Nine of 15 patients were clinically unchanged and gallium-67 scans remained positive (group IIa). Six patients had significant improvement and resolution of myocardial gallium-67 uptake (group IIb). The mean change in ejection fraction was +0.2% in group I, -4.8% in Group IIa, and +13.8% in group IIb. There were five deaths in group I (25% mortality), three in group IIa (33% mortality), and no deaths in group IIb. The only significant difference between patients in group IIa and those in group IIb was a greater left ventricular posterior wall thickness in group IIa patients. Twenty control patients without cardiac disease had negative gallium-67 scans. We conclude that gallium-67 myocardial scintigraphy may be a useful test for predicting the response to prednisone and azathioprine therapy.

  8. Pneumocystis jiroveci pneumonia and pneumomediastinum in an anti-TNFα naive patient with ulcerative colitis

    Directory of Open Access Journals (Sweden)

    James C Lee, Deborah C Bell, Richard M Guinness, Tariq Ahmad

    2009-04-01

    Full Text Available We report the case of a 21-year-old man who was noted to have pneumomediastinum during an admission for an acute flare of ulcerative colitis. At that time, he was on maintenance treatment with azathioprine at a dose of 1.25 mg/kg per day, and had not received supplementary steroids for 9 mo. He had never received anti-tumor necrosis factor (TNFα therapy. Shortly after apparently effective treatment with intravenous steroids and an increased dose of azathioprine, he developed worsening colitic and new respiratory symptoms, and was diagnosed with Pneumocystis jiroveci (carinii pneumonia (PCP. Pneumomediastinum is rare in immunocompetent hosts, but is a recognized complication of PCP in human immunodeficiency virus (HIV patients, although our patient’s HIV test was negative. Treatment of PCP with co-trimoxazole resulted in resolution of both respiratory and gastrointestinal symptoms, without the need to increase the steroid dose. There is increasing vigilance for opportunistic infections in patients with inflammatory bowel disease following the advent of anti-TNFα therapy. This case emphasizes the importance of considering the possibility of such infections in all patients with inflammatory bowel disease, irrespective of the immunosuppressants they receive, and highlights the potential of steroid-responsive opportunistic infections to mimic worsening colitic symptoms in patients with ulcerative colitis.

  9. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Pennock, J.L. (Stanford Univ. School of Medicine, CA); Reitz, B.A.; Beiber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either Cy A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  10. Immunosuppressive therapy in patients with congestive cardiomyopathy and myocardial uptake of gallium-67

    Energy Technology Data Exchange (ETDEWEB)

    O' Connell, J.B.; Robinson, J.A.; Henkin, R.E.; Gunnar, R.M.

    1981-10-01

    Thirty-nine patients with idiopathic congestive cardiomyopathy underwent gallium-67 scintigraphy. Twenty had no evidence of myocardial uptake (group I) and 19 had demonstrable myocardial gallium-67 activity (group II). There was no significant difference in age, sex, duration of symptoms, antecedent viral illness, left ventricular end-diastolic pressure, pulmonary artery systolic pressure, or ejection fraction between the two groups. Fifteen patients in group II were treated with prednisone and azathioprine for a minimum of 8 months. Nine of 15 patients were clinically unchanged and gallium-67 scans remained positive (group IIa). Six patients had significant improvement and resolution of myocardial gallium-67 uptake (group IIb). The mean change in ejection fraction was +0.2% in group I, -4.8% in Group IIa, and +13.8% in group IIb. There were five deaths in group I (25% mortality), three in group IIa (33% mortality), and no deaths in group IIb. The only significant difference between patients in group IIa and those in group IIb was a greater left ventricular posterior wall thickness in group IIa patients. Twenty control patients without cardiac disease had negative gallium-67 scans. We conclude that gallium-67 myocardial scintigraphy may be a useful test for predicting the response to prednisone and azathioprine therapy.

  11. Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Pennock, J.L.; Reitz, B.A.; Bieber, C.P.; Aziz, S.; Oyer, P.E.; Strober, S.; Hoppe, R.; Kaplan, H.S.; Stinson, E.B.; Shumway, N.E.

    1981-12-01

    Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.

  12. Perfusatory recovery of the grafted lung during convalescence from acute rejection.

    Science.gov (United States)

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Yamashita, C

    2000-01-01

    The aim of this study was to evaluate whether or not perfusatory recovery of the grafted lung occurs is the early stage of convalesce from acute rejection following a single lung transplantation. Eight adult mongrel dogs underwent an allotransplantation of the left lung with treatment of 10 mg/kg cyclosporine and 4 mg/kg azathioprine. Doppler flow probes were placed to the ascending aorta and the left pulmonary artery. Immunosuppressant therapy was discontinued to induce rejection after postoperative day 14. When the left pulmonary artery flow rate (l-PAFR) decreased to less than 20%, methylprednisolone (20 mg/kg) was administered for 3 days along with a resumption of cyclosporine and azathioprine. Pulmonary circulation and chest roentgenograms were evaluated every day through the rejection episode. An open lung biopsy was also performed in each dog to obtain specimens of the grafts and native lungs for histologic examination. When l-PAFR decreased to less than 20%, mild acute rejection was found in all dogs. l-PAFR increased significantly on the third day after methylprednisolone treatment. Thereafter, a histologic examination revealed minimal acute rejection in one dog and no abnormality in seven dogs. The perfusatory recovery of the grafted lung was thought to reflect the histological change in the course of convalescence. PMID:10664339

  13. Thiopurine methyltransferase activity in red blood cells of dogs.

    Science.gov (United States)

    Kidd, Linda Benjamin; Salavaggione, Oreste E; Szumlanski, Carol L; Miller, Jackie L; Weinshilboum, Richard M; Trepanier, Lauren

    2004-01-01

    Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of thiopurine medications such as azathioprine. In humans, activity varies widely among individuals, primarily because of genetic polymorphisms. Low TPMT activity increases the risk of myelosuppression from azathioprine and 6-mercaptopurine, whereas high TPMT activity is associated with poor drug efficacy. The purpose of this study was to determine whether dogs also show a wide range of TPMT activity. Heparinized blood samples were obtained from 177 dogs associated with a veterinary teaching hospital. Red blood cell (RBC) TPMT activity was measured by means of a modification of a radiochemical method as established for use in people. TPMT activity varied across a 9-fold range (7.9-71.8 U of RBC per milliliter; median, 21.7). Variation in TPMT activity was not associated with age, sex, or neutering status. Giant Schnauzers had much lower TPMT activity (7.9-20 U of RBC per milliliter; median, 13.1; P dogs could affect thiopurine drug toxicity and efficacy in canine patients. PMID:15058773

  14. Canine symmetrical lupoid onychodystrophy: a retrospective study with particular reference to management.

    Science.gov (United States)

    Auxilia, S T; Hill, P B; Thoday, K L

    2001-02-01

    The records of six dogs in which a diagnosis of symmetrical lupoid onychodystrophy (SLO) had been made were examined retrospectively. The age at onset ranged from six months to eight years. All the dogs had been presented with onycholysis, onychomadesis, onychalgia and onychodystrophy. The diagnosis of SLO was confirmed in all cases by histological examination. Histological features were similar in all cases and included hydropic degeneration of the basal cell layer, pigmentary incontinence and a cell-rich interface dermatitis. Response (defined as good, partial or failure) to various therapies was compared. Treatments (as initial therapy or following previous treatment failure) included essential fatty acids (EFA) (three cases), a combination of tetracycline and nicotinamide (four cases) and azathioprine and/or prednisolone (one case each). EFA therapy resulted in one good response, one partial and one failure, tetracycline and nicotinamide in two good responses, one partial and one failure, and azathioprine and/or prednisolone in one good and one partial response. Although all treatments were successful in some cases, none was universally effective. PMID:11263704

  15. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet’s Disease

    Directory of Open Access Journals (Sweden)

    Feridoun Sabzi

    2016-05-01

    Full Text Available We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet’s disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued.

  16. Right Ventricular Thrombus and Cerebral Artery Aneurysm in a Patient with Behçet's Disease.

    Science.gov (United States)

    Sabzi, Feridoun; Mirzaei, Samaneh; Faraji, Reza

    2016-05-01

    We report a 35-year-old woman referred to the Imam Ali Hospital, Kermanshah, Iran, in July 2014 for evaluation of postoperative dyspnoea after neurosurgery performed seven days previously for a ruptured cerebral artery aneurysm. She was known to have Behçet's disease with a history of recurrent oral and genital aphthous ulcers and uveitis. At referral, her symptoms included vertigo, dysarthria, palpitations and chest pain. Transthoracic echocardiography (TTE) revealed a large thrombus in her right ventricle outflow tract and open-heart surgery was performed eight days after the previous surgery to remove the clot. The postoperative period was complicated by transient acute renal failure, which resolved spontaneously. The patient was discharged 13 days after the cardiac surgery on warfarin, prednisolone, azathioprine and cyclophosphamide. Cyclophosphamide and azathioprine were discontinued after three months as the symptoms had completely resolved; however, prednisolone was continued due to recurrent uveitis. A 10-month follow-up TTE scan revealed no thrombus recurrence and treatment with warfarin and prednisolone was continued. PMID:27226921

  17. Non comparative study on various pulse regimens (DCP, DAP and DMP in pemphigus: Our experience

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2014-01-01

    Full Text Available Background: Pemphigus has been treated with Dexamethasone Cyclophosphamide Pulse (DCP Therapy since 1981.Various modifications have been suggested in the original regimen. These include Dexamethasone Azathioprine Pulse (DAP and Dexamethasone Methotrexate Pulse (DMP therapies. Aims: To report our experience on the noncomparative study of various Pulse regimens DCP, DAP AND DMP therapies in patients with Pemphigus. Materials and Methods: The patients were put on three regimens depending upon the situation-Conventional DCP, DAP in the reproductive age group, DMP in patients who showed prolonged Phase I more than 12 months while on DCP. Results: 30 patients were put on DCP therapy. The duration of phase I was on an average six months. Relapse was seen in 3 patients in phase IV. 12 patients on DAP therapy were considered. In Phase III 5 patients relapsed in phase IV four patients relapsed. Five patients were put on the DMP. Disease activity was poorly controlled and in three DMP was discontinued. Conclusion: DCP remains the most effective regimen with quickest onset of remission and continuance of remission. In DAP therapy fixation of dose of azathioprine at 50 mgs daily may be counterproductive. DMP does not fulfil the promise of a viable treatment option in recalcitrant pemphigus and this lacunae needs to be plugged.

  18. Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

    Science.gov (United States)

    Mejía-Vilet, J M; Córdova-Sánchez, B M; Arreola-Guerra, J M; Morales-Buenrostro, L E; Uribe-Uribe, N O; Correa-Rotter, R

    2016-03-01

    We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease. PMID:26405028

  19. The Flare Up of Catastrophic Antiphospholipid Syndrome: a Report of an Immunosuppressive Withdrawal-Induced Case

    Directory of Open Access Journals (Sweden)

    Sayyed Gholamreza Mortazavimoghaddam

    2011-09-01

    Full Text Available Antiphospholipid syndrome (APS is a systemic disease that causes venous and arterial thrombosis in virtually any organ. Sometimes it is complicated into pulmonary infarction and cavitation, pulmonary hypertension, and catastrophic course with high morbidity and mortality. The present case is a 35-year-old woman with one episode of postpartum deep veins thrombosis (DVT 12 years earlier and the second one after the second labor two years later. In spite of usual therapy for each episode of DVT, the condition had progressed into severe pulmonary hypertension. The diagnosis of primary APL syndrome was confirmed four years ago. She had been on warfarin, low dose of steroid, and azathioprine since the diagnosis of APL syndrome. After one year treatment with steroid and azathiprine the patient showed progressive well being; however, because of hyperglycemia the steroid tapered and discontinued. She had several attacks of paroxismal atrial tachycardia in the last year. On the last time, she presented with severe dyspnea, hemoptesis, and lower limbs edema. Chest radiography and Lung CT scan demonsterated the presence of lung cavitations. Because of high suspicious for fungal pulmonary infection, azathioprine was also discontinued. However, constellation renal failure, hemodynamic instability, and confusion caused the patient to succumb to death. The definite diagnosis of lung cavitations was not obtained

  20. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    excretion can be reduced by diuretics or fluoxetine. When drugs such as antifungal imidazoles, azapropazone, or phenylbutazone are permitted to inhibit the metabolism of sulphonylureas, hypoglycemic effects are enhanced and, if unnoticed, may cause brain damage. Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy. Patients taking non-selective monoamine oxidase inhibitors should avoid amine-containing foods and drugs such as matured cheeses, meat, yeast extracts, some wines, unfresh protein, and cold-curing medications. The metabolism of azathioprine is inhibited by allopurinol, and this combination requires a reduced dosage of azathioprine. Mercaptopurine, used in the treatment of leukemia, is also a metabolite of azathioprine. Sources of comprehensive information on drug interactions are 1) the "British National Formulary," appendix 1; 2) Chapter 10 of "The Oxford Textbook of Clinical Pharmacology and Drug Therapy"; and 3) a monograph by Stockley entitled "Drug Interactions." PMID:7903448

  1. A case of rapid growing colonic NK/T cell lymphoma complicated by Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Shumei Zheng; Hui Xu; Qin Ouyang; Linyun Xue; Yong Zhang; Dejun Cui

    2013-01-01

    A 37-year-old man developed abdominal pain and bloody diarrhea 11 months before admission.The colonoscopy revealed multifocal ulcers in the colon.Histology showed active chronic inflammation.Although anti-tuberculosis medication was effective,his symptoms repeated 2 months later.The subsequent colonoscopy revealed more extensive irregular ulcers than before,and he was clinically suspected with intestinal malignant lymphoma.He underwent subtotal colectomy and was histologically suggested Crohn's disease,then 5-aminosalicylic and a combination of prednisone and azathioprine were administered in succession postoperatively,but they achieved minimal relief of symptoms for a period of 7 months.The third colonoscopy showed a large irregular ulcer in the ileocolon stomas,and primary colonic NK/T cell lymphoma was diagnosed through histological and immunophenotypic studies.Malignant lymphoma should be taken into consideration when clinically diagnosed Crohn's disease was refractory to medication or when its clinical course became aggressive.

  2. Innovative therapeutics for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Jesus K Yamamoto-Furusho

    2007-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract,which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade;(4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

  3. Crohnology: A tale of time and times and inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Femando Gomollón; Javier P Gisbert; Miquel (A)ngel Gassull

    2008-01-01

    Time, times and timing are key words in inflammatory bowel diseases (IBD).The leifmotif of this issue or World Journal of Gastroenterology is time. We have asked experts to review on the epidemiology of these diseases over time,the changes in innate immunity that could be present in the first time, and then the timing of key treatments. The correct time of using azathioprine, mercaptopurine, infliximab, cyclosporine and surgery are reviewed.We have chosen experts with not only great clinical expertise but also personal interest in clinical and basic investigation. Our goal in this monograph is to get an idea not only of the present but of the immediate future in some of the key management issues in IBD. To this end, we think that the authors are the most adequate.

  4. New and emerging therapies for diseases of the oral cavity.

    Science.gov (United States)

    Popovsky, J L; Camisa, C

    2000-01-01

    It is obvious from the review of the literature that most treatments for oral diseases such as lichen planus, pemphigoid, and pemphigus are based on case reports, anecdotes, and small uncontrolled studies. Efforts must be made to perform more controlled studies to evaluate the efficacy of new treatments. Small numbers of patients at each site and multiple-drug therapy make this task difficult. Dermatologists should familiarize themselves with the newer immunosuppressive agents available. Use of these drugs requires knowledge of their pharmacokinetics and potential side effects, so that they may be used effectively and safely. Relatively low doses of azathioprine, cyclophosphamide, and cyclosporine should then be added to the dermatologist's armamentarium for the treatment of severe or recalcitrant diseases. Old drugs are resurfacing with new (but often off-label) uses as the underlying mechanisms of disease become understood. Thalidomide and mycophenolate mofetil are two examples of promising drugs for the future of dermatology. PMID:10626117

  5. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies, and questions

    Directory of Open Access Journals (Sweden)

    Jay Desai

    2015-01-01

    Full Text Available Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children′s Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  6. Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory Neuronopathy in Sjögren's Syndrome

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Danieli

    2012-01-01

    Full Text Available Sensory neuronopathy is described in association with the Sjögren's syndrome (SS. We studied a 55-year-old woman with a 4-year history of progressive asymmetric numbness, distal tingling, and burning sensation in upper and lower limbs. In a few months, she developed ataxia with increased hypoanaesthesia. Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve action potential in upper and lower limbs. Cervical spine magnetic resonance showed a signal hyperintensity of posterior columns. Previous treatment with high-dose glucocorticoids and azathioprine was ineffective. A combined treatment with intravenous immunoglobulin and mycophenolate mofetil was followed by a progressive and persistent improvement. This case documented the efficacy and the safety of the coadministration of intravenous immunoglobulin and mycophenolate mofetil in sensory neuronopathy associated with SS refractory to conventional immunosuppressive therapy.

  7. Management of granulomatous lymphocytic interstitial lung disease in a patient with common variable immune deficiency.

    Science.gov (United States)

    Pathria, Mohini; Urbine, Daniel; Zumberg, Marc Stuart; Guarderas, Juan

    2016-01-01

    A 61-year-old woman presented with longstanding cough and progressive dyspnoea. She underwent an extensive evaluation and was diagnosed with common variable immunodeficiency (CVID) with granulomatous lymphocytic interstitial lung disease (GLILD). She was initially treated with subcutaneous immunoglobulin therapy, having declined intravenous immunoglobulin (IVIG) therapy. She also declined treatment with oral glucocorticoids. Over several months, she became increasingly symptomatic and developed increased pulmonary infiltrates, pleural effusions, mediastinal adenopathy, splenomegaly, pancytopenia and ascites. An interdisciplinary team composed of an immunologist, pulmonologist and haematologist deliberated over a therapeutic management approach. The patient received a recently reported immunotherapy regimen with azathioprine and rituximab. The therapy led to rapid improvement of her constitutional and respiratory symptoms, with clinical and radiographic improvement in her interstitial lung disease, lymphadenopathy, pleural effusions and ascites. This case report reviews the literature surrounding the diagnosis and management of GLILD. PMID:27335365

  8. Pure red cell aplasia following autoimmune hemolytic anemia: An enigma

    Directory of Open Access Journals (Sweden)

    M Saha

    2013-01-01

    Full Text Available A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA, prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  9. Eosinophilic gastroenteritis: a challenge to diagnose and treat.

    Science.gov (United States)

    Phaw, Naw April; Tsai, Her Hsin

    2016-01-01

    The patient presented with bloody diarrhoea, and crampy abdominal pains. She was diagnosed with eosinophilic gastroenteritis (EGE) after the finding of persistently high peripheral eosinophil counts and histology of endoscopic biopsies. She responded to steroids but became dependent on it and her symptoms recurred on steroid tapering. There was little improvement with alternative treatment such as budesonides, azathioprine and montelukast. Surprisingly her symptoms improved significantly after she was treated with clarithromycin for chest infection and she was continued on clarithromycin. Her eosinophil counts fell dramatically and follow-up CT (thorax, abdomen and pelvic) scan showed the mucosal thickening had improved. She became completely free of the symptoms since she was on clarithromycin and her eosinophils counts fell within the normal range during the follow-up. PMID:27613263

  10. Hepatotoxicity by Drugs: The Most Common Implicated Agents

    Directory of Open Access Journals (Sweden)

    Einar S. Björnsson

    2016-02-01

    Full Text Available Idiosyncratic drug-induced liver injury (DILI is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov. According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab.

  11. Ulcerative colitis in infancy

    Directory of Open Access Journals (Sweden)

    Md Rukunuzzaman

    2011-01-01

    Full Text Available Ulcerative colitis (UC is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100 000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel′s diverticulitis, Crohn′s disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis.

  12. Inflammatory pseudotumour of the maxilla.

    Science.gov (United States)

    Kichenaradjou, A; Barrett, A W; Norris, P; Rowell, N; Newman, L

    2016-09-01

    Inflammatory pseudotumour (IP), also known as inflammatory myofibroblastic tumour (IMT), is a rare lesion of the maxillofacial skeleton and a diagnosis by exclusion. We describe three cases which affected the maxilla, two women and one man of ages 67, 56 and 70 years at presentation. All showed the typical, rather non-specific histopathological features. IgG4-positive plasma cells varied greatly in prominence, and none of the three lesions expressed ALK-1. Both women responded to steroids and radiotherapy, though one also required azathioprine. Despite maxillectomy, radiotherapy, steroids and cyclophosphamide, the man suffered intracranial spread and succumbed to persistent disease. The cases described here demonstrate the clinicopathological difficulties presented by this entity and its aggressive, unpredictable behaviour. PMID:27052813

  13. Preemptive Renal Transplantation-The Best Treatment Option for Terminal Chronic Renal Failure.

    Science.gov (United States)

    Arze Aimaretti, L; Arze, S

    2016-03-01

    Renal transplantation is the best therapeutic option for end-stage chronic renal disease. Assuming that it is more advisable if performed early, we aimed to show the clinical, social, and economic advantages in 70% of our patients who were dialyzed only for a short period. For this purpose, we retrospectively collected data over 28 years in 142 kidney transplants performed in patients with sports, and reproduction. Immunosuppression consisted of 3 drugs, including steroids, cyclosporine, and azathioprine or mycophenolate. The cost in the 1st year, including patient and donor evaluation, surgery, immunosuppression, and follow-up, was $13,300 USD versus $22,320 for hemodialysis. We conclude that preemptive renal transplantation with <6 weeks on dialysis is the best therapeutic option for end-stage renal failure, especially in developing countries such as Bolivia, where until last year, full public support for renal replacement therapy was unavailable. PMID:27110013

  14. CUTANEOUS NECROTISING VASCULITIS – THERAPEUTIC FACT -A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Kiran

    2012-08-01

    Full Text Available ABSTRACT: INTRODUCTION: Mixed connective tissue disorder, unlike other conn ective tissue disorders have a milder course. MTCD with only nec rotizing cutaneous vasculitis without organ damage respond well to Immunosuppresents and Steroids. CASE REPORT : Middle aged Young lady presented with multiple non healing large pressur e sores and multiple nonblanchable purpuric lesions. She was bedridden, anaemic and wit h significant weight loss. All her major organ functions were normal. Her U 1 RNP Antibody is positive and Skin Biopsy showed positive direct fluorescent test for IgG. She respond ed well to immunosuppresants and steroids. CONCLUSION: This patient who presented with MTCD, with predominant necrotizing cutaneous vasculitis and without major organ involv ement showed good recovery and responded well to cyclophosphamide pulse therapy, daily azathioprine and good wound care

  15. Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

    Science.gov (United States)

    Flanagan, Frances; Glackin, Louisa; Slattery, Dubhfeasa M

    2013-03-01

    Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC. PMID:22573417

  16. Treatment of progressive IgA nephropathy: an update.

    Science.gov (United States)

    Wang, Weiming; Chen, Nan

    2013-01-01

    IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. About 25-30% of IgAN patients will progress to end-stage kidney disease in 20-25 years. Early-onset symptoms that are highly suggestive of progressive IgAN include massive proteinuria, hypertension, renal damage, glomerular sclerosis, crescent formation, and tubulointerstitial fibrosis. Progressive IgAN may progress to renal failure in a short time. Optimized supportive therapy is the fundamental treatment for progressive IgAN patients, and includes renin-angiotensin system blockers, blood pressure control, antiplatelet and anticoagulant drugs, statins, and allopurinol. In progressive IgAN patients whose clinical and pathological manifestations are more severe, active therapy may be considered including glucocorticoid therapy, cyclophosphamide, azathioprine, mycophenolate mofetil, tacrolimus, and other immunosuppressants. However, there are currently controversies on the definition and treatment of progressive IgAN. PMID:23689569

  17. [Life-threatening adverse effects of pharmacologic antihyperuricemic therapy].

    Science.gov (United States)

    Russmann, St; Lauterburg, B

    2004-09-01

    Minor hypersensitivity reactions to allopurinol presenting as skin rash occur in approximately 2% of patients. A more severe, albeit rare, hypersensitivity reaction with fever, eosinophilia, dermatitis, renal failure, vasculitis and hepatic dysfunction carries a mortality of up to 20%. The incidence of this severe reaction can probably be reduced by adjusting the dose of allopurinol in patients with impaired renal function. Azathioprine and mercaptopurine are metabolised by xanthine oxidase, the enzyme that is inhibited by allopurinol. Concomitant administration can result in life-threatening neutropenia unless the dose of allopurinol is reduced by approximately 75%. The uricosuric agent benzbromarone has recently been withdrawn from the market because of several cases of fulminant hepatic failure with subsequent death of the patient or liver transplantation. PMID:15493119

  18. Excellent uricosuric efficacy of benzbromarone in cyclosporin-A-treated renal transplant patients: a prospective study.

