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Sample records for tacrolimus alternative treatment

  1. Tacrolimus treatment of atopic eczema/dermatitis syndrome.

    PubMed

    Thestrup-Pedersen, Kristian

    2003-10-01

    Atopic dermatitis is today the most common chronic disease of children in Europe, the US and Japan. The 'golden standard' of therapy is topical glucocorticosteroids and emollients. The steroids have been on the market for four decades, are efficacious, but only advised for short-term treatment due to their risks of side effects. More than 16,000 persons suffering from atopic dermatitis have been enrolled in clinical studies of tacrolimus. One third of patients with moderate to severe atopic dermatitis experience over 90% improvement in their disease over a 12-week treatment period and up to 70% of patients have over 50% improvement. A 1-year treatment leads to more than 90% improvement in 75% of patients. The most pronounced side effect is a burning sensation occurring in up to 60% of patients. Atopic dermatitis is a chronic skin disease leading to a demand for long-term treatment control. Such treatment options have not previously been available--except for emollients which are not efficacious for controlling skin inflammation. Tacrolimus and pimecrolimus are new treatment options, free from the potential side effects of topical steroids, which are known for their efficacy in short-term treatment. The new treatment modalities prevent the eczema from relapsing and at the same time they control active eczema. The future will see a shift towards the long-term use of tacrolimus which is able to control the skin inflammation and, hopefully, shorten the course of the eczema.

  2. Efficacy and safety of tacrolimus treatment for rheumatoid arthritis patients undergoing hemodialysis.

    PubMed

    Yamashita, Misuzu; Natsumeda, Masamitsu; Takasugi, Koji; Ueno, Akiko; Ezawa, Kayo; Ezawa, Kazuhiko

    2008-01-01

    Rheumatoid arthritis (RA) is an autoimmune disorder characterized by progressive joint destruction that requires aggressive treatment using appropriate disease-modifying antirheumatic drugs (DMARDs). RA patients with renal failure, however, are intolerant to most DMARDs due to the potential toxicity. In Japan, tacrolimus was approved for the treatment of RA in 2005. Based on its pharmacokinetics, tacrolimus may be administered to the patients undergoing hemodialysis. We report two cases of RA patients on hemodialysis treated effectively and safely with tacrolimus.

  3. Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

    PubMed

    Szeto, C-C; Kwan, B C-H; Lai, F M-M; Tam, L-S; Li, E K-M; Chow, K-M; Gang, W; Li, P K-T

    2008-11-01

    The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

  4. Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review.

    PubMed

    Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

    2018-06-01

    TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients' laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome.

  5. Successful treatment with tacrolimus in TAFRO syndrome: two case reports and literature review

    PubMed Central

    Shirai, Taiichiro; Onishi, Akira; Waki, Daisuke; Saegusa, Jun; Morinobu, Akio

    2018-01-01

    Abstract Rationale: TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. In contrast to that in multicentric Castleman disease, interleukin-6 targeting strategies seem ineffective in some TAFRO syndrome cases; however, the optimal treatment remains unclear. Here, we report 2 cases of TAFRO syndrome, where 1 with cardiomyopathy, successfully treated with tacrolimus. This is the first case report of successful treatment with tacrolimus in TAFRO syndrome. Patient concerns: Both patients (cases 1 and 2) developed fever, anasarca, thrombocytopenia, renal dysfunction, and mild hepatosplenomegaly. Diagnoses: In both patients, lymph node pathology revealed mixed type Castleman disease-like features, and bone marrow showed reticulin myelofibrosis. TAFRO syndrome was diagnosed based on the patients’ laboratory, clinical, and pathologic findings. In case 2, we observed a rare complication of cardiomyopathy with no evidence of takotsubo cardiomyopathy or viral myocarditis. Interventions and outcomes: In case 1, tocilizumab combined with glucocorticoids was ineffective and caused septic shock; additionally, cyclosporine A was discontinued because of hepatotoxicity. However, tacrolimus was effective in resolving TAFRO syndrome without any adverse events. In case 2, tacrolimus completely reversed TAFRO syndrome and was also effective in cardiomyopathy. Lessons: This report suggests that tacrolimus is potentially effective and safe as an initial treatment and a glucocorticoid-sparing agent. Our literature review shows that calcineurin inhibitors, including tacrolimus, may be effective in TAFRO syndrome. Since previous studies indicate a role of Th1 inflammation in TAFRO syndrome pathogenesis, tacrolimus may, therefore, be effective in treating TAFRO syndrome. PMID:29879072

  6. Increased bioavailability of tacrolimus after rectal administration in rats.

    PubMed

    Sakai, Masayuki; Hobara, Norio; Hokama, Nobuo; Kameya, Hiromasa; Ohshiro, Susumu; Sakanashi, Matao; Saitoh, Hiroshi

    2004-09-01

    The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

  7. The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report.

    PubMed

    Morita, Mayu; Asoda, Seiji; Tsunoda, Kazuyuki; Soma, Tomoya; Nakagawa, Taneaki; Shirakawa, Masayori; Shoji, Hirofumi; Yagishita, Hisao; Nishikawa, Takeji; Kawana, Hiromasa

    2017-04-01

    Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.

  8. Preliminary study on the treatment of vitiligo with carbon dioxide fractional laser together with tacrolimus.

    PubMed

    Chen, Wei; Zhou, Yuan; Huang, Fei-Ran; Luo, Dan; Wang, Da-Guang

    2018-04-10

    Tacrolimus is a conventional medication for the treatment of vitiligo, but the effect of a single medication is limited. This paper aims at observing the effects, adverse responses, and repigmentation results of the joint treatment of vitiligo by Carbon dioxide (CO 2 ) fractional laser together with tacrolimus. Forty-five patients with vitiligo were randomly divided into two groups: treatment (T) group and control (C) group, and each group was further divided into three subgroups (face, torso and limbs, and hand and foot) according to the location of the skin defect. Both groups used topical 0.1% tacrolimus cream, but the T group was given one CO 2 fractional laser treatment each month. We observed the clinical efficacy, adverse responses, and repigmentation results after 6 months. Compared to the C group, the T group showed better improvement in both objective and subjective assessments. When the treatment time was increased, the efficacy was also improved, and the repigmentation in the T group occured in three ways: perifollicular repigmentation, marginal repigmentation and diffuse repigmentation. There were three cases of isomorphic responses (2 cases in the rapid progression stage, one case in the progression stage), and 1 case formed scarring on the neck in the T group. The treatment of vitiligo by CO 2 fractional laser together with tacrolimus is significantly effective and is most suitable for patients in the progression stage. Patients in the rapid progression stage should use this approach with caution, and its efficacy was limited for patients in the stable stage. An extended course of treatment is helpful for the repigmentation of white patches. All three forms of repigmentation can occur in the joint treatment of vitiligo by CO 2 fractional laser together with tacrolimus. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  9. Comparison between the efficacy of microneedling combined with 5-fluorouracil vs microneedling with tacrolimus in the treatment of vitiligo.

    PubMed

    Mina, Mary; Elgarhy, Lamia; Al-Saeid, Hanan; Ibrahim, Zeinab

    2018-03-12

    Several treatment modalities had been used for the treatment of vitiligo, but the optimal treatment has not yet been identified. To study the efficacy of microneedling with 5-flurouracil vs its efficacy with tacrolimus in the treatment of vitiligo. Twenty-five patients with vitiligo were subjected to microneedling of 2 patches of vitiligo with dermapen, then application of 5-fluorouracil to 1 patch and tacrolimus on the other patch. This procedure was repeated every 2 weeks for every patient for maximum 6 months (12 sessions). The patients were followed up for 3 months after the last session. The overall repigmentation was significantly higher in 5-fluorouracil-treated patches compared with tacrolimus. Excellent improvement occurred in 48% of 5- flurouracil-treated patches while only in 16% of tacrolimus-treated patches. In the acral parts, 40% of the patches treated with 5-fluorouracil achieved excellent improvement (repigmentation >75%), while no patch in the acral parts achieved excellent improvement with tacrolimus. However, there was significant difference between the 2 drugs,regarding inflammation, ulceration, and hyperpigmentation which occurred with 5-fluorouracil. Microneedling combined with 5-fluorouracil or tacrolimus is safe and effective treatment of vitiligo. However, 5-fluorouracil achieved a greater percentage of repigmentation than tacrolimus particularly in the acral parts. © 2018 Wiley Periodicals, Inc.

  10. Tacrolimus in the treatment of myasthenia gravis in patients with an inadequate response to glucocorticoid therapy: randomized, double-blind, placebo-controlled study conducted in China.

    PubMed

    Zhou, Lei; Liu, Weibin; Li, Wei; Li, Haifeng; Zhang, Xu; Shang, Huifang; Zhang, Xu; Bu, Bitao; Deng, Hui; Fang, Qi; Li, Jimei; Zhang, Hua; Song, Zhi; Ou, Changyi; Yan, Chuanzhu; Liu, Tao; Zhou, Hongyu; Bao, Jianhong; Lu, Jiahong; Shi, Huawei; Zhao, Chongbo

    2017-09-01

    To determine the efficacy of low-dose, immediate-release tacrolimus in patients with myasthenia gravis (MG) with inadequate response to glucocorticoid therapy in a randomized, double-blind, placebo-controlled study. Eligible patients had inadequate response to glucocorticoids (GCs) after ⩾6 weeks of treatment with prednisone ⩾0.75 mg/kg/day or 60-100 mg/day. Patients were randomized to receive 3 mg tacrolimus or placebo daily (orally) for 24 weeks. Concomitant glucocorticoids and pyridostigmine were allowed. Patients continued GC therapy from weeks 1-4; from week 5, the dose was decreased at the discretion of the investigator. The primary efficacy outcome measure was a reduction, relative to baseline, in quantitative myasthenia gravis (QMG) score assessed using a generalized linear model; supportive analyses used alternative models. Of 138 patients screened, 83 [tacrolimus ( n = 45); placebo ( n = 38)] were enrolled and treated. The change in adjusted mean QMG score from baseline to week 24 was -4.9 for tacrolimus and -3.3 for placebo (least squares mean difference: -1.7, 95% confidence interval: -3.5, -0.1; p = 0.067). A post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group (68.2%) versus the placebo group (44.7%; p = 0.044). Adverse event profiles were similar between treatment groups. Tacrolimus 3 mg treatment for patients with MG and inadequate response to GCs did not demonstrate a statistically significant improvement in the primary endpoint versus placebo over 24 weeks; however, a post-hoc analysis demonstrated a statistically significant difference for QMG score reduction of ⩾4 points in the tacrolimus group versus the placebo group. This study was limited by the low number of patients, the absence of testing for acetylcholine receptor antibody and the absence of stratification by disease duration (which led to a disparity between the two groups). Clinical

  11. Topical tacrolimus for atopic dermatitis.

    PubMed

    Cury Martins, Jade; Martins, Ciro; Aoki, Valeria; Gois, Aecio F T; Ishii, Henrique A; da Silva, Edina M K

    2015-07-01

    Atopic dermatitis (AD) (or atopic eczema) is a chronic inflammatory skin condition that affects children and adults and has an important impact on quality of life. Topical corticosteroids (TCS) are the first-line therapy for this condition; however, they can be associated with significant adverse effects when used chronically. Tacrolimus ointment (in its 2 manufactured strengths of 0.1% and 0.03%) might be an alternative treatment. Tacrolimus, together with pimecrolimus, are drugs called topical calcineurin inhibitors (TCIs). To assess the efficacy and safety of topical tacrolimus for moderate and severe atopic dermatitis compared with other active treatments. We searched the following databases up to 3 June 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 5, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), and the Global Resource of Eczema Trials (GREAT database). We searched six trials registers and checked the bibliographies of included studies for further references to relevant trials. We contacted specialists in the field for unpublished data.A separate search for adverse effects of topical tacrolimus was undertaken in MEDLINE and EMBASE on 30 July 2013. We also scrutinised the U.S. Food and Drug Administration (FDA) websites for adverse effects information. All randomised controlled trials (RCTs) of participants with moderate to severe atopic dermatitis (both children and adults) using topical tacrolimus at any dose, course duration, and follow-up time compared with other active treatments. Two authors independently screened and examined the full text of selected studies for compliance with eligibility criteria, risk of bias, and data extraction. Our three prespecified primary outcomes were physician's assessment, participant's self-assessment of improvement, and adverse effects. Our secondary outcomes included assessment of improvement of the disease by validated or objective measures, such as

  12. Successful treatment of oral lichen planus-like chronic graft-versus-host disease with topical tacrolimus: a case report.

