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Tacrolimus Treatment (tacrolimus + treatment)
Selected AbstractsEfficacy and safety of tacrolimus in refractory ulcerative colitis and Crohn's disease: A single-center experienceINFLAMMATORY BOWEL DISEASES, Issue 1 2008Aaron Benson MD Abstract Background: The published experience regarding the use of tacrolimus in Crohn's disease (CD) and ulcerative colitis (UC) refractory to more commonly used medical therapy has been fairly limited. Our objective was to describe our experience with its use in a cohort of patients which, to our knowledge, represents the largest North American cohort described to date. Methods: This was a retrospective, single-center chart analysis. Patients were identified by compiling all hospital discharges with principle diagnoses of ICD-9 codes for 555.0-555.9 (regional enteritis) and 556.0-556.9 (ulcerative colitis) from January 1, 2000, to October 31, 2005, and then cross-referencing the electronic charts for tacrolimus serum concentrations ordered during this time period. Additional patients were identified through verbal communication with participating clinicians. Information abstracted included proportion with clinical response and remission (using a modified disease activity index), ability to wean from steroids, need for surgery / time to surgery, and side-effect profile. Results: In all, 32 UC patients and 15 CD patients were identified. The mean disease duration was: UC 81 months (range, 1 month to 37 years), CD 100 months (range, 1 month to 35 years). The disease distribution for UC was: pancolitis 12 (37.5%), extensive colitis 6 (18.8%), left-sided 11 (34.4%), and proctitis 3(9.4%). For CD this was: TI 2 (13.3%), small bowel 2 (13.3%), colonic 3 (20.7%), ileocolonic 7(46.7%), and perianal 1 (6.7%). The duration of tacrolimus treatment for UC was mean, 29 weeks. For CD it was mean, 9.9 weeks. In all, 30/32 UC and 7/15 CD patients were on steroids; 4/30 UC and 0/7 CD patients were able to subsequently wean off steroids. In all, 12/32 UC patients proceeded to colectomy. Mean time to colectomy was 28 weeks and 6/15 CD patients proceeded to a resective surgery. The mean time to surgery was 22 weeks. In all, 22/32 UC patients achieved a clinical response; 3/32 achieved remission and 8/15 CD patients achieved a clinical response; 1/15 achieved remission. Adverse reactions were generally mild. In 6 patients the drug had to be discontinued because of an adverse reaction. There were no opportunistic infections identified, no cases of renal insufficiency related to drug administration, and no deaths while on the medicine. Conclusions: Our experience with tacrolimus in UC and CD indicates that it is safe and relatively well tolerated, although its clinical efficacy is quite variable. More prospective studies assessing its use are necessary. (Inflamm Bowel Dis 2007) [source] Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Siew C. Ng MRCP Abstract Background: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Methods: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5,10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Results: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35,203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted. (Inflamm Bowel Dis 2007) [source] Reduction of ciclosporin and tacrolimus nephrotoxicity by plant polyphenolsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2006Zhi Zhong The immunosuppressants ciclosporin (cyclosporin A, CsA) and tacrolimus can cause severe nephrotoxicity. Since CsA increases free radical formation, this study investigated whether an extract from Camellia sinensis, which contains several polyphenolic free radical scavengers, could prevent nephrotoxicity caused by CsA and tacrolimus. Rats were fed powdered diet containing polyphenolic extract (0-0.1%) starting 3 days before CsA or tacrolimus. Free radicals were trapped with ,-(4-pyridyl-1-oxide)- N - tert -butylnitrone (POBN) and measured using an electron spin resonance spectrometer. Both CsA and tacrolimus decreased glomerular filtration rates (GFR) and caused tubular atrophy, vacuolization and calcification and arteriolar hyalinosis, effects that were blunted by treatment with dietary polyphenols. Moreover, CsA and tacrolimus increased POBN/radical adducts in urine nearly 3.5 fold. Hydroxyl radicals attack dimethyl sulfoxide (DMSO) to produce a methyl radical fragment. Administration of CsA or tacrolimus with 12C-DMSO produced a 6-line spectrum, while CsA or tacrolimus given with 13C-DMSO produced a 12-line ESR spectrum, confirming formation of hydroxyl radicals. 