    Science.gov (United States)

    Zürcher, R M; Bock, H A; Thiel, G

    1994-01-01

    Patients on cyclosporin A (CsA) often develop hyperuricaemia and gout. In transplant patients the use of uricosuric drugs for treating hyperuricaemia may be preferable to allopurinol because of the known interaction of the latter with azathioprine. We therefore prospectively studied the uricosuric efficacy of 100 mg benzbromarone (Bbr;Desuric) daily in 25 CsA-treated renal transplant patients with stable graft function and hyperuricaemia (> 359 mumol/l for females, > 491 mumol/l for males). Benzbromarone decreased plasma uric acid from 579 + 18 mumol/l to 313 +/- 24 mumol/l (mean +/- SEM; P 25 ml/min. Due to its excellent efficacy and lack of significant side-effects, benzbromarone appears to be preferable to allopurinol in CsA-treated renal transplant recipients with a creatinine clearance over 25 ml/min. PMID:8090336

  19. Colchicine myoneuropathy in a renal transplant patient.

    Science.gov (United States)

    Dupont, Peter; Hunt, Ian; Goldberg, Lawrence; Warrens, Anthony

    2002-07-01

    Colchicine is widely employed for the treatment of gout in renal transplant patients where NSAIDs are contra-indicated and allopurinol prophylaxis is often avoided due to concomitant azathioprine immunosuppression. We report here a case of colchicine-induced myoneuropathy in a renal transplant recipient. Our patient had myalgia, muscle weakness, elevated creatine kinase levels, myopathic changes on electromyography and peripheral neuropathy. Withdrawal of colchicine resulted in recovery within 4 weeks. Renal transplant recipients are likely to be at greater risk of colchicine-induced myoneuropathy due to the unique concurrence of risk factors predisposing to toxicity in such patients. These risk factors include the high incidence of gout in this population, widespread use of colchicine as first-line therapy, impaired renal function and concomitant cyclosporin treatment. The diagnosis should be considered in any renal transplant recipient receiving the drug who develops myopathy. Prompt withdrawal of colchicine therapy should result in rapid clinical and biochemical improvement. PMID:12122515

  20. Case reports: treatment of nevirapine-associated dress syndrome with intravenous immune globulin (IVIG).

    Science.gov (United States)

    Fields, Katherine S; Petersen, Marta J; Chiao, Elizabeth; Tristani-Firouzi, Payam

    2005-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse drug reaction most commonly associated with aromatic antiepileptic agents. It is characterized by the triad of skin eruption, fever, and systemic involvement, with the latter usually manifesting as hepatitis and lymphadenopathy. Mortality is primarily due to hepatic failure and can be as high as 10%. Formerly referred to by names such as Dilantin hypersensitivity syndrome and anticonvulsant hypersensitivity syndrome, DRESS syndrome is a more precise term since this reaction pattern can be seen with other agents. DRESS syndrome has also been reported in association with sulfonamides, allopurinol, terbinafine, minocycline, azathioprine, and dapsone as well as with several antiretroviral agents such as abacavir and nevirapine. We describe a patient with HIV who developed nevirapine hypersensitivity syndrome who was successfully treated with intravenous immune globulin (IVIG). PMID:16004028

  1. Pregnancy in renal transplant recipients.

    Science.gov (United States)

    Hou, Susan

    2013-05-01

    Fertility in women with kidney failure is restored by transplantation. It requires careful planning and is only advisable in women with good kidney function, controlled blood pressure, and general good health. Immunosuppressive drugs carry risks for the fetus, but the risks of prednisone, azathioprine, cyclosporine, and tacrolimus are surprisingly low. Mycophenolate is teratogenic. The success rate for pregnancy in kidney transplant recipients is lower than in the general population with 70% to 80% of pregnancies resulting in surviving infants. Prematurity, intrauterine growth restriction, and preeclampsia are all increased. Complications are higher and outcomes are worse for women with serum creatinine levels over 1.3 mg/dL. Ten to 15% of women have a temporary or permanent decline in kidney function, particularly if prepregnancy creatinine is high. Transplant-related infections can be serious for the mother and fetus. A multidisciplinary team should coordinate care. PMID:23928390

  2. [Combination biological therapy for fistular Crohn's disease: clinical demonstration].

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Konoplyannikov, A G; Ruchkina, I N; Lischchinskaya, A A

    2014-01-01

    Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD. PMID:24772517

  3. Generalized subcutaneous edema as a rare manifestation of dermatomyositis: clinical lesson from a rare feature.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-04-01

    Generalized subcutaneous edema is a very rare manifestation of inflammatory myopathies. A 61-year-old woman presented with classic signs and symptoms of dermatomyositis. She was also noted to have generalized edema that was so florid that an alternative diagnosis was considered. Her disease was resistant to corticosteroids, azathioprine, and mycophenolate mofetil. Intravenous administration of immunoglobulins was started because of marked worsening of her disease-muscle weakness, generalized anasarca, and involvement of her bulbar muscles. This led to dramatic resolution of her subcutaneous edema and significant improvement of her skin and muscle disease. As the initial screen for malignancy was negative, a positron emission tomography-computed tomography scan was requested, which interestingly showed a metabolically active cervical tumor. Anasarca is an unusual manifestation of dermatomyositis. In treatment-refractory cases, it seems reasonable to consider positron emission tomography scan in excluding underlying malignant disease.

  4. Memory in myasthenia gravis: neuropsychological tests of central cholinergic function before and after effective immunologic treatment.

    Science.gov (United States)

    Glennerster, A; Palace, J; Warburton, D; Oxbury, S; Newsom-Davis, J

    1996-04-01

    There are reports of central cholinergic deficits in myasthenia gravis (MG) describing impaired performance on a variety of tests of memory with varying benefits from plasmapheresis. We tested 11 patients with symptomatic MG at the start of a trial of immunosuppressive treatment (prednisolone plus azathioprine or placebo) and again when in remission. The tests included the Logical Memory and Design Reproduction parts of the Wechsler Memory Scale, the Rey Auditory Verbal Learning Test, Peterson-Peterson task, and an auditory vigilance task. Muscle strength improved significantly over the period of treatment, but overall performance on tests of memory or attention did not. These results fail to substantiate reports of functionally significant and reversible central deficits in myasthenia gravis. PMID:8780106

  5. Crohn S Disease and Acne Fulminans as Associated Disoders (Case Report

    Directory of Open Access Journals (Sweden)

    Pecova K

    2015-09-01

    Full Text Available The authors are presenting a rare case of recurrent acne fulminans (AF in man with Crohn‘s disease (CD. First attak of AF as associated disorder was observed at the age of 21 with positivity rheumatoid factor (28.0 U/ml, Creactive protein (86.7 m/l, ANA (1:160, p-ANCA (1:40 and 82 erythrocyte sedimentation rate/1 hour. The second attak of AF was observed after the 4th infliximab (5mg/kg administration, with azathioprine (100mg/day, with positivity Epstein-Barr (EBV Real Time PCR - 1835 copies/ml. The effect of AF therapy was observed after methylprednisolone (0.5-1.0mg/kg/day with isotretinoin (0.2-1.0mg/kg/day administration, with continual infliximab administration.

  6. Update on autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Peter R Galle; Stephan Kanzler

    2009-01-01

    Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.

  7. Xanthoma disseminatum: A progressive case with multisystem involvement

    Directory of Open Access Journals (Sweden)

    A M Attia

    2014-01-01

    Full Text Available Xanthoma disseminatum (XD is a rare, benign, non-Langerhans cell histiocytic disorder. The pathogenesis is not clear. It manifests with multiple, grouped, red-brown to yellow papules and nodules involving the skin, mucous membranes, and internal organs. We present a case of progressive XD in a 10-year-old male child. The patient presented with progressive, bilateral and symmetrical, reddish-brown, coalescent papules on the neck, around both eyes and all over his trunk and extremities. Skin lesions were accompanied by blurred vision and hoarseness of voice. Examination revealed xanthomatous infiltration of cornea, oral, pharyngeal, and laryngeal mucosae. The patient had diabetes insipidus that was diagnosed 2 years before the appearance of skin lesions. Medical treatment with corticosteroids (20 mg/day and azathioprine (2 mg/kg/day did not stop the disease progression.

  8. Endolymphatic irradiation

    International Nuclear Information System (INIS)

    The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic 131I as a pre-transplantation immunesuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunesuppressive therapy. Significant differences were observed between the two groups regarding such factors a incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunesuppressive action, its administration being advised for receptores of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel. (Author)

  9. [Ulcerous colitis and infection with cytomegalovirus, herpes simplex virus and clostridium difficile].

    Science.gov (United States)

    Arnold, C; von Sanden, S; Theilacker, C; Blum, H E

    2008-08-01

    The treatment of severe flares of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and in some cases TNF-alpha-antagonists, respectively. These immunosuppressed patients are susceptible for infectious pathogens. Here we report the case of a patient with a severe flare of ulcerative colitis that was first treated with systemic corticosteroids combined with immunomodulators and subsequent with infliximab. The patient then experienced an infection with Clostridium difficile and cytomegalovirus of the colon and a Herpes simplex esophagitis, respectively. After specific treatment the patient responded well to the immunosuppressive therapy. This case illustrates that infections have to be considered before systemic treatment of an acute flare of ulcerative colitis is instituted especially in the case of disease activation during immunosuppressive treatment. PMID:18759202

  10. Herpes zoster motor neuropathy in a patient with previous motor paresis secondary to Vogt-Koyanagi-Harada disease.

    Science.gov (United States)

    Sifuentes Giraldo, Walter Alberto; de la Puente Bujidos, Carlos; de Blas Beorlegui, Gema; López San Román, Antonio; Peña Arrebola, Andrés

    2013-04-01

    Motor involvement in herpes zoster is very infrequent, occurring in 3%-5% of cases, and it is caused by extension of the inflammatory process to the anterior horn motor neurons, with the subsequent development of segmental motor paralysis. The authors report a 37-yr-old woman with history of paresis in both lower limbs secondary to spinal cord atrophy associated with Vogt-Koyanagi-Harada disease and immunosuppression caused by chronic corticosteroid and azathioprine treatment of ulcerative colitis, who developed worsening of her baseline residual muscle strength in the right lower limb shortly after herpes zoster eruption. Electromyography revealed acute denervation in territories corresponding to L3-L4 and moderate widespread axonal polyneuropathy affecting both lower limbs. The patient recovered her baseline muscle strength after this event. To the best of the authors' knowledge, this is the first reported case of herpes zoster motor neuropathy in a patient with a previous motor sequel. PMID:23221673

  11. Herpes Simplex Virus Sepsis in a Young Woman with Crohn's Disease.

    Science.gov (United States)

    Haag, Lea-Maxie; Hofmann, Jörg; Kredel, Lea Isabell; Holzem, Christina; Kühl, Anja A; Taube, Eliane T; Schubert, Stefan; Siegmund, Britta; Epple, Hans-Jörg

    2015-12-01

    We present the case of a herpes simplex virus-1 [HSV-1] sepsis with severe herpes hepatitis in a young female treated with triple immunosuppressive therapy [adalimumab, azathioprine, prednisolone] for refractory Crohn's disease [CD]. The patient presented with high fever, generalised abdominal tenderness, strongly elevated transaminases, coagulopathy, and pancytopenia. Comprehensive diagnostics including blood HSV-1 polymerase chain reaction [PCR], liver biopsy, and immunohistochemistry revealed the diagnosis of fulminant herpes hepatitis. HSV-1 positivity of cutaneous lesions proved the disseminated nature of the infection. Early treatment with intravenous acyclovir led to a rapid improvement of the patient's condition and resulted in a full recovery of her liver function. This is the first reported case of HSV-sepsis in a patient with CD. Physicians treating inflammatory bowel disease [IBD] patients with combined immunosuppressive therapy should be aware of the possibility of herpes hepatitis, and early empirical antiviral therapy should be considered in immunosuppressed patients presenting with fever and severe anicteric hepatitis. PMID:26351382

  12. Plasma exchange therapy for a severe relapse of Devic's disease in a pregnant woman: A case report and concise review.

    Science.gov (United States)

    Rubio Tabares, Jonathan; Amaya Gonzalez, Pablo Felipe

    2016-09-01

    Neuromyelitis optica (NMO) or Devic's disease is an autoimmune inflammatory demyelinating condition affecting the central nervous system (CNS). It was initially believed to be a variant of multiple sclerosis (MS). However, the discovery of NMO-IgG anti-AQP4 antibodies marked an objective distinction between these conditions. Treatment of acute attacks is generally based on pulsed steroids, followed by long-term immunosuppression with azathioprine, oral steroids, and rituximab as first-line therapies. Plasma exchange therapy is indicated for steroid-resistant relapses. We describe a case report of a pregnant woman with a severe relapse of Devic's disease, initially misdiagnosed as MS, unresponsive to pulsed steroids, and who underwent plasma exchange therapy safely, with excellent clinical response and with no adverse outcome for the fetus. PMID:27428489

  13. Asymptomatic giant coronary aneurysm in an adolescent with Behcet's syndrome

    Directory of Open Access Journals (Sweden)

    Kahn Philip J

    2012-01-01

    Full Text Available Abstract Objective Behcet's is an idiopathic multi-organ syndrome, which may have onset during childhood. Vascular involvement is uncommon, with rarely reported coronary aneurysm formation. We present a case report of a teenager girl who developed recalcitrant life-threatening Behcet's vasculitis, involving both small and large venous and arterial systems including a giant coronary aneurysm. Case report De-identified data were collected retrospectively in case report format. Although our sixteen year old female with Behcet's vasculitis had resolution of many arterial aneurysms, she had persistent venous thrombosis of large vessels, as well as persistent, giant arterial aneurysms requiring intra-arterial coiling of a lumbar artery and coronary bypass grafting despite intensive immunosuppression including glucocorticoids, cyclophosphamide, infliximab, methotrexate, azathioprine and intravenous immunoglobulin. Conclusions Vascular manifestations may be seen in Behcet's syndrome, including asymptomatic coronary aneurysm, which may be refractory to immunosuppression and ultimately require surgical intervention. Increased awareness is essential for prompt diagnosis and management.

  14. A rare prenatal case with two de novo inversions and a translocation: 48, XX,t(9;12)(q32;p24.3), inv(11)(p15.1q25), inv(13)(q12.q22)

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, B.; Balaban, L.; Eldred, C. [Albany Medical College, Albany, NY (United States)] [and others

    1994-09-01

    Ultrasound examination of a para 1, gravida 2, 26 y.o. showed severe hydrocephalus and polyhydramnios. Amniocentesis was performed at 27 weeks. High resolution chromosome analysis revealed a karyotype with a 9;12 translocation, a pericentric inversion of chromosome 11, and a paracentric inversion of chromosome 13. Parental chromosome studies were normal. The mother was not on medication prior to her pregnancy and there was no known exposure to radiation. Delivery was at 34 weeks gestation. The phenotype consisted of micrognathia, low set ears, hypertelorism, and hydrodcephaly. Review of the literature revealed a single report with multiple de novo aberrations consisting of a 6;14 translocation and a deleted 7. This was diagnosed in the child of a woman with systemic lupus erythematous treated with azathioprine. These types of abnormalities have been known to be induced by chemical and radiation exposure. High resolution banding combined with molecular studies presently improve our ability to detect subtle structural aberrations.

  15. Pro: Cyclophosphamide in lupus nephritis.

    Science.gov (United States)

    Kallenberg, Cees G M

    2016-07-01

    Based on efficacy and toxicity considerations, both low-dose pulse cyclophosphamide as part of the Euro-Lupus Nephritis protocol and mycophenolate mofetil (MMF) with corticosteroids may be considered for induction of remission in patients with proliferative lupus nephritis. The long-term follow-up data available for low-dose pulse cyclophosphamide, the fact that compliance is guaranteed with this regimen and economic issues all favour the Euro-Lupus regimen in this author's opinion. For maintenance treatment, either azathioprine (AZA) or MMF may be used; AZA is preferred in case pregnancy is planned, while MMF is preferred when the disease relapses during use of AZA and, possibly, after successful induction of remission with MMF. PMID:27190359

  16. Intravenous Immunoglobulin and Mycophenolate Mofetil for Long-Standing Sensory Neuronopathy in Sjögren's Syndrome.

    Science.gov (United States)

    Danieli, Maria Giovanna; Pettinari, Lucia; Morariu, Ramona; Monteforte, Fernando; Logullo, Francesco

    2012-01-01

    Sensory neuronopathy is described in association with the Sjögren's syndrome (SS). We studied a 55-year-old woman with a 4-year history of progressive asymmetric numbness, distal tingling, and burning sensation in upper and lower limbs. In a few months, she developed ataxia with increased hypoanaesthesia. Electrodiagnostic tests revealed undetectable distal and proximal sensory nerve action potential in upper and lower limbs. Cervical spine magnetic resonance showed a signal hyperintensity of posterior columns. Previous treatment with high-dose glucocorticoids and azathioprine was ineffective. A combined treatment with intravenous immunoglobulin and mycophenolate mofetil was followed by a progressive and persistent improvement. This case documented the efficacy and the safety of the coadministration of intravenous immunoglobulin and mycophenolate mofetil in sensory neuronopathy associated with SS refractory to conventional immunosuppressive therapy. PMID:25383230

  17. Mycobacterium avium-intracellulare cellulitis occurring with septic arthritis after joint injection: a case report

    Directory of Open Access Journals (Sweden)

    Murdoch David M

    2007-02-01

    Full Text Available Abstract Background Cellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases. Case presentation A 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection. Conclusion Although rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.

  18. [Auto-immune liver diseases and their treatment].

    Science.gov (United States)

    Hess, J; Thorens, J; Pache, I; Troillet, F X; Moradpour, D; Gonvers, J J

    2005-01-19

    There are three main types of auto-immune liver disease, auto-immune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. In the case of auto-immune hepatitis, prednisone therapy, with or without azathioprine, can improve quality of life and halt progression to cirrhosis. If there is no response or if the therapy is poorly tolerated, mycophenolate mofetil or cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13 to 15 mg/kg/day slows the progression of fibrosis in patients with primary biliary cirrhosis. Pruritus may be treated with cholestyramine, rifampicin or opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will slow the evolution of fibrosis. PMID:15770819

  19. Interaction between atracurium and drugs used in anaesthesia.

    Science.gov (United States)

    Chapple, D J; Clark, J S; Hughes, R

    1983-01-01

    The effects of various drugs used during anaesthesia on the neuromuscular blocking activity of atracurium have been studied in anaesthetized cats. Clinically effective doses of diazepam, morphine, pentazocine, pethidine, ketamine, Althesin, methohexitone, Septrin, lignocaine, propranolol, calcium chloride or azathioprine did not significantly alter the neuromuscular blocking action of atracurium. Recovery from atracurium was not prolonged during an infusion of hexamethonium or sodium nitroprusside, indicating that, despite the severe hypotension, the inactivation of atracurium was unimpaired. Similar to that of other competitive neuromuscular blocking agents, the action of atracurium was enhanced by tubocurarine, halothane, gentamycin, neomycin and polymixin and was antagonized by adrenaline and transiently antagonized by suxamethonium. However, pretreatment with suxamethonium did not affect the subsequent block by atracurium. PMID:6688011

  20. Successful treatment of idiopathic pulmonary capillaritis with intravenous cyclophosphamide.

    LENUS (Irish Health Repository)

    Flanagan, Frances

    2013-03-01

    Idiopathic pulmonary hemosiderosis (IPH), a subtype of diffuse alveolar hemorrhage is a rare condition, first described by Virchow in 1864. Historically, it manifests in children in the first decade of life with the combination of hemoptysis, iron deficiency anemia, and alveolar infiltrates on chest radiograph. More recently, diffuse alveolar hemorrhage has been classified by the absence or presence of pulmonary capillaritis (PC), the latter carrying a potential for a poorer outcome. While systemic corticosteroids remain the first line treatment option, other immune modulators have been trailed including hydroxychloroquine, azathioprine, 6-mercaptopurine, and cyclophosphamide with varying results. Our case demonstrates for the first time, the successful use of intravenous cyclophosphamide in the management of chronic idiopathic PC.

  1. An overlap syndrome involving autoimmune hepatitis and systemic lupus erythematosus in childhood

    Institute of Scientific and Technical Information of China (English)

    Yusuf Usta; Figen Gurakan; Zuhal Akcoren; Seza Ozen

    2007-01-01

    We report a 12 years old female patient with an overlap syndrome involving autoimmune hepatitis (ALM) and systemic lupus erythematosus (SLE). The patient presented with jaundice, hepatosplenomegaly, malAlse, polyarthralgia, arthritis and butterfly rash on the face. Laboratory tests revealed severe liver dysfunction, Coombs positive hemolytic anemia and a positive ANA/ anti-dsDNA test. Renal biopsy showed class IIA kidney disease, while liver biopsy showed chronic hepatitis with severe inflammatory activity. The patient satisfied the international criteria for both SLE and ALM. Clinical symptoms and laboratory findings of SLE improved with high dose treatment with corticosteroids and azathioprine, however, remission of the liver disease could not be achieved. Repeat biopsy of the liver after three years of therapy revealed ongoing chronic hepatitis with high level of inflammatory activity. The present case indicates that children with liver dysfunction and SLE should be investigated for ALM. There is much diagnostic and therapeutic dilemma in patients with ALH-SLE overlap syndrome.

  2. Endolymphatic irradiation. A useful method for immunosuppression in renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Galvao, M.M.; Ianhez, L.E.; Sabbaga, E. (Sao Paulo Univ. (Brazil). Faculdade de Medicina)

    1982-02-01

    The authors analysed the clinical evolution and the result of renal transplantation some years after irradiation in 24 patients (group I) who received endolymphatic /sup 131/I as a pre-transplantation immunosuppresive measure. The control group (group II) consisted of 24 non-irradiated patients comparable to group I in age, sex, primary disease, type of donor and immunosuppressive therapy. Significant differences were observed between the two groups regarding such factors as incidence and reversibility of rejection crises in the first 60 post-transplantation days, loss of kidney due to rejection, and dosage of azathioprine. The authors conclude that this method, besides being harmless, has prolonged immunosuppressive action, its administration being advised for receptors of cadaver kidneys, mainly those who show positive cross-match against HLA antigens for painel.

  3. A short history of anti-rheumatic therapy - VI. Rheumatoid arthritis drugs

    Directory of Open Access Journals (Sweden)

    G. Pasero

    2011-09-01

    Full Text Available The treatment of rheumatoid arthritis traditionally includes symptomatic drugs, showing a prompt action on pain and infl ammation, but without any infl uence on disease progression, and other drugs that could modify the disease course and occasionally induce clinical remission (DMARDs or disease modifying anti-rheumatic drugs. This review describes the historical steps that led to the use of the main DMARDs in rheumatoid arthritis, such as gold salts, sulphasalazine, chloroquine and hydroxychloroquine, D-penicillamine, and other immunoactive drugs, including methotrexate, azathioprine, cyclosporin and lefl unomide. The historical evolution of use of these drugs is then discussed, including the strategy of progressive (“therapeutic pyramid” or of more aggressive treatment, through the simultaneous use of two or more DMARDs (“combination therapy”.

  4. Enfermedad pulmonar intersticial como manifestación inicial de síndrome antisintetasa Interstitial lung disease as initial manifestation of anti-synthetase syndrome

    Directory of Open Access Journals (Sweden)

    Miguel Mesa

    2010-09-01

    Full Text Available Se reporta el caso de un paciente que presentó un síndrome antisintetasa en el cual la miopatía fue precedida por EPID grave de instalación rápida y buena respuesta al manejo inmunosupresor con corticosteroides, ciclofosfamida y azatioprina. El cuadro clínico inicial con fiebre, infiltrados pulmonares, SDRA y ausencia de miopatía fue muy sugestivo de infección.We report a patient with antisintetase síndrome with rapid and progressive interstitial difuse pulmonary disease preceding the muscular weakness. The patient was successfully treated with steroids, cyclophosphamide and azathioprine. The initial compromise: fever, dispnoea and pulmonary infiltrates without miopathy was misdiagnosed as pneumonia.

  5. Severe transaminitis in a paediatric patient with systemic lupus erythaematosus and a discussion of the literature.

    Science.gov (United States)

    Sarda, Garima; Harvey, Rohini

    2016-01-01

    A 15-year-old African-American girl with known systemic lupus erythaematosus (SLE) presented to the emergency room with fever, abdominal distension, pain and vomiting. She was found to have severe transaminitis on laboratory examination, which prompted further work up including imaging and liver biopsy. Although complete diagnostic criteria were not met, histology was suggestive of autoimmune hepatitis (AIH). She was treated with steroids and azathioprine with good response and resolution of liver function tests. Availability of the literature discussing patients of any age with SLE and AIH is minimal, and consists mostly of small case series and some case reports. The juvenile literature on SLE and AIH occurring in the same patient is even scarcer and should be further studied at a multicentre level. PMID:27090540

  6. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    International Nuclear Information System (INIS)

    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated

  7. Efficacy of prophylactic irradiation in altering renal allograft survival

    International Nuclear Information System (INIS)

    Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids

  8. Usefulness of Novel Immunotherapeutic Strategies for Idiopathic Recurrent Pericarditis.

    Science.gov (United States)

    Lotan, Dor; Wasserstrum, Yishay; Fardman, Alexander; Kogan, Michael; Adler, Yehuda

    2016-03-01

    Idiopathic recurrent pericarditis (IRP) is a debilitating illness which leads to great suffering and multiple hospitalizations. Management of acute pericarditis and subsequent recurrences has evolved significantly as the use of colchicine-based strategies become more prevalent, yet there still remains a subset of patients who remain refractory to colchicine therapy, and these patients require prolonged corticosteroid (CS) therapy for the control of symptoms. Since the 1960s, there have been reports of successful management of these cases with immunosuppressive therapy. Current guidelines support the use of anakinra, intravenous immunoglobulins, and azathioprine for management of IRP, with the goals of both control of symptoms and withdrawal of CS. Recent reports supply evidence for both auto-inflammatory and autoimmune activity in these patients. We herein review the current available reports regarding the evidence regarding the pathophysiology and reported cases and case series of IRP cases managed with immunomodulation therapy. PMID:26742476

  9. Síndrome miasteniforme de Lambert-Eaton idiopático: Report of one case Idiopathic Lambert-Eaton myasthenic syndrome

    Directory of Open Access Journals (Sweden)

    Carlos Guevara O

    2006-02-01

    Full Text Available Lambert-Eaton myasthenic syndrome (LEMS is an autoinmune idiopathic or paraneoplastic syndrome producing antibodies agaisnt presynaptic voltage calcium channels. The clinical features of patients with LEMS are muscle weakness and autonomic dysfunction. We report a 40 years old man with a four years history of proximal weakness, absent tendon reflexes and dry mouth. The diagnosis was confirmed by characteristic electromyographic findings, showing a low-amplitude muscle response that increased dramatically after activation. Circulating antibodies to voltage-gated calcium channel were present. The search for malignant tumors was negative. The patient was treated with prednisone and azathioprine and after four months, he was able to walk and signs of autonomic dysfunction started to subside

  10. Clinical utility of labeled cells for detection of allograft rejection and myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Fawwaz, R.A.