    PubMed

    Sánchez, Andrés R; Sheridan, Phillip J; Rogers, Roy S

    2004-04-01

    Bone marrow transplantation (BMT) is a common treatment used for deficiencies of host marrow or in the control of blood malignancies. Post-allogeneic BMT complications include graft-versus-host disease (GVHD). GVHD occurs when immunologically active T lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the donor. In this case report we describe the occurrence of oral lichen planus-like lesions as the first manifestation of chronic GVHD (c-GVHD) and the subsequent management of this disease with topical tacrolimus. Diagnostic aids included routine histology and direct immunofluorescence studies to rule out immunobullous diseases and to confirm the c-GVHD. Treatment consisted of topical application of 0.1% tacrolimus ointment three times a day. Routine histology confirmed the clinical diagnosis of oral lichen planus-like c-GVHD. Treatment with tacrolimus ointment completely resolved the oral lesions after 2 months of therapy. Topical tacrolimus at low concentrations (0.1%) shows promise in the management of oral lichen planus-like c-GVHD. Controlled studies are necessary to assess the efficacy, the duration of therapy required for effective results, and the safety of this treatment over the long-term.

  13. Clinical study of double dose of valsartan combined with tacrolimus in treatment of diabetic nephropathy.

    PubMed

    Jin, H; Zhang, H-N; Hou, X-L; Zhang, B; Wu, J; Zhang, H-B

    2016-01-01

    To investigate the clinical effect of double dose of valsartan combined with tacrolimus in the treatment of diabetic nephropathy (DN). HA total of 86 cases diagnosed with DN were selected from October 2013 to October 2014 in Zaozhuang Municipal Hospital, China. The study was approved by our hospital Ethics Committee and written consent was obtained from patients and their family members. Patients were randomly divided into three groups according to the sequence of admission, group A (conventional dose of valsartan group, n = 28 cases), group B (double dose of valsartan group, n = 29 cases) and group C (double dose of valsartan combined with tacrolimus group, n = 29). Clinical effects were compared by analyzing the renal function tests after 8 weeks. 24h urine protein, serum creatinine level of patients in group B and group C were significantly lower than that of group A. Those in group C was much lower. The glomerular filtration rates were significantly higher for group B and C than that of group A, and those in group C were much higher. The difference is statistically significant (p < 0.05). High-sensitivity C-reactive protein (hs CRP) and adiponectin levels of patients in group B and C of were significantly lower than that of group A and those in group C were much lower. The difference is statistically significant (p < 0.05). The high mobility group protein 1 (HMGB1) and renal tubular and interstitial damage index (TDI) of patients in B and C groups were significantly lower than those in the A group, and those in C group were significantly lower. The difference was statistically significant p < 0.05). The clinical effective rates of patients in group B and C were significantly higher than that in group A, and those of group C were much higher. The difference is statistically significant (p < 0.05). The recurrence rates of patients in group B and group C were significantly lower than those of group A and those in group C were much lower. The difference is

  14. Tacrolimus Topical

    MedlinePlus

    ... ointment is used to treat the symptoms of eczema (atopic dermatitis; a skin disease that causes the ... use other medications for their condition or whose eczema has not responded to another medication. Tacrolimus is ...

  15. Successful treatment for ulcerative proctitis with rectal tacrolimus in an 8-year-old girl with intolerance to mesalamine.

    PubMed

    Navas-López, Víctor Manuel; Blasco-Alonso, Javier; Girón Fernández-Crehuet, Francisco; Serrano Nieto, Maria Juliana; Gallego-Gutiérrez, Silvia; Luque Pérez, Silvia; Sierra Salinas, Carlos

    2014-08-01

    Ulcerative colitis (UC) is defined as a chronic inflammatory condition causing continuous mucosal inflammation of the colon without granulomas on biopsy. It affects the rectum, and, to a variable extent, the colon in continuity and is characterized by a relapsing and remitting course. Oral 5-aminosalicylic acid (5-ASA) regimens are recommended as first-line induction therapy for mild to moderately active pediatric UC and for maintenance of remission regardless of other initial treatments. In large clinical trials in adults, mesalamine intolerance was found in 2-5 % of the patients. We present a case of an 8-year-old female patient with intolerance to mesalamine and proctitis resistant to conventional therapy who responded to rectal tacrolimus treatment. The patient started with a dose of 2 mg/day at night with an excellent response. She reported feeling better than any of the previously prescribed treatments and without feeling the discomfort of previously administered enemas. After four weeks of treatment, the dose was reduced to 2 mg/week with no relapses. Tacrolimus suppositories were very well tolerated, and no adverse effects have been reported. Although only very little data has been published, rectal tacrolimus seems to be safe and of efficacy in ulcerative proctitis resistant to standard therapy.

  16. Successful treatment of eosinophilic pustular folliculitis with topical tacrolimus 0.1 percent ointment.

    PubMed

    Ng, Shanna Shan-Yi; Tay, Yong-Kwang

    2012-02-15

    Classic eosinophilic pustular folliculitis (EPF), otherwise known as Ofugi disease, is a rare condition commonly treated with topical glucocorticosteroids. If this fails, oral indomethacin is frequently the next line. Because the condition is recurrent, the use of long term steroids may cause side effects such as skin atrophy, hypertrichosis, and dyspigmentation. Topical tacrolimus is an immunosuppressant that is generally used as a steroid-sparing agent in atopic dermatitis. We report a case of classic EPF, which was recurrent over 5 years that had failed topical glucocorticosteroids but was successfully treated with topical tacrolimus 0.1 percent ointment.

  17. Successful treatment with 308-nm monochromatic excimer light and subsequent tacrolimus 0.03% ointment in refractory plasma cell cheilitis.

    PubMed

    Yoshimura, Kazuhiro; Nakano, Shunji; Tsuruta, Daisuke; Ohata, Chika; Hashimoto, Takashi

    2013-06-01

    Plasma cell cheilitis is a chronic inflammatory disease that presents with erythema, erosions, ulcers and occasional nodules within the mucosa, including the lips. It is histopathologically characterized by dense plasma cell infiltration in the lamina propria of the mucous membranes. Several treatments for plasma cell cheilitis have been reported, including topical steroids, topical antibiotics or topical tacrolimus. However, 308-nm monochromatic excimer light (MEL) has never been reported as a treatment option, while it was reported to be very effective in treating erosive oral lichen planus. We report a 62-year-old man who had chronic plasma cell cheilitis on the lower lip, which was refractory to topical and systemic corticosteroid. The lesion and severe pain were significantly improved by the treatment with nine sessions of 308-nm MEL twice per week with a total dose of 1120 mJ/cm(2). However, the lesion gradually worsened after treatment frequency was reduced to once per month. Subsequent tacrolimus 0.03% ointment cleared the lesion completely in a month and no recurrence was observed a year later. Refractory plasma cell cheilitis and concomitant severe pain quickly responded to 308-nm MEL when administrated twice per week. Because the long interval between each MEL treatment seemed ineffective to improve the lesion, appropriate frequency and adequate total dose of MEL treatment may be necessary for a successful treatment. © 2013 Japanese Dermatological Association.

  18. Alternative Menopause Treatments

    MedlinePlus

    ... symptoms—non-estrogen prescription drugs, and complementary and alternative medicine (CAM). What is CAM? CAM refers to practices ... my menopause symptoms without medicine? Are there any alternative medicine treatments you would recommend I try for relief ...

  19. Successful treatment of plasma cell cheilitis with topical tacrolimus: report of two cases.

    PubMed

    Hanami, Yuka; Motoki, Yoshikazu; Yamamoto, Toshiyuki

    2011-02-15

    Plasma cell cheilitis is an uncommon chronic inflammatory dermatitis that presents with flat to slightly elevated erosive erythematous plaques. It is histologically characterized by plasma cell infiltrates into the mucosa. Other than the lip, genital areas are often involved, which is called plasma cell balanitis or vulvitis. Plasma cell cheilitis is sometimes resistant to conventional topical corticosteroid therapy. Other choices include oral griseofulvin, topical cyclosporine, and intralesional corticosteroid injection, all of which occasionally fail to produce satisfactory results. Recent reports show that topical calcineurin inhibitors are effective for plasma cell cheilitis, balanitis, and vulvitis. However, there are so far only 2 reports of plasma cell cheilitis successfully treated with topical pimecrolimus and tacrolimus. We present herein two cases of plasma cell cheilitis, in which topical tacrolimus showed beneficial effects, suggesting that this immunomodulatory agent is a promising option for plasma cell cheilitis.

  20. Autoimmune hepatitis: Standard treatment and systematic review of alternative treatments

    PubMed Central

    Terziroli Beretta-Piccoli, Benedetta; Mieli-Vergani, Giorgina; Vergani, Diego

    2017-01-01

    Autoimmune hepatitis is a rare chronic inflammatory liver disease, affecting all ages, characterised by elevated transaminase and immunoglobulin G levels, positive autoantibodies, interface hepatitis at liver histology and good response to immunosuppressive treatment. If untreated, it has a poor prognosis. The aim of this review is to summarize the evidence for standard treatment and to provide a systematic review on alternative treatments for adults and children. Standard treatment is based on steroids and azathioprine, and leads to disease remission in 80%-90% of patients. Alternative first line treatment has been attempted with budesonide or cyclosporine, but their superiority compared to standard treatment remains to be demonstrated. Second-line treatments are needed for patients not responding or intolerant to standard treatment. No randomized controlled trials have been performed for second-line options. Mycophenolate mofetil is the most widely used second-line drug, and has good efficacy particularly for patients intolerant to azathioprine, but has the major disadvantage of being teratogenic. Only few and heterogeneous data on cyclosporine, tacrolimus, everolimus and sirolimus are available. More recently, experience with the anti-tumour necrosis factor-alpha infliximab and the anti-CD20 rituximab has been published, with ambivalent results; these agents may have severe side-effects and their use should be restricted to specialized centres. Clinical trials with new therapeutic options are ongoing. PMID:28970719

  1. Treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop: Prospective double-blind randomized study.

    PubMed

    Moscovici, Bernardo Kaplan; Holzchuh, Ricardo; Sakassegawa-Naves, Fernando Eiji; Hoshino-Ruiz, Diego Ricardo; Albers, Marcos Bottene Villa; Santo, Ruth Miyuki; Hida, Richard Yudi

    2015-10-01

    To describe the clinical efficacy of the treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop. Prospective double-blind randomized study. Institutional outpatient clinic. Forty-eight eyes of twenty-four patients with dry eye related to Sjögren syndrome were enrolled in this study. The patients were randomized in 2 groups: tacrolimus (n=14) and vehicle (n=10) group. The tacrolimus group received a vial containing tacrolimus 0.03% (almond oil as vehicle) and the other group received the almond oil vehicle. All patients were instructed to use the eye drops every 12h in the lower conjunctival sac. Schirmer I test, break-up-time (BUT), corneal fluorescein and Rose Bengal staining scores were evaluated in all patients one day before the treatment (baseline), 7, 14, 28 and 90 days after treatment with the eye drops. The average fluorescein and Rose Bengal scores improved statistically after 7 days of treatment and even more after 90 days. The average Schirmer I and BUT values were unchanged after 7, 14 and 21 days but did show an improvement relative to baseline after 28 days of treatment. Schirmer I, BUT, fluorescein and Rose Bengal did not show any statistical significance in the vehicle group. Topical 0.03% tacrolimus eye drop improved tear stability and ocular surface status in cases of inflammatory or SS-related dry eye. ClinicalTrials.gov Identifier: NCT01850979. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  2. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation.

    PubMed

    Benítez, C E; Puig-Pey, I; López, M; Martínez-Llordella, M; Lozano, J J; Bohne, F; Londoño, M C; García-Valdecasas, J C; Bruguera, M; Navasa, M; Rimola, A; Sánchez-Fueyo, A

    2010-10-01

    We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with <5 ng/mL trough levels) at 12 months after transplantation. Acute rejection occurring during the first 3 months after transplantation was more frequent in the ATG group (52.4% vs. 25%). Moreover, late acute rejection episodes occurred in all recipients in whom weaning was attempted and no recipients reached the primary end-point. This motivated the premature termination of the trial. Tacrolimus trough levels were lower in the ATG-Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Topical tacrolimus in alopecia areata.

    PubMed

    Price, Vera H; Willey, Andrea; Chen, Bryan K

    2005-01-01

    Eleven patients with alopecia areata affecting 10% to 75% of the scalp, average duration 6 years, had no terminal hair growth in response to tacrolimus ointment 0.1% applied twice daily for 24 weeks. Treatment failure may reflect insufficient depth of penetration of the ointment formulation and less than optimal patient selection.

  4. A pilot comparative study of topical latanoprost and tacrolimus in combination with narrow-band ultraviolet B phototherapy and microneedling for the treatment of nonsegmental vitiligo.