4-Hydroxynonenal (4-HNE), a product of lipid peroxidation, accumulated in proximal and distal tubules after CsA or tacrolimus treatment. ESR changes and 4-HNE formation were largely blocked by polyphenols. Taken together, these results demonstrate that both CsA and tacrolimus stimulate free radical production in the kidney, most likely in tubular cells, and that polyphenols minimize nephrotoxicity by scavenging free radicals. [source] Successful treatment of severe recalcitrant erosive oral lichen planus with topical tacrolimusJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2006R Shichinohe Abstract Oral lichen planus (LP) is a severe, painful form of LP, and is often resistant to topical corticosteroid therapy. Recently, open trials demonstrated that topical tacrolimus therapy was effective for the treatment of chronic erosive oral LP. We report two cases with severe recalcitrant erosive oral LP, who dramatically benefited from topical tacrolimus therapy. In case 1, a 64-year-old man presented with a 5-month history of painful erosions on his entire lower lip and buccal mucosa. Physical and histological examination confirmed a diagnosis of LP. He experienced rapid relief from pain and a dramatic improvement was obtained within 5 weeks of topical tacrolimus treatment. No significant irritation was observed and blood tacrolimus level was kept within a safe level (2.5 ng/mL). In case 2, a 68-year-old man developed painful erosions on his right lower lip and buccal mucosa 2 months before his arrival at our hospital. Histopathological analysis confirmed a diagnosis of oral LP. He experienced a rapid dramatic improvement of both lesions within 4 weeks of the start of tacrolimus application. No significant irritation or recurrence was observed. Thus, topical tacrolimus is suggested as a well-tolerated, effective therapy for oral LP. [source] Effects of immunosuppressant FK-506 on tooth movementORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2010RL Santos To cite this article: Santos RL, de Farias MLF, de Mendonça LMC, Gonçalves RT, Martins MA, de Souza MMG: Effects of immunosuppressant FK-506 on tooth movement Orthod Craniofac Res 2010;13:153,161 Structured Abstract Authors,,, Santos RL, de Farias MLF, de Mendonça LMC, Gonçalves RT, Martins MA, de Souza MMG Objective,,, To test the hypothesis that immunosuppressant tacrolimus treatment can interfere with bone turnover and rate of tooth movement. Material and Methods,,, One-hundred twenty Wistar male rats were divided into four groups: Group 1 (rats subjected to orthodontic movement plus treatment with saline solution vehicle), Group 2 (rats subjected to orthodontic movement plus treatment with FK506), Group 3 (rats treated with FK506 only), and Group 4 (rats treated with saline solution vehicle). The maxillary incisors were laterally moved with a reciprocal load of 35 cN. The dosage of FK506 was 2 mg/kg/day. Howship's lacunae, osteoclasts, and macrophages were counted. Results,,, Tooth movement was found to be greater in Group 1 than in Group 2 for all time periods (on days 3, 7, and 14), although a significant difference was observed only on days 7 and 14 (p < 0.05). The number of osteoclasts was smaller in Group 1 than in Group 2, whereas the number of Howship's lacunae was greater. Conclusion,,, FK506 has the capacity of promoting osteoclasts inhibition with probable osteoclastic apoptosis of alveolar bone following tooth movement. [source] Early and Limited Use of Tacrolimus to Avoid Rejection in an Alemtuzumab and Sirolimus Regimen for Kidney Transplantation: Clinical Results and Immune MonitoringAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009S. J. Knechtle Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27,39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3,4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients. [source] Wet-wrap treatment using dilutions of tacrolimus ointment and fluticasone propionate cream in human APOC1 (+/+) mice with atopic dermatitisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2009A.P. Oranje Summary Background, Wet-wrap treatment (WWT) with diluted topical steroids is widely used in atopic dermatitis (AD). Mice with transgenic overexpression of human apolipoprotein C1 (APOC1) in the liver and the skin are not only characterized by hyperlipidaemia and raised IgE levels, but also by pruritic dermatitis and a disturbed skin barrier function, providing a novel in vivo mouse model for AD. Objectives, We investigated an adapted WWT method in the AD model in APOC1 mice in order to establish its efficacy. Methods, The effect of topical 0·1% and 0·03% tacrolimus ointment, tacrolimus base ointment, different dilutions of 0·05% fluticasone propionate (FP) cream and emollient on the development of dermatitis in APOC1 mice was investigated. WWT was performed with 0·03% tacrolimus ointment or 0·017% FP cream. Results, AD in APOC1 mice responded to topical treatment with tacrolimus or FP. In contrast to tacrolimus treatment, FP treatment was associated with loss of body weight. WWT reinforced several therapeutic aspects, notably improvements in transepidermal water loss and in epidermal thickness. WWT using tacrolimus 0·03% ointment was more effective than WWT using FP 0·017% cream. Conclusions, AD in APOC1 mice responds to treatment with (diluted) tacrolimus or FP; treatment with FP cream, but not tacrolimus ointment, was associated with weight loss. In this study, the adapted WWT using tacrolimus or FP in mice had a limited improving effect as compared with open application of tacrolimus or FP. [source] Herpes simplex of the vulva evoked by topical tacrolimus treatmentCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2005A. A. Lonsdale-Eccles No abstract is available for this article. [source] | ||||||||||