    1984-07-01

    The choice of a specific radiolabeled blood component for use in detection of allograft rejection depends on several factors including the immunosuppressive agents used, the type of organ allografted, and particularly the length of time the allograft resides in the host and the duration of rejection. To date, only the use of 111In-labeled platelets in renal allograft recipients immunosuppressed with azathioprine and corticosteroids has shown clinical promise in the detection of early allograft rejection. Radiolabeled blood components are unlikely to play a significant role in detection of myocardial infarction. The use of these agents for monitoring therapeutic interventions or as indicators of prognosis in patients with myocardial infarction continues to be investigated.

  11. Behçet's pulmonary artery aneurysms treated with infliximab and monitored with the 6-min walk test.

    Science.gov (United States)

    Kotecha, Jalpa; Kamath, Ajay V; Mukhtyar, Chetan

    2016-04-01

    Pulmonary involvement in Behçet's disease (BD) is uncommon; however, it is potentially fatal due to the risk of massive haemoptysis. We describe the case of a 36-year-old male presenting with a 2-month history of worsening dyspnoea, weight loss, haemoptysis, oral ulceration, erythema nodosum and superficial thrombophlebitis. He was diagnosed with pulmonary vasculitis secondary to BD; however, his symptoms were refractory to initial treatment with cyclophosphamide, azathioprine and prednisolone. We therefore trialled infliximab alongside methotrexate, which led to a remarkable improvement in his condition, enabling eventual discontinuation of prednisolone. Whilst not being one of the treatments currently recommended for managing pulmonary involvement in BD, infliximab has previously been successfully used in cases refractory to conventional therapy. We used the 6-min walk test (distance covered and lowest oxygen saturations) to monitor his progress, which correlated with his symptoms. This may represent a useful adjunct in monitoring the activity of pulmonary vasculitis. PMID:27123312

  12. Use of /sup 99/Tc/sup m/ radionuclides to show nephrotoxicity of cyclosporin A in transplanted kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, H.S.; Munck, O.

    In 60 patients, /sup 99/Tc/sup m/ pertechnetate or /sup 99/Tc/sup m/ methylene diphosphonate was injected through an arm vein within 36 h after renal transplantation and repeated 24 or 48 h later. Thirty-one were treated with azathioprine and prednisone, 27 of the grafts had a well-defined peak on the histograms similar to that from the iliac artery histograms at both examinations. In contrast, of the 29 patients treated with cyclosporin A, only 5 of the grafts had a well-defined peak at both examinations. The difference is highly significant. Treatment with cyclosporin A causes a decrease in renal blood flow in the days immediately after transplantation.

  13. Reduction of the incidence of post-transplant renal artery stenosis associated with local graft irradiation

    International Nuclear Information System (INIS)

    The authors report the results of 170 sequential renal transplantations performed at Georgetown University Hospital from 1978 until 1982. All patients were treated with an uniform regimen consisting of azathioprine, prednisone, dypyridamole, and local graft irradiation (LGI). No cases of renal artery stenosis (RAS) have been found among the 170 transplants despite an expectant incidence based upon previously published reports of 4.5%(p=.01). They hypothesize that LGI soon after transplantation leads to a temporary inhibition of fibroblast growth and smooth muscle cell proliferation within the renal vessel wall aborting future stenotic lesions. The effect is comparable to keloid prevention by irradiation. Correlation with fibroblast radiation survival curves lends support to this hypothesis

  14. Efficacy of prophylactic irradiation in altering renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    Faber, R.; Johnson, H.K.; Braren, H.V.; Richie, R.E.

    1974-01-01

    Renal allograft rejection is a complex phenomenon involving both cell-mediated and humoral antibody responses. Most transplant programs have used a combination of therapeutic modalites to combat the immune system in an attempt to prolong both allograft and patient survival. Corticosteroids (methylprednisolone (Solu-Medrol) and prednisone and azathioprine (Imuran) are widely accepted as immunosuppressive drugs; however, both are non-specific and have the disadvantage of compromising the recipients' defense mechanisms. Nevertheless, these drugs have proved to be essential to the success of renal transplantation and they are routinely used while the efficacy of other modalities continues to be evaluated. We could find no reports of a prospective study to evaluate the efficacy of prophylactic irradiation in the complex therapeutic situation of renal transplantation with the only variable being the administration of local graft irradiation. The purpose of this study was to evaluate prophylactic graft irradiation for its effectiveness in preventing graft rejection in conjunction with Imuran and corticosteroids.

  15. Rare case of eosinophilic granulomatosis with polyangiitis in two patients with α-1-antitrypsin deficiency (PiSZ).

    Science.gov (United States)

    Moxey, Jordan Maureen; Low, Emma Victoria; Turner, Alice Margaret

    2016-01-01

    We present two cases of eosinophilic granulomatosis with polyangiitis occurring with α-1-antitrypsin deficiency, both PiSZ phenotype. The simultaneous occurrence of these two conditions has seldom been described in the literature, despite evidence of an association between α-1-antitrypsin deficiency and other forms of vasculitis. Both patients had pulmonary involvement and reported intermittent exacerbations of vasculitic symptoms. Both patients were managed on low-dose oral steroids and azathioprine remaining well with occasional exacerbations. It is important to consider whether there is an association between eosinophilic granulomatosis with polyangiitis and α-1-antitrypsin deficiency, as this may lead to more severe pulmonary symptoms during exacerbations. If a genetic association between the two conditions is found, clinicians should be aware of the possible need to screen for α-1-antitrypsin deficiency in appropriate patients. PMID:27118743

  16. Aneurisma de la arteria pulmonar en Enfermedad de Behçet Pulmonary artery aneurism in a patient with Behçet disease. Report of one case

    Directory of Open Access Journals (Sweden)

    DANIEL G FERNÁNDEZ A

    2010-01-01

    Full Text Available Behçet disease is a systemic disease with diverse clinical symptoms which vary according to the organs and systems involved. Typically, patients have oral and genital ulcers and episodic ocular involvement with periods of clinical improvement. We report an 18-year-old mole presenting with chest pain and hemoptysis and a history of ulcers in the oral cavity and scrotum. A chest CAT scan showed a mass located adjacent to the heart that a pulmonary arteriography defined as a left pulmonary artery aneurism. The patient was operated, excising left inferior pulmonary lobe. Due to skin and ocular involvement, the patient complied with criteria for Behçet disease. Immunosuppressive treatment with prednisone and azathioprine was started and the patient was discharged from the hospital.

  17. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  18. Immune-mediated haemolytic anaemia associated with a sarcoma in a flat-coated retriever.

    Science.gov (United States)

    Mellanby, R J; Holloway, A; Chantrey, J; Herrtage, M E; Dobson, J M

    2004-01-01

    A seven-year-old flat-coated retriever presented with a history of lethargy, dyspnoea and inappetence of several days' duration. Clinical examination revealed pale mucous membranes and tachypnoea, and haematology demonstrated marked autoagglutination. Thoracic radiographs revealed an increased opacity in the perihilar region. The owners declined further evaluation and the dog was treated symptomatically with immunosuppressive doses of prednisolone and azathioprine. The dog's demeanour improved, although it was eventually euthanased seven weeks later because of dysphagia and worsening dyspnoea. Postmortem examination revealed a widespread, poorly differentiated sarcoma involving the lungs, pericardium, thoracic lymph nodes and spleen. Immune-mediated haemolytic anaemia is a well recognised condition in dogs and is occasionally associated with neoplastic conditions. This is the first case report to describe immune-mediated haemolytic anaemia associated with a diffuse, poorly differentiated sarcoma. PMID:14756205

  19. Epidermolysis bullosa acquisita in a Great Dane.

    Science.gov (United States)

    Hill, P B; Boyer, P; Lau, P; Rybnicek, J; Hargreaves, J; Olivry, T

    2008-02-01

    Autoimmune subepidermal blistering diseases in dogs were all classified as bullous pemphigoid until 1998. Since then, refinements in reagents and immunological techniques have allowed diseases which are histologically similar but which have a different molecular pathogenesis to be described. This report describes the first case of one such disease, epidermolysis bullosa acquisita, to be documented in the UK. The dog presented with a severe blistering and ulcerative disease affecting the oral cavity, pinnae and distal limbs. The diagnosis was confirmed by histopathology and direct and indirect immunofluorescent demonstration of immunoglobulin G reactivity to basement membrane antigens. Treatment with glucocorticoids, azathioprine, colchicine and an intravenous infusion of immunoglobulins resulted in complete resolution. The drugs were discontinued 12 months after the start of treatment and the dog remained in remission. PMID:17784932

  20. Long-term management of vaccine-induced refractory ischemic dermatopathy in a Miniature Pinscher puppy.

    Science.gov (United States)

    Kim, Ha-Jung; Kang, Min-Hee; Kim, Ju-Won; Kim, Dae-Young; Park, Hee-Myung

    2011-09-01

    A 2-month-old intact female Miniature Pinscher puppy presented with footpad swelling and crusted pustules of ear pinnae. The dog had been vaccinated with a polyvalent canine vaccine 5 days prior to the onset of clinical signs. With the history of recent vaccination, the clinical presentation and the histopathological observations were suggestive of ischemic dermatopathy. Treatment involved oral prednisolone, azathioprine, and other immune modulating drugs, which did not work. Chlorambucil plus cyclosporine therapy was initiated for vigorous immune suppression after rush therapy using intravenous immunoglobulin. Clinical signs again gradually improved with no relapse or side effects, even at a 4-month follow-up. The case report is suggested ischemic dermatopathy refractory to conventional therapy and suggests effective approaches to long-term management of the disease. PMID:21566400

  1. Effect of a single plasma transfusion on thromboembolism in 13 dogs with primary immune-mediated hemolytic anemia.

    Science.gov (United States)

    Thompson, Mary F; Scott-Moncrieff, J Catharine; Brooks, Marjory B

    2004-01-01

    Thirteen dogs with primary immune-mediated hemolytic anemia received fresh-frozen plasma within 12 hours of admission, in addition to unfractionated heparin and other therapies, such as prednisone, azathioprine, and packed red blood cell transfusion. Antithrombin activity was quantified prior to transfusion and at 30 minutes and 48 hours after transfusion. Plasma antithrombin activity did not change significantly after a single plasma transfusion. There were no deaths in the first 48 hours of treatment. Thromboembolism was identified at necropsy in six of 10 dogs that died within 12 months of admission. There was no significant difference in the incidence of thromboembolism between the current treatment group and a historical control group. PMID:15533964

  2. Clinical renal allograft transplantation in a Dalmatian dog: case report.

    Science.gov (United States)

    Németh, T; Tóth, J; Balogh, L; Jánoki, G; Manczur, F; Vörös, K; Dallos, G

    1998-01-01

    A case of successful renal allograft transplantation performed in a two-year-old female Dalmatian dog suffering from end-stage chronic renal failure is reported. A one-year-old male German shepherd with severely injured spinal cord was used as kidney donor. Simultaneous kidney allograft transplantation combined with hypothermic initial perfusion as graft conservation was done, placing the donor kidney into the right iliac fossa of the recipient. The immunosuppression protocol consisted of prednisolone and azathioprine. Regular physical, laboratory, ultrasonographic and scintigraphic examinations were used for assessing both the morphology and the function of the allograft. After a two-week period of hospitalisation the patient was discharged in a remarkably improving condition. The recipient died on postoperative day 45 of respiratory insufficiency resulting from secondary pneumonia and pulmonary oedema. Neither macroscopic nor microscopic abnormalities of the allograft were revealed by necropsy. PMID:9704530

  3. Canine pemphigus foliaceus with concurrent immune-mediated thrombocytopenia.

    Science.gov (United States)

    Kawarai, Shinpei; Hisasue, Masaharu; Matsuura, Shinobu; Ito, Tetsuro; Inoue, Yukari; Neo, Sakurako; Fujii, Yoko; Madarame, Hiroo; Shirota, Kinji; Tsuchiya, Ryo

    2015-01-01

    A 3 yr old wirehaired fox terrier was presented to his primary care veterinarian with fever, thrombocytopenia, and generalized crusting dermatitis. The skin lesion had progressed for at least 18 days, and thrombocytopenia had developed 3 days before presentation. Histopathology and direct immunofluorescence studies of the skin were consistent with pemphigus foliaceus (PF). Immunofluorescence revealed immunoglobulin G deposition around the keratinocytes in the stratum spinosum. A diagnosis of immune-mediated thrombocytopenia (IMT) was confirmed by the presence of platelet surface-associated immunoglobulin using flow cytometry. Systemic immunosuppressive therapy with cyclosporine and azathioprine was effective, and the dog survived for >2 years from the initial presentation. IMT is rarely associated with PF. This appears to be the first detailed report of a definitive diagnosis of concurrent PF and IMT in a dog. The authors' findings indicate that canine PF could be complicated by hematologic immune-mediated diseases such as IMT. PMID:25415212

  4. Complete heart block associated with lupus in a dog.

    Science.gov (United States)

    Malik, R; Zunino, P; Hunt, G B

    2003-07-01

    A 5-year-old Poodle-cross was initially presented for exercise intolerance and difficulty in chewing and yawning. Some months later it acutely developed lethargy referable to complete heart block. Further investigations before and after permanent pacemaker implantation demonstrated Coombs-positive immune-mediated haemolytic anaemia, presumptive masticatory myositis and hypoadrenocorticism, suggesting the possibility of multisystem auto-immune disease. A diagnosis of systemic lupus erythematosus (SLE) was made based on these findings and a positive anti-nuclear antibody titre. It was thought that immune-mediated destruction of cardiac conduction tissues was responsible for the development of atrioventricular conduction block. Glucocorticoid deficiency was corrected using cortisone replacement therapy. SLE was controlled successfully for 10 months using azathioprine monotherapy until signs, subsequently shown to be due to subacute bacterial endocarditis, resulted in the death of the patient. Lupus should be considered as a potential underlying aetiology in dogs that develop heart block. PMID:15084050

  5. Dermatological medication effects on male fertility.

    Science.gov (United States)

    Millsop, Jillian Wong; Heller, Misha M; Eliason, Mark J; Murase, Jenny E

    2013-01-01

    Many drugs have been reported to impair semen parameters, leading to temporary or persistent infertility. Therefore, potential fathers may be concerned about the effect of medications on fertility. We searched the MEDLINE database of articles in English combining key terms including "male infertility," "spermatogenesis," "fertility," "drug effects," and "dermatology." Administration of methotrexate and finasteride has resulted in severe oligospermia and reversible infertility. Ketoconazole has had negative effects on sperm motility and testosterone production. Few individual case reports and a limited number of studies have demonstrated negative effects of tetracyclines, erythromycin, chloroquine, glucocorticoids, spironolactone, and antihistamines on fertility. It is important to counsel male patients when appropriate about the reversible negative effect on fertility when taking methotrexate and finasteride, and the adverse effect of ketoconazole. Patients may be reassured that taking oral retinoids, cyclosporine, azathioprine, and tumor necrosis factor alpha inhibitors should not affect their fertility. PMID:23914891

  6. Birth outcome in women with ulcerative colitis and Crohn's disease, and pharmacoepidemiological aspects of anti-inflammatory drug therapy

    DEFF Research Database (Denmark)

    Nørgård, Bente Mertz

    2011-01-01

    conception, iii) the risk of adverse birth outcome in women with Crohn's disease according to type of anti-inflammatory drug treatment in pregnancy (sulfasalazine/5-aminosalicylic acid, steroids or azathioprine/6-mercaptopurine), and iv) the impact of disease activity in women with Crohn's disease on adverse......, including patients with ulcerative colitis and Crohn's disease. The third part (and the latest publications) includes birth outcome in women with Crohn's disease; and the methods of cohort establishment in these studies are developed and improved due to the knowledge gathered from conducting the earlier...... increased risk of preterm birth when women give birth 0-6 months after establishment of the diagnosis. It is considered whether the increased risk may be influenced by disease activity around the time of establishing the diagnosis. 2) No increased risk of giving birth to children with low birth weight...

  7. Biotherapies in large vessel vasculitis.

    Science.gov (United States)

    Ferfar, Y; Mirault, T; Desbois, A C; Comarmond, C; Messas, E; Savey, L; Domont, F; Cacoub, P; Saadoun, D

    2016-06-01

    Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV. PMID:26883459

  8. [Treatment of pulmonary fibrosis. New substances and new interventions].

    Science.gov (United States)

    Costabel, U; Bonella, F

    2011-12-01

    Idiopathic pulmonary fibrosis is a chronic progressive lung disease with poor prognosis. The IFIGENIA trial showed that antioxidative therapy with N-acetylcysteine versus placebo for patients under treatment with prednisone plus azathioprine significantly slowed the deterioration of pulmonary function after 12 months. A number of other drugs have recently been evaluated in large multicenter placebo-controlled trials. Etanercept, interferon-γ, bosentan, ambrisentan, imatinib, and sildenafil did not show efficacy. The antifibrotic active ingredient pirfenidone is the first drug approved for the treatment of adult patients with mild to moderate idiopathic pulmonary fibrosis in the European Union. Approval was based on the results of 4 randomized, placebo-controlled clinical trials including more than 1,100 patients. Pirfenidone slowed the decline in lung function and reduced the risk of disease progression. Side effects include gastrointestinal discomfort, skin reactions, including photosensitivity, and rarely increased liver enzymes. PMID:22095049

  9. Themes of liver transplantation.

    Science.gov (United States)

    Starzl, Thomas E; Fung, John J

    2010-06-01

    Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation

  10. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2015-01-01

    Full Text Available Objective: To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants. Data Sources: We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators. The following terms were used: "inflammatory bowel disease (IBD" OR "Crohn′s disease" OR "ulcerative colitis" AND ("vaccination" OR "vaccine" AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]" AND "immunomodulators." Study Selection: The inclusion criteria of articles were that the studies: (1 Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical, radiographic, endoscopic, and histologic criteria; (2 exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping, 15 mg or more MTX per week or within 3 months of stopping; (3 exposed patients received nonimmunomodulators (no therapy, antibiotics only, mesalazine only, biological agent only such as infliximab, adalimumab, certolizumab or natalizumab or within 3 months of stopping one of these agents. The exclusion criteria of articles were that the studies: (1 History of hepatitis B virus (HBV, influenza or streptococcus pneumoniae infection; (2 patients who had previously been vaccinated against HBV, influenza or streptococcus pneumoniae; (3 any medical condition known to cause immunosuppression (e.g. chronic renal failure and human immunodeficiency virus infection; (4 individuals with positive hepatitis markers or liver cirrhosis; (5 patients with a known allergy to eggs or other components of the vaccines and (6 pregnancy. Results: Patients treated with immunomodulators were associated with lower response rates to

  11. Treatment of severe steroid refractory ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Gert Van Assche; Séverine Vermeire; Paul Rutgeerts

    2008-01-01

    Although systemic steroids are highly efficacious in ulcerative colitis (UC),failure to respond to steroids sUll poses an important challenge to the surgeon and physician alike. Even if the life Lime risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options: intravenous cyclosporine (2 mg/kg for 7 d, and serum level controlled),infliximab (5 mg/kg N,0-2-6 wk) or total colectomy.The choice between these three options is a medicalsurgical decision based on clinical signs, radiological and endoscopic findings and blood analysis (CRP, serum albumin).Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine (bridging strategy).The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor (TNF) monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore,patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.

  12. Epidermolysis bullosa acquisita with moderately severe dysphagia due to esophageal strictures

    Directory of Open Access Journals (Sweden)

    Jenny Tu

    2011-01-01

    Full Text Available Epidermolysis bullosa acquisita (EBA is a chronic, autoimmune condition involving the skin and mucous membranes. Symptomatic mucosal involvement is rare, but can impact on quality of life, due to esophageal strictures and dysphagia. We report a case involving a 60-year-old male presenting with bullous skin lesions on areas of friction on his hands, feet and mouth. Milia were visible on some healed areas. Biopsy showed a subepidermal vesicle. Direct immunofluorescence showed intense linear junctional IgG and C3 at the dermo-epidermal junction. Serological tests also supported the diagnosis of EBA. Screening tests for underlying malignancies were negative. Despite treatment with systemic steroids, the patient developed increasing dysphagia, requiring further investigation with esophagoscopy and a barium swallow. Confirmation of extensive esophageal stricturing prompted adjustment of medications including an increase in systemic steroids and addition of azathioprine. Currently, the patient′s disease remains under control, with improvement in all his symptoms and return of anti-basement membrane antibody levels to normal, whilst he remains on azathioprine 150 mg daily and prednisolone 5 mg daily. This case highlights the fact that the treatment of a given patient with EBA depends on severity of disease and co-morbid symptoms. Newer immunoglobulin and biological therapies have shown promise in treatment resistant disease. Considering that long-term immunosuppressants or biologicals will be required, potential side effects of the drugs should be considered. If further deterioration occurs in this patient, cyclosporin A or intravenous immunoglobulin (IV Ig will be considered. Vigilance for associated co-morbidities, especially malignancies, should always be maintained.

  13. Characteristics, Treatment, and Long-Term Outcome of Gastrointestinal Involvement in Behcet's Syndrome

    Science.gov (United States)

    Hatemi, Ibrahim; Esatoglu, Sinem Nihal; Hatemi, Gulen; Erzin, Yusuf; Yazici, Hasan; Celik, Aykut Ferhat

    2016-01-01

    Abstract Gastrointestinal involvement is rare in Behçet's syndrome (BS) patients from the Mediterranean basin. We report the demographic and disease characteristics, treatment modalities, and outcome of patients with gastrointestinal involvement in BS (GIBS). We retrospectively reviewed the charts of all BS patients in our BS clinic with a diagnosis of GIBS. Patients were invited to the clinic to assess their outcome. Among 8763 BS patients, we identified 60 with GIBS (M/F: 32/28, mean age at diagnosis: 34 ± 10, mean follow-up: 7.5 ± 4 years), after excluding 22 patients with mimicking symptoms. Six (10%) had juvenile-onset BS. The most common intestinal localization was ileocecal region (36/59, 61%) mainly as big oval ulcer/s. Initial treatment was azathioprine for moderate to severe (n = 37) and 5-ASA for mild cases (n = 16). Anti-TNFs and/or thalidomide provided remission in 12 of 18 (67%) refractory patients. Emergency surgery was required in 22 patients. Nine patients did not receive postoperative immunomodulators and 8 relapsed. Overall, 48 of 60 (80%) patients were in remission (29/48 without treatment) at the time of survey. Three recently treated and 2 refractory patients were still active, 3 had died due to non-GI-related reasons, and 4 were lost to follow-up. Careful evaluation for excluding mimickers is important during the diagnosis of GIBS. Azathioprine seems to be a good choice as first-line treatment with high remission rates and few adverse events. Thalidomide and/or TNF-alpha antagonists may be preferred in resistant cases. Surgery may be required for perforations or massive bleeding, and postoperative immunosuppressive treatment is necessary for preventing postoperative recurrences. PMID:27100417

  14. The indirect antioxidant sulforaphane protects against thiopurine-mediated photooxidative stress.

    Science.gov (United States)

    Benedict, Andrea L; Knatko, Elena V; Dinkova-Kostova, Albena T

    2012-12-01

    Long-term treatment with thiopurines, such as the widely used anticancer, immunosuppressive and anti-inflammatory agent azathioprine, combined with exposure to ultraviolet (UV) radiation is associated with increased oxidative stress, hyperphotosensitivity and high risk for development of aggressive squamous cell carcinomas of the skin. Sulforaphane, an isothiocyanate derived from broccoli, is a potent inducer of endogenous cellular defenses regulated by transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), including cytoprotective enzymes and glutathione, which in turn act as efficient indirect and direct antioxidants that have long-lasting effects. Treatment with 6-thioguanine, a surrogate for azathioprine, leads to profound sensitization to oxidative stress and glutathione depletion upon exposure to UVA radiation, the damaging effects of which are primarily mediated by generation of reactive oxygen species. The degree of sensitization is greater for irradiation exposures spanning the absorption spectrum of 6-thioguanine, and is dependent on the length of treatment and the level of guanine substitution with 6-thioguanine, suggesting that the 6-thioguanine that is incorporated in genomic DNA is largely responsible for this sensitization. Sulforaphane provides protection against UVA, but not UVB, radiation without affecting the levels of 6-thioguanine incorporation into DNA. The protective effect is lost under conditions of Nrf2 deficiency, implying that it is due to induction of Nrf2-dependent cytoprotective proteins, and that this strategy could provide protection against any potentially photosensitizing drugs that generate electrophilic or reactive oxygen species. Thus, our findings support the development of Nrf2 activators as protectors against drug-mediated photooxidative stress and encourage future clinical trials in populations at high risk for cutaneous photodamage and photocarcinogenesis. PMID:22983983

  15. Successful pregnancy in pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Streit Michael

    2009-06-01

    Full Text Available Abstract Introduction Pulmonary arterial hypertension is a complication of systemic lupus erythematosus. Mortality in pregnant patients with pulmonary arterial hypertension related to connective tissue disease is as high as 56%. The authors report the first case of a successful maternal-fetal outcome in a pregnant patient with systemic lupus erythematosus-associated pulmonary arterial hypertension treated with sildenafil and inhaled iloprost during pregnancy and until several weeks after caesarean section. Case presentation The case presented is of a 29-year-old woman with systemic lupus erythematosus and associated severe pulmonary arterial hypertension. Vasodilator therapy with bosentan and sildenafil, immunosuppressive therapy with prednisone, hydroxychloroquine and azathioprine and oral anticoagulation (phenprocoumon had normalized her right ventricular over right atrial pressure when she was diagnosed in her 5th week of pregnancy. The teratogenic drugs bosentan and phenprocoumon were stopped, the latter replaced by low molecular weight heparin. During the 35th week, a slight increase in pulmonary pressure was found. Therapy with inhaled iloprost was established. A caesarean section was performed in the 37th week and a healthy baby was delivered. The patient remained stable until 11 weeks after delivery, when an increase in right ventricular over right atrial pressure was noted. Bosentan was reintroduced and prednisone and azathioprine doses were increased. The patient has remained stable until the present time. Conclusion Pulmonary arterial hypertension has been considered a contraindication for pregnancy. Novel vasodilator therapy, combined with immunosuppressants in this patient with systemic lupus erythematosus, may "cure" pulmonary arterial hypertension and permit pregnancy with successful outcome. However, postpartum exacerbation of systemic lupus erythematosus and pulmonary arterial hypertension have to be considered.