    PubMed

    Korobko, Igor V; Lomonosov, Konstantin M

    2016-11-01

    Prostaglandins and their analogues are beneficial as topical agents in vitiligo treatment, yet neither of the previous study addressed their comparative efficiency with conventional topical agents used in vitiligo treatment. In this pilot (24 patients) left-right comparative study we addressed efficiency of prostaglandin F2α analogue latanoprost versus tacrolimus when combined with narrow-band ultraviolet B and microneedling in repigmentation of nonsegmental vitiligo lesions. Our results confirm potency of prostaglandins, in particular, that of latanoprost, in inducing repigmentation, with the efficiency being at least comparable to that of tacrolimus, while contribution of microneedling remains unclear. In summary, results of our study provide further evidences for justified use of prostaglandins, in particular, latanoprost, in vitiligo treatment. In turn, this warrants future studies on the topic aiming to conclusively introduce prostaglandin-based formulations as conventional agents for vitiligo management. © 2016 Wiley Periodicals, Inc.

  5. Tacrolimus Optic Neuropathy.

    PubMed

    Rasool, Nailyn; Boudreault, Katherine; Lessell, Simmons; Prasad, Sashank; Cestari, Dean M

    2018-06-01

    Tacrolimus (FK506, Prograf) is a potent immunosuppressant, which inhibits cytokine synthesis and blocks T-cell development. Optic neuropathy from tacrolimus toxicity is very uncommon but, when present, can result in severe vision loss. Case series and review of the literature. We present 3 patients with tacrolimus optic neuropathy after bone marrow transplantation complicated by graft-vs-host disease and demonstrate the differing clinical and radiologic presentation of this presumed toxic optic neuropathy. Tacrolimus optic neuropathy can manifest in a multitude of clinical presentations and can have devastating visual consequences.

  6. Systematic conversion to generic tacrolimus in stable kidney transplant recipients.

    PubMed

    Rosenborg, Staffan; Nordström, Annica; Almquist, Tora; Wennberg, Lars; Bárány, Peter

    2014-04-01

    Tacrolimus (Prograf ® ) is a key drug in the immunosuppressive treatment of renal transplant patients. Since the expiration of the patent for Prograf ® , generic preparations have been approved in Europe as bioequivalence has been shown in healthy volunteers. However, few studies have investigated whether patients can be successfully converted from Prograf ® to generic tacrolimus. Tacrolimus drug costs are by far the largest single item in the total drug expenditure for patients with renal disease in the Stockholm area. Considerable reductions in drug costs could be achieved if generic tacrolimus were to be used. The aim of this quality assurance study was to evaluate whether a switch from Prograf ® to generic tacrolimus (Tacrolimus Sandoz ® ) could be safely performed in renal transplant patients. It further aimed to investigate changes of renal function (measured in estimated glomerular filtration rate, eGFR), need for dose changes and to calculate potential drug cost savings as a result of the conversion. We planned to recruit at least 50 patients. Plasma creatinine levels and trough concentrations of tacrolimus were collected from patients with renal transplants at three occasions during treatment with Prograf ® and three times after conversion to Tacrolimus Sandoz ® . The eGFR was calculated before and after the conversion. Sixty-three of 67 enrolled patients (69% males, age 28-80 years) are included in this analysis. The ratio of mean trough concentrations of tacrolimus after comparison with before conversion was 1.02 (90% confidence interval 0.95-1.09). Fourteen patients experienced a change in tacrolimus levels >20% compared with baseline, no patients changed >20% in eGFR. The drug cost saving per daily dose was 33.40 SEK (∼€3.60, -23%). Stable kidney transplant patients treated with Prograf ® can be converted to Tacrolimus Sandoz ® if trough concentrations of tacrolimus and plasma creatinine levels are closely monitored. The conversion brought

  7. Ranolazine, tacrolimus, and diltiazem might be a hazardous combination in a transplant patient.

    PubMed

    Patni, Hitesh; Gitman, Michael; Hazzan, Azzour; Jhaveri, Kenar D

    2012-01-01

    We report a case of a renal transplant patient who was maintained on tacrolimus and diltiazem therapy and developed tacrolimus toxicity leading to reversible acute kidney injury when started on ranolazine. A 62-year-old Caucasian male status post renal transplant in 2009 (on prednisone and tacrolimus) was evaluated for ischemic heart disease and was initiated on ranolazine 500 mg tablets twice daily, which was later increased to 1000 mg twice daily. After 2 weeks, he developed fatigue, loss of appetite, tremors, and decreased urine output and was admitted to our hospital. His other significant medications included enalapril 2.5 mg and diltiazem 240 mg daily. The patient was awake and alert, but lethargic. He was found to be bradycardic with a heart rate of 42/min. The rest of his physical examination was benign. His electrocardiogram revealed sinus bradycardia. Laboratory studies revealed serum creatinine of 2.4 mg/dL from a baseline of 1.5 mg/dL (stable for the past 2 years). The tacrolimus trough was elevated at 14 ng/mL, which decreased after stopping ranolazine, reaching 7 ng/mL after 3 days, while continuing the same dose of tacrolimus. His creatinine trended downward and reached his baseline of 1.5 mg/dL over the next 2 days. His bradycardia and other symptoms resolved after cessation of ranolazine. He was discharged to follow up, to initiate an alternate agent for ischemic heart disease. Specific pharmacokinetic studies are warranted to study these drug interactions, and tacrolimus levels should be closely monitored in transplant patients who initiate ranolazine treatment.

  8. Conversion from twice-daily tacrolimus to once-daily extended release tacrolimus (LCPT): the phase III randomized MELT trial.

    PubMed

    Bunnapradist, S; Ciechanowski, K; West-Thielke, P; Mulgaonkar, S; Rostaing, L; Vasudev, B; Budde, K

    2013-03-01

    Phase III noninferiority trial examining efficacy and safety of converting stable renal transplant recipients from twice-daily tacrolimus to a novel extended-release once-daily tacrolimus formulation (LCPT) with a controlled agglomeration technology. Controls maintained tacrolimus twice daily. The primary efficacy endpoint was proportion of patients with efficacy failures (death, graft failure, locally read biopsy-proven acute rejection [BPAR], or loss to follow-up) within 12 months. Starting LCPT dose was 30% lower (15% for blacks) than preconversion tacrolimus dose; target trough levels were 4-15 ng/mL. A total of 326 patients were randomized; the mITT population (n = 162 each group) was similar demographically in the two groups. Mean daily dose of LCPT was significantly (p < 0.0001) lower than preconversion tacrolimus dose at each visit; mean trough levels between groups were similar. There were four efficacy failures in each group; safety outcomes were similar between groups. Frequency of premature study drug discontinuation was LCPT: 12% versus tacrolimus twice daily: 5% (p = 0.028). LCPT demonstrated noninferiority to tacrolimus twice daily in efficacy failure rates. LCPT may offer a safe and effective alternative for converting patients to a once-daily formulation. Compared to currently available tacrolimus formulation, LCPT requires lower doses to achieve target trough levels. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. EFFICACY OF TACROLIMUS FOR INDUCTION OF REMISSION IN PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

    PubMed

    Lasa, Juan; Olivera, Pablo

    2017-01-01

    There is evidence that shows that calcineurin inhibitors may be useful for the treatment of severe ulcerative colitis. However, evidence regarding the efficacy of tacrolimus for remission induction in this setting is scarce. To develop a systematic review on the existing evidence regarding the clinical efficacy of tacrolimus for the induction of remission in patients with moderate-to-severe ulcerative colitis. A literature search was undertaken from 1966 to August 2016 using MEDLINE, Embase, LILACS and the Cochrane Library. The following MeSH terms were used: "Inflammatory Bowel Diseases" or "Ulcerative Colitis" and "Calcineurin Inhibitors" or "Tacrolimus" or "FK506". Studies performed in adult ulcerative colitis patients that evaluated the clinical efficacy of tacrolimus for the induction of remission were considered for revision. A meta-analysis was performed with those included studies that were also placebo-controlled and randomized. Clinical response as well as clinical remission and mucosal healing were evaluated. Overall, 755 references were identified, from which 22 studies were finally included. Only two of them were randomized, placebo-controlled trials. A total of 172 patients were evaluated. A significantly lower risk of failure in clinical response was found for tacrolimus versus placebo [RR 0.58 (0.45-0.73)]; moreover, a lower risk of failure in the induction of remission was also found versus placebo [RR 0.91 (0.82-1)]. Tacrolimus seems to be a valid therapeutic alternative for the induction of remission in patients with moderate-to-severe ulcerative colitis.

  10. Systematic conversion to generic tacrolimus in stable kidney transplant recipients

    PubMed Central

    Rosenborg, Staffan; Nordström, Annica; Almquist, Tora; Wennberg, Lars; Bárány, Peter

    2014-01-01

    Background Tacrolimus (Prograf®) is a key drug in the immunosuppressive treatment of renal transplant patients. Since the expiration of the patent for Prograf®, generic preparations have been approved in Europe as bioequivalence has been shown in healthy volunteers. However, few studies have investigated whether patients can be successfully converted from Prograf® to generic tacrolimus. Tacrolimus drug costs are by far the largest single item in the total drug expenditure for patients with renal disease in the Stockholm area. Considerable reductions in drug costs could be achieved if generic tacrolimus were to be used. The aim of this quality assurance study was to evaluate whether a switch from Prograf® to generic tacrolimus (Tacrolimus Sandoz®) could be safely performed in renal transplant patients. It further aimed to investigate changes of renal function (measured in estimated glomerular filtration rate, eGFR), need for dose changes and to calculate potential drug cost savings as a result of the conversion. Methods We planned to recruit at least 50 patients. Plasma creatinine levels and trough concentrations of tacrolimus were collected from patients with renal transplants at three occasions during treatment with Prograf® and three times after conversion to Tacrolimus Sandoz®. The eGFR was calculated before and after the conversion. Results Sixty-three of 67 enrolled patients (69% males, age 28–80 years) are included in this analysis. The ratio of mean trough concentrations of tacrolimus after comparison with before conversion was 1.02 (90% confidence interval 0.95–1.09). Fourteen patients experienced a change in tacrolimus levels >20% compared with baseline, no patients changed >20% in eGFR. The drug cost saving per daily dose was 33.40 SEK (∼€3.60, −23%). Conclusions Stable kidney transplant patients treated with Prograf® can be converted to Tacrolimus Sandoz® if trough concentrations of tacrolimus and plasma creatinine levels are closely

  11. Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

    PubMed Central

    Borba-Santos, Luana P.; Reis de Sá, Leandro F.; Ramos, Juliene A.; Rodrigues, Anderson M.; de Camargo, Zoilo P.; Rozental, Sonia; Ferreira-Pereira, Antonio

    2017-01-01

    Calcineurin inhibitors – such as the clinically used drug tacrolimus – are active against important fungal pathogens, particularly when combined with azoles. However, tacrolimus has not been tested against sporotrichosis, an endemic subcutaneous mycosis with worldwide distribution. Here, we evaluated the activity of tacrolimus and cyclosporine A in vitro – as monotherapy and in combination with itraconazole or fluconazole – against yeasts of Sporothrix brasiliensis and S. schenckii, the main sporotrichosis agents in Brazil. We also analyzed the effect of tacrolimus treatment on intracellular neutral lipid levels, which typically increase after azole treatment. Tacrolimus inhibited the growth of yeasts from S. brasiliensis and S. schenckii reference isolates, with minimum inhibitory concentration (MIC) values (required for ≥50% growth inhibition) of 1 and 2 mg/L, respectively. Importantly, the combination of tacrolimus and azoles exhibited high synergy toward reference Sporothrix isolates. Tacrolimus combined with itraconazole significantly increased neutral lipid accumulation in S. brasiliensis, but not in S. schenckii. Clinical isolates of S. brasiliensis and S. schenckii were more sensitive to tacrolimus as monotherapy than feline-borne isolates, however, synergy between tacrolimus and azoles was only observed for feline-borne isolates. Cyclosporine A was effective against S. brasiliensis and S. schenckii as monotherapy (MIC = 1 mg/L), but exhibited no synergy with itraconazole and fluconazole. We conclude that tacrolimus has promising antifungal activity against sporotrichosis agents, and also increases the activity of the current anti-sporotrichosis therapy (itraconazole and fluconazole) in combination assays against S. brasiliensis feline-borne isolates. PMID:28966608

  12. Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp.

    PubMed

    Borba-Santos, Luana P; Reis de Sá, Leandro F; Ramos, Juliene A; Rodrigues, Anderson M; de Camargo, Zoilo P; Rozental, Sonia; Ferreira-Pereira, Antonio

    2017-01-01

    Calcineurin inhibitors - such as the clinically used drug tacrolimus - are active against important fungal pathogens, particularly when combined with azoles. However, tacrolimus has not been tested against sporotrichosis, an endemic subcutaneous mycosis with worldwide distribution. Here, we evaluated the activity of tacrolimus and cyclosporine A in vitro - as monotherapy and in combination with itraconazole or fluconazole - against yeasts of Sporothrix brasiliensis and S. schenckii , the main sporotrichosis agents in Brazil. We also analyzed the effect of tacrolimus treatment on intracellular neutral lipid levels, which typically increase after azole treatment. Tacrolimus inhibited the growth of yeasts from S. brasiliensis and S. schenckii reference isolates, with minimum inhibitory concentration (MIC) values (required for ≥50% growth inhibition) of 1 and 2 mg/L, respectively. Importantly, the combination of tacrolimus and azoles exhibited high synergy toward reference Sporothrix isolates. Tacrolimus combined with itraconazole significantly increased neutral lipid accumulation in S. brasiliensis , but not in S. schenckii . Clinical isolates of S. brasiliensis and S. schenckii were more sensitive to tacrolimus as monotherapy than feline-borne isolates, however, synergy between tacrolimus and azoles was only observed for feline-borne isolates. Cyclosporine A was effective against S. brasiliensis and S. schenckii as monotherapy (MIC = 1 mg/L), but exhibited no synergy with itraconazole and fluconazole. We conclude that tacrolimus has promising antifungal activity against sporotrichosis agents, and also increases the activity of the current anti-sporotrichosis therapy (itraconazole and fluconazole) in combination assays against S. brasiliensis feline-borne isolates.