  16. Efficacy of immunosoppressive therapy and steroid sparing effect in interstitial lung disease associated to antisynthetase syndrome

    Directory of Open Access Journals (Sweden)

    G. De Marchi

    2011-09-01

    Full Text Available Objective: To evaluate the role of bronchoalveolar lavage (BAL in patients with interstitial lung disease associated to antisynthetase syndrome. Methods: We describe 5 patients, anti-Jo1 positive, with interstitial lung disease (lung fibrosis and/or diffusion capacity of CO <80%. Patients were monitored with lung function tests every 6 months, with high-resolution computed tomography (HRCT every 12 months, and with bronchoalveolar lavage (BAL at baseline and in the subsequent follow-up. Patients were treated as follows: a azathioprine with colchicine, or cyclosporine alone b cyclophosphamide when high neutrophil or eosinophil count on BAL was observed. Only low-dose steroids were used for mild muscular or articular involvement. Results: Pulmonary involvement remained stable in all patients at months +24. Lung function remained unchanged compared to the baseline evaluation; HRCT was stable in patients with fibrosis and no progression into fibrosis was observed in patients with ground glass areas at baseline. Bacterial pneumonia occurred in one patient treated with cyclophosphamide and resolved after antibiotic therapy. Conclusions: Clinical manifestations, instrumental tests and BAL may be of value to choice the best immunosuppressive therapy in the single case. An early less aggressive approach (azathioprine with colchicine, or cyclosporine alone may be useful. BAL could be performed when a progression of the lung involvement is demonstrated in the subsequent follow-up. Cyclophosphamide may be a valid alternative treatment in the presence of a neutrophilic or eosinophilic alveolitis. Efficacy and safety of the aforementioned immunosuppressive approach were observed in our series, avoiding prolonged high-dose steroid administration.

  17. Recurrent Pericarditis: Modern Approach in 2016.

    Science.gov (United States)

    Imazio, Massimo; Adler, Yehuda; Charron, Philippe

    2016-06-01

    Recurrent pericarditis is one of the most troublesome complications of pericarditis occurring in about one third of patients with a previous attack of pericarditis. The pathogenesis is presumed to be autoimmune and/or autoinflammatory in most cases. The mainstay of therapy for recurrences is physical restriction and anti-inflammatory therapy based on aspirin or NSAID plus colchicine. Corticosteroids at low to moderate doses (e.g., prednisone 0.2 to 0.5 mg/kg/day) should be considered only after failure of aspirin/NSAID (and more than one of these drugs) or for specific indications (e.g., pregnancy, systemic inflammatory diseases on steroids, renal failure, concomitant oral anticoagulant therapy). One of the most challenging issues is how to cope with patients who have recurrences despite colchicine. A small subset of patients (about 5 %) may develop corticosteroid-dependence and colchicine resistance. Among the emerging treatments, the three most common and evidence-based therapies are based on azathioprine, human intravenous immunoglobulin (IVIG), and anakinra. After failure of all options of medical therapy or for those patients who do not tolerate medical therapy or have serious adverse events related to medical therapy, the last possible option is the surgical removal of the pericardium. Total or radical pericardiectomy is recommended in these cases in experienced centers performing this surgery. A stepwise approach is recommended starting from NSAID and colchicine, corticosteroid and colchicine, a combination of the three options (NSAID, colchicine and corticosteroids), then azathioprine, IVIG, or anakinra as last medical options before pericardiectomy. PMID:27108360

  18. Long-term bone loss after renal transportation. Comparison of immunosuppressive regimens

    International Nuclear Information System (INIS)

    Serial measurements of serum and urine markers of bone metabolism and of forearm bone density (BMD) by dual photon absorptiometry were performed in 22 patients undergoing renal transplantation in 1986. Patients were randomised to immunosuppression with (1) cyclosporin alone (CsA group, n = 10), (2) cyclosporin for 3 months followed by azathioprine-prednisone (CsA/AzP group, n = 3) or (3) long-term azathioprine-prednisone (LT AzP group, n = 9). As no reduction in bone mineral density (BMD) was noted in the first 6 months, groups 2 and 3 were considered together (AzP group, n = 12). Mean±SEM BMD fell by 19±2% at 36 months (n = 19,m p<0.01), with similar reductions seen in the CsA and AzP groups. At 60 months, BMD of the AzP group was 25±3% below baseline (p<0.01), while the CsA group were only 5±4% belov baseline (p = NS vs baseline, p<0.05 vs AzP group). The degree of reduction in BMD over 5 years correlated with total glucocorticoid dose (r = 0.63, p<0.05), but not with biochemical markers of bone turnover. Serum alkaline phosphatase fell post-transplant in patients treated with AzP, but not in the CsA group. These results demonstrate significant loss of forearm bone mineral with long-term follow-up after renal transplantation, but suggest that patients treated with cyclosporin monotherapy may be at lower risk of this complication. (au) (15 refs.)

  19. Characteristics, Treatment, and Long-Term Outcome of Gastrointestinal Involvement in Behcet's Syndrome: A Strobe-Compliant Observational Study From a Dedicated Multidisciplinary Center.

    Science.gov (United States)

    Hatemi, Ibrahim; Esatoglu, Sinem Nihal; Hatemi, Gulen; Erzin, Yusuf; Yazici, Hasan; Celik, Aykut Ferhat

    2016-04-01

    Gastrointestinal involvement is rare in Behçet's syndrome (BS) patients from the Mediterranean basin. We report the demographic and disease characteristics, treatment modalities, and outcome of patients with gastrointestinal involvement in BS (GIBS).We retrospectively reviewed the charts of all BS patients in our BS clinic with a diagnosis of GIBS. Patients were invited to the clinic to assess their outcome.Among 8763 BS patients, we identified 60 with GIBS (M/F: 32/28, mean age at diagnosis: 34 ± 10, mean follow-up: 7.5 ± 4 years), after excluding 22 patients with mimicking symptoms. Six (10%) had juvenile-onset BS. The most common intestinal localization was ileocecal region (36/59, 61%) mainly as big oval ulcer/s. Initial treatment was azathioprine for moderate to severe (n = 37) and 5-ASA for mild cases (n = 16). Anti-TNFs and/or thalidomide provided remission in 12 of 18 (67%) refractory patients. Emergency surgery was required in 22 patients. Nine patients did not receive postoperative immunomodulators and 8 relapsed. Overall, 48 of 60 (80%) patients were in remission (29/48 without treatment) at the time of survey. Three recently treated and 2 refractory patients were still active, 3 had died due to non-GI-related reasons, and 4 were lost to follow-up.Careful evaluation for excluding mimickers is important during the diagnosis of GIBS. Azathioprine seems to be a good choice as first-line treatment with high remission rates and few adverse events. Thalidomide and/or TNF-alpha antagonists may be preferred in resistant cases. Surgery may be required for perforations or massive bleeding, and postoperative immunosuppressive treatment is necessary for preventing postoperative recurrences. PMID:27100417

  20. 10-Year Observation of Bullous Pemphigoid Patients

    Directory of Open Access Journals (Sweden)

    Bengu Nisa Akay

    2010-06-01

    Full Text Available Background and Design: Bullous pemphigoid (BP is an autoimmune skin disorder characterized by large, tense blisters of the skin. It occurs mainly in the elderly. The one year mortality associated with bullous pemphigoid ranges from 19% to 41%. We aim to analyse the etiologic factors, demographic features, clinical course and response to treatment in patients with BP. Material and Method: Between January 1999 and January 2008, 31 patients with BP were evaluated retrospectively. We assessed duration of the disease, presence of associated symptoms, clinical findings, drug intake, response to treatment, recurrence rates and also extensive laboratory testing and radiologic evaluations on each patient to clarify a possible underlying malignancy. Results: In a 10-year period, 31 patients with BP, female male ratio was 19/12, ranging in age from 59 to 96 (mean 78.8±8.67 years were evaluated. Duration of the disease was 16.58±18.48 months. Direct immunoflourescence of the perilesional skin showed linear deposition of IgG and C3 along the dermoepidermal junction in 24 patients (77.4%. There was no significant relationship between drug usage and bullous pemphigoid. No malignancy was detected. Medium dosage of prednisolone (50-60 mg/day was the first choice of treatment in 8 patients with a complete response rate in all but two patients died during therapy. Four patients died during hospitalization with unknown reasons before any treatment was started. In 16 cases the initial treatment was prednisolone and azathioprine. The mean follow-up period was 12 months and 11 (35% cases had relapsed. The longest remission was achieved with prednisolone and azathioprine combination. Conclusion: In conclusion, no association was found between BP and drug usage or malignancy. All patients responded well to treatment. Therapy with prednisone maintained with azathiopyrine significantly reduced the recurrences. However, disease-specific mortality is found to be high and

  1. Long-term bone loss after renal transportation. Comparison of immunosuppressive regimens

    Energy Technology Data Exchange (ETDEWEB)

    Menzies, B.; Rigby, R.; Hawley, CJ.M.; Hardie, I.R. [Princess Alexandra Hospital, Renal Transplant Unit, Woolloongabba (Australia); McIntyre, H.D. [Mater Adult Hospital, Department of Medicine, South Brisbane (Australia); Perry-Keene, D.A. [Royal Brisbane Hospital, Department of Endocrinology, Herston, Queensland (Australia)

    1995-02-01

    Serial measurements of serum and urine markers of bone metabolism and of forearm bone density (BMD) by dual photon absorptiometry were performed in 22 patients undergoing renal transplantation in 1986. Patients were randomised to immunosuppression with (1) cyclosporin alone (CsA group, n = 10), (2) cyclosporin for 3 months followed by azathioprine-prednisone (CsA/AzP group, n = 3) or (3) long-term azathioprine-prednisone (LT AzP group, n = 9). As no reduction in bone mineral density (BMD) was noted in the first 6 months, groups 2 and 3 were considered together (AzP group, n = 12). Mean{+-}SEM BMD fell by 19{+-}2% at 36 months (n = 19,m p<0.01), with similar reductions seen in the CsA and AzP groups. At 60 months, BMD of the AzP group was 25{+-}3% below baseline (p<0.01), while the CsA group were only 5{+-}4% belov baseline (p = NS vs baseline, p<0.05 vs AzP group). The degree of reduction in BMD over 5 years correlated with total glucocorticoid dose (r = 0.63, p<0.05), but not with biochemical markers of bone turnover. Serum alkaline phosphatase fell post-transplant in patients treated with AzP, but not in the CsA group. These results demonstrate significant loss of forearm bone mineral with long-term follow-up after renal transplantation, but suggest that patients treated with cyclosporin monotherapy may be at lower risk of this complication. (au) (15 refs.).

  2. Esquistossomose mansoni experimental: carga parasitária e distribuição de vermes adultos no sistema porta de ratos albinos tratados com Azatioprina

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    Carlos Alberto Moreira Campos

    1983-09-01

    Full Text Available Estudou-se o curso da infecção esquistossomótica experimental no rato albino, um hospedeiro singular para o Schistosoma mansoni, e quatro semanas após a infecção houve uma rápida diminuição na carga parasitária, fato esse denominado por alguns pesquisadores como ' fenômeno de autocura Contudo, após a administração de um imunossupressor - a Azatioprina - observou-se uma maior susceptibilidade dos ratos à infecção, com os animais apresentando um significativo retardamento no chamado "fenômeno de autocura A grande maioria dos vermes é recuperada nos vasos intra-hepáticos do sistema porta, sem que haja migração para as veias mesentéricas. Quando os ratos foram tratados com Azatioprina observou-se uma significativa localização mesentérica dos vermes adultos neste hospedeiro.The course of experimental Schistosoma mansoni infection in the albino rat, a singular host for schistosomes was studied. Four weeks after infection there was a decrease of worm burden, a sélf-cure phenomenon reported by other investigators. However, after administration of a immunosupressive drug - Azathioprine - an increase in susceptibility of rats to infection was observed, with the animals presenting a significant delay in the to period selfcure. The majority of worms were recovered from the intra-hepatic veins of the portal system, but there was no migration to mesenteric veins. When rats were treated with Azathioprine a significant mesenteric localization of schistosomes was observed in this host.

  3. Demonstration of thiopurine methyltransferase activity in the erythrocytes of cats.

    Science.gov (United States)

    Foster, A P; Shaw, S E; Duley, J A; Shobowale-Bakre, E M; Harbour, D A

    2000-01-01

    Azathioprine is a purine analogue used as an immunosuppressive and immunomodulator agent in various mammals, including cats. Several adverse reactions have been reported and have limited the use of the drug in the cat. Adverse reactions to azathioprine in humans have been correlated with reduced activity of thiopurine methyltransferase (TPMT) in erythrocytes. The purpose of this preliminary study was to determine if cats have TPMT activity in their erythrocytes and to compare the values obtained with the normal range for humans and the normal range for dogs in a preliminary report. Activity of the enzyme was measured in blood samples drawn from 41 cats. Blood also was taken from 5 dogs. The mean erythrocyte TPMT activity in the cats was 2.4 +/- 0.4 nmol (range, 1.2-3.9 nmol) per hour per milliliter of red blood cells (U/mL RBC) or 2-8 nmol per hour per gram of hemoglobin (U/g Hb). This range was far lower than the normal human range (8-15 U/mL RBC; 16-33 U/g Hb) and was of monopolar distribution. This observation apparently precludes any diagnostic purpose in assaying erythrocyte TPMT in this species. Erythrocyte TPMT activity in the 5 dogs ranged from 5.5 to 13.1 U/mL RBC (11-27 U/g Hb), which was comparable with normal and carrier ranges for humans, but proof of TPMT genetic polymorphism in either species will require genotyping studies. PMID:11012121

  4. Effects of Immunosuppressants on Immune Response to Vaccine in Inflammatory Bowel Disease

    Institute of Scientific and Technical Information of China (English)

    Yuan Cao; Di Zhao; An-Tao Xu; Jun Shen; Zhi-Hua Ran

    2015-01-01

    Objective:To evaluate the response rate to vaccination in different treatment groups (nonimmunosuppressants and immunosuppressants).Data Sources:We completed an online systematic search using PubMed to identify all articles published in English between January 1990 and December 2013 assessing the effect of the response rate to vaccination in different treatment groups (with and without immunomodulators).The following terms were used:"inflammatory bowel disease (IBD)" OR "Cmhn's disease" OR "ulcerative colitis"AND ("vaccination" OR "vaccine") AND ("corticosteroids" OR "mercaptopurine" OR "azathioprine" OR "methotrexate [MTX]") AND "immunomodulators."Study Selection:The inclusion criteria of articles were that the studies:(1) Randomized controlled trials which included patients with a diagnosis of IBD (established by standard clinical,radiographic,endoscopic,and histologic criteria); (2) exposed patients received immunomodulators for maintenance (weight-appropriate doses of 6-mercaptopurine/azathioprine or within 3 months of stopping,15 mg or more MTX per week or within 3 months of stopping; (3) exposed patients received nonimmunomodulators (no therapy,antibiotics only,mesalazine only,biological agent only such as infliximab,adalimumab,certolizumab or natalizumab or within 3 months of stopping one of these agents).The exclusion criteria of articles were that the studies:(1) History of hepatitis B virus (HBV),influenza or streptococcus pneumoniae infection; (2) patients who had previously been vaccinated against HBV,influenza or streptococcus pneumoniae; (3) any medical condition known to cause immunosuppression (e.g.chronic renal failure and human immunodeficiency virus infection); (4) individuals with positive hepatitis markers or liver cirrhosis; (5) patients with a known allergy to eggs or other components of the vaccines and (6) pregnancy.Results:Patients treated with immunomodulators were associated with lower response rates to vaccination

  5. Co occurrence of Hepatitis B Virus Infection and Autoimmune Hepatitis with Marked Hepatitis B Virus Replication Following Treatment of Autoimmune Hepatitis

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    Tyagi I

    2015-10-01

    Full Text Available Background: Children have different natural history of Hepatitis B virus (HBV infection. They commonly develop asymptomatic chronic carrier state which is less frequently seen in adults. We describe a rare case of acute on chronic liver failure (ACLF in the course of concurrent autoimmune hepatitis (AIH and HBV infection and replication of HBV following the treatment for autoimmune hepatitis. Case Report: A 15 year old male child presented with jaundice and altered sensorium. Physical examination showed hepatosplenomegaly. The liver function tests were markedly altered. Serology was positive for anti liver kidney microsomal antibody (LKM, hepatitis B surface antigen (HBsAg and immunoglobulin M (IgM anti hepatitis B core antigen (HBc Ag. Liver biopsy showed chronic hepatitis with features of acute exacerbation. Patient was started on treatment with azathioprine and prednisolone for AIH following which clinical and biochmemical improvement was noted. After two years of continued treatment a repeat biopsy performed showed fairly reduced histological activity, but marked replication of the HBV (immunohistochemistry for HBsAg and anti HBcAg showed diffuse cytoplasmic and nuclear positivity respectively. These findings suggest viral replication although the patient was clinically stable. At six months follow-up after the second biopsy and cessation of azathioprine and prednisolone, there were raised liver enzymes and viral load, hence the patient was started on antiviral drug Entecavir to which there was good response and the patient is presently doing well. Conclusion: We describethe rare co occurrence of HBV infection and AIH with marked HBV replication following the treatment for AIH

  6. Eosinophilia in a patient with cyclical vomiting: a case report

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    Fitzgerald S Matthew

    2004-05-01

    Full Text Available Abstract Background Eosinophilic gastritis is related to eosinophilic gastroenteritis, varying only in regards to the extent of disease and small bowel involvement. Common symptoms reported are similar to our patient's including: abdominal pain, epigastric pain, anorexia, bloating, weight loss, diarrhea, ankle edema, dysphagia, melaena and postprandial nausea and vomiting. Microscopic features of eosinophilic infiltration usually occur in the lamina propria or submucosa with perivascular aggregates. The disease is likely mediated by eosinophils activated by various cytokines and chemokines. Therapy centers around the use of immunosuppressive agents and dietary therapy if food allergy is a factor. Case presentation The patient is a 31 year old Caucasian female with a past medical history significant for ulcerative colitis. She presented with recurrent bouts of vomiting, abdominal pain and chest discomfort of 11 months duration. The bouts of vomiting had been reoccurring every 7–10 days, with each episode lasting for 1–3 days. This was associated with extreme weakness and cachexia. Gastric biopsies revealed intense eosinophilic infiltration. The patient responded to glucocorticoids and azathioprine. The differential diagnosis and molecular pathogenesis of eosinophilic gastritis as well as the molecular effects of glucocorticoids in eosinophilic disorders are discussed. Conclusions The patient responded to a combination of glucocorticosteroids and azathioprine with decreased eosinophilia and symptoms. It is likely that eosinophil-active cytokines such as interleukin-3 (IL-3, granulocyte macrophage colony stimulating factor (GM-CSF and IL-5 play pivotal roles in this disease. Chemokines such as eotaxin may be involved in eosinophil recruitment. These mediators are downregulated or inhibited by the use of immunosuppressive medications.

  7. Mycophenolate mofetil for maintenance of remission in steroid-dependent autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jamie B Sodikoff; Steven A Keilin; Qiang cai; Sheila J Bharmal; Melinda M Lewis; Gottumukkala S Raju; Field F Willingham

    2012-01-01

    Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis.For steroid-dependent disease,azathioprine has been used for maintenance of remission.Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however,there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis.A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil,which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production.Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events.The patient was managed without a biliary stent.However,there was a return of symptoms,jaundice,increase in transaminases,and hyperbilirubinemia when the prednisone dose reached 11 mg per day.In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis,the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events,but it did not enable discontinuation of the steroids.Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.

  8. Long term results of total lymphoid irradiation in the treatment of cardiac allograft rejection

    International Nuclear Information System (INIS)

    Purpose: To evaluate the short and long term effects of total lymphoid irradiation (TLI) in the treatment of allograft rejection in cardiac transplant patients. Materials and Methods: From 1986 to 1995, 48 courses of TLI were delivered to 47 patients who had received cardiac transplants at Stanford University. In 38 cases, TLI was administered for chronic, intractable allograft rejection despite conventional anti-rejection therapy, including corticosteroids, azathioprine, cyclosporine, OKT3, DHPG, RATG, and methotrexate. Ten patients received TLI prophylactically, beginning radiation between 5 and 16 days after heart transplantation. The prescribed radiation dose was 800 cGy given in 80 cGy fractions twice weekly to all major lymph node regions using mantle and inverted Y fields. Patients continued to receive all medications except azathioprine which was held during TLI to prevent severe marrow suppression. All patients were closely monitored for episodes of rejection, infection, prednisone requirements, blood counts, and complications of treatment. Post-irradiation follow up ranged from 6 months to 9.1 years with a mean of 3.1 years. Results: The actual mean dose of radiation was 730 cGy delivered over a mean of 39 calendar days. Fifty six percent of patients required treatment delay or abbreviation because of thrombocytopenia, leukopenia, infection, or unrelated problems. In patients treated for intractable rejection, the frequency of rejection dropped from 0.46 episodes/patient/month before radiation to 0.14 episodes/patient/month during TLI (p 3 during TLI (p = 0.01) and remained low at 167.6 cells/mm3 2-4 months after treatment (p = 0.05). CD8+ lymphocytes also decreased during treatment from 233.2 to 65.8 cells/mm3 (p = 0.003) but rose significantly above normal to 381.3 cells/mm3 2-4 months after TLI (p 0.05). Thus, the ratio of helper/suppresser T-cells was chronically decreased. Infection rates were not significantly different before, during or after

  9. Gout in solid organ transplantation: a challenging clinical problem.

    Science.gov (United States)

    Stamp, Lisa; Searle, Martin; O'Donnell, John; Chapman, Peter

    2005-01-01

    Hyperuricaemia occurs in 5-84% and gout in 1.7-28% of recipients of solid organ transplants. Gout may be severe and crippling, and may hinder the improved quality of life gained through organ transplantation. Risk factors for gout in the general population include hyperuricaemia, obesity, weight gain, hypertension and diuretic use. In transplant recipients, therapy with ciclosporin (cyclosporin) is an additional risk factor. Hyperuricaemia is recognised as an independent risk factor for cardiovascular disease; however, whether anti-hyperuricaemic therapy reduces cardiovascular events remains to be determined. Dietary advice is important in the management of gout and patients should be educated to partake in a low-calorie diet with moderate carbohydrate restriction and increased proportional intake of protein and unsaturated fat. While gout is curable, its pharmacological management in transplant recipients is complicated by the risk of adverse effects and potentially severe interactions between immunosuppressive and hypouricaemic drugs. NSAIDs, colchicine and corticosteroids may be used to treat acute gouty attacks. NSAIDs have effects on renal haemodynamics, and must be used with caution and with close monitoring of renal function. Colchicine myotoxicty is of particular concern in transplant recipients with renal impairment or when used in combination with ciclosporin. Long-term urate-lowering therapy is required to promote dissolution of uric acid crystals, thereby preventing recurrent attacks of gout. Allopurinol should be used with caution because of its interaction with azathioprine, which results in bone marrow suppression. Substitution of mycophenylate mofetil for azathioprine avoids this interaction. Uricosuric agents, such as probenecid, are ineffective in patients with renal impairment. The exception is benzbromarone, which is effective in those with a creatinine clearance >25 mL/min. Benzbromarone is indicated in allopurinol-intolerant patients with

  10. Medical management of chronic liver diseases in children (part I): focus on curable or potentially curable diseases.

    Science.gov (United States)

    El-Shabrawi, Mortada H F; Kamal, Naglaa M

    2011-12-01

    The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic

  11. Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis

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    van Bodegraven Adriaan A

    2011-05-01

    Full Text Available Abstract Background Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG and azathioprine (AZA in a murine model of IBD. Methods We induced acute or chronic colitis in BALB/c mice by one or four cycles of 3% dextran sulphate sodium (DSS, respectively. Mice were treated by daily gavages of various dosages of 6-tioguanine, azathioprine, or by phosphate buffered saline (PBS starting the first day of DSS or after two cycles of DSS, respectively. We monitored the efficacy and toxicity by measuring the weight change and serum alanine aminotransferase (ALT activity and by disease severity and histology, at the end of the experiment. Moreover, we measured cytokine production after colon fragment cultivation by enzyme-linked immunoabsorbent assay and numbers of apoptotic cells in the spleen by flow cytometry. Results 6-TG is effective in the treatment of acute DSS-induced colitis in a dose-dependent manner and 40 μg of 6-TG is significantly more effective in the treatment of acute colitis than both AZA and PBS. This effect is accompanied by decrease of IL-6 and IFN-γ production in colon. We did not observe histological abnormalities in liver samples from control (PBS or 6-TG treated mice. However, liver samples from most mice treated with AZA showed mild, yet distinct signs of hepatotoxicity. In chronic colitis, all thiopurine derivatives improved colitis, 20 μg of 6-TG per dose was superior. High doses of 6-TG led to significant weight loss at the end of the therapy, but none of the thiopurine derivatives increased levels of serum ALT. Both thiopurine derivatives reduced the proportion of apoptotic T helper cells, but a high production of both IL-6 and TGF-β was observed only in colon of AZA-treated mice. Conclusions Use of 6-TG in the treatment

  12. Pyoderma gangrenosum associated with ulcerative colitis: response to infliximab Pioderma gangrenoso asociado a colitis ulcerosa: respuesta a infliximab

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    A. López San Román

    2004-06-01

    Full Text Available Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease that can be therapeutically troublesome. We comment on the case of a patient with clinically inactive ulcerat-ive colitis who progressively developed necrotic lesions on both tibial aspects of his legs, which corresponded both clinically and histologically to pyoderma gangrenosum. Treatment with steroids and azathioprine could not control this complication. A single dose of infliximab 5 mg/kg was given, achieving an impressive response of the skin lesions followed by complete healing 3 months later. Infliximab can be useful in the management of refractory extraintestinal manifestations of inflammatory bowel disease.Dentro de las manifestaciones extraintestinales de la enfermedad inflamatoria intestinal, el pioderma gangrenoso plantea con frecuencia dificultades terapéuticas. Presentamos el caso de un enfermo diagnosticado de colitis ulcerosa, inactiva en ese momento, que presentó un pioderma gangrenoso en miembros inferiores y no respondió a esteroides y azatioprina. Se administró una dosis de 5 mg/kg de infliximab obteniendo una rápida mejoría de las lesiones y la completa curación a los 3 meses. Infliximab puede ser útil en manifestaciones extraintestinales de la enfermedad inflamatoria intestinal, como el pioderma gangrenoso, si no responden a los tratamientos habituales.

  13. HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

  14. Critical review of preclinical approaches to evaluate the potential of immunosuppressive drugs to influence human neoplasia.

    Science.gov (United States)

    Bugelski, Peter J; Volk, Amy; Walker, Mindi R; Krayer, John H; Martin, Pauline; Descotes, Jacques

    2010-01-01

    Many immunosuppressive drugs are associated with an increased risk of B-cell lymphoma, squamous cell carcinoma, and Kaposi sarcoma. Thirteen immunosuppressive drugs have been tested in 2-year carcinogenicity studies (abatacept; azathioprine; busulfan; cyclophosphamide; cyclosporine; dexamethasone; everolimus; leflunomide; methotrexate; mycophenolate mofetil; prednisone; sirolimus; and tacrolimus) and in additional models including neonatal and genetically modified mice; chemical, viral, ultraviolet, and ionizing radiation co-carcinogenesis, and in models with transplanted tumor cells. The purpose of this review is to outline the mechanisms by which immunosuppressive drugs can influence neoplasia, to summarize the available preclinical data on the 13 drugs, and to critically review the performance of the models. A combination of primary tumor and metastasis assays conducted with transplanted cells may provide the highest value for hazard identification and can be applied on a case-by-case basis. However, for both small molecules and therapeutic proteins, determining the relative risk to patients from preclinical data remains problematic. Classifying immunosuppressive drugs based on their mechanism of action and hazard identification from preclinical studies and a prospective pharmacovigilance program to monitor carcinogenic risk may be a feasible way to manage patient safety during the clinical development program and postmarketing. PMID:20884856

  15. Treatment of neurosarcoidosis: Innovations and challenges

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    Stjepanović Mihailo I.

    2014-01-01

    Full Text Available Introduction: Sarcoidosis affects the central nervous system more frequently than it used to be believed. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system tissues as well. Treatment of Neurosarcoidosis: Although a lot of drugs have proved useful in treating neurosarcoidosis, corticosteroids are still the gold standard in treatment of these patients. Therapeutic protocols differ regarding the dose of these drugs. Symptomatic neurosarcoidosis should always be treated with pulse corticosteroid therapy. People with diabetes, high blood pressure, osteoporosis and tuberculosis should be carefully monitored, as they are prone to complications associated with treatment with corticosteroids. In cases when treatment with corticosteroids does not show the desired results or therapy is discontinued due to the development of side effects, there are other pharmacologic options, such as methotrexate, mycophenolate mofetil, cyclophosphamide, chloroquine, azathioprine, thalidomide, and infliximab. It should be noted that the treatment response to the above mentioned regimens, except for infliximab, is relatively slow compared to corticosteroids; therefore, corticosteroids should be taken into account in all states and particularly in the acute phase of the disease. Conclusion: It is the existence of different forms of the disease, lack of local diagnostic criteria and different and non standardized therapy that makes the treatment of this disease difficult. Despite advances in pharmacotherapy and radiological diagnosis, it is necessary to develop better diagnostic strategies in order to set the optimal therapeutic approach.

  16. Adamantiades-Behcet's disease-complicated gastroenteropathy.

    Science.gov (United States)

    Wu, Qing-Jun; Zhang, Feng-Chun; Zhang, Xuan

    2012-02-21

    Adamantiades-Behcet's disease (ABD) is a chronic, relapsing, systemic vasculitis of unknown etiology. It is more prevalent in populations along the ancient Silk Road from Eastern Asia to the Mediterranean Basin, and most frequently affects young adults between the second and fourth decades of life. ABD-complicated gastroenteropathy is a significant cause of morbidity and mortality, with abdominal pain as the most common symptom. The ileocecal region is affected predominantly, with ulcerations that may lead to penetration and/or perforation, whereas other parts of the gastrointestinal system including the esophagus and stomach can also be affected. Endoscopy is useful to locate the site and extent of the lesions, and tissue biopsy is often warranted to examine the histopathology that is often suggestive of underlying vasculitis of small veins/venules or, alternatively in some cases, nonspecific inflammation. Bowel wall thickening is the most common finding on computed tomography scan. Treatment is largely empirical since well-controlled studies are difficult to conduct due to the heterogeneity of the disease, and the unpredictable course with exacerbation and remission. Corticosteroids with or without other immunosuppressive drugs, such as cyclophosphamide, azathioprine, sulfasalazine, tumor necrosis factor α antagonist or thalidomide should be applied before surgery, except in emergency. PMID:22363131

  17. New and emerging trends in the treatment of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Christina M Gelbard

    2009-01-01

    Full Text Available Christina M Gelbard1, Adelaide A Hebert1,21Departments of Dermatology; 2Pediatrics, University of Texas-Houston, Houston, TX, USAAbstract: Atopic dermatitis is a chronic, inflammatory skin condition that affects 10% to 20% of children and 1% to 3% of adults in the US. Symptoms often result in sleeplessness, psychological stress, poor self-esteem, anxiety, and poor school or work performance. The cost of atopic dermatitis is estimated to be US$0.9 to 3.8 billion every year. Topical steroids are first-line treatment for atopic dermatitis, and recent advances in vehicle technologies have resulted in improved patient tolerability and compliance. Topical calcineurin inhibitors are also safe and effective topical treatments for atopic dermatitis, and provide an additional therapeutic option for patients with this disease. Systemic immunomodulators are used in the treatment of severe refractory disease. Cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, and interferon gamma have been used in the management of severe atopic dermatitis. This review highlights the current and emerging trends in the treatment of atopic dermatitis.Keywords: atopic dermatitis, topical corticosteroids, calcineurin inhibitors, methotrexate, cyclosporine, mycophenolate mofetil, IFN-γ

  18. Golimumab in unresponsive ulcerative colitis

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    Lippert E

    2014-05-01

    Full Text Available Elisabeth Lippert, Martina Müller, Claudia Ott University Hospital Regensburg, Department of Internal Medicine I, Regensburg, Germany Abstract: Ulcerative colitis (UC is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines and the biologics providing blockade of tumor necrosis factor (TNF, the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC. Keywords: anti-TNF, biological therapy, inflammatory bowel disease

  19. Advances in the treatment of cutaneous lupus erythematosus.

    Science.gov (United States)

    Kuhn, A; Landmann, A; Wenzel, J

    2016-07-01

    Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE. PMID:27252259

  20. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values

  1. Long-term outcomes of children after solid organ transplantation

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    Jon Jin Kim

    2014-01-01

    Full Text Available Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation.

  2. Atualização do tratamento das vasculites associadas a anticorpo anticitoplasma de neutrófilos Treatment of antineutrophil cytoplasmic antibody-associated vasculitis: update

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    Alfredo Nicodemos Cruz Santana

    2011-12-01

    Full Text Available As vasculites antineutrophil cytoplasmic antibody (ANCA, anticorpo anticitoplasma de neutrófilos associadas (VAAs são caracterizadas por uma inflamação sistêmica das artérias de pequeno e médio calibre (especialmente no trato respiratório superior e inferior, e nos rins. As VAAs compreendem a granulomatose de Wegener (agora chamada de granulomatose com poliangeíte, poliangeíte microscópica, VAA limitada ao rim e a síndrome de Churg-Strauss. Neste artigo, discutiremos as fases de tratamento dessas vasculites, como fase de indução (com ciclofosfamida ou rituximab e fase de manutenção (com azatioprina, metotrexato ou rituximab. Além disso, discutiremos como manusear os casos refratários à ciclofosfamida.In its various forms, antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV is characterized by a systemic inflammation of the small and medium-sized arteries (especially in the upper and lower respiratory tracts, as well as in the kidneys. The forms of AAV comprise Wegener's granulomatosis (now called granulomatosis with polyangiitis, microscopic polyangiitis, renal AAV, and Churg-Strauss syndrome. In this paper, we discuss the phases of AAV treatment, including the induction phase (with cyclophosphamide or rituximab and the maintenance phase (with azathioprine, methotrexate, or rituximab. We also discuss how to handle patients who are refractory to cyclophosphamide.

  3. [Anti-MOG + neuromyelitis optica spectrum disorders treated with plasmapheresis].

    Science.gov (United States)

    Oshiro, Azusa; Nakamura, Sadao; Tamashiro, Kunihito; Fujihara, Kazuo

    2016-05-01

    A 10-year-old boy developed bilateral optic neuritis and myelitis after a suspected viral infection and appendicitis. Magnetic resonance imaging (MRI) showed multiple lesions in both optic nerves, the optic chiasm, and the spinal cord. Several small lesions were also observed in the cerebellum and cerebral white matter. The serum tested negative for anti-aquaporin (AQP)-4 antibody and positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The diagnosis was neuromyelitis optica spectrum disorder (NMOSD). Two courses of high-dose methylprednisolone were administered; however, only a small improvement in his visual acuity was achieved. He underwent 3 courses of plasma exchange to achieve sufficient visual acuity. After the serum anti-MOG antibody titer decreased to the cut-off level, oral prednisolone and azathioprine administration were also stopped, 10 months after onset. Recently, NMO and NMOSD cases positive for anti-MOG antibodies have been reported, which showed clinical features different from those of NMO cases positive for anti-AQP4 antibody. Although most of the reported cases responded to steroid therapy, plasma exchange was required in our case. Further analysis on larger numbers of cases is needed to establish treatments for anti-MOG antibody-positive NMO and NMOSD. PMID:27349083

  4. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

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    Suk Chon

    2011-02-01

    Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

  5. Normalization of lung function following treatment of secondary usual interstitial pneumonia: a case report.

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    Hohberger, Laurie A; Montero-Arias, Felicia; Roden, Anja C; Vassallo, Robert

    2015-01-01

    Usual interstitial pneumonia (UIP) is the most common idiopathic interstitial pneumonia (IIP) and is associated with a poor prognosis and poor responsiveness to immunosuppressive therapy. We present a case of a woman with steroid-responsive biopsy-proven UIP with significant and sustained improvement in pulmonary function. A female in her 40s presented following a one-year history of progressive dyspnea, a 20 lb weight loss, and fatigue. Imaging of the chest with computed tomography (CT) showed bibasilar subpleural reticular opacities and minimal peripheral honeycombing. Comprehensive connective tissue disease (CTD) antibody testing was negative. Pulmonary function testing showed moderate impairment with reduction in forced vital capacity (FVC, 69% predicted), forced expiratory volume in one second (FEV1 73% predicted), and diffusing capacity for carbon monoxide (DLCO, 52% predicted). Surgical lung biopsy showed UIP with prominent inflammatory infiltrates. Following treatment with prednisone and azathioprine, the patient's symptoms resolved, while objective pulmonary function testing showed normalization of lung function, which is sustained at >4 years of follow-up. Improvement in lung function following immunosuppressive therapy is distinctly uncommon in either idiopathic or secondary UIP. This report suggests that occasionally, patients with secondary UIP occurring in the context of otherwise undefinable autoimmune clinical syndromes may be responsive to immunosuppressive therapy. PMID:25922588

  6. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  7. [Interstitial nephritis in rheumatic diseases].

    Science.gov (United States)

    Korsten, P; Müller, G A

    2015-05-01

    Interstitial nephritis is responsible for about 12 % of end-stage renal disease in Germany. It comprises an etiologically heterogenous group of inflammatory renal disorders which primarily affect the renal interstitium and tubuli. Drugs, predominantly antibiotics, nonsteroidal anti-inflammatory drugs and proton pump inhibitors are causative in the majority of cases. Rheumatic diseases frequently affect the kidneys, either the glomeruli or the interstitial tissues. Inflammatory interstitial processes can be accompanied by complex functional tubular disorders. This review gives an overview about clinical and laboratory findings of interstitial nephritis in the context of rheumatic diseases. Sarcoidosis, tubulointerstitial nephritis and uveitis (TINU) syndrome, primary Sjogren's syndrome, and IgG4-related disease often show an interstitial nephritis when the kidneys are affected. Other diseases, such as systemic lupus erythematosus, systemic sclerosis, drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, and granulomatosis with polyangiitis are more rarely associated with predominant interstitial nephritis. Glucocorticoids are the mainstay of therapy for most cases; in refractory cases or when side effects occur, second-line immunosuppressants such as mycophenolate mofetil, azathioprine and others, rarely biologics, can be used. PMID:25962450

  8. A cell culture assay for the detection of cardiotoxicity

    International Nuclear Information System (INIS)

    An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. The authors propose the use of shock protein formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing shock protein formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of shock proteins. Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes shock protein formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce shock protein synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive

  9. September 2014 imaging case of the month

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    Gotway MB

    2014-09-01

    Full Text Available No abstract available. Article truncated at 150 words. Clinical History: A 57-year-old non-smoking woman presented to her physician as an outpatient with complaints of worsening cough, fever, chills, and shortness of breath. The patient’s past medical history includes systemic lupus erythematosus diagnosed 18 years earlier, for which the patient has been variably treated with corticosteroids, hydroxychloroquine, and azathioprine. Additional past medical and surgical history includes migraines, mood disorder, diabetes mellitus treated with metformin, hysterectomy for endometriosis, and iron-deficient anemia. The patient was also diagnosed with small lymphocytic lymphoma 3 years earlier following a right breast biopsy when an abnormal opacity was discovered incidentally at routine screening breast imaging. She has not been treated for this neoplasm as no B symptoms have been reported. Frontal and lateral chest radiography (Figure 1 was performed. Which of the following statements regarding the chest radiograph is most accurate? 1. The chest radiograph shows asymmetric pulmonary vascularity; 2. The chest radiograph shows bilateral ...

  10. Bimonthly Evolution of Cortical Atrophy in Early Relapsing-Remitting Multiple Sclerosis over 2 Years: A Longitudinal Study

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    Robert Zivadinov

    2013-01-01

    Full Text Available We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR multiple sclerosis (MS and its association with lesion volume (LV accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD at baseline of ≤24 months were classified in the early group (DD of 1.2 years, n=37, while patients with DD > 24 months were classified in the late group (DD of 7.1 years, n=99. Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV (P<0.001, cortical volume (CV (P<0.001, and in T2-LV (P<0.001 were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P<0.01. No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P=0.01. Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.

  11. Myeloproliferative disorders in patients with rheumatoid arthritis treated with total body irradiation

    International Nuclear Information System (INIS)

    Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation

  12. Subcutaneous Histiocytoid Sweet Syndrome Associated with Crohn Disease in an Adolescent

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    Rosa María Fernández-Torres

    2014-01-01

    Full Text Available We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, and upper extremities. Laboratory studies revealed neutrophilia, microcytic anemia, and elevation of both erythrocyte sedimentation rate and C-reactive protein rate. A skin biopsy specimen showed deep dermal and predominantly septal inflammatory infiltrate in the subcutaneous tissue composed of polymorphonuclears, eosinophils, and mononuclear cells of histiocytic appearance. These histiocytoid cells stained positive for myeloperoxidase. Subcutaneous Sweet syndrome is a rare subtype of acute neutrophilic dermatosis, in which the infiltrate is exclusively or predominantly located in the subcutaneous tissue, causing lobular or septal panniculitis. It is often described in patients with an underlying haematological disorder or caused by drugs, but very rare in patients with inflammatory bowel disease, especially in childhood or adolescence. To our knowledge, this is the first case of subcutaneous histiocytoid type in a paediatric patient.

  13. Subcutaneous histiocytoid sweet syndrome associated with crohn disease in an adolescent.

    Science.gov (United States)

    Fernández-Torres, Rosa María; Castro, Susana; Moreno, Ana; Alvarez, Roberto; Fonseca, Eduardo

    2014-01-01

    We report a case of subcutaneous histiocytoid Sweet syndrome in an adolescent with Crohn disease. A 14-year-old boy with a 1-year history of ileocolonic and perianal Crohn disease, treated with infliximab and azathioprine, was admitted to the Pediatrics Department with malaise, abdominal pain, bloody diarrhea, and fever (39°C) from 15 days ago. Two days later, he developed cutaneous lesions consisting of tender, erythematous, and violaceous papules and nodules scattered over his legs, soles, and upper extremities. Laboratory studies revealed neutrophilia, microcytic anemia, and elevation of both erythrocyte sedimentation rate and C-reactive protein rate. A skin biopsy specimen showed deep dermal and predominantly septal inflammatory infiltrate in the subcutaneous tissue composed of polymorphonuclears, eosinophils, and mononuclear cells of histiocytic appearance. These histiocytoid cells stained positive for myeloperoxidase. Subcutaneous Sweet syndrome is a rare subtype of acute neutrophilic dermatosis, in which the infiltrate is exclusively or predominantly located in the subcutaneous tissue, causing lobular or septal panniculitis. It is often described in patients with an underlying haematological disorder or caused by drugs, but very rare in patients with inflammatory bowel disease, especially in childhood or adolescence. To our knowledge, this is the first case of subcutaneous histiocytoid type in a paediatric patient. PMID:24839565

  14. Induction of specific unresponsiveness to heart allografts in mongrel dogs treated with total lymphoid irradiation and antithymocyte globulin

    International Nuclear Information System (INIS)

    The survival of heterotopic heart allografts was determined in mongrel dogs treated with total lymphoid irradiation (TLI) alone or in combination with other immunosuppressive agents. TLI alone (total dose, 1800 rad) minimally prolonged graft survival as compared with untreated controls. However, marked synergy was observed when TLI was combined with a 10-day post-transplant course of rabbit anti-dog thymocyte globulin (ATG). Approximately 40% of recipients given TLI and ATG showed specific unresponsiveness, as judged by the lack of rejection on serial biopsies for more than 1 year and the prompt rejection of third party hearts. The addition of post-transplant azathioprine (90 to 180 days) to the TLI and ATG regimen increased the mortality of recipients and reduced the fraction of dogs showing specific unresponsiveness. Infusion of donor bone marrow cells at the time of heart transplantation failed to induced specific unresponsiveness in recipients given TLI alone or TLI in combination with post-transplant methotrexate, cyclosporine A, or ATG. The results indicate that the combination of TLI and a brief course of ATG without marrow transplantation was the most effective regimen for the induction of specific unresponsiveness in mongrel dogs

  15. Oxidative damage to RPA limits the nucleotide excision repair capacity of human cells

    Science.gov (United States)

    Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

    2015-01-01

    Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin, interact with UVA radiation to generate reactive oxygen species (ROS) that diminish NER capacity by causing protein damage. The RPA DNA binding protein plays a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself is likely to be an important contributor to skin cancer risk. PMID:26134950

  16. Clinical characteristics and response to therapy of autoimmune hepatitis in an urban Latino population

    Science.gov (United States)

    Zahiruddin, Ayesha; Farahmand, Abtin; Gaglio, Paul; Massoumi, Hatef

    2016-01-01

    Aim: We hypothesized that AIH outcomes might be different in our patient population that consists of a large number of Latinos. Background: Literature has suggested that the presentation and outcome of autoimmune hepatitis can be different among different ethnicity and communities. Patients and methods: We performed a retrospective chart review of Latino patients with AIH diagnosed between 2002-2012. Complete and partial remissions were defined as normalization of liver enzyme values, or achieving less than twice the upper limit normal (ULN), respectively. Results: A total of 28 patients were identified. 26 (93%) were female. 13 (46%) had an acute presentation, one with type 2 AIH and 3 with ANA seronegative disease. The average pathologic stage (Ishak score) was 3.44±1.67 (range: 0-6). Complete and partial remission was achieved in 20 (71%) and 5 (18%) patients respectively. Ten patients (38%) required maintenance prednisone either alone (2), or in combination with Azathioprine (6) or Mycophenolate Mofetil (2). Remission in the majority of patients, including 14 (50%) who were cirrhotic. Six of 14 (43%) cirrhotic patients were asymptomatic at the time of diagnosis. Conclusion: In an urban Latino population, cirrhosis was the initial presentation of AIH in a significant percentage of patients raising concerns regarding insufficient screening for AIH in this patient population. A large number of patients required continuous prednisone to avoid relapse. PMID:27458516

  17. Effects of synthetic and naturally occurring flavonoids on mitogen-induced proliferation of human peripheral-blood lymphocytes

    International Nuclear Information System (INIS)

    Examination was made of the effects of 17 synthetic and naturally occurring flavonoids on human lymphocyte proliferation in the presence of concanavalin A as a mitogen. Twelve of the flavonoids examined were mono-hydroxy of methoxy derivatives. The mitogen-induced response of lymphocytes was evaluated from the extent of the incorporation of [3H]thymidine into cells in vitro. All the compounds showed inhibitory effects; 4.5-77.7% of [3H] thymidine incorporation was blocked by an 1.0 μg/ml concentration. The viability of lymphocytes before and after treatment, as assessed by a dye exclusion test, indicated no change, and thus the flavonoids may inhibit DNA synthesis. The flavonoids possessing 5-hydroxyl, 5-methoxyl and 6-methoxyl groups, and those with cyclohexyl instead of phenyl substituent (i.e. 2-cyclohexyl-benzopyran-4-one), showed the greatest inhibition. The inhibitory effect of any one of them was less than one half that of prednisolone, but essentially the same or somewhat exceeding that of bredinine of azathioprine. It would thus appear that the well-known anti-inflammatory effects of flavonoids may possibly arise in part from the inhibition of the proliferative response of lymphocytes

  18. Heart transplantation in neonates and children. Intermediate-term results

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    Estela Azeka

    2000-03-01

    Full Text Available OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years. We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9% patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

  19. Influence of patient medication on diagnostic accuracy in nuclear medicine

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    Sampson, C.B. [Addenbrooke`s Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine

    1997-12-31

    Full text. In recently years many reports have published of unusual or unexpected changes in the biodistribution of radiopharmaceuticals which do not correlate with normality or disease. Whilst many extraneous factors can alter tracer kinetics it has become apparent that concomitant patient medication can be such a factor. If the clinician is unaware that patient is on drug therapy difficulties arise in making a accurate diagnosis. Most drug/radio pharmaceutical effects are those in which the functional status of the organ is altered as a result of the pharmacological action of the drug. Examples here are narcotic analgesics such as methadone, pethidine and morphine which cause spasm of the biliary tract due to contraction of the sphincter of Oddi and an altered transit time of the technetium labelled tracer. Cytotoxic drugs such as cyclophosphamide and vincristine can markedly affect tumour uptake of 67-gallium so that litter or no activity is taken up by the tumour. Nifedipine, because of its powerful calcium channel blocking activity is known to affect the radiolabelling of white cells and red cells and to affect uptake of Tc-99 m MDP into bones. Other important and confusing effects are caused by phenothiazines, cimetidine and oral contraceptives. In recent years it has been reported that drugs such as cyclosporin, azathioprine and heparin and derivatives of heparin can markedly interfere with cell labelling procedures. This review will consider some of the clinical effects of drugs and will also address the reporting of instances of drug/radio pharmaceutical interactions

  20. Giant coronary artery aneurysms in juvenile polyarteritis nodosa: a case report

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    Canares Therese L

    2012-01-01

    Full Text Available Abstract Juvenile polyarteritis nodosa (PAN is a rare, necrotizing vasculitis, primarily affecting small to medium-sized muscular arteries. Cardiac involvement amongst patients with PAN is uncommon and reports of coronary artery aneurysms in juvenile PAN are exceedingly rare. We describe a 16 year old girl who presented with fever, arthritis and two giant coronary artery aneurysms, initially diagnosed as atypical Kawasaki disease and treated with IVIG and methylprednisolone. Her persistent fevers, arthritis, myalgias were refractory to treatment, and onset of a vasculitic rash suggested an alternative diagnosis. Based on angiographic abnormalities, polymyalgia, hypertension and skin involvement, this patient met criteria for juvenile PAN. She was treated with six months of intravenous cyclophosphamide and high dose corticosteroids for presumed PAN related coronary vasculitis. Maintenance therapy was continued with azathioprine and the patient currently remains without evidence of active vasculitis. She remains on anticoagulation for persistence of the aneurysms. This case illustrates a rare and unusual presentation of giant coronary artery aneurysms in the setting of juvenile PAN.

  1. Idiopathic pulmonary hemosiderosis in a 9-year-old girl

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    Kamienska E

    2009-12-01

    Full Text Available Abstract Diffuse alveolar hemorrhage (DAH is a rare and life-threatening condition characterized by hemoptysis, dyspnoea, alveolar infiltrates on chest radiograph and various degrees of anemia. It may occur either as a primary disease of the lungs or a secondary condition due to cardiac, systemic vascular, collagen or renal diseases. Idiopathic pulmonary hemosiderosis (IPH is a separate form of DAH of unknown origin, associated in some cases with celiac disease. The estimated incidence of IPH in children is 0.24-1.23 cases per million, with a mortality rate as high as 50%. Only about 500 cases of this disease have been described in medical literature. We present a case of a 9-year-old girl diagnosed with IPH, which was confirmed by the presence of many hemosiderin-laden macrophages in bronchoalveolar lavage obtained by bronchofiberoscopy. Therapy with glucocorticoids was initiated with a partial and transient response. Azathioprine and a gluten-free diet were subsequently introduced. However, the girl still suffers from recurrent episodes of hemoptysis, dyspnea and anemia.