  13. Alternative approaches to epilepsy treatment.

    PubMed

    McElroy-Cox, Caitlin

    2009-07-01

    Complementary and alternative medicine (CAM) is a diverse group of health care practices and products that fall outside the realm of traditional Western medical theory and practice and that are used to complement or replace conventional medical therapies. The use of CAM has increased over the past two decades, and surveys have shown that up to 44% of patients with epilepsy are using some form of CAM treatment. This article reviews the CAM modalities of meditation, yoga, relaxation techniques, biofeedback, nutritional and herbal supplements, dietary measures, chiropractic care, acupuncture, Reiki, and homeopathy and what is known about their potential efficacy in patients with epilepsy.

  14. 850nm light-emitting-diode phototherapy plus low-dose tacrolimus (FK-506) as combination therapy in the treatment of Dermatophagoides farinae-induced atopic dermatitis-like skin lesions in NC/Nga mice.

    PubMed

    Kim, Chang-Hyun; Cheong, Kyung Ah; Lee, Ai-Young

    2013-11-01

    Light emitting diode (LED) phototherapy is an effective alternative for the treatment of inflammatory skin disorders. Tacrolimus (FK-506) is a potent immunomodulating agent, which has been used to treat AD. Combination therapy is often used in the treatment of AD to improve therapeutic efficacy or to reduce the dose of each drug. To investigate the therapeutic efficacy of monotherapy with either 850nm LED phototherapy or low-dose FK-506, and combination therapy in Dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with LED (10 and 25J/cm(2)) alone, low-dose FK-506 (1mg/kg) or in combination. The synergistic effects of combined therapy were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, such as IgE, NO, Th2-mediated cytokines and chemokines. Combination therapy with 850nm (25J/cm(2)) LED and low-dose FK-506 showed a significant reduction in the severity of skin lesions. Combined therapy decreased in the serum level of IgE, NO, and in the splenic level of Th2-mediated cytokines and chemokines. Combination therapy significantly also reduced the inflammatory cellular infiltrate into the skin lesions. Moreover, combination therapy led to recovery of skin barrier function in the skin lesions. The use of combination of LED phototherapy and low-dose immunosuppressant improved Df-induced AD-like skin lesions in an NC/Nga mouse model by dominantly reducing IgE, NO, suppressing Th2-mediated immune responses, and inhibiting inflammatory cells, as well as improving skin barrier function. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. The evaluation of potential pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers.

    PubMed

    Tortorici, Michael A; Parks, Virginia; Matschke, Kyle; Korth-Bradley, Joan; Patat, Alain

    2013-04-01

    Sirolimus and tacrolimus are immunosuppressive compounds that have been used concomitantly in renal transplant patients. Both drugs are dosed orally and have common intestinal and hepatic metabolism and intestinal transport mechanisms. As such, there is a potential for pharmacokinetic drug interaction. A single-dose, open-label, four-period, four-treatment, randomized crossover study was conducted in 27 healthy fasting volunteers. Each subject received a 15-mg oral dose of sirolimus alone, a 10-mg oral dose of tacrolimus alone, sirolimus and tacrolimus administered simultaneously, and tacrolimus administered 4 h before sirolimus. Whole blood and plasma samples for sirolimus and tacrolimus testing were analyzed by liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were assessed using noncompartmental methods and were compared using analysis of variance (ANOVA). The geometric mean ratio and 90 % confidence interval (CI) area under the concentration-time curve from time 0 to infinity (AUCinf) for sirolimus administered simultaneously with tacrolimus versus sirolimus alone were 97 and 89-106, respectively, and, when administered in a staggered approach versus sirolimus alone, 107 and 98-117, respectively. The geometric mean ratio (%) and 90 % CI AUCinf for tacrolimus administered simultaneously with sirolimus versus tacrolimus alone were 92 and 82-102, respectively, and, when administered in a staggered approach versus tacrolimus alone, 94 and 84-105, respectively. The results of this study demonstrate a lack of any clinically important drug interaction between sirolimus and tacrolimus in healthy subjects after single-dose administration. However, due to the complexity of anti-rejection immunosuppressive therapy dosing, we suggest that sirolimus and tacrolimus concentration monitoring be performed when changes in dosing are made for either drug regimen.

  16. Effects of traditional chinese medicine Wuzhi capsule on pharmacokinetics of tacrolimus in rats.

    PubMed

    Wei, Hua; Tao, Xia; Di, Peng; Yang, Yingbo; Li, Jingxian; Qian, Xiaofeng; Feng, Jin; Chen, Wansheng

    2013-07-01

    Wuzhi capsule (WZC) is a preparation of an ethanol herbal extract of Schisandra sphenanthera (Nan-Wuweizi), with its main active ingredients that include schisandrin, schizandrol B, schisantherin A, schisanhenol, and deoxyschizandrin. WZC and tacrolimus are often coadministered for the treatment of drug-induced hepatitis in organ transplant recipients in China. Recently, it was reported that WZC could significantly increase the blood concentration of tacrolimus. The purpose of this study was to investigate whether and how WZC affects the pharmacokinetics of tacrolimus in rats. Liquid chromatography-tandem mass spectrometry method was used to determine the plasma concentration of tacrolimus. The results showed that WZC increased the mean plasma concentration of tacrolimus. Compared with administration of tacrolimus alone [maximum plasma concentration (C(max)), 18.87 ± 10.29 ng/ml; area under the plasma concentration-time curve from time zero to last sampling time (AUC(0→t)), 40.98 ± 37.07 ng h/ml], a single intragastric administered dose of WZC increased the pharmacokinetic parameters of tacrolimus (C(max), 59.42 ± 30.32 ng/ml; AUC(0→t), 239.71 ± 28.86 ng h/ml) by 5-fold in rat plasma. After pretreatment with WZC for 12 days, there were still significant increases in AUC(0→t) (from 40.98 ± 37.07 to 89.21 ± 26.39 ng h/ml; P < 0.05) and C(max) (from 18.87 ± 10.29 to 43.16 ± 10.61 ng/ml; P < 0.05) of tacrolimus, compared with oral of tacrolimus alone, suggesting that WZC increased the exposure of tacrolimus by one or more mechanisms. The increase in tacrolimus C(max) by WZC was dose-dependent. The effect of WZC on tacrolimus AUC(0→t) also increased with dose, with a maximal effect observed at 450 mg/kg (825.34 ng h/ml). No further increases in tacrolimus AUC(0→t) were observed at WZC dose above 450 mg/kg. It is suggested that, because of the effect of WZC on the pharmacokinetics of tacrolimus, the herb-drug interaction between WZC and tacrolimus

  17. A high performance liquid chromatography tandem mass spectrometry for the quantification of tacrolimus in human bile in liver transplant recipients.

    PubMed

    Tron, Camille; Rayar, Michel; Petitcollin, Antoine; Beaurepaire, Jean-Marie; Cusumano, Caterina; Verdier, Marie-Clémence; Houssel-Debry, Pauline; Camus, Christophe; Boudjema, Karim; Bellissant, Eric; Lemaitre, Florian

    2016-12-02

    Tacrolimus whole-blood concentrations imperfectly reflect concentrations at the effect site. Tacrolimus concentrations in the transplanted organ could be more relevant to predict rejection events. Because liver biopsy cannot be repeatedly performed after liver transplantation, we suggested measuring tacrolimus in the bile to have a cost-effective and clinically implementable surrogate marker of intra-hepatic tacrolimus concentration. We developed and fully validated a liquid chromatography-tandem mass spectrometry method for the determination of tacrolimus in human bile. Sample purification was achieved using protein precipitation and liquid-liquid extraction with ethyl-acetate. Gradient elution was performed using a C18 analytical column with a 5min run-time. The method was linear from 0.5ng/mL to 20ng/mL. In this concentration range, within-day and between-day precisions as well as overall bias were within ±15%. Matrix effect was fully corrected by the internal standard (ascomycin). The assay was optimized to achieve good selectivity in this complex biological matrix. Tacrolimus was found to be stable in bile stored 6 months at -80°C, after 3 freeze and thaw cycles, 20h at room temperature and 24h in extracts kept at 15°C in the auto-sampler. The method was applied to quantify tacrolimus in bile from liver transplant recipients. It allowed getting preliminary data about tacrolimus excretion profile in bile and showed the lack of correlation between tacrolimus whole blood concentration and tacrolimus liver exposition. This alternative and innovative analytical approach of tacrolimus bio-analysis appears suitable for further studies evaluating relevance of biliary tacrolimus concentration as a new pharmacological marker of immunosuppressive activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. [Alternative treatment methods in ENT].

    PubMed

    Friese, K H

    1997-08-01

    In this review, the most important complementary und alternative therapies are discussed, focusing particularly on their use in otorhinolaryngology. These therapies include balneology, Kneipp therapy, microbiological therapy, fasting, excretion therapy, different oxygen therapies, hydro-colon therapy, urine therapy, own-blood therapy, Bach therapy, orthomolecular therapy, order therapy, environmental medicine, phytotherapy, homeopathy, complex homeopathy, anthroposophy, neural therapy, electroaccupuncture according to Voll and similar therapies, nasal reflex therapy, reflex-zone massage, manual therapy, massage, lymph drainage, aroma therapy, thermotherapy, bioresonance, kinesiology, hopi candles, and dietetics. Some of these methods and regimens can be recommended, but others should be rejected. In universities, these methods are only represented to a minor extend, but are more accepted by otorhinolaryngologists in practice. This paper provides a guide to which alternative therapies are sensible and possible in otorhinolaryngology. The aim is to stimulate interest in these methods. It is necessary to discuss these alternative methods reasonably and credibly with patients.

  19. [Alternative treatments for interstitial cystitis].

    PubMed

    Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

    2009-06-01

    Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

  20. Cheilitis Glandularis of Both Lips: Successful Treatment with a Combination of an Intralesional Steroid Injection and Tacrolimus Ointment

    PubMed Central

    2018-01-01

    Cheilitis glandularis (CG) is an inflammatory condition of unknown cause that predominantly affects the minor salivary glands of the lips. Although a diagnosis of CG is not difficult, its treatment is a challenge. This article highlights the clinical presentation of the disease together with a case of successful management of this disease using a combination of a steroid injection followed by a topical immunosuppressor. PMID:29744227

  1. A Low Concentration of Tacrolimus/Semifluorinated Alkane (SFA) Eyedrop Suppresses Intraocular Inflammation in Experimental Models of Uveitis.