  2. Refractory Celiac Disease

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    K Khatami

    2014-04-01

    Full Text Available Refractory celiac disease (RCD is when malabsorption symptoms and villous atrophy persist despite strict adherence to a gluten free diet (GFD for more than 12 months and other causes of villous atrophy have been ruled out.  RCD is considered a rare disease and almost exclusively occurs in adults. Persistent diarrhea, abdominal pain, weight loss are the most common symptoms in RCD. Also, anemia, fatigue, malaise, thromboembolic events and coexisting autoimmune disorders are frequent. Diagnosis of RCD is based on other causes of unresponsiveness to the GFD, particularly collagenous sprue, ulcerative jejunitis, and enteropathy-associated T-cell lymphoma. Many disorders such as autoimmune enteropathy, tropical sprue, common variable immunodeficiency, and intolerance to non-gluten dietary proteins may have similar histological findings but not necessarily identical with CD and therefore should be excluded. Repeat intestinal biopsy may help to differentiate causes of non-responsive CD associated with ongoing villous atrophy (e.g., gluten contamination, small-bowel bacterial overgrowth, RCD. There are 2 subtypes of RCD according to absence (type I or presence (type II of an abnormal intraepithelial lymphocyte population. RCD type 1 usually becomes better with a combination of aggressive nutritional support, adherence to GFD, and pharmacologic therapies such as prednisone, budesonide and azathioprine. For RCD type 2, more aggressive therapeutic approach is needed since clinical response to therapies is less certain and may evolve into aggressive enteropathy associated T-cell lymphoma and the prognosis is poor.   Key words: Celiac Disease, Refractory.  

  3. Managing new-onset gout in pediatric renal transplant recipients: when, how, to what extent.

    Science.gov (United States)

    Assadi, Farahnak

    2013-01-01

    Hyperuricemia and gout are common among adult renal transplant recipients, but it is rarely reported following pediatric renal transplantations. Treating gout in pediatric kidney transplant recipients presents clinical challenges to the management of both immunosuppressive regimen and hyperuricemia for their effects on serum uric acid levels, renal function and drug interactions. Most renal transplant recipients have a relative impairment of renal clearance of urate due to abnormalities in renal transport, explaining the association of hyperuricemia and decreased glomerular filtration rate. Risk factors for the development of gout include impaired renal function, hypertension, heart failure and diabetes mellitus. Calcineurin inhibitors, particularly cyclosporine, are the most important risk factor for gout in transplant recipients and should not be used in pediatric renal transplant recipients. Diuretic therapy increases the risk of gout by causing extracellular volume contraction with consequent enhancement of proximal tubular reabsorption. Corticosteroids are increasingly replacing nonsteroidal antiinflammatory drugs and colchicine for the treatment of acute gout flares because they have little effect on kidney function. Proper management is aimed at lowering serum uric acid level below 6.0 mg/dL with xanthine oxidase inhibitors such as allopurinol or febuxostat. Allopurinol and mycophenolate mofetil are safer to use in combination than are allopurinol and azathioprine. Febuxostat is an alternative to allopurinol in patients with allopurinol intolerance or hypersensitivity. Pegloticase is indicated for patients with severe gout in whom allopurinol and febuxostat have not been effective or tolerated. PMID:22941874

  4. Antiepileptic drug hypersensitivity syndrome.

    Science.gov (United States)

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  5. Use of allopurinol to optimize thiopurine immunomodulator efficacy in inflammatory bowel disease.

    Science.gov (United States)

    Sparrow, Miles P

    2008-07-01

    The thiopurine immunomodulators azathioprine and 6-mercaptopurine are integral to the management of inflammatory bowel disease (IBD), particularly as corticosteroid-sparing and maintenance agents; however, up to 50% of patients do not adequately respond to these agents. Advances in pharmacogenomics and an increased understanding of thiopurine metabolism have led to the practice of measuring the thiopurine metabolites 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP) to help achieve optimal immunomodulator dosages. Metabolite profiles are also useful for categorizing the reasons for thiopurine treatment failures. A desirable metabolite profile favors 6-TGN production over 6-MMP formation; however, a significant subgroup of IBD patients, perhaps 15%, preferentially metabolizes thiopurines toward the inefficacious and potentially hepatotoxic metabolite 6-MMP. The xanthine oxidase inhibitor allopurinol has been shown recently to advantageously switch thiopurine metabolism toward 6-TGN production in this subgroup of patients, and small studies have shown this switch to be safe and clinically beneficial. This article reviews evidence describing the use of allopurinol to optimize immunomodulator metabolism, provides careful practice guidelines to clinicians considering this strategy, and briefly discusses the potential mechanisms by which this favorable interaction occurs. PMID:21960930

  6. Drug hypersensitivity syndrome.

    Science.gov (United States)

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins. PMID:21220873

  7. Gout and organ transplantation.

    Science.gov (United States)

    Stamp, Lisa K; Chapman, Peter T

    2012-04-01

    Acute and chronic gout are common complications following organ transplantation. Risk factors include those shared with the general population (eg, diuretic use) and transplant-specific risk factors (eg, cyclosporine). Clinical features of gout are similar to those seen in the general population, although tophi may be more common. A definitive diagnosis requires demonstration of monosodium urate crystals within synovial fluid or tophi. Treatment is often empiric, although a poor response should prompt joint aspiration to exclude septic arthritis. Corticosteroids are commonly used to treat acute gout due to the adverse profile and drug interactions with NSAIDs and colchicine. Sustained reduction of serum urate (≤6 mg/dL) is critical in long-term management. Allopurinol is the most commonly used agent, although vigilant monitoring is required if combined with azathioprine. Other options include febuxostat and benzbromarone. The role of newer agents such as interleukin-1 inhibitors and uricases remains to be determined. General measures should include minimizing diuretic use. PMID:22258500

  8. Oxidation-mediated DNA cross-linking contributes to the toxicity of 6-thioguanine in human cells.

    Science.gov (United States)

    Brem, Reto; Karran, Peter

    2012-09-15

    The thiopurines azathioprine and 6-mercaptopurine have been extensively prescribed as immunosuppressant and anticancer agents for several decades. A third member of the thiopurine family, 6-thioguanine (6-TG), has been used less widely. Although known to be partly dependent on DNA mismatch repair (MMR), the cytotoxicity of 6-TG remains incompletely understood. Here, we describe a novel MMR-independent pathway of 6-TG toxicity. Cell killing depended on two properties of 6-TG: its incorporation into DNA and its ability to act as a source of reactive oxygen species (ROS). ROS targeted DNA 6-TG to generate potentially lethal replication-arresting DNA lesions including interstrand cross-links. These triggered processing by the Fanconi anemia and homologous recombination DNA repair pathways. Allopurinol protected against 6-TG toxicity by acting as a ROS scavenger and preventing DNA damage. Together, our findings provide mechanistic evidence to support the proposed use of thiopurines to treat HR-defective tumors and for the coadministration of 6-TG and allopurinol as an immunomodulation strategy in inflammatory disorders. PMID:22822082

  9. Two brothers with skewed thiopurine metabolism in ulcerative colitis treated successfully with allopurinol and mercaptopurine dose reduction.

    Science.gov (United States)

    Hoentjen, Frank; Hanauer, Stephen B; de Boer, Nanne K; Rubin, David T

    2012-01-01

    Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members. PMID:22147254

  10. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  11. Urate-oxidase for the treatment of tophaceous gout in heart transplant recipients. A report of three cases.

    Science.gov (United States)

    Rozenberg, S; Roche, B; Dorent, R; Koeger, A C; Borget, C; Wrona, N; Bourgeois, P

    1995-05-01

    Gout in heart transplant recipients is common and poses a significant therapeutic challenge. Concomitant administration of azathioprine and allopurinol therapy carries a high risk of leukopenia. Uricosuric agents can cause renal lithiasis and/or acute renal failure in patients with renal failure and/or high urinary levels of uric acid. We report our experience with urate-oxidase in three heart transplant recipients with severe polyarticular and tophaceous gout, a history of leukopenia under allopurinol and unresponsiveness or contraindications to uricosuric agents. Urate-oxidase was given parenterally in a dosage of 1000 units per day, seven days a month. The injections were done intramuscularly in one patient and intravenously in the other two, who were under anticoagulant therapy. Patients 1 and 2 received 12 and 6 courses, respectively. The third patient had had four courses and was still under treatment at the time of this writing. Shrinking of the tophi and improved mobility of the fingers were seen in all three patients after the second course. No adverse effects were recorded. Our experience suggests that urate-oxidase therapy may decrease the urate burden in patients with severe tophaceous gout. Urate-oxidase therapy should be viewed as a phase in the treatment of gout, which must be followed by administration of another agent. PMID:7655872

  12. An update on liver transplantation: A critical review.

    Science.gov (United States)

    Neuberger, James

    2016-01-01

    Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems. PMID:26350881

  13. Unusual Case of Cerebral Venous Thrombosis in Patient with Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Inha Kim

    2015-05-01

    Full Text Available The development of cerebral venous thrombosis (CVT as a secondary complication of Crohn's disease (CD seems to be rare, but it is generally accepted that the disease activity of CD contributes to the establishment of a hypercoagulable state. Here, we describe a case of CVT that developed outside the active phase of CD. A 17-year-old male visited the emergency room because of a sudden onset of right-sided weakness and right-sided hypesthesia. He had been diagnosed with CD 1 year before and was on a maintenance regimen of mesalazine and azathioprine. He did not exhibit any symptoms indicating a CD flare-up (bloody stools, abdominal pain, complications, or weight loss. A brain MRI scan revealed an acute infarction of the left frontal cortex and a cortical subarachnoid hemorrhage. Additionally, a magnetic resonance venography revealed a segmental filling defect in the superior sagittal sinus and also the non-visualizability of some bilateral cortical veins. The characteristics of the present case suggest that the risk of CVT is most likely related to CD per se rather than disease activity associated with CD.

  14. Management of difficult inflammatory bowel disease: where are we now?

    Institute of Scientific and Technical Information of China (English)

    D.S. Rampton

    2000-01-01

    Management of inflammatory bowel disease includes not only drug, endoscopic and surgical therapy but alsopsychosocial support, dietary and specific nutritional measures: a multidisciplinary medical, surgical, nursingand dietetic approach is essential for all patients, particularly those with complex or refractory disease. Inthis paper, current treatment of acute severe ulcerative colitis and steroid-refractory or -dependent Crohn'sdisease is reviewed. Adjunctive intravenous cyclosporin is an alternative to urgent colectomy in steroid-refractory patients with acute severe ulcerative colitis, while the place of intravenous heparin for thisindication awaits clarification. Azathioprine or 6-mercaptopurine are useful options in chronically active,steroid-refractory or -dependent Crohn's disease, but may take up to 4 months to work. Methotrexate is amore recent immunomodulatory alternative. Of new therapies selectively aimed at specific pathophysiologicaltargets, the first to reach clinical application is anti-TNF-alpha antibody (infliximab) for refractory Crohn'sdisease: its benefits are promising, but experience with it is limited to date, its cost is high and there areuncertainties about long-term safety. In view of the increasing variety and complexity of management optionsin inflammatory bowel disease, whether apparently responsive or difficult to treat, patients must participatein decisions about which therapies they are to be given.

  15. Noncirrhotic Portal Hypertension due to Nodular Regenerative Hyperplasia Treated with Surgical Portacaval Shunt

    Directory of Open Access Journals (Sweden)

    Lisa M. Louwers

    2012-01-01

    Full Text Available Nodular regenerative hyperplasia (NRH is an uncommon condition, but an important cause of noncirrhotic intrahepatic portal hypertension (NCIPH, characterized by micronodules of regenerative hepatocytes throughout the liver without intervening fibrous septae. Herein, we present a case of a thirty-seven-year-old female with systemic lupus erythematosus (SLE who was discovered to have significant esophageal varices on endoscopy for dyspepsia. Her labs revealed a slight elevation in the alkaline phosphatase and mild thrombocytopenia. Abdominal MRI revealed seven focal hepatic masses, splenomegaly, no ascites, and a patent portal vein. Ultrasound-guided core biopsy was reported as focal nodular hyperplasia. However, her varices persisted despite treatment with beta-blockers and four additional upper endoscopies with banding. She was subsequently referred for a surgical opinion. At that time, given her history of SLE, azathioprine use, and portal hypertension, suspicion for NRH was raised. Given her normal synthetic function and lack of parenchymal liver disease, the patient was offered surgical shunting. During shunt surgery, a liver wedge biopsy was also performed and this confirmed NRH. An upper endoscopy six weeks after shunting verified complete resolution of varices. Currently, fifteen months after surgery duplex ultrasonography demonstrates shunt patency and the patient is without recurrence of her portal hypertension.

  16. Risk factors for lung diseases after renal transplantation

    Directory of Open Access Journals (Sweden)

    Ventsislava P Pencheva

    2015-01-01

    Full Text Available Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001, arterial hypertension (OR = 1.95; P = 0.015, living related donor (OR = 2.69; P = 0.004, therapy for acute graft rejection (OR = 2.06; P = 0.038, immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011, azathioprine (OR = 2.25; P = 0.023, and tacrolimus (OR = 1.83; P = 0.041. The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001. Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation.

  17. Epidemiology and clinical course of Crohn's disease: Results from observational studies

    Institute of Scientific and Technical Information of China (English)

    φistein Hovde; Bjφrn A Moum

    2012-01-01

    The authors review the clinical outcome in patients with Crohn's disease (CD) based on studies describing the natural course of the disease.Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s.The authors search for English language articles from 1980 until 2011.Geographical variations,incidence,prevalence,smoking habits,sex,mortality and medications are investigated.An increasing incidence and prevalence of CD have been found over the last three decades.The disease seems to be most common in northern Europe and North America,but is probably increasing also in Asia and Africa.Smoking is associated with an increased risk of developing CD.Age < 40 at diagnosis,penetrating/stricturing complications,need for systemic steroids,and disease location in terminal ileum are factors associated with higher relapse rates.A slight predominance of women diagnosed with CD has been found.Ileocecal resection is the most commonly performed surgical procedure,and within the first five years after the diagnosis about one third of the patients have had intestinal surgery.Smoking is associated with a worse clinical course and with increased risk of flare-ups.In most studies the overall mortality is comparable to the background population.To date,the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers.Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.

  18. Pharmacogenetics in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Marie Pierik; Paul Rutgeerts; Robert Vlietinck; Severine Vermeire

    2006-01-01

    Pharmacogenetics is the study of the association between variability in drug response and (or) drug toxicity and polymorphisms in genes. The goal of this field of science is to adapt drugs to a patient's specific genetic background and therefore make them more efficacious and safe. In this article we describe the variants in genes that influence either the efficacy or toxicity of common drugs used in the treatment of inflammatory bowel diseases (IBD), ulcerative colitis (UC),and Crohn's disease (CD) including sulfasalazine and mesalazine, azathioprine (AZA) and 6-mercaptopurine (6-MP), methotrexate (MTX), glucocorticosteroids (CSs) and infliximab. Furthermore, difficulties with pharmacogenetic studies in general and more specifically in IBD are described. Although pharmacogenetics is a promising field that already contributed to a better understanding of some of the underlying mechanisms of action of drugs used in IBD, the only discovery translated until now into daily practice is the relation between thiopurine S-methyltransferase (TPMT) gene polymorphisms and hematological toxicity of thiopurine treatment. In the future it is necessary to organize studies in well characterized patient cohorts who have been uniformly treated and systematically evaluated in order to quantitate drug response more objectively. An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies.

  19. 炎症性肠病联合治疗中的药物相互作用

    Institute of Scientific and Technical Information of China (English)

    武丽娜; 张波; 鲁重美

    2015-01-01

    Polypharmacy is an increasing concern in the management of inflammatory bowel disease.This review describes drug interactions in the combination therapy of inflammatory bowel disease,including aminosalicylate ,corticosteroid,azathioprine,methotrexate,cyclosporine,thalidomide,cyclophosphamide and antibiotics,TNF inhibitor.%氨基水杨酸制剂、肾上腺糖皮质激素、硫唑嘌呤、甲氨蝶呤、环孢素、沙利度胺、环磷酰胺、抗肿瘤坏死因子α单克隆抗体等药物在炎症性肠病(Inflammatory bowel dis-ease,IBD)治疗应用较广。目前多种药物联合应用在 IBD 治疗中越来越常见,药物之间的相互作用也日益受到医学界的重视。现介绍 IBD 治疗中常见的药物联用对彼此血药浓度、毒副作用、治疗效果等的影响。

  20. Interstitial lung disease in systemic sclerosis: where do we stand?

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    Susanna Cappelli

    2015-09-01

    Full Text Available Interstitial lung disease (ILD is common in systemic sclerosis (SSc patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease. Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described. Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation, medium intensity (CYC and RTX and low intensity (azathioprine (AZA and mycophenolate mofetil (MMF. After obtaining remission, maintenance treatment with AZA or MMF should be started. In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD.

  1. Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis

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    İlknur Tuğal-Tutkun

    2016-04-01

    Full Text Available Pediatric uveitis may be a serious health problem because of the lifetime burden of vision loss due to severe complications if the problem is not adequately treated. Juvenile idiopathic arthritis (JIA-associated uveitis is characterized by insidious onset and potentially blinding chronic anterior uveitis. Periodic ophthalmologic screening is of utmost importance for early diagnosis of uveitis. Early diagnosis and proper immunomodulatory treatment are essential for good visual prognosis. The goal of treatment is to achieve enduring drug-free remission. The choice of therapeutic regimen needs to be tailored to each individual case. One must keep in mind that patients under immunomodulatory treatment should be monitored closely due to possible side effects. Local and systemic corticosteroids have long been the mainstay of therapy; however, long-term corticosteroid therapy should be avoided due to serious side effects. Steroid-sparing agents in the treatment of JIA-associated uveitis include antimetabolites and biologic agents in refractory cases. Among the various immunomodulatory agents, methotrexate is generally the first choice, as it has a well-established safety and efficacy profile in pediatric cases and does not appear to increase the risk of cancer. Other classic immunomodulators that may also be used in combination with methotrexate include azathioprine, mycophenolate mofetil, and cyclosporin A. Biologic agents, primarily tumor necrosis factor alpha inhibitors including infliximab or adalimumab, should be considered in cases of treatment failure with classic immunomodulatory agents.

  2. Behçet′s uveitis

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    Tugal-Tutkun Ilknur

    2009-01-01

    Full Text Available Behcet′s disease is a multisystem inflammatory disorder that is most common in countries along the ancient "Silk Road". The eye is the most commonly involved vital organ in Behηet′s patients and the typical form of involvement is a relapsing remitting panuveitis and retinal vasculitis. Uveitis is the initial manifestation of the disease in 10-15% of the patients. Anterior uveitis is always nongranulomatous. Diffuse vitritis, retinal infiltrates, sheathing of predominantly retinal veins, and occlusive vasculitis are the typical signs of posterior segment inflammation. Spontaneous resolution of acute inflammatory signs is a diagnostic feature. Fundus fluorescein angiography is the gold standard in monitoring inflammatory activity. Laser flare photometry is a useful noninvasive tool since flare readings correlate with fluorescein angiographic leakage. The most common complications are cataract, maculopathy, and optic atrophy. Male patients have a more severe disease course and worse visual prognosis. Immunomodulatory therapy is indicated in all patients with posterior segment involvement. Corticosteroids combined with azathioprine and/or cyclosporine is used initially. Biologic agents, including interferon alfa and infliximab, are used in resistant cases. Visual prognosis has improved in recent years with an earlier and more aggressive use of immunomodulatory therapy and the use of biologic agents in resistant cases.

  3. Inhibition of the immune response to experimental fresh osteoarticular allografts

    International Nuclear Information System (INIS)

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed

  4. The application, mechanism of action and side-effects of immunosuppressive agents in clinical transplantation

    International Nuclear Information System (INIS)

    The conventional agents (azathioprine and steroids) have been the mainstay of organ allograft immuno-suppression for the past 20 years. The main drawback of the immunosuppressive agents at present in use is that they act nonspecifically with sequential general depression of the immune system. The introduction of cyclosporin, an undecapeptide of fungal origin, which selectively inhibits T-cell-dependent immuno-reaction has made a significant impact on organ allograft survival rates. Clinical application has been complicated because of renal or hepatotoxicity. Thoracic duct drainage is of historical interest but the use of antilymphocyte serum, despite its chequered history, has recently been shown to be safe and effective in cadaver kidney transplant recipients. There has also been a resurgence of interest in the use of total lymphoid irradiation as an immuno-suppressive agent. The introduction of xenogenic monoclonal antibodies with anti-T-cell specificity opened a new era in clinical immunology and OKT3-PAN has emerged as a powerful major immunosuppressive agent with low toxicity

  5. Tratamiento del liquen plano oral: una revisión Treatment of oral lichen planus: a review

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    M.J. García-Pola Vallejo

    2008-02-01

    Full Text Available El objetivo del presente estudio fue realizar una revisión sobre los actuales tratamientos del liquen plano oral (LPO. Antes de iniciar el tratamiento al paciente, debe de realizarse una biopsia para establecer el correcto diagnóstico. Dado que para el LPO no hay tratamiento curativo, el primer objetivo en los pacientes sintomáticos es el efecto paliativo. Entre las alternativas terapéuticas se incluyen: corticosteroides tópicos, sistémicos e intralesionales; retinoides tópicos o sistémicos; ciclosporina tópica, tacrolimus tópico, azatioprina, fototerapia y tratamiento quirúrgico.The aim of the present study was to review about the current treatment of oral lichen planus (OLP. Before a patients is started on therapy a biopsy must be done to establish an accurate diagnosis. Because there is no curative therapy for OLP, the primary goal for symtomatic patients is palliative. Treatment modalities include the use of: topical, systemic and intralesional corticosteroids; topical and systemic retinoids, topical cyclosoporine; topical tacrolimus; azathioprine; phototherapy and surgical procedures.

  6. Evidence-based treatments for pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid: A systematic review

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    Sanjay Singh

    2011-01-01

    Full Text Available Background: Pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita are autoimmune diseases of skin associated with considerable morbidity and sometimes mortality. There is no cure for these diseases. Aims: To summarize evidence-based treatments for these diseases by performing a systematic review. Methods: The research protocol included the following steps: identification of databases to be searched, defining search strategy, searching the databases for references, first-stage screening of the abstracts, second-stage screening of full texts of articles identified after the first-stage screening, data extraction from the identified articles after second-stage screening, quality appraisal of the studies using the Delphi list, and summarizing the findings. Results: No randomized controlled trials of interventions in pemphigus vegetans, pemphigus erythematosus, and epidermolysis bullosa acquisita could be found. After the second-stage screening, 12 randomized controlled trials were analyzed, which included patients with pemphigus vulgaris or pemphigus vulgaris and pemphigus foliaceus, and 7 which included patients with bullous pemphigoid. Conclusions: Number of high-quality randomized controlled trials conducted on pemphigus and bullous pemphigoid is small. Oral corticosteroid along with a steroid-sparing agent appears to be the most effective treatment for pemphigus. Azathioprine may be most effective as a steroid-sparing agent. Topical corticosteroid therapy (as studied is effective for bullous pemphigoid and appears to be superior to oral corticosteroid for extensive disease. Some suggestions about future research are made.

  7. Nodular Epiescleritis Granulomatous Canine. Case Report

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    Camilo Guarín Patarroyo

    2011-12-01

    Full Text Available Granulomatous epiescleritis nodular disease in canines is a very unusual presentation that affects or external fibrous tunic of the eyeball and conjunctiva, which was an increase similar to a unilateral or bilateral tumor. Suspected immune-mediated disease due to lack of identification of an etiologic agent and the response to treatment with immunosuppressive drugs (Couto, 1992. The ideal therapy is the application of steroids via intralesional, topical or systemic, or other immunosuppressants such as cyclosporine and azathioprine; it is still advisable to apply antibiotic is the ideal combination of tetracycline and neomycin (Gilger & Whitley, 1999. The diagnostic method of episcleritis is made by histopathology, which is evident in changes similar to chronic granulomatous inflammation. Are claiming a racial bias in Alsatian, Shepherd Collie Shetland Shepherd, Coker Spaniel, Rottweiler and Labrador Retriever (Gough & Thomas, 2004. The following case is a report of a nodular epiescleritis affecting the cornea, sclera, and the corneoscleral limbus, which describes the diagnosis, signology and treatment.

  8. Atypical Mycobacterial Infection Presenting as Persistent Skin Lesion in a Patient with Ulcerative Colitis

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    Giorgos Bamias

    2011-01-01

    Full Text Available Immunosuppressive drugs are commonly used for the treatment of inflammatory bowel disease. Patients receiving immunosuppressants are susceptible to a variety of infections with opportunistic pathogens. We present a case of skin infection with Mycobacterium chelonae in a 60-year-old Caucasian woman with ulcerative colitis who had been treated with corticosteroids and azathioprine. The disease manifested with fever and rash involving the right leg. Infliximab was administered due to a presumptive diagnosis of pyoderma gangrenosum, leading to worsening of the clinical syndrome and admission to our hospital. Routine cultures from various sites were all negative. However, Ziehl-Neelsen staining of pus from the lesions revealed acid-fast bacilli, and culture yielded a rapidly growing mycobacterium further identified as M. chelonae. The patient responded to a clarithromycin-based regimen. Clinicians should be aware of skin lesions caused by atypical mycobacteria in immunocompromised patients with inflammatory bowel disease. Furthermore, they should be able to thoroughly investigate and promptly treat these conditions.

  9. Macular serpiginous choroiditis

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    Sahu Dinesh

    2002-01-01

    Full Text Available Purpose: To report a variant form of serpiginous choroiditis, that initially or predominantly involved the macular area. Methods: Nine eyes of 6 patients with the macular form of serpiginous choroiditis were evaluated clinically and angiographically in a longitudinal fashion for a period of 12-36 months. The active stage and the recurrences were treated by oral and periocular cortico steroids; and two patients were supplemented with oral azathioprine. Most of these patients were referred to our center with varied diagnoses. Results: In this group, 4 were male and 2 were female with an average age of 30.5 years. Three patients had bilateral macular lesions, two had typical serpiginous choroiditis in the fellow eye and the remaining one had unilateral macular involvement alone. The initial visual acuity was 6/60 or less in 60% eyes whereas the final visual acuity was 6/18 or better in 66% eyes. Angiographic findings were typical of serpiginous choroiditis characterised by early hypofluorescence followed by leakage and staining of the borders and the lesion itself without any evidence of choroidal ischaemia or retinal vascular abnormalities. Conclusion: The macular variant of serpiginous choroiditis can mimic many other macular pathologic lesions, thus posing a diagnostic dilemma. Because of its relentless destructive course, early diagnosis and prompt treatment is required to prevent sight-threatening complications.

  10. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    María Luisa Manzano-Alonso; Gregorio Castellano-Tortajada

    2011-01-01

    Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus (HBV) replication,often accompanied by an increase in serum transaminase levels, and both events occurring in a patient with a previous inactive hepatitis B infection. This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered. It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases. Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis, which are sometimes serious and result in acute liver failure with risk of death, and usually occur in the periods between cycles or at the end of chemotherapy. Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen (HBsAg) or anti-HBc, but much less frequently than chemotherapy treatments. The tumor necrosis factor α inhibitors infliximab, etanercept and adalimumab may cause reactivation of hepatitis B, and the overall frequency with infliximab may be similar (50%-66%) to that caused by chemotherapy. Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs, and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.

  11. Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

    Institute of Scientific and Technical Information of China (English)

    Li-Juan Huang; Qin Zhu; Min Lei; Qian Cao

    2009-01-01

    AIM: To investigate immunosuppressive agents used to treat inflammatory bowel disease (IBD) in East China. METHODS: A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University from June 2000 to December 2007. Data regarding demographic, clinical characteristics and immunosuppressants usage were analyzed. RESULTS: A total of 227 eligible patients were evaluated in this study, including 104 patients with Crohn's disease and 123 with ulcerative colitis. Among the patients, 61 had indications for immunosuppressive agents use. However, only 21 (34.4%) received immunosuppressive agents. Among the 21 patients, 6 (37.5%) received a subtherapeutic dose of azathioprine with no attempt to increase the dosage. Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo, 15 patients went into remission, four patients were not affected and one relapsed. Among these 20 patients, four patients suffered from myelotoxicity and one suffered from hepatotoxicity. CONCLUSION: Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries. Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.

  12. Adverse Event Burden, Resource Use, and Costs Associated with Immunosuppressant Medications for the Treatment of Systemic Lupus Erythematosus: A Systematic Literature Review

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    A. Oglesby

    2013-01-01

    Full Text Available This paper assessed the burden of adverse events (AEs associated with azathioprine (AZA, cyclophosphamide (CYC, mycophenolate mofetil (MMF, methotrexate (MTX, and cyclosporine (CsA in patients with systemic lupus erythematosus (SLE. Thirty-eight publications were included. Incidence of AEs ranged from 42.8% to 97.3%. Common AEs included infections (2.4–77%, gastrointestinal AEs (3.2–66.7%, and amenorrhea and/or ovarian complications (0–71%. More hematological cytopenias were associated with AZA (14 episodes than MMF (2 episodes. CYC was associated with more infections than MMF (40–77% versus 12.5–32%, resp. or AZA (17–77% versus 11–29%, resp.. Rates of hospitalized infections were similar between MMF and AZA patients, but higher for those taking CYC. There were more gynecological toxicities with CYC than MMF (32–36% versus 3.6–6%, resp. or AZA (32–71% versus 8–18%, resp.. Discontinuation rates due to AEs were 0–44.4% across these medications. In summary, the incidence of AEs associated with SLE immunosuppressants was consistently high as reported in the literature; discontinuations due to these AEs were similar across treatments. Studies on the economic impact of these AEs were sparse and warrant further study. This paper highlights the need for more treatment options with better safety profiles.

  13. Optimal Method to Stimulate Cytokine Production and Its Use in Immunotoxicity Assessment

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    Huiming Chen

    2013-08-01

    Full Text Available Activation of lymphocytes can effectively produce a large amount of cytokines. The types of cytokines produced may depend on stimulating reagents and treatments. To find an optimal method to stimulate cytokine production and evaluate its effect on immunotoxicity assessments, the authors analyzed production of IL-2, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, GM-CSF, RANTES and TGF-β in undiluted rat whole blood culture (incubation for 0, 2, 4, 6, 8 or 10 h with different concentrations of PMA/ionomycin, PHA, Con A, LPS and PWM. We also evaluated the effects of cyclosporin A and azathioprine on cytokine production. The results revealed a rapid increase of IL-2, IFN-γ, TNF-α, RANTES and TGF-β secretion within 6 h after stimulation with 25 ng/mL PMA and 1 μg/mL ionomycin. The inhibition of these cytokine profiles reflected the effects of immunosuppressants on the immune system. Therefore, the results of this is study recommend the detection of cytokine profiles in undiluted whole blood stimulated 6 h with 25 ng/mL PMA and 1 μg/mL ionomycin as a powerful immunotoxicity assessment method.

  14. A subset of ulcerative colitis with positive proteinase-3antineutrophil cytoplasmic antibody

    Institute of Scientific and Technical Information of China (English)

    Jin Xu; Chuan-Hua Yang; Xiao-Yu Chen; Xu-Hang Li; Min Dai; Shu-Dong Xiao

    2008-01-01

    A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies.We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission.Four of these 5 patients were steroid-dependence,and immunosuppressants, such as azathioprine and cyclophosphamide, were ineffective. In 3 patients,only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates that ulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients,with additional advantages of having no noticeable sideeffects and less financial burden.

  15. The Use of Immunosuppressant Therapy for Multiple Sclerosis in Italy: A Multicenter Retroprospective Study.

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    Emanuele D'Amico

    Full Text Available Immunosuppressive agents (ISA have been used in multiple sclerosis (MS for decades, frequently as off label licensed therapies. Given the new MS treatment landscape, what place do ISA have in combating MS?We conducted a retrospective multicentre study to investigate the frequency of ISA prescription in 17 Italian MS centres, and to describe the clinical factors related to ISA use.Out of 6,447 MS patients, 2,034 (31.6% were treated with ISA, with Azathioprine being the most frequently used ISA overall. MS patients treated with ISA alone were more frequently affected by the progressive course (both primary and secondary of the disease (RRR 5.82, 95% CI 4.14-8.16, p<0.0001, had higher EDSS (RRR 3.69, 95% CI 2.61-5.21, p<0.0001, higher assignment age (RRR 1.04, 95% CI 1.03-1.06, p<0.0001 than patients treated with only disease modifying drugs (DMDs.Progressive course, higher EDSS, higher assignment age were the strongest predictors of ISA prescription and use in our population.

  16. The effect of somatostatin 201-995 on the early course of porcine pancreaticoduodenal allotransplantation.

    Science.gov (United States)

    Nicholson, C P; Barr, D; Oeltjen, M R; Munn, S R; DiMagno, E P; Carpenter, H A; Sarr, M G; Perkins, J D

    1991-01-01

    This study was undertaken to determine the effects of somatostatin 201-995 (SMS) on the maintenance dose of intravenous cyclosporine and on graft blood flow, exocrine secretion, and rejection after porcine pancreaticoduodenal allotransplantation (PDA). For seven days, 12 pigs (6 control, 6 SMS-treated) were studied to determine the effects of SMS on serum CsA concentrations. Twenty-six pigs (14 control, 12 SMS) with streptozocin-induced diabetes underwent PDA. Blood flow was measured through graft celiac and superior mesenteric arteries 15 and 60 min after reperfusion. SMS (75 micrograms s.c.) was given after the 15-min blood-flow measurement in the SMS group. Sixteen pigs (8 control, 8 SMS) were followed postoperatively with daily measurements of serum glucose and amylase concentrations, and urine amylase and trypsin activities. All pigs were immunosuppressed with azathioprine, prednisone, and i.v. CsA. SMS pigs also received SMS (75 micrograms s.c.) every 8 hr. SMS had no effect on maintenance dose of CsA or on serum amylase, urine amylase, or urine trypsin activities. Mean days to rejection were also not affected. Intraoperative graft blood flow was significantly decreased by SMS, but incidence of graft thrombosis was unchanged. These results suggest that in the porcine PDA model, SMS does not appear to inhibit exocrine secretion and potentially may adversely affect the early course of PDA by decreasing graft blood flow. PMID:1670973

  17. Successful Renal Transplantation in a Patient with Behcet Disease and Hodgkin Lymphoma in Remission

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    Vural Taner YILMAZ

    2011-05-01

    Full Text Available Behcet's disease (BD is an inflammatory multisystemic disease characterized by perivascular inflammation and generally presents with recurrent oral and genital ulcers and uveitis. It is known that BD may also involve the kidneys. Amyloidosis, glomerulonephritis (crescentic, proliferative, IgA nephropathy, interstitial nephritis are commonly described renal lesions which may lead to end-stage renal disease (ESRD in BD. Immunosuppressive therapies used for the treatment of BD may cause malignant diseases (lymphoma, skin and solid organ malignancies, etc. The risk with azathioprin is especially high after 10 years of treatment. Cyclosporine, another immunosuppressive agent frequently used for treatment of BD, also has tumorigenic potential and is associated with renal toxicity and renal failure. Renal transplantation may be performed in patients with malignancies after a 2-5 year complete remission period, although it may differ according to the type of tumor. We report a case of end-stage renal disease and Hodgkin's lymphoma occurring after treatment with immunosuppressive medicine for BD. The patient was successfully treated with renal transplantation.

  18. Pulmonary Langerhans Histiocytosis: an uncommon cause of interstitial pneumonia in a patient with Sjögren syndrome.

    Science.gov (United States)

    González García, Andrés; Callejas Rubio, José Luis; Ríos Fernández, Raquel; Ortego Centeno, Norberto

    2016-03-01

    Sjögren syndrome is a chronic, systemic, and autoimmune disorder that targets exocrine glands by remarkable B cell hyperactivity. Eventually, it is associated with extra-glandular clinical manifestations that affect essentially any organ system, including pulmonary involvement. Interstitial lung disease is one of the most serious pulmonary complications, and the early diagnosis is essential to initiate a prompt therapy. On the other hand, Sjögren syndrome could present concomitantly with several rheumatologic diseases such as systemic lupus erythematosus or rheumatoid arthritis. Pulmonary Langerhans Histiocytosis is a rare clonal proliferative disease characterized by pulmonary involvement by cells phenotypically similar to Langerhans cells. We describe the case of a nonsmoker 62-year-old woman with Sjögren syndrome who presented concomitantly a Pulmonary Langerhans Histiocytosis mimicking a pulmonary complication of its Sjögren. Fortunately, she had a well response to corticosteroids and azathioprine regimen. The aim of the paper is to emphasize the importance of the good differential diagnosis related to the pulmonary involvement. To the best of our knowledge, this is the first description of these two entities in the literature. PMID:25894436

  19. Long-term outcome of intensive initial immunosuppression protocol in pediatric deceased donor renal transplantation.

    LENUS (Irish Health Repository)

    Olaitan, Oyedolamu K

    2010-02-01

    To report the long-term outcome of deceased donor kidney transplantation in children with emphasis on the use of an intensive initial immunosuppression protocol using R-ATG as antibody induction. Between January 1991 and December 1997, 82 deceased donor kidney transplantations were performed in 75 pediatric recipients. Mean recipient age at transplantation was 12.9 yr and the mean follow-up period was 12.6 yr. All patients received quadruple immunosuppression with steroid, cyclosporine, azathioprine, and antibody induction using R-ATG-Fresenius. Actual one, five, and 10 yr patient survival rates were 99%, 97%, and 94%, respectively; only one patient (1.2%) developed PTLD. Actual one, five, and 10 yr overall graft survival rates were 84%, 71%, and 50%, respectively; there were five cases (6%) of graft thrombosis and the actual immunological graft survival rates were 91%, 78%, and 63% at one, five, and 10 yr, respectively. The use of an intensive initial immunosuppression protocol with R-ATG as antibody induction is safe and effective in pediatric recipients of deceased donor kidneys with excellent immunological graft survival without an increase in PTLD or other neoplasms over a minimum 10-yr follow up.

  20. Efficient DNA interstrand crosslinking by 6-thioguanine and UVA radiation.

    Science.gov (United States)

    Brem, Reto; Daehn, Ilse; Karran, Peter

    2011-08-15

    Patients taking the immunosuppressant and anticancer thiopurines 6-mercaptopurine, azathioprine or 6-thioguanine (6-TG), develop skin cancer at a very high frequency. Their DNA contains 6-TG which absorbs ultraviolet A (UVA) radiation, and their skin is UVA hypersensitive, consistent with the formation of DNA photodamage. Here we demonstrate that UVA irradiation of 6-TG-containing DNA causes DNA interstrand crosslinking. In synthetic duplex oligodeoxynucleotides, the interstrand crosslinks (ICLs) can form between closely opposed 6-TG bases and, in a less favoured reaction, between 6-TG and normal bases on the opposite strand. In vivo, UVA irradiation of cultured cells containing 6-TG-substituted DNA also causes ICL formation and induces the chromosome aberrations that are characteristically associated with this type of DNA lesion. 6-TG/UVA activates the Fanconi anemia (FA) pathway via monoubiquitination of the FANCD2 protein. Cells defective in the FA pathway or other factors involved in ICL processing, such as XPF and DNA Polζ, are all hypersensitive to killing by 6-TG/UVA-consistent with a significant contribution of photochemical ICLs to the cytotoxicity of this treatment. Our findings suggest that sunlight-exposed skin of thiopurine treated patients may experience chronic photochemical DNA damage that requires constant intervention of the FA pathway. PMID:21723207

  1. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  2. Treatment of Intraepidermal Autoimmune Bullous Diseases Sürekli Eğitim

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    Tamer İrfan Kaya

    2011-06-01

    Full Text Available Pemfigus is an autoimmune bullous skin disease, characterized by intraepidermal blisters. It is a severe and potentially life-threatening chronic disease with blisters and erosions on the mucosae and the skin. Treatment options do not differ for two most common types of pemphigus, pemphigus vulgaris and pemphigus foliaceus, except that the latter is usually less resistant to treatment and corticosteroids can often be started at lower doses. Systemic corticosteroids are still the most widely used drugs in the treatment of pemphigus and continue to be the mainstay of therapy for this disease. Adjuvant drugs are commonly used in combination with the aims of increasing efficacy and of having a steroid-sparing action, thereby allowing reduced corticosteroid side-effects. Mortality and complete remission rates have improved since the introduction of adjuvant drugs to pemphigus. Adjuvant drugs include immunoadsorbtion, corticosteroid pulse therapy, intravenous immunoglobulin (IVIG, immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate mofetil and and anti-CD20 monoclonal antibody (rituximab. The lack of consensus in the published literature about the treatment of this disorder is responsible for different treatment strategies. Treatments need to be chosen after careful consideration of the potential benefits and side effects according to the patients’ medical condition. Here, both conventional therapies and novel treatment regimens for pemphigus are discussed. (Turkderm 2011; 45 Suppl 1: 44-53

  3. Successful Discontinuation of Infliximab in a Refractory Case of Vasculo-Behçet Disease

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    Akihiro Nakamura

    2016-01-01

    Full Text Available Reports have shown that antitumor necrosis factor alpha (anti-TNF-α agents including infliximab (IFX can dramatically suppress the disease activity of refractory vasculo-Behçet disease (vasculo-BD. However, it is completely unknown whether we can discontinue anti-TNF-α agents under clinical remission. A 31-year-old patient with vasculo-BD was initially treated with a high dose of steroid and intravenous cyclophosphamide therapy. Six months later, however, the disease recurred. IFX was administered and immediately the disease activity was reduced. Fortunately, we could discontinue IFX after 18-month remission and no recurrence has been observed. Based on previous reports and our patient, all patients who could discontinue IFX sustained clinical remission for at least one year, continued taking immunosuppressive agents such as methotrexate and azathioprine, and had vascular involvements only in non-life-threatening major vessels such as leg or arm arteries/veins. This is a report suggesting the possibility of discontinuation of IFX in vasculo-BD.

  4. Pemphigus: Our Clinical Experiences and Treatment Alternatives in the Resistant Cases

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    Soner Uzun

    2008-08-01

    Full Text Available Pemphigus is an autoimmune blistering disease affecting skin and mucous membranes which threatens the life. In our country it is the most common disease in this group. In our region, among the pemphigus cases, the most common variant is pemphigus vulgaris. Pemphigus vulgaris consists of the 80% of pemphigus cases and it occurs 10 times more than pemphigus foliaceus. Treatment of pemphigus is accepted as a miracle in clinical medicine. The disease, which had an almost always fatal outcome, had been turned to the disease which long-term remissions or “cure” can be achievable. However, in the past the cause of the death was the disease itself, nowadays, with decreasing frequency, all of the mortalities is due to the treatment side effects. In treatment of pemphigus which drug to use and when to use it has varieties according to the intended effect. Corticosteroids are the main treatment; besides IVIg, plasmapheresis or pulse steroid prefers to control the disease rapidly. Mainly immunosuppressive agents (azathioprine, methotrexate, cyclophosphamide, cyclosporine, and mycophenolate besides gold, dapsone, antibiotics or rituximab are using for late-term effect and to reduce the corticosteroid requirement.

  5. Pulse cyclophosphamide therapy for inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Zsolt Barta; László Tóth; Margit Zeher

    2006-01-01

    AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.

  6. Pediatric live-donor kidney transplantation in Mansoura Urology & Nephrology Center: a 28-year perspective.

    Science.gov (United States)

    El-Husseini, Amr A; Foda, Mohamed A; Bakr, Mohamed A; Shokeir, Ahmed A; Sobh, Mohamed A; Ghoneim, Mohamed A

    2006-10-01

    Our objective was to evaluate our overall experience in pediatric renal transplantation. Between March 1976 and March 2004, 1,600 live-donor kidney transplantations were carried out in our center; 216 of the patients were 18 years old or younger (mean age 12.9 years). There were 136 male patients and 80 female patients. The commonest causes of end-stage renal disease (ESRD) were renal dysplasia (22%), nephrotic syndrome (20%), hereditary nephritis (16%), and obstructive uropathy (16%). Of the donors, 94% were one-haplotype matched and the rest were identical. Pre-emptive transplantation was performed in 51 (23%) patients. Triple-therapy immunosuppression (prednisone + cyclosporine + azathioprine) was used in 78.2% of transplants. Rejection-free recipients constituted 47.7%. Hypertension (62%) was the commonest complication. A substantial proportion of patients (48%) were short, with height standard deviation score (SDS) less than -1.88. The overall infection rate was high, and the majority (53%) of infections were bacterial. The graft survival at 1 year, 5 years and 10 years were 93.4%, 73.3% and 48.2%, respectively, while the patients' survival at 1, 5 and 10 years were 97.6%, 87.8% and 75.3%, respectively. Despite long-term success results of pediatric renal transplantation in a developing country, there is a risk of significant morbidity. PMID:16791608

  7. Comparative study of efficacy of excimer light therapy vs intralesional triamcinolone vs topical 5% minoxidil: an observational study

    Directory of Open Access Journals (Sweden)

    Zonunsanga

    2015-01-01

    Full Text Available Introduction: Alopecia Areota is a chronic inflammatory disease that involves hair follicles, and sometimes nails, caused by T-cell mediated autoimmune mechanism. Current treatment modalities includes corticosteroids (oral, topical or intralesional, Minoxidil, Contact sensitizers like DNCB, DPCP and SADBE, Immunosuppressants like Methotrexate or Azathioprine, DMARDs like Sulfasalazine, and Phototherapy. Materials and methods: After taking consent, 40 patients treated with excimer light, 46 patients treated with triamcinolone injection intralesionally and 14 patients treated with topical minoxidil 5% were compared by their photographs taken prior to treatments, at 2 months and 6 months follow up. Results: Among the excimer group, 21/32 (61.76% with single patch and 1/6 (16.67% with multiple patches achieved >50% hair regrowth. Among Triamcinolone group, 23/30 (76.67% with single patch and 10/16 (62.5% with multiple patches achieved >50% hair regrowth. Among the Minoxidil group, 4/12 (33.33% with single patch and none .i.e 0/2 with multiple patches achieved >50% regrowth. Conclusion: After comparing the efficacy of Excimer light therapy, intralesional triamcinolone and 5% Minoxidil, it was concluded that intralesional triamcinolone seems to be the most efficacious. Multiple patches were more resistant than single patch. Scalp response much better than beard.

  8. Influence of patient medication on diagnostic accuracy in nuclear medicine

    International Nuclear Information System (INIS)

    Full text. In recently years many reports have published of unusual or unexpected changes in the biodistribution of radiopharmaceuticals which do not correlate with normality or disease. Whilst many extraneous factors can alter tracer kinetics it has become apparent that concomitant patient medication can be such a factor. If the clinician is unaware that patient is on drug therapy difficulties arise in making a accurate diagnosis. Most drug/radio pharmaceutical effects are those in which the functional status of the organ is altered as a result of the pharmacological action of the drug. Examples here are narcotic analgesics such as methadone, pethidine and morphine which cause spasm of the biliary tract due to contraction of the sphincter of Oddi and an altered transit time of the technetium labelled tracer. Cytotoxic drugs such as cyclophosphamide and vincristine can markedly affect tumour uptake of 67-gallium so that litter or no activity is taken up by the tumour. Nifedipine, because of its powerful calcium channel blocking activity is known to affect the radiolabelling of white cells and red cells and to affect uptake of Tc-99 m MDP into bones. Other important and confusing effects are caused by phenothiazines, cimetidine and oral contraceptives. In recent years it has been reported that drugs such as cyclosporin, azathioprine and heparin and derivatives of heparin can markedly interfere with cell labelling procedures. This review will consider some of the clinical effects of drugs and will also address the reporting of instances of drug/radio pharmaceutical interactions

  9. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    Science.gov (United States)

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse. PMID:26804376

  10. Crohn’s disease and Takayasu’s arteritis: An uncommon association

    Science.gov (United States)

    Taddio, Andrea; Maschio, Massimo; Martelossi, Stefano; Barbi, Egidio; Ventura, Alessandro

    2013-01-01

    Takayasu’s arteritis (TA) and Crohn’s disease (CD) are two rare autoimmune disorders; however some reports describe the presence of both diseases in the same patient. This finding has suggested the possibility that both diseases could share some common etiologic origin. We describe a case of a 13-year-old male affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and elevation of inflammatory markers. Clinical and histological features from colonic specimens were consistent with CD. Treatment with steroids and azathioprine was started, however disease flared every time steroids were tapered. One year later, while still on treatment, he came back to our attention for dyspnea at rest and at night, tiredness and weakness. At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit. A transthoracic echocardiography showed mild aortic valve insufficiency, left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch. A computed tomography scan showed abdominal aorta thickening, dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA associated with CD was diagnosed and medical treatment with cyclophosphamide, steroids and aminosalicylic acid was started, with good clinical response at 6 mo follow-up. We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease. PMID:24124342

  11. Crohn's disease and Takayasu's arteritis: an uncommon association.

    Science.gov (United States)

    Taddio, Andrea; Maschio, Massimo; Martelossi, Stefano; Barbi, Egidio; Ventura, Alessandro

    2013-09-21

    Takayasu's arteritis (TA) and Crohn's disease (CD) are two rare autoimmune disorders; however some reports describe the presence of both diseases in the same patient. This finding has suggested the possibility that both diseases could share some common etiologic origin. We describe a case of a 13-year-old male affected by CD characterized by fever, diarrhea, weight loss, abdominal pain and elevation of inflammatory markers. Clinical and histological features from colonic specimens were consistent with CD. Treatment with steroids and azathioprine was started, however disease flared every time steroids were tapered. One year later, while still on treatment, he came back to our attention for dyspnea at rest and at night, tiredness and weakness. At physical examination a diastolic heart murmur was found as well as a left carotid artery bruit. A transthoracic echocardiography showed mild aortic valve insufficiency, left ventricular hypertrophy and a dilated ascending aorta with same findings at the aortic arch. A computed tomography scan showed abdominal aorta thickening, dilated thoracic aorta and the presence of a thoracic aortic aneurysm. TA associated with CD was diagnosed and medical treatment with cyclophosphamide, steroids and aminosalicylic acid was started, with good clinical response at 6 mo follow-up. We discuss the presence of possible common causes for the two diseases and the importance of differential diagnosis in those patients characterized for intractable disease. PMID:24124342

  12. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  13. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  14. Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Bipul Nath

    2013-01-01

    Full Text Available The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed , prolonged absorption time, decreased , and absorption rate constant (Ka, indicating a reduced systemic toxicity of the drug as compared to other dosage forms.

  15. Benign and malignant skin lesions in renal transplant recipients

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    Ghaninejad H

    2009-01-01

    Full Text Available Background: Skin lesions - benign and malignant - occur frequently in organ transplant recipients receiving long-term immunosuppressive therapy. These patients are at greater risk of skin cancers. Aims: To study dermatologic problems in renal transplant recipients (RTRs. Methods: One hundred patients (53 men and 47 women were consecutively examined for benign and malignant skin complications since transplantation in Razi Hospital in Tehran Medical University. The main immunosuppressive therapy regimen in these patients was a combination of prednisolone, azathioprine, and cyclosporine. Results: The early and most common complication was cosmetic side effects that occurred in 98% patients. Skin infections occurred in 83% of the patients and most of them were viral infections (65%, especially of human papilloma viruses (HPVs in 40% of the patients. We found six cases of malignancy in these patients in that four cases were skin cancers, including one case of SCC, one BCC, and two cases of Kaposi′s sarcoma. Dermatologic problems occur most frequently in RTRs, especially skin cancers which have higher frequency in these patients than general population, particularly, Kaposi sarcoma. Sun exposure has an important role in developing epithelial skin cancers following transplantation. The age of developing skin cancer in these patients was early than normal population. Conclusion: Our results emphasize the importance of dermatologic examinations and monitoring RTRs to obtain an early diagnosis and treatment of cutaneous manifestations.