    PubMed

    De Majumdar, S; Subinya, M; Korward, J; Pettigrew, A; Scherer, D; Xu, H

    2017-01-01

    Corticosteroids remain the mainstay therapy for uveitis, a major cause of blindness in the working age population. However, a substantial number of patients cannot benefit from the therapy due to steroids resistance or intolerance. Tacrolimus has been used to treat refractory uveitis through systemic administration. The aim of this study was to evaluate the therapeutic potential of 0.03% tacrolimus eyedrop in mouse models of uveitis. 0.03% tacrolimus in perfluorobutylpentane (F4H5) (0.03% Tacrolimus/SFA) was formulated using a previously published protocol. Tacrolimus suspended in PBS (0.03% Tacrolimus/PBS) was used as a control. In addition, 0.1% dexamethasone (0.1% DXM) was used as a standard therapy control. Endotoxin-induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU) were induced in adult C57BL/6 mice using protocols described previously. Mice were treated with eyedrops three times/day immediately after EIU induction for 48 h or from day 14 to day 25 post-immunization (for EAU). Clinical and histological examinations were conducted at the end of the experiment. Pharmacokinetics study was conducted in mice with and without EIU. At different times after eyedrop treatment, ocular tissues were collected for tacrolimus measurement. The 0.03% Tacrolimus/SFA eyedrop treatment reduced the clinical scores and histological scores of intraocular inflammation in both EIU and EAU to the levels similar to 0.1% DXM eyedrop treatment. The 0.03% Tacrolimus/PBS did not show any suppressive effect in EIU and EAU. Pharmacokinetic studies showed that 15 min after topical administration of 0.03% Tacrolimus/SFA, low levels of tacrolimus were detected in the retina (48 ng/g tissue) and vitreous (2.5 ng/ml) in normal mouse eyes, and the levels were significantly higher in EIU eyes (102 ng/g tissue in the retina and 24 ng/ml in the vitreous). Tacrolimus remained detectable in intraocular tissues of EIU eyes 6 h after topical administration (68 ng/g retinal tissue, 10

  2. The carcinogenic potential of tacrolimus ointment beyond immune suppression: a hypothesis creating case report.

    PubMed

    Becker, Jürgen C; Houben, Roland; Vetter, Claudia S; Bröcker, Eva B

    2006-01-11

    Since tacrolimus ointment was approved by the U.S. Food and Drug Administration (FDA) as a promising treatment for atopic dermatitis, it has been approved in more than 30 additional countries, including numerous European Union member nations. Moreover, in the current clinical routine the use of this drug is no longer restricted to the approved indication, but has been extended to a wide variety of inflammatory skin diseases including some with the potential of malignant transformation. So far, the side-effects reported from the topical use of tacrolimus have been relatively minor (e.g. burning, pruritus, erythema). Recently, however, the FDA reviewed the safety of topical tacrolimus, which resulted in a warning that the use of calcineurin inhibitors may be associated with an increased risk of cancer. Oral lichen planus (OLP) was diagnosed in a 56-year-old women in February 1999. After several ineffective local and systemic therapeutic measures an off-label treatment of this recalcitrant condition using Tacrolimus 0.1% ointment was initiated in May 2002. After a few weeks of treatment most of the lesions ameliorated, with the exception of the plaques on the sides of the tongue. Nevertheless, the patient became free of symptoms which, however, reoccurred once tacrolimus was weaned, as a consequence treatment was maintained. In April 2005, the plaques on the left side of the tongue appeared increasingly compact and a biopsy specimen confirmed the suspected diagnosis of an oral squamous cell carcinoma. The suspected causal relationship between topical use of tacrolimus and the development of a squamous cell carcinoma prompted us to test the notion that the carcinogenicity of tacrolimus may go beyond mere immune suppression. To this end, tacrolimus has been shown to have an impact on cancer signalling pathways such as the MAPK and the p53 pathway. In the given case, we were able to demonstrate that these pathways had also been altered subsequent to tacrolimus therapy.

  3. Sirolimus Versus Tacrolimus as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    PubMed

    Liu, Jin-Yu; Song, Ming; Guo, Min; Huang, Feng; Ma, Bing-Jun; Zhu, Lan; Xu, Gang; Li, Juan; You, Ru-Xu

    Sirolimus and tacrolimus are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of sirolimus and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane controlled trials register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection (AR), and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and QALYs gained and incremental cost-effectiveness. Altogether, 1189 patients from 8 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of AR and patient withdrawn. Nevertheless, tacrolimus increased the risk of infection. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events after renal transplant. Tacrolimus is an effective and safe immunosuppressive agent, and it may be more cost-effective than cyclosporine for the primary prevention of AR in renal transplant recipients. However, it should be noted that such superiority was reversal when the cost of sirolimus and tacrolimus changed.

  4. Distinct effects of omeprazole and rabeprazole on the tacrolimus blood concentration in a kidney transplant recipient.

    PubMed

    Takahashi, Kazushige; Yano, Ikuko; Fukuhara, Yuga; Katsura, Toshiya; Takahashi, Takeshi; Ito, Noriyuki; Yamamoto, Shingo; Ogawa, Osamu; Inui, Ken-ichi

    2007-12-01

    Proton-pump inhibitors (PPIs, e.g. omeprazole and rabeprazole) are often administered to transplant patients as a treatment or prophylaxis for ulcers after surgery. Since tacrolimus and PPIs share the CYP3A4 system for metabolism, pharmacokinetic interactions are anticipated when they are administered simultaneously. We present a Japanese male patient who underwent a living-donor kidney transplantation having received tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression. The concentration/dose (C/D) ratio for tacrolimus was markedly higher during the period of treatment with omeprazole than ranitidine or rabeprazole. The results of liver functional tests were within the normal range during the use of these three antacid drugs. Since the higher C/D ratio for tacrolimus when omeprazole was being administered did not result from a decrease in the elimination of tacrolimus due to hepatic dysfunction, drug interaction between omeprazole and tacrolimus was strongly suspected. The present case indicates that rabeprazole can be used safely in place of omeprazole in kidney transplant recipients receiving tacrolimus.

  5. ALTERNATIVE ENERGY SOURCES FOR WASTEWATER TREATMENT PLANTS

    EPA Science Inventory

    The technology assessment provides an introduction to the use of several alternative energy sources at wastewater treatment plants. The report contains fact sheets (technical descriptions) and data sheets (cost and design information) for the technologies. Cost figures and schema...

  6. Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema.

    PubMed

    Jin, Hyunju; Kim, Jeong-Min; Kim, Gun-Wook; Kim, Hoon-Soo; Ko, Hyun-Chang; Kim, Moon-Bum; Kim, Byung-Soo

    2017-06-01

    The limited efficacy of topical tacrolimus may result from insufficient frequency of application or amount applied in eczema patients. To investigate the frequency of application and amount of use of topical tacrolimus in patients with various types of eczema. The frequency of application and the applied amount of topical tacrolimus were assessed over two weeks. A total of 200 eczema patients completed this study. The average number of applications per day was 1.75 ± 0.53, despite instructions to apply the topical tacrolimus twice daily. With respect to the frequency of application, 147 (73.5%) and 122 (61.0%) of patients followed the prescription in the first and second weeks, respectively. The average amount applied per 2% of total body surface area (TBSA) was 0.54 ± 0.52 g. Only 53 (26.5%) patients applied between 80 and 120% of expected amount of topical tacrolimus. The frequency of application was self-reported, possibly resulting in limited accuracy. Korean patients with eczema tend to apply topical tacrolimus less frequently and in inappropriate amounts. Clear instructions regarding both the frequency and amount of application are needed to improve the therapeutic outcome with treatment with topical tacrolimus.

  7. [Alternative treatments in irritable bowel syndrome].

    PubMed

    Hagège, H

    2009-02-01

    Managing irritable bowel syndrome (IBS) is difficult and often a source of dissatisfaction for the patient, explaining the increasingly frequent recourse to alternative treatments. These highly varied treatments are often associated. They can be classed into four categories: reflexology methods, interventions on the psyche, biological therapies, and treatments using certain forms of energy. Although some studies show interesting results, currently there are not sufficient scientific arguments to recommend one or another of these alternative treatments. Multicenter controlled studies are needed to better evaluate the strategies that appear to be cost-effective.

  8. Generic tacrolimus in solid organ transplantation.

    PubMed

    Taube, D; Jones, G; O'Beirne, J; Wennberg, L; Connor, A; Rasmussen, A; Backman, L

    2014-05-01

    The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which are similar in quality, safety, and efficacy to their approved innovator drugs. There are data available for three generic brands, tacrolimus (Intas), tacrolimus (PharOS), and tacrolimus (Sandoz). Bioequivalence has been demonstrated for generic tacrolimus (Sandoz) within a narrow therapeutic range to its innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other SOT patients, including lung and heart recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Alternatives to Drug Treatment for Hyperactivity.

    ERIC Educational Resources Information Center

    Den Houtter, Kathryn

    1980-01-01

    Results from recent studies on the effectiveness of Ritalin for "hyperactivity" show that this treatment is dubious at best. This article presents an alternative treatment approach, placing emphasis on devising an appropriate learning situation that meets the needs of the so-called hyperactive child. (Author)

  10. Listening Clearly: Alternative Treatments for Adolescent Depression

    ERIC Educational Resources Information Center

    McGlasson, Terry D.

    2012-01-01

    For many years now, Cognitive Behavioral Therapy and anti-depressant medications have been the primary treatments for adolescent depression. However, there are many youth today with mild to moderate depressive symptoms for whom these treatments are not necessary. This article briefly summarizes several alternative therapeutic approaches for…

  11. Alternative methods of ophthalmic treatment in Russia.

    PubMed

    Vader, L

    1994-04-01

    Russian ophthalmic nurses and physicians are using alternative methods of treatment to supplement traditional eye care. As acupuncture and iridology become more popular in the United States, ophthalmic nurses need to be more knowledgeable about these treatments and the implications for patients.

  12. Lactobacillus Fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.

    PubMed

    Toral, Marta; Romero, Miguel; Rodríguez-Nogales, Alba; Jiménez, Rosario; Robles-Vera, Iñaki; Algieri, Francesca; Chueca-Porcuna, Natalia; Sánchez, Manuel; de la Visitación, Néstor; Olivares, Mónica; García, Federico; Pérez-Vizcaíno, Francisco; Gálvez, Julio; Duarte, Juan

    2018-05-30

    Our aim was to analyse whether the probiotic Lactobacillus fermentum CECT5716 (LC40) could prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. Tacrolimus increased systolic blood pressure (SBP) and impaired endothelium-dependent relaxation to acetylcholine and these effects were partially prevented by LC40. Endothelial dysfunction induced by tacrolimus was related to both increased NADPH oxidase (NOX2) and uncoupled eNOS driven-superoxide production and Rho-kinase mediated eNOS inhibition. LC40 treatment prevented all the aortic changes induced by tacrolimus. LC40 restored the imbalance between T-helper 17 (Th17)/ regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and spleen. Tacrolimus induced gut dysbiosis, i.e. it decreased microbial diversity, increased Firmicutes/Bacteroidetes ratio and decreased acetate- and butyrate-producing bacteria and these effects were prevented by LC40. Fecal microbiota transplantation from LC40 treated mice to control mice prevented the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus. LC40 treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 down-regulation and prevention of eNOS-uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Unraveling Nutritional Regulation of Tacrolimus Biosynthesis in Streptomyces tsukubaensis through omic Approaches.

    PubMed

    Ordóñez-Robles, María; Santos-Beneit, Fernando; Martín, Juan F

    2018-05-01

    Streptomyces tsukubaensis stands out among actinomycetes by its ability to produce the immunosuppressant tacrolimus. Discovered about 30 years ago, this macrolide is widely used as immunosuppressant in current clinics. Other potential applications for the treatment of cancer and as neuroprotective agent have been proposed in the last years. In this review we introduce the discovery of S. tsukubaensis and tacrolimus, its biosynthetic pathway and gene cluster ( fkb ) regulation. We have focused this work on the omic studies performed in this species in order to understand tacrolimus production. Transcriptomics, proteomics and metabolomics have improved our knowledge about the fkb transcriptional regulation and have given important clues about nutritional regulation of tacrolimus production that can be applied to improve production yields. Finally, we address some points of S. tsukubaensis biology that deserve more attention.

  14. Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum

    PubMed Central

    Hebert, Mary F.; Zheng, Songmao; Hays, Karen; Shen, Danny D.; Davis, Connie L.; Umans, Jason G.; Miodovnik, Menachem; Thummel, Kenneth E.; Easterling, Thomas R.

    2012-01-01

    Summary Pregnancy following solid organ transplantation, although considered high risk for maternal, fetal and neonatal complications, has been quite successful. Tacrolimus pharmacokinetic changes during pregnancy make interpretation of whole blood trough concentrations particularly challenging. There are multiple factors that can increase the fraction of unbound tacrolimus, including but not limited to low albumin concentration and low RBC count. The clinical titration of dosage to maintain whole blood tacrolimus trough concentrations in the usual therapeutic range can lead to elevated unbound concentrations and possibly toxicity in pregnant women with anemia and hypoalbuminemia. Measurement of plasma or unbound tacrolimus concentrations for pregnant women might better reflect the active form of the drug, though these are technically-challenging and often unavailable in usual clinical practice. Tacrolimus crosses the placenta with in utero exposure being approximately 71% of maternal blood concentrations. The lower fetal blood concentrations are likely due to active efflux transport of tacrolimus from the fetus toward the mother by placental P-glycoprotein. To date, tacrolimus has not been linked to congenital malformations, but can cause reversible nephrotoxicity and hyperkalemia in the newborn. In contrast, very small amounts of tacrolimus are excreted in the breast milk and are unlikely to elicit adverse effects in the nursing infant. PMID:23274970

  15. Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers.

    PubMed

    Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

    2014-11-01

    The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. © 2014 The British Pharmacological Society.

  16. Rectal and sublingual administration of tacrolimus: a single-dose pharmacokinetic study in healthy volunteers

    PubMed Central

    Stifft, Frank; Vanmolkot, Floris; Scheffers, Ingrid; van Bortel, Luc; Neef, Cees; Christiaans, Maarten

    2014-01-01

    Aims The immunosuppressant tacrolimus is usually administered orally. When this is not feasible, other routes of administration may be useful. Previous research suggested that tacrolimus may be applied sublingually or rectally. Pharmacokinetic data are sparse. The aim of this study was to investigate and compare the pharmacokinetics of these alternative formulations with orally administered tacrolimus. Methods Three single, fixed-dose formulations of tacrolimus were administered in a random sequence in 18 healthy subjects, using a cross-over study design. For sublingual administration, 3 mg of powder obtained from oral capsules was applied under the tongue for a period of 15 min without swallowing, with mouth rinsing afterwards. For rectal administration, a suppository containing 15 mg of the oral powder was used. Oral administration consisted of 7 mg of instant-release tacrolimus capsules (Prograf). Main pharmacokinetic outcome parameters were compared by anova. Results Sublingual administration showed no clinically significant exposure, contrary to rectal administration, where all subjects had clinically relevant exposure, with a lower relative bioavailability (78%), a lower maximal blood concentration and a later time of maximal blood concentration compared with oral administration. Conclusions Sublingual administration of a single dose of tacrolimus does not result in systemic exposure if care is taken not to swallow saliva and to rinse the oral cavity afterwards. Rectal administration of tacrolimus results in clinically relevant systemic exposure and might represent an alternative formulation in case oral administration is not feasible. When used as a topical agent, systemic side-effects should be considered. PMID:24809233

  17. Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

    PubMed Central

    Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

    2016-01-01

    Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

  18. Early alteration of kidney function in nonuremic type 1 diabetic islet transplant recipients under tacrolimus-mycophenolate therapy.

    PubMed

    Gillard, Pieter; Rustandi, Maria; Efendi, Achmad; Lee, Da Hae; Ling, Zhidong; Hilbrands, Robert; Kuypers, Dirk; Mathieu, Chantal; Jacobs-Tulleneers-Thevissen, Daniel; Gorus, Frans; Pipeleers, Daniel; Keymeulen, Bart

    2014-08-27

    Transplant patients on tacrolimus therapy exhibit a reduced glomerular filtration rate (GFR). The type of graft and immune treatment protocol may influence the extent and reversibility of this side effect. The present single-center study is conducted in 48 nonuremic type 1 diabetic recipients of an intraportal islet-cell graft under maintenance immunosuppression (IS) with tacrolimus and mycophenolate mofetil. Estimated GFR (eGFR) and albuminuria were followed up to 5 years posttransplantation. Mean eGFR values decreased by 19 mL/min/1.73 m after 1 to 2 weeks of IS (P<0.0001) and then remained stable throughout the complete treatment period. The decrease was related to predose trough tacrolimus concentrations or doses and disappeared upon its discontinuation; it was also associated with the presence of albuminuria at the time of transplantation. Tacrolimus treatment resulted in a reduction of albuminuria; its discontinuation restored albuminuria to the initial levels. The use of tacrolimus in our islet-cell transplant protocol caused an initial 20% reduction in eGFR, which was reversible following its discontinuation, at least within the 5-year follow-up period. The associated reduction in albuminuria was also reversible, compatible with a tacrolimus-induced preglomerular vasoconstriction. These observations support further use of our tacrolimus regimen in this patient population.

  19. Multi-site analytical evaluation of the Abbott ARCHITECT tacrolimus assay.

    PubMed

    Wallemacq, Pierre; Goffinet, Jean-Sebastien; O'Morchoe, Susan; Rosiere, Thomas; Maine, Gregory T; Labalette, Myriam; Aimo, Giuseppe; Dickson, Diana; Schmidt, Ed; Schwinzer, Reinhard; Schmid, Rainer W

    2009-04-01

    versus the Dade Dimension Tacrolimus immunoassay (2 sites) yielded average biases of -0.46 and +0.11 ng/mL; and ARCHITECT assay versus LC-MSMS methods at 2 sites yielded average biases of +0.51 and +1.63 ng/mL. Spearman correlation coefficients were >/=0.90 on all method comparisons. The ARCHITECT Tacrolimus assay is a semiautomated, robust, and highly sensitive immunoassay, representing an alternative approach for laboratories not equipped with LC-MSMS, and meets the 1 ng/mL recommendation of LOQ by the European Consensus Conference on Tacrolimus Optimization.

  20. A multicenter experience with generic tacrolimus conversion.

    PubMed

    McDevitt-Potter, Lisa M; Sadaka, Basma; Tichy, Eric M; Rogers, Christin C; Gabardi, Steven

    2011-09-27

    The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

  1. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    PubMed

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  2. Evaluation of the Ocular Tolerance of Three Tacrolimus Topical Pharmaceutical Preparations by Bovine Corneal Opacity and Permeability Test.

    PubMed

    Pastor-Clerigues, Alfonso; Serrano, Adela; Milara, Javier; Marti-Bonmati, Ezequiel; Lopez-Perez, Francisco J; Garcia-Montanes, Sara; Sanfeliu, Joan; Saval-Victoria, Ana C; Cortijo, Julio

    2016-07-01

    Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated. Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent junctions E-cadherin, VE-cadherin and zonula occludens-1 were examined and scored to evaluate and to confirm corneal disruption and irritation scores obtained with the BCOP method. Commercial brand ointment (Protopic®), topical compounded eye ointment (pharmacy elaboration) and tacrolimus suspension eye drops (elaborated from parenteral prograf®) were tested as potential ocular preparations to be used in clinics. Tacrolimus preparations hereby studied do not alter the opacity and permeability of the bovine cornea by more than three units, measured by the In Vitro Irritancy Score, neither affected the immunohistochemical parameters, composite score or transepithelial electrical resistance. Tacrolimus preparations studied can be safely applied as a topical ocular treatment.

  3. Cobicistat Significantly Increases Tacrolimus Serum Concentrations in a Renal Transplant Recipient with Human Immunodeficiency Virus Infection.

    PubMed

    Han, Zhe; Kane, Brenna M; Petty, Lindsay A; Josephson, Michelle A; Sutor, Jozefa; Pursell, Kenneth J

    2016-06-01

    Cobicistat is a pharmacokinetic booster in several fixed-dose combination products for treatment of human immunodeficiency virus (HIV) infection. As a potent inhibitor of cytochrome P450 (CYP) 3A enzymes, significant drug-drug interactions are expected between cobicistat and medications that are metabolized primarily through the CYP3A pathway, including calcineurin inhibitors (e.g., tacrolimus and cyclosporine). We describe a case of tacrolimus toxicity due to supratherapeutic tacrolimus concentrations when Stribild (elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate) was initiated for newly diagnosed HIV infection in a 50-year-old renal transplant recipient who was previously receiving a stable tacrolimus regimen. Drug-drug interaction via CYP3A inhibition was acknowledged, and weekly labs were ordered to allow for close monitoring of renal function and tacrolimus serum concentrations as recommended by Stribild prescribing information. The patient reported headache, insomnia, stomachache, and decreased urine output within 1 week of starting Stribild and was found to have acute kidney injury (serum creatinine [S cr ]concentration increasing from 1.5-2.3 mg/dl) and a serum tacrolimus concentration of 111.2 ng/ml at 1 week follow-up (goal trough level 4-6 ng/ml). Both tacrolimus and Stribild were withheld. In 15 days, the patient's tacrolimus serum concentration returned to goal. In the interim, he required twice/week clinic visits for laboratory assessments and an emergency department visit for management of hyperkalemia (potassium 6.5 mEq/L). Triumeq (abacavir, dolutegravir, and lamivudine) was started about 4 weeks later after S cr returned to baseline, and his tacrolimus serum trough concentrations subsequently remained stable. To our knowledge, this is the first case report describing the extent, significance, and onset of cobicistat and tacrolimus drug-drug interaction in clinical practice. As more fixed-dose combination products

  4. Tacrolimus

    MedlinePlus

    ... rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people ... It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

  5. Noninvasive treatment alternative for intractable startle epilepsy

    PubMed Central

    Klinkenberg, Sylvia; Ubbink, Sander; Vles, Johannes; de Louw, Anton; van Hall, Mariette Debeij; Scheijen, Dyon; Brokx, Jan

    2014-01-01

    We describe a treatment alternative for intractable, startle-provoked, epileptic seizures in four children aged between 8 and 14. Three of the four children had symptomatic localization-related epilepsy. They all suffered from intractable epilepsy precipitated by sudden sounds. The fact that seizures tended to occur with high frequency – more than one seizure a day – had a clear impact on daily life. Clinical seizure pattern demonstrated asymmetric tonic posturing in all four children. Three children experienced several seizure types including focal seizure onset. All children had focal neurological signs or learning disabilities or a combination of both. Our noninvasive treatment method using psychoeducational counseling and sound generators was applied in four children, resulting in a seizure frequency reduction of ≥ 50% in two of them. PMID:25667869

  6. Evaluation of gingival alterations in rats medicated with cyclosporine A, tacrolimus and sirolimus: a stereological study.

    PubMed

    Pamuk, F; Cetinkaya, B O; Ayas, B; Keles, G C; Gacar, A

    2015-10-01

    It has previously been shown that both cyclosporine A and tacrolimus cause gingival overgrowth in the rat. We proposed that sirolimus may play an important role in decreasing the severity of gingival overgrowth. Therefore, the aim of this study was to evaluate the gingival changes induced by immunosuppressants, in the presence and absence of sirolimus, using histopathology and stereological methods. Thirty-six male Sprague-Dawley rats were distributed into six treatment groups, each containing six rats, as follows: (i) cyclosporine A for 8 wk; (ii) tacrolimus for 8 wk; (iii) sirolimus for 8 wk; (iv) cyclosporine A + sirolimus for 8 wk; (v) tacrolimus + sirolimus for 8 wk; and (vi) distilled water for 8 wk. Histomorphometric analyses included measurements of epithelial thickness and connective tissue width and height. Stereological analyses included measurements of volumetric densities of fibroblasts (Vf ), collagen fibers (Vcf ) and blood vessels (Vbv ). Connective tissue width and height were significantly increased in cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05), and epithelial thickness was significantly increased in the cyclosporine A group and tacrolimus group compared with the control group (p < 0.05). Vf was significantly increased in the cyclosporine A group and the tacrolimus group compared with the control group (p < 0.05), whereas Vcf and Vbv were significantly increased in the cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05). The results of the study suggest that sirolimus seems not to be associated with gingival overgrowth, and combined usage of sirolimus and immunosuppressants decreases the severity of gingival overgrowth. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The calcineurin inhibitor tacrolimus as a new therapy in severe cherubism.

    PubMed

    Kadlub, Natacha; Vazquez, Marie-Paule; Galmiche, Louise; L'Herminé, Aurore Coulomb; Dainese, Linda; Ulinski, Tim; Fauroux, Brigitte; Pavlov, Ioana; Badoual, Cécile; Marlin, Sandrine; Deckert, Marcel; Leboulanger, Nicolas; Berdal, Ariane; Descroix, Vianney; Picard, Arnaud; Coudert, Amélie E

    2015-05-01

    Cherubism is a rare genetic disorder characterized by extensive growth of a bilateral granuloma of the jaws, resulting in facial disfigurement. Cherubism is caused by gain-of-function mutations in the SH3BP2 gene, leading to overactivation of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-dependent osteoclastogenesis. Recent findings in human and mouse cherubism have suggested that calcineurin inhibitors might be drug candidates in cherubism medical treatment. A 4-year-old boy with aggressive cherubism was treated with the calcineurin inhibitor tacrolimus for 1 year, and clinical, radiological, and molecular data were obtained. Immunohistologic analysis was performed to compare preoperative and postoperative NFATc1 staining and tartrate resistant acid phosphatase (TRAP) activity. Real-time PCR was performed to analyze the relative expression levels of OPG and RANKL. After tacrolimus therapy, the patient showed significant clinical improvement, including stabilization of jaw size and intraosseous osteogenesis. Immunohistologic analyses on granuloma showed that tacrolimus caused a significant reduction in the number of TRAP-positive osteoclasts and NFATc1 nuclear staining in multinucleated giant cells. Molecular analysis showed that tacrolimus treatment also resulted in increased OPG expression. We present the first case of effective medical therapy in cherubism. Tacrolimus enhanced bone formation by stimulating osteogenesis and inhibiting osteoclastogenesis. © 2014 American Society for Bone and Mineral Research.

  8. Exploring alternative treatments for Helicobacter pylori infection

    PubMed Central

    Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

    2014-01-01

    Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621

  9. Complementary and alternative treatment in functional dyspepsia

    PubMed Central

    Chiarioni, Giuseppe; Pesce, Marcella; Fantin, Alberto; Sarnelli, Giovanni

    2017-01-01

    Introduction and aim The popularity of complementary and alternative medicine (CAM) in treating functional gastrointestinal disorders (FGIDs) has steadily increased in Western countries. We aimed at analyzing available data on CAM effectiveness in functional dyspepsia (FD) patients. Methods A bibliographical search was performed in PubMed using the following keywords: “complementary/alternative medicine,” “hypnosis,” “acupuncture” and/or “functional dyspepsia.” Results In community settings, almost 50% of patients with FGIDs used CAM therapies. Herbal remedies consist of multi-component preparations, whose mechanisms of action have not been systematically clarified. Few studies analyzed the effectiveness of acupuncture in Western countries, yielding conflicting results and possibly reflecting a population bias of this treatment. Hypnosis has been extensively used in irritable bowel syndrome, but few data support its role in treating FD. Conclusions Although some supporting well-designed studies have been recently performed, additional randomized, controlled trials are needed before stating any recommendation on CAM effectiveness in treating FD. PMID:29435308

  10. 40 CFR 142.46 - Alternative treatment techniques.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Alternative treatment techniques. 142... Administrator Under Section 1415(a) of the Act § 142.46 Alternative treatment techniques. The Administrator may... that an alternative treatment technique not included in such requirement is at least as efficient in...