  16. Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services.

    Science.gov (United States)

    Hicks, J Kevin; Stowe, David; Willner, Marc A; Wai, Maya; Daly, Thomas; Gordon, Steven M; Lashner, Bret A; Parikh, Sumit; White, Robert; Teng, Kathryn; Moss, Timothy; Erwin, Angelika; Chalmers, Jeffrey; Eng, Charis; Knoer, Scott

    2016-08-01

    The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist-managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, and TPMT-thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty-three custom rules and alerts (20 for TPMT-thiopurines, 8 for HLA-B*57:01-abacavir, and 35 for HLA-B*15:02-anticonvulsants) were developed and deployed to the EHR for the purpose of providing point-of-care pharmacogenomic decision support. In addition, a pharmacist and physician-geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented. PMID:27312955

  17. Progressive Multifocal Leukoencephalopathy and Systemic Lupus Erythematosus: Focus on Etiology

    Directory of Open Access Journals (Sweden)

    Shala Ghaderi Berntsson

    2016-03-01

    Full Text Available Progressive multifocal leukoencephalopathy (PML caused by reactivation of the JC virus (JCV, a human polyomavirus, occurs in autoimmune disorders, most frequently in systemic lupus erythematosus (SLE. We describe a HIV-negative 34-year-old female with SLE who had been treated with immunosuppressant therapy (IST; steroids and azathioprine since 2004. In 2011, she developed decreased sensation and weakness of the right hand, followed by vertigo and gait instability. The diagnosis of PML was made on the basis of brain MRI findings (posterior fossa lesions and JCV isolation from the cerebrospinal fluid (700 copies/ml. IST was immediately discontinued. Cidofovir, mirtazapine, mefloquine and cycles of cytarabine were sequentially added, but there was progressive deterioration with a fatal outcome 1 year after disease onset. This report discusses current therapeutic choices for PML and the importance of early infection screening when SLE patients present with neurological symptoms. In the light of recent reports of PML in SLE patients treated with rituximab or belimumab, we highlight that other IST may just as well be implicated. We conclude that severe lymphopenia was most likely responsible for JCV reactivation in this patient and discuss how effective management of lymphopenia in SLE and PML therapy remains an unmet need.

  18. Induction of specific unresponsiveness to heart allografts in mongrel dogs treated with total lymphoid irradiation and antithymocyte globulin

    Energy Technology Data Exchange (ETDEWEB)

    Strober, S.; Modry, D.L.; Hoppe, R.T.; Pennock, J.L.; Bieber, C.P.; Holm, B.I.; Jamieson, S.W.; Stinson, E.B.; Schroder, J.; Suomalainen, H.; Kaplan, H.S.

    1984-02-01

    The survival of heterotopic heart allografts was determined in mongrel dogs treated with total lymphoid irradiation (TLI) alone or in combination with other immunosuppressive agents. TLI alone (total dose, 1800 rad) minimally prolonged graft survival as compared with untreated controls. However, marked synergy was observed when TLI was combined with a 10-day post-transplant course of rabbit anti-dog thymocyte globulin (ATG). Approximately 40% of recipients given TLI and ATG showed specific unresponsiveness, as judged by the lack of rejection on serial biopsies for more than 1 year and the prompt rejection of third party hearts. The addition of post-transplant azathioprine (90 to 180 days) to the TLI and ATG regimen increased the mortality of recipients and reduced the fraction of dogs showing specific unresponsiveness. Infusion of donor bone marrow cells at the time of heart transplantation failed to induced specific unresponsiveness in recipients given TLI alone or TLI in combination with post-transplant methotrexate, cyclosporine A, or ATG. The results indicate that the combination of TLI and a brief course of ATG without marrow transplantation was the most effective regimen for the induction of specific unresponsiveness in mongrel dogs.

  19. Multiple sclerosis and HLA-B27 negative sacroiliitis in a Crohn’s disease patient

    Directory of Open Access Journals (Sweden)

    K.H. Katsanos, N. Tzambouras, E.V. Tsianos

    2007-03-01

    Full Text Available SUMMARY A relationship between inflammatory bowel disease and MS is supported by a higher than expected coexistence of these diseases among families and individuals. A 32 year-old male with Crohn’s disease of the terminal ileum diagnosed 4 years earlier and HLA-B27 bilateral sacroiliitis diagnosed two years earlier, was admitted to our hospital because of an acute episode of blurred vision. In addition the patient complained of urine incontinence. Before this admission the patient had been elsewhere administered three doses of Remicade and 16mg of methylprednisolone p.os. During admission the diagnosis of multiple sclerosis was made (MRI and IgG Index and Remicade was discontinued. The patient was started on therapy with interferon-beta for MS, oxybutynin hydrochloride (10mg/day for urine incontinence, prednizolone (10mg/day, methotrexate (10mg/week and azathioprine (100mg/day for Crohn’s disease and is now in excellent clinical status. To the best of our knowledge this is one of the very rare cases of Crohn’s disease with HLA-B27 negative sacroiliitis preceding multiple sclerosis diagnosis. Key words: Crohn’s disease, inflammatory bowel disease, ulcerative colitis, multiple sclerosis, Remicade

  20. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-10-22

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweek mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy.

  1. Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies

    International Nuclear Information System (INIS)

    Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation

  2. Total lymphoid irradiation and discordant cardiac xenografts

    International Nuclear Information System (INIS)

    Total lymphoid irradiation can prolong concordant cardiac xenografts. The effects of total lymphoid irradiation in a discordant xenograft model (guinea pig to rat) were studied with and without adjuvant pharmacologic immunosuppression. Inbred Lewis rats were randomly allocated to one of four groups. Group 1 (n = 6) served as a control group and rats received no immunosuppression. Group 2 (n = 5) received triple-drug therapy that consisted of intraperitoneal azathioprine (2 mg/kg), cyclosporine (20 mg/kg), and methylprednisolone (1 mg/kg) for 1 week before transplantation. Group 3 animals (n = 5) received 15 Gy of total lymphoid irradiation in 12 divided doses over a 3-week period. Group 4 (n = 6) received both triple-drug therapy and total lymphoid irradiation as described for groups 2 and 3. Complement-dependent cytotoxicity assay was performed to determine if a correlation between complement-dependent cytotoxicity and rejection-free interval existed. Rejection was defined as cessation of graft pulsation and was confirmed by histologic test results. Only groups 1 and 2 showed a difference in survival (group 1, 6.9 +/- 1.0 minutes; group 2, 14.2 +/- 2.7 minutes, p = 0.02). Although total lymphoid irradiation did decrease complement-dependent cytotoxicity, linear regression revealed no correlation between complement-dependent cytotoxicity and graft survival (coefficient of correlation, 0.30). Unlike concordant cardiac xenografts, total lymphoid irradiation with or without triple-drug therapy does not prolong graft survival

  3. Case of acute hepatitis E with concomitant signs of autoimmunity

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    Catarina Lima Vieira

    2013-01-01

    Full Text Available Sporadic cases of acute viral hepatitis E have been described in developed countries, despite the more common occurrence in endemic areas and developing countries. We present the case of a 58 years old Portuguese female, with no epidemiological relevant factors, admitted with acute hepatitis with positive anti-nuclear antibodies, anti-smooth muscle antibody and high serum gamma globulin (> 1.5 fold increase. Serologies for hepatitis A virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, hereditary sensory neuropathy and varicella zoster virus were negative. Liver biopsy histology revealed changes compatible with autoimmune hepatitis. Prednisolone and azathioprine was started. She tested positive for immunoglobulin M anti hepatitis E virus (HEV with detectable viremia by reverse transcription polymerase chain reaction (RT-PCR technique. HEV-RNA was confirmed through RT-PCR in a liver specimen, establishing the diagnosis of acute hepatitis E. Immunosuppression was stopped. She clinically improved, with resolution of laboratory abnormalities. Therefore, we confirmed acute hepatitis E as the diagnosis. We review the literature to elucidate about HEV infection and its autoimmune effects.

  4. A cell culture assay for the detection of cardiotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Loew-Friedrich, Iv.; von Bredow, F.; Schoeppe, W. (Department of Nephrology, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main (Germany))

    1991-04-01

    An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. The authors propose the use of shock protein formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing shock protein formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of shock proteins. Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes shock protein formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce shock protein synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive.

  5. Historia del tratamiento de las vasculitis primarias History of treatment of primary vasculitis

    Directory of Open Access Journals (Sweden)

    Antonio Iglesias-Gamarra

    2012-07-01

    Full Text Available Las vasculitis primarias constituyen un grupo de enfermedades reumáticas con expresión clínica variable y pronóstico reservado cuando no se tratan adecuadamente. En esta revisión haremos un análisis pormenorizado del tratamiento en las diferentes formas de vasculitis primaria, iniciando con el uso de los corticoides, desde casi su descubrimiento en 1949, pasando por otros inmunosupresores como: ciclofosfamida, metotrexate, azatioprina, mofetil, micofenolato, al igual que medicamentos biológicos como rituximab y anti-TNF. Una mención especial se hace sobre las guías de tratamientos para las vasculitis, tanto de grandes como de pequeños vasos, implementadas desde 2009 por el Grupo Europeo de Estudio de las Vasculitis.Primary vasculitis is one of the rheumatic diseases with variable clinical expression and poor prognosis when not treated properly. In this review we analyze detailed treatment of this disease in different forms of primary vasculitis, starting with the use of corticosteroids from almost its discovery in 1949, to other immunosuppressant's such as cyclophosphamide, methotrexate, azathioprine, mycophenolate mofetil, as well as biological drugs such as rituximab and anti-TNF. Special mention is made on the guidelines of treatment for vasculitis of both large and small vessel, implemented since 2009 by the European Group Study of Vasculitis.

  6. Inhibition of the immune response to experimental fresh osteoarticular allografts

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. 3d.; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M. (Univ. of California, Davis, Sacramento (USA))

    1989-06-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

  7. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Waer, M.; Vanrenterghem, Y.; Ang, K.K.; van der Schueren, E.; Michielsen, P.; Vandeputte, M.

    1984-02-01

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced.

  8. A case of aortitis syndrome diagnosed by digital subtraction angiography

    International Nuclear Information System (INIS)

    A 45-year-old female was admitted to our hospital with complaints of anemia, hypertension, and a dull, throbbing pain in the right side of the neck. On physical examination, a pulsating tumor in the right side of the neck and a ''to-and-fro'' murmur at the right 2nd intercostal space were noted. Laboratory tests revealed ESR 90 mm/hour and CRP 5+. Digital subtraction angiography (DSA) showed an aneurysm distal to the narrowing of the right common carotid artery, in addition to winding and narrowing of the right vertebral and the left common carotid arteries. These findings are typical of Type I aortitis syndrome. Aortogram showed aortic regurgitation (AR). Furthermore, we found the presence of HLA Bw52 and a conspicuous increase of tromboxane B2. Treatment involving a combination of prednisolone, azathioprine and estriol was effective, resulting in marked improvement of the patient's general condition as well as laboratory test results. In cases of aortitis syndrome combined with an aneurysm of a large artery and AR, direct opacification of the aorta with a catheter is occasionally hazardous and is difficult to perform repeatedly. DSA is useful in such circumstances because it can be performed repeatedly with little risk and it offers an image as clear as these obtained by direct injection of contrast medium in the aorta. (author)

  9. 2000-centiGray total lymphoid irradiation for refractory rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Trentham, D.E.; Belli, J.A.; Bloomer, W.D.; Anderson, R.J.; Lane, H.; Reinherz, E.L.; Austen, K.F.

    1987-09-01

    Because toxicity with the use of 3000 centiGray (cGy) of total lymphoid irradiation (TLI) was observed in an earlier study, 2000-cGy treatments were delivered in a 2-portal format to 7 patients and in a modified 3-portal fashion to 6 patients, as part of a randomized, investigator-blinded trial of TLI treatment for refractory rheumatoid arthritis. Analysis of combined data from the 13 patients revealed statistically significant improvement in 5 clinical indicators of disease activity at the end of TLI and 6 and 12 months later, accompanied by T4-specific immunosuppression. Management considerations resulted in the introduction of prednisone therapy in 5 patients, methotrexate in 4, and azathioprine in 1 during the interval of 8-12 months post-TLI. Herpes zoster occurred in 5 patients prior to the initiation of this additional therapy. These data indicate that, in patients with rheumatoid arthritis, a TLI dose of 2000 cGy is sufficient to produce measurable benefit that lasts for 6 months, and that the improvement can be maintained at 12 months by the use of prednisone and methotrexate.

  10. Comparison of the immunosuppressive effect of fractionated total lymphoid irradiation (TLI) vs conventional immunosuppression (CI) in renal cadaveric allotransplantation

    International Nuclear Information System (INIS)

    Beginning in November 1981, eight patients with end stage diabetic nephropathy underwent renal cadaveric transplantation after TLI. Transplantation was done between 2 to 11 days after the end of a fractionated TLI to a total dose of 20 to 30 Gy. During the same observation period, 60 nondiabetic patients with end stage renal disease of different origin also received a cadaveric kidney graft, with a conventional regimen of immunosuppression that consists of anti-lymphocyte-globulin, tapering high doses of prednisone, and azathioprine. Phytohemagglutinin (PHA)-, concanavalin A (con A)-, and pokeweed mitogen (PWM)-induced blastogenesis, as well as the mixed lymphocyte reaction (MLR) and the cell-mediated lympholysis (CML) decreased progressively during the first months after conventional immunosuppression to 50% of the pretransplantation level, and remained there for the first year after transplantation. These tests were much more impaired after TLI and again no recovery occurred during the first year. In the clinic, the more profound immunosuppression in TLI patients was more frequently associated with viral infections (cytomegalovirus and herpes zoster). The incidence of rejections, however, was somewhat less frequent in the TLI-treated group and occurred significantly later. After TLI, the mean cumulative dose of steroids needed for kidney transplantation during the first year after transplantation could be substantially reduced

  11. Clinical features and outcomes of ANCA-associated renal vasculitis

    Directory of Open Access Journals (Sweden)

    Sidy Mohamed Seck

    2012-01-01

    Full Text Available To determine the patterns and outcomes of the pauci-immune vasculitis in the nephrology department at hospital La Conception in Marseille, we conducted a retrospective study including all patients with diagnosis of pauci-immune renal vasculitis between January 1, 2000 and December 31, 2007. Among 33 cases, 25 were diagnosed as Wegener granulomatosis (WG, seven as microscopic polyangitis (MPA and one as Churg-Strauss syndrome (SCS. The median age of the patients was 57.7 years and the sex-ratio (M/F was 1.6. The visceral mani-festations included kidneys (100% of patients, lungs (75%, ENT (52% of WG, and nervous system (57% of MPA. The mean serum creatinine at admission was 3.3 mg/dL. Renal biopsies revealed a pauci-immune crescentic gromerulonephritis in 96% of the cases. Two patients with WG received plasmapheresis and seven patients required emergency hemodialysis. Induction therapy comprised cyclophosphamide IV and corticosteroids, while maintenance therapy included azathioprine for the majority of patients. Eighty four percent of the patients experienced complete remission after induction therapy. During maintenance therapy relapses were more frequent among patients with MPA (28% compared to WG cases (12%. After 35 months of follow-up, eight patients ended on chronic hemodialysis, and five patients died. ANCA associated vasculitis are frequent in our patients. Long-term outcomes are relatively good despite a mortality rate of 15% and 25% of the patients entering dialysis after three years of follow-up.

  12. Are we giving biologics too late? The case for early versus late use

    Directory of Open Access Journals (Sweden)

    Elena Ricart, Orlando García-Bosch, Ingrid Ordás, Julián Panés

    2008-09-01

    Full Text Available Corticosteroids and immunomodulators have been the mainstay therapies for Crohn’s disease. Corticosteroids are highly effective to control symptoms in the short-term, but they are not effective in maintaining remission, they heal the mucosa in a reduced proportion of cases, and long-time exposure is associated with an increased risk of infections and mortality. Immunomodulators, azathioprine and methotrexate, heal the mucosa in a higher proportion of patients that corticosteroids but their onset of action is slow and they benefit less than half of patients with Crohn’s disease. In the last decade, medical therapy for Crohn’s disease has experienced a remarkable change due to the introduction of biologic therapy, and particularly the use of anti-tumour necrosis factor-alpha agents. Infliximab, adalimumab, and certolizumab pegol have demonstrated efficacy for induction and maintenance of remission in active Crohn’s disease. These agents have raised the bar for what is a suitable symptomatic response in Crohn’s disease and modification of the natural history of the disease has become a major goal in the treatment of Crohn’s disease. There are several data in the literature that suggest that early use of biologic therapy and achievement of mucosal healing contribute to disease course modification. However, many questions on early biological therapy for Crohn’s disease remain still unanswered.

  13. Immunosuppressive agents prevent guanethidine-induced destruction of rat sympathetic neurons

    International Nuclear Information System (INIS)

    Chronic administration of guanethidine to rats causes destruction of peripheral sympathetic neurons. Neuronal destruction characterized morphologically by small cell infiltration and the reduction in the number of neurons within sympathetic ganglia, and biochemically by a marked reduction in tyrosine hydroxylase activity, occurred reproducibly by day 7 of treatment following 5 daily injections of 50 mg/kg guanethidine sulfate. Several observations in the literature suggested that guanethidine-induced destruction may occur by an immunologically mediated mechanism. Experiments were therefore designed to test the effects of immunosuppressive agents on guanethidine sympathectomy. A single exposure to either γ-irradiation or cyclophosphamide, administered 8 h prior to the initiation of guanethidine treatment, protected against guanethidine-induced destruction in a dose-related manner and was virtually complete with either 900 rads of irradiation or with 100 or 150 mg/kg of cyclophosphamide. Cyclophosphamide afforded complete protection only if administered immediately prior to guanethidine treatment suggesting that it was acting during the proliferative phase of an immune response rather than non-specifically. Pretreatment with either irradiation or cyclophosphamide had no effect on the sympathectomy produced by treatment with either 6-hydroxydopamine or antibodies to nerve growth factor, nor did it prevent the accumulation of guanethidine within the sympathetic ganglia. Concurrent treatment with either azathioprine or dexamthazone also provided partial protection against guanethidine sympathectomy. These results strongly suggest that the destruction of sympathetic neurons induced by guanethidine occurs by immunologically mediated mechanism. (Auth.)

  14. Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab

    Directory of Open Access Journals (Sweden)

    Ileana Duca

    2013-01-01

    Full Text Available Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis. Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective. We describe a patient with long-standing ulcerative colitis, which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis (biochemical stage II/IV in the course of his pancolitis. Treatment with infliximab (5 mg/kg as an induction dose followed by maintenance doses every two months was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprine-related hepatic toxicity. At present, after two years of follow-up, the patient is asymptomatic with normal liver tests and complete resumption of daily life activities. This case draws attention to the usefulness of anti-tumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.

  15. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions.

    Science.gov (United States)

    Czaja, Albert J

    2016-03-23

    Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms. PMID:26934884

  16. Case of aortitis syndrome diagnosed by digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Tamaki, Atsushi; Sakai, Masashi; Yano, Kimio

    1984-11-01

    A 45-year-old female was admitted to our hospital with complaints of anemia, hypertension, and a dull, throbbing pain in the right side of the neck. On physical examination, a pulsating tumor in the right side of the neck and a ''to-and-fro'' murmur at the right 2nd intercostal space were noted. Laboratory tests revealed ESR 90 mm/hour and CRP 5+. Digital subtraction angiography (DSA) showed an aneurysm distal to the narrowing of the right common carotid artery, in addition to winding and narrowing of the right vertebral and the left common carotid arteries. These findings are typical of Type I aortitis syndrome. Aortogram showed aortic regurgitation (AR). Furthermore, we found the presence of HLA Bw52 and a conspicuous increase of tromboxane B/sub 2/. Treatment involving a combination of prednisolone, azathioprine and estriol was effective, resulting in marked improvement of the patient's general condition as well as laboratory test results. In cases of aortitis syndrome combined with an aneurysm of a large artery and AR, direct opacification of the aorta with a catheter is occasionally hazardous and is difficult to perform repeatedly. DSA is useful in such circumstances because it can be performed repeatedly with little risk and it offers an image as clear as these obtained by direct injection of contrast medium in the aorta. (author).

  17. Clinical and immunological studies of cadaveric renal transplant recipients given total-lymphoid irradiation and maintained on low-dose prednisone

    Energy Technology Data Exchange (ETDEWEB)

    Saper, V.; Chow, D.; Engleman, E.D.; Hoppe, R.T.; Levin, B.; Collins, G.; Strober, S.

    1988-03-01

    Twenty-five recipients of cadaveric renal transplants were given total lymphoid irradiation (TLI), perioperative antithymocyte globulin, and low-dose prednisone as the sole maintenance immunosuppressive drug. Nine patients were diabetic, and follow-up was between 19 and 37 months. One-year graft and patient survival was 76% and 87%, respectively, Serious complications included four deaths from cardiovascular disorders, and two deaths from viral infections. Studies of peripheral blood T cell subsets showed a prolonged reduction in the absolute number of helper (Leu-3+) cells, and a rapid recovery of cytotoxic/suppressor (Leu-2+) cells. Analysis of the latter subset, using the monoclonal antibody 9.3, showed that the ratio of suppressor/cytotoxic cells was approximately 10:1. The normal ratio is 1:1. The mean mixed leukocyte reaction remained below 30% of the pre-TLI value for 6 months, and approached 80% at two years. Similar kinetics were observed in the proliferative response to mitogens. The results show that maintenance immunosuppressive drug therapy can be reduced after TLI as compared with conventional drug regimens that use prednisone in combination with cyclosporine and/or azathioprine.

  18. Alterations of the blood pool in the femoral head before and after renal transplantation

    International Nuclear Information System (INIS)

    The pathogenesis of idiopathic osteonecrosis of the femoral head (ION) is thought to be an ischemic event. The purpose of this study is to investigate alterations of the blood pool in the femoral head before and after renal transplantation. After renal transplantation, all patients received the same immunosuppressive therapy: corticosteroids, cyclosporin-A, and azathioprine. We performed 3-phase bone scintigraphy on 16 renal allograft recipients within 1 week before renal transplantation, and between week 4 and 9 after renal transplantation. Regions of interest (ROI) were assigned bilaterally in the femoral head, diaphysis, and soft tissue. The head-to-diaphysis ratios (HD ratios) were then calculated. Idiopathic osteonecrosis of the femoral head occurred in 2 femoral heads of 1 patient. The HD ratio before renal transplantation (mean HD±SD, 1.52±0.30) and the HD ratio after renal transplantation (1.28±0.30) were significantly different (P=0.000024). The HD ratios before and after renal transplantation were significantly different, indicating that the administration of steroids diminished the blood pool in the femoral head. A low HD ratio before renal transplantation revealed a poor blood pool in the femoral head, which may be a risk factor for ION. (author)

  19. Drugs used in incident systemic lupus erythematosus - results from the Finnish nationwide register 2000-2007.

    Science.gov (United States)

    Elfving, P; Puolakka, K; Kautiainen, H; Virta, L J; Pohjolainen, T; Kaipiainen-Seppänen, O

    2016-05-01

    The objectives of the study were to examine the initial, first-year anti-rheumatic outpatient therapy in patients with incident SLE, as well as the concomitant use of drugs for certain comorbidities, compared to the use in the general population. The Finnish nationwide register data on special reimbursements for medication costs was screened to identify the inception cohort of 566 adult SLE patients (87% females, mean age 46.5 ± 15.9 years) over the years 2000-2007. The patients were linked to the national Drug Purchase Register. Of those, 90% had purchased at least once some disease-modifying anti-rheumatic drugs (DMARDs) during the first year. Hydroxychloroquine was the most common (76%), followed by azathioprine (15%) and methotrexate (13%). With the exception of increase in mycophenolate mofetil, the proportions remained stable over the whole study period 2000-2007. Drugs for cardiovascular diseases, dyslipidemia, diabetes mellitus, hypothyroidism and obstructive pulmonary disease were more frequently purchased than in the sex- and age-adjusted population, with rate ratios ranging from 1.6 to 7.8. Over the years 2000-2007, almost all the patients with incident SLE in Finland started with a DMARD. Higher percentages of SLE patients were on medication for several common chronic diseases than in the population as a whole. PMID:26821964

  20. Effect of blood transfusions on canine renal allograft survival

    Energy Technology Data Exchange (ETDEWEB)

    van der Linden, C.J.; Buurman, W.A.; Vegt, P.A.; Greep, J.M.; Jeekel, J.

    1982-04-01

    In this study significantly prolonged canine renal allograft survival has been demonstrated after transfusion of 100 ml of third-party whole blood given peroperatively. Peroperative transfusions of third-party leukocyte-free blood or pure lymphocyte cell suspensions did not influence graft survival. Furthermore, no improvement in graft survival has been found after a peroperative transfusion of irradiated whole blood (2500 rad). These data suggest that delayed graft rejection after blood transfusions can only be expected after the administration of whole blood. The role of competent lymphocytes in whole blood is questionable, since a transfusion or irradiated whole blood in combination with nonirradiated lymphocytes did not lead to prolonged graft survival. Immunosuppression of the recipient directly after transfusion seems to be essential to induce the beneficial effect of blood transfusions. This has been demonstrated for a transfusion of whole blood 14 days before transplantation. A single transfusion of 100 ml of whole blood 14 days before transplantation could effectively prolong graft survival if immunosuppression with azathioprine and prednisone was started on the day of transfusion. No improvement in graft survival has been found with such a transfusion if preoperative immunosuppression has been omitted.