  11. Complementary and alternative treatment of musculoskeletal pain.

    PubMed

    Grazio, Simeon; Balen, Diana

    2011-12-01

    The use of complementary and alternative medicine (CAM) is high and increasing worldwide. Patients usually use CAM in addition to conventional medicine, mainly to treat pain. In a large number of cases, people use CAM for chronic musculoskeletal pain as in osteoarthritis, back pain, neck pain, or fibromyalgia. Herewith, a review is presented of CAM efficacy in treating musculoskeletal pain for which, however, no scientific research has so far provided evidence solid enough. In some rare cases where adequate pain control cannot be achieved, CAM might be considered in rational and individual approach based on the first general rule in medicine "not to harm" and on the utility theory of each intervention, i.e. according to the presumed mechanism of painful stimulus and with close monitoring of the patient's response. Further high quality studies are warranted to elucidate the efficacy and side effects of CAM methods. Therefore, conventional medicine remains the main mode of treatment for patients with musculoskeletal painful conditions.

  12. False Elevation of the Blood Tacrolimus Concentration, as Assessed by an Affinity Column-mediated Immunoassay (ACMIA), Led to Acute T Cell-mediated Rejection after Kidney Transplantation.

    PubMed

    Kono, Momoko; Hasegawa, Jumpei; Ogawa, Hina; Yoshikawa, Kanae; Ishiwatari, Ayumi; Wakai, Sachiko; Tanabe, Kazunari; Shirakawa, Hiroki

    2018-05-01

    Tacrolimus is the most commonly used immunosuppressant. Because of its narrow therapeutic range, it is necessary to frequently monitor its concentration. We report the case of a 25-year-old man who underwent kidney transplantation whose tacrolimus concentrations, as measured by an affinity column-mediated immunoassay, were falsely elevated. As we reduced the dose of tacrolimus, the recipient developed T cell-mediated rejection. Using the same blood samples, an enzyme-multiplied immunoassay technique showed that the patient's levels of tacrolimus were extremely low. A further examination indicated that the false increase in the tacrolimus concentration was likely due to an unknown interfering substance. We administered methylprednisolone and antithymocyte-globulin. The patient's serum creatinine level decreased and remained stable after these treatments.

  13. A randomized pharmacokinetic study of generic tacrolimus versus reference tacrolimus in kidney transplant recipients.

    PubMed

    Alloway, R R; Sadaka, B; Trofe-Clark, J; Wiland, A; Bloom, R D

    2012-10-01

    Pharmacokinetic analyses comparing generic tacrolimus preparations versus the reference drug in kidney transplant patients are lacking. A prospective, multicenter, open-label, randomized, two-period (14 days per period), two-sequence, crossover and steady-state pharmacokinetic study was undertaken to compare twice-daily generic tacrolimus (Sandoz) versus reference tacrolimus (Prograf®) in stable renal transplant patients. AUC(0-12h) and peak concentration (C(max) ) were calculated from 12 h pharmacokinetic profiles at the end of each period (days 14 and 28). Of 71 patients enrolled, 68 provided evaluable pharmacokinetic data. The ratios of geometric means were 1.02 (90% CI 97-108%, p = 0.486) for AUC(0-12h) and 1.09 (90% CI 101-118%, p = 0.057) for C(max) . Mean (SD) C(0) was 7.3(1.8) ng/mL for generic tacrolimus versus 7.0(2.1) ng/mL for reference tacrolimus based on data from days 14 and 28. Correlations between 12 h trough levels and AUC were r = 0.917 for generic tacrolimus and r = 0.887 for reference drug at day 28. These data indicate that generic tacrolimus (Sandoz) has a similar pharmacokinetic profile to the reference drug and is bioequivalent in kidney transplant recipients according to US Food and Drug Administration and European Medicines Agency guidelines. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  14. A Randomized Pharmacokinetic Study of Generic Tacrolimus Versus Reference Tacrolimus in Kidney Transplant Recipients

    PubMed Central

    Alloway, R R; Sadaka, B; Trofe-Clark, J; Wiland, A; Bloom, R D

    2012-01-01

    Pharmacokinetic analyses comparing generic tacrolimus preparations versus the reference drug in kidney transplant patients are lacking. A prospective, multicenter, open-label, randomized, two-period (14 days per period), two-sequence, crossover and steady-state pharmacokinetic study was undertaken to compare twice-daily generic tacrolimus (Sandoz) versus reference tacrolimus (Prograf®) in stable renal transplant patients. AUC0–12h and peak concentration (Cmax) were calculated from 12 h pharmacokinetic profiles at the end of each period (days 14 and 28). Of 71 patients enrolled, 68 provided evaluable pharmacokinetic data. The ratios of geometric means were 1.02 (90% CI 97–108%, p = 0.486) for AUC0–12h and 1.09 (90% CI 101–118%, p = 0.057) for Cmax. Mean (SD) C0 was 7.3(1.8) ng/mL for generic tacrolimus versus 7.0(2.1) ng/mL for reference tacrolimus based on data from days 14 and 28. Correlations between 12 h trough levels and AUC were r = 0.917 for generic tacrolimus and r = 0.887 for reference drug at day 28. These data indicate that generic tacrolimus (Sandoz) has a similar pharmacokinetic profile to the reference drug and is bioequivalent in kidney transplant recipients according to US Food and Drug Administration and European Medicines Agency guidelines. PMID:22759200

  15. Alternative treatment of symptomatic pancreatic fistula.

    PubMed

    Wiltberger, Georg; Schmelzle, Moritz; Tautenhahn, Hans-Michael; Krenzien, Felix; Atanasov, Georgi; Hau, Hans-Michael; Moche, Michael; Jonas, Sven

    2015-06-01

    The management of symptomatic pancreatic fistula after pancreaticoduodenectomy is complex and associated with increased morbidity and mortality. We here report continuous irrigation and drainage of the pancreatic remnant to be a feasible and safe alternative to total pancreatectomy. Between 2005 and 2011, patients were analyzed, in which pancreaticojejunal anastomosis was disconnected because of grade C fistula, and catheters for continuous irrigation and drainage were placed close to the pancreatic remnant. Clinical data were monitored and quality of life was evaluated. A total of 13 of 202 patients undergoing pancreaticoduodenectomy required reoperation due to symptomatic pancreatic fistula. Ninety-day mortality of these patients was 15.3%. Median length of stay on the intensive care unit and total length of stay was 18 d (range 3-45) and 46 d (range 33-96), respectively. Patients with early reoperation (<10 d) had significantly decreased length of stay on the intensive care unit and operation time (P < 0.05). Global health status after a median time of 22 mo (range 6-66) was nearly identical, when compared with that of a healthy control group. Mean follow-up was 44.4 mo (±27.2). Four patients (36.6 %) died during the follow-up period; two patients from tumor recurrence, one patient from pneumonia, and one patient for unknown reasons. Treatment of pancreatic fistula by continuous irrigation and drainage of the preserved pancreatic remnant is a simple and feasible alternative to total pancreatectomy. This technique maintains a sufficient endocrine function and is associated with low mortality and reasonable quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis.

    PubMed

    Hamel, Blaise; Wu, May; Hamel, Elizabeth O; Bass, Dorsey M; Park, K T

    2018-01-01

    Severe colitis flare from ulcerative colitis (UC) or Crohn's disease (CD) may be refractory to corticosteroids and antitumour necrosis factor (TNF) agents resulting in high colectomy rates. We aimed to describe the utility of tacrolimus to prevent colectomy during second-line vedolizumab initiation after corticosteroid and anti-TNF treatment failure in paediatric severe colitis. A retrospective cohort analysis was performed between 1 October 2014 and 31 October 2016 at a single tertiary care centre. Inclusion criteria were patients with severe colitis who received tacrolimus before or during vedolizumab induction and previous exposure to anti-TNF therapy with or without corticosteroids. The initiation of tacrolimus was clinician dependent based on an institutional protocol. Twelve patients (10 UC, two CD; median age 16 years; three female) received at least one dose of vedolizumab 10 mg/kg (max of 300 mg) due to anti-TNF therapy failure and persistent flare not responsive to corticosteroids. Of the 12 patients, eight (67%) and four (33%) had failed one or two anti-TNF agents, respectively. Tacrolimus was initiated for acute disease severity during hospitalisation (58%) or ongoing flare during outpatient care (42%). 9 (75%) of 12 patients avoided colectomy or inflammatory bowel disease-related surgery at 24 weeks and eight (68%) continued on vedolizumab maintenance with no adverse events out to 80 weeks. We report real-world data on the outcome of tacrolimus around vedolizumab initiation in paediatric UC or CD after corticosteroid and anti-TNF therapy treatment failure. Our pilot experience indicates a potential benefit of concomitant tacrolimus when initiating vedolizumab therapy.

  17. Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation.

    PubMed

    Liu, Jin-Yu; You, Ru-Xu; Guo, Min; Zeng, Lu; Zhou, Pu; Zhu, Lan; Xu, Gang; Li, Juan; Liu, Dong

    2016-01-01

    Tacrolimus and cyclosporine are the major immunosuppressants for renal transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this study was to evaluate the efficacy, safety, and pharmacoeconomics of cyclosporine and tacrolimus in the treatment of renal transplantation and provide evidence for the selection of essential drugs. Trials were identified through a computerized literature search of PubMed, EMBASE, Cochrane Controlled Trials Register, Cochrane Renal Group Specialized Register of randomized controlled trials, and Chinese Biomedical database. Two independent reviewers assessed trials for eligibility and quality and then extracted data. Data were extracted for patient and graft mortality, acute rejection, and adverse events. Dichotomous outcomes were reported as relative risk with 95% confidence intervals. A decision tree model was populated with data from a literature review and used to estimate costs and quality-adjusted life years gained and incremental cost-effectiveness. Altogether, 6137 patients from 27 randomized controlled trials were included. The results of our analysis were that tacrolimus reduced the risks after renal transplantation of patient mortality, graft loss, acute rejection, and hypercholesterolemia. Nevertheless, tacrolimus increased the risk of new-onset diabetes. Pharmacoeconomic analysis showed that tacrolimus represented a more cost-effective treatment than does cyclosporine for the prevention of adverse events following renal transplant. Tacrolimus is an effective and safe immunosuppressive agent and it may be more cost-effective than cyclosporine for the primary prevention of graft rejection in renal transplant recipients. However, new-onset diabetes should be closely monitored during the medication period.

  18. Stability of tacrolimus solutions in polyolefin containers.

    PubMed

    Lee, Jun H; Goldspiel, Barry R; Ryu, Sujung; Potti, Gopal K

    2016-02-01

    Results of a study to determine the stability of tacrolimus solutions stored in polyolefin containers under various temperature conditions are reported. Triplicate solutions of tacrolimus (0.001, 0.01, and 0.1 mg/mL) in 0.9% sodium chloride injection or 5% dextrose injection were prepared in polyolefin containers. Some samples were stored at room temperature (20-25 °C); others were refrigerated (2-8 °C) for 20 hours and then stored at room temperature for up to 28 hours. The solutions were analyzed by stability-indicating high-performance liquid chromatography (HPLC) assay at specified time points over 48 hours. Solution pH was measured and containers were visually inspected at each time point. Stability was defined as retention of at least 90% of the initial tacrolimus concentration. All tested solutions retained over 90% of the initial tacrolimus concentration at all time points, with the exception of the 0.001-mg/mL solution prepared in 0.9% sodium chloride injection, which was deemed unstable beyond 24 hours. At all evaluated concentrations, mean solution pH values did not change significantly over 48 hours; no particle formation was detected. During storage in polyolefin bags at room temperature, a 0.001-mg/mL solution of tacrolimus was stable for 24 hours when prepared in 0.9% sodium chloride injection and for at least 48 hours when prepared in 5% dextrose injection. Solutions of 0.01 and 0.1 mg/mL prepared in either diluent were stable for at least 48 hours, and the 0.01-mg/mL tacrolimus solution was also found to be stable throughout a sequential temperature protocol. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  19. Overview of extended release tacrolimus in solid organ transplantation

    PubMed Central

    Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

    2016-01-01

    Tacrolimus (Prograf©, Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf©, Astagraf XL©) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient’s due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher. PMID:27011912

  20. Overview of extended release tacrolimus in solid organ transplantation.

    PubMed

    Patel, Neha; Cook, Abigail; Greenhalgh, Elizabeth; Rech, Megan A; Rusinak, Joshua; Heinrich, Lynley

    2016-03-24

    Tacrolimus (Prograf(©), Astellas Pharma Europe Ltd, Staines, United Kingdom; referred to as tacrolimus-BID) is an immunosuppressive agent to prevent and treat allograft rejection in kidney transplant recipients in combination with mycophenolate mofetil, corticosteroids, with or without basiliximab induction. The drug has also been studied in liver, heart and lung transplant; however, these are currently off-label indications. An extended release tacrolimus formulation (Advagraf(©), Astagraf XL(©)) allows for once-daily dosing, with the potential to improve adherence. Extended release tacrolimus has similar absorption, distribution, metabolism and excretion to tacrolimus-BID. Phase I pharmacokinetic trials comparing extended release tacrolimus and tacrolimus-BID have demonstrated a decreased maximum concentration (Cmax) and delayed time to maximum concentration (tmax) with the extended release formulation; however, AUC0-24 was comparable between formulations. Overall extended release tacrolimus has a very similar safety and efficacy profile to tacrolimus-BID. It is not recommended in the use of liver transplant patient's due to the increased risk of mortality in female recipients. There has been minimal data regarding the use of extended release tacrolimus in heart and lung transplant recipients. With the current data available for all organ groups the extended release tacrolimus should be dosed in a 1:1 fashion, the exception may be the cystic fibrosis population where their initial dose may need to be higher.

  1. The Pittsburgh Randomized Trial of Tacrolimus Compared to Cyclosporine for Hepatic Transplantation

    PubMed Central

    Fung, John J.; Eliasziw, Michael; Todo, Satoru; Jain, Ashok; Demetris, Anthony J.; McMichael, John P.; Starzl, Thomas E.; Meier, Paul; Donner, Allan

    2009-01-01

    Background Tacrolimus (formerly FK 506) was first used clinically in 1989 to successfully replace cyclosporine in hepatic transplant recipients who were experiencing intractable rejection or as the baseline drug from the time of operation. After extensive pilot experience, an institutional review board-mandated clinical trial comparing cyclosporine with tacrolimus was performed. Study Design From February 16, 1990 to December 26, 1991, 154 patients were recruited. The competing drugs were combined with equal induction doses of prednisone in both arms of the study for the first 81 patients and with subsequently higher doses of prednisone in the remaining 35 patients who received cyclosporine and were entered into the trial. Drug crossover was permitted for lack of efficacy or adverse events. End points were rejection confirmed by biopsy and treatment failure leading to retransplantation or death. Results Seventy-nine patients were randomized to the tacrolimus arm and 75 to the cyclosporine arm during 1990 and 1991. All patients were available for follow-up throughout the trial, which terminated on May 30, 1995. The mean duration of follow-up was four years. Patients randomized to the tacrolimus arm were less likely to experience acute rejection than were those receiving cyclosporine, with 36.2 percent of the patients receiving tacrolimus and 16.8 percent of the patients receiving cyclosporine showing freedom from rejection at one year (p=0.003, likelihood ratio test). Survival of patients over the course of the study was virtually the same in the two groups. Conclusions Tacrolimus was more effective than cyclosporine in preventing acute rejection. PMID:8696542

  2. Lawsonia inermis - an alternative treatment for hyperthyroidism?

    PubMed

    Zumrutdal, E; Karateke, F; Daglioglu, K; Gulkaya, M; Colak, O; Koksal, F

    2014-01-01

    The goal of our study was to determine the effects of Lawsonia inermis (L. inermis) in mice, in which hyperthyroidism had been caused by thyroid stimulant hormone (TSH). The first phase of the study aimed to detect the effects of L. inermis on the amount of ionized hydrogen (pH) in cells. For this aim, the effect of L. inermis on pH levels in the liver tissues of mice, in whom Escherichia coli (E. coli) had caused peritonitis, was examined. In the second phase of the study, the effect of L. inermis on the serum T4 levels in the 24th and 48th hour in mice, whose thyroid cells showed an increased activity by TSH was measured. In the first phase, in mice, in whom E.coli had caused peritonitis, the pH in the liver tissue of the group that had been given L. inermis was found to be significantly alkaline (p<0.05). In the second phase, in mice, in whom TSH had caused hyperthyroidism, it was noted that serum total T4 levels were significantly lower than in the group that had been given L. inermis in the 48th hour (p<0.05). In our study, we detected that L. inermis significantly decreased serum total T4 levels in the 48th hour in mice in whom TSH had caused hyperthyroidism. These results suggest that L. inermis can be used as an alternative treatment for the Graves' disease (Tab. 2, Fig. 1, Ref. 34).

  3. Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

    PubMed

    Aridon, Paolo; Ragonese, Paolo; Di Benedetto, Norma; Grasso, Giovanni; Conaldi, Pier Giulio; D'Amelio, Marco; Savettieri, Giovanni

    2009-12-01

    Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

  4. Complementary and Alternative Medicine (CAM) Treatments and Pediatric Psychopharmacology

    ERIC Educational Resources Information Center

    Rey, Joseph M.; Walter, Garry; Soh, Nerissa

    2008-01-01

    Children and adolescents often use complementary and alternative medicine (CAM) treatments outside their indications, particularly to lose weight. Some of the herbal remedies and dietary supplements that may of relevance for psychopharmacological practice are discussed with respect to CAM treatments.

  5. Alternative Treatment Technologies – Working With the Pathogen Equivalency Committee

    EPA Science Inventory

    Under current Federal regulations (40 CFR 503), municipal sludge must be treated prior to land application. The regulations identify two classes of treatment with respect to pathogen reduction: Class B (three alternatives) which provides a minimum acceptable level of treatment;...

  6. Effects of topical corticosteroid and tacrolimus on ceramides and irritancy to sodium lauryl sulphate in healthy skin.

    PubMed

    Jungersted, Jakob Mutanu; Høgh, Julie K; Hellegren, Lars I; Jemec, Gregor B E; Agner, Tove

    2011-05-01

    The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p = 0.008) and tacrolimus-treated (p = 0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p = 0.01) or with tacrolimus (p = 0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.

  7. Topical tacrolimus for parastomal pyoderma gangrenosum: a report of two cases.

    PubMed

    Altieri, Maria; Vaziri, Khashayar; Orkin, Bruce A

    2010-09-01

    Pyoderma gangrenosum (PG) is an idiopathic, ulcerative, inflammatory dermatologic condition that occurs in patients with systemic diseases such as inflammatory bowel disease (IBD). This inflammatory skin disorder is presumably caused by an autoimmune mechanism and the diagnosis is one of exclusion. PG is not a common condition but it is thought to account for approximately 50% of chronic parastomal ulcers. Refractory parastomal PG (PPG) occurs in patients with inactive disease or after bowel resection. Multiple medical treatments, ranging from topical agents for mild disease to systemic immunosuppressive therapy for severe disease, have been used with varying rates of success. Using topical tacrolimus, an immunosuppressant that inhibits T-lymphocyte proliferation, and meticulous stoma care can result in successful treatment. Two women (ages 59 and 62 years) with a history of ulcerative colitis and colon resection presented with parastomal ulcers consistent with PPG. The 59-year patient presented with a painful 2 cm x 2 cm parastomal ulcer that improved following daily application of topical tacrolimus 0.1%. The 62-year old woman first was prescribed daily appliance changes and application of topical triamcinolone 0.5% to her 3-cm ulcer. The ulcer increased in size and treatment was changed to daily application of tacrolimus 0.1%. After 2 months and a reduction in ulcer size and severity, the dosage was changed to daily application of tacrolimus 0.03%. Both patients reported resolution of pain and itching, the most common symptoms of PPG, and no adverse effects were observed. The encouraging results observed in these two cases confirm that tacrolimus helps resolve PPG lesions even at concentrations previously thought to be ineffective. Additional studies to help clinicians optimize care of these painful lesions are needed.

  8. Nationwide conversion to generic tacrolimus in pediatric kidney transplant recipients.

    PubMed

    Naicker, Derisha; Reed, Peter W; Ronaldson, Jane; Kara, Tonya; Wong, William; Prestidge, Chanel

    2017-11-01

    Bioequivalence between Tacrolimus Prograf® and generic tacrolimus formulations has been demonstrated in adult populations, however clinical experience and safety data regarding generic tacrolimus in pediatric transplant recipients is limited. This study aimed to evaluate conversion from Tacrolimus Prograf® to Sandoz® in pediatric renal transplant recipients nationwide. The primary outcome was a change in mean trough tacrolimus concentration. Additionally, changes in tacrolimus intra-patient coefficient of variation (CoV), allograft function, requirement for dose adjustments, and episodes of biopsy-proven rejection were evaluated. Retrospective cohort study in 37 pediatric renal transplant recipients who switched to Tacrolimus Sandoz®. Each patient had three pre-conversion tacrolimus trough and creatinine concentrations within the 4 months prior and three post-conversion concentrations on day 3, 10, and the next subsequent level. Mean pre- and post-conversion tacrolimus trough concentrations and glomerular filtration rate (eGFR) were calculated. Tacrolimus concentration, CoV, and creatinine differences were compared by paired t test. Thirty-seven patients (41% females, age 3-18 years) were included. Average intra-patient difference in trough tacrolimus concentration was 0.05μg/l (95% CI -0.37 to 0.47). Average intra-patient difference in eGFR was -1.20 ml/min/1.73 2 (95% CI -3.53 to 1.13). Three patients had acute rejection during 12 months post-conversion compared to none during 12 months pre-conversion. Pediatric renal transplant recipients can be converted from Tacrolimus Prograf® to Sandoz® with negligible change in trough concentration, dose adjustments, or immediate allograft function. Of concern was the number of acute rejection episodes, however non-adherence contributed to at least one episode and this difference was determined clinically and statistically not significant.

  9. Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil

    PubMed Central

    Guerra, Augusto Afonso; Silva, Grazielle Dias; Andrade, Eli Iola Gurgel; Cherchiglia, Mariângela Leal; Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Acurcio, Francisco de Assis

    2015-01-01

    OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. However, regimens containing cyclosporine were more cost-effective. PMID:25741648

  10. Cyclosporine versus tacrolimus: cost-effectiveness analysis for renal transplantation in Brazil.

    PubMed

    Guerra Júnior, Augusto Afonso; Silva, Grazielle Dias; Andrade, Eli Iola Gurgel; Cherchiglia, Mariângela Leal; Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Acurcio, Francisco de Assis

    2015-01-01

    OBJECTIVE To analyze the cost-effectiveness of treatment regimens with cyclosporine or tacrolimus, five years after renal transplantation. METHODS This cost-effectiveness analysis was based on historical cohort data obtained between 2000 and 2004 and involved 2,022 patients treated with cyclosporine or tacrolimus, matched 1:1 for gender, age, and type and year of transplantation. Graft survival and the direct costs of medical care obtained from the National Health System (SUS) databases were used as outcome results. RESULTS Most of the patients were women, with a mean age of 36.6 years. The most frequent diagnosis of chronic renal failure was glomerulonephritis/nephritis (27.7%). In five years, the tacrolimus group had an average life expectancy gain of 3.96 years at an annual cost of R$78,360.57 compared with the cyclosporine group with a gain of 4.05 years and an annual cost of R$61,350.44. CONCLUSIONS After matching, the study indicated better survival of patients treated with regimens using tacrolimus. Moreover, regimens containing cyclosporine were more cost-effective [corrected].

  11. Endometriosis: alternative methods of medical treatment

    PubMed Central

    Muñoz-Hernando, Leticia; Muñoz-Gonzalez, Jose L; Marqueta-Marques, Laura; Alvarez-Conejo, Carmen; Tejerizo-García, Álvaro; Lopez-Gonzalez, Gregorio; Villegas-Muñoz, Emilia; Martin-Jimenez, Angel; Jiménez-López, Jesús S

    2015-01-01

    Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “anti-angiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs. PMID:26089705

  12. ALTERNATIVE DISINFECTION FOR DRINKING WATER TREATMENT

    EPA Science Inventory

    During a one-yr study at Jefferson Parish, La., the chemical, microbiological, and mutagenic effects os using the major drinkgin water disinfectants (chlorine, chlorine dioxide, chloramine, ozone) were evaluated. Tests were performed on samples collected from various treatment s...

  13. Regulatory effect of calcineurin inhibitor, tacrolimus, on IL-6/sIL-6R-mediated RANKL expression through JAK2-STAT3-SOCS3 signaling pathway in fibroblast-like synoviocytes

    PubMed Central

    2013-01-01

    Introduction This study investigated whether the calcineurin inhibitor, tacrolimus, suppresses receptor activator of NF-κB ligand (RANKL) expression in fibroblast-like synoviocytes (FLS) through regulation of IL-6/Janus activated kinase (JAK2)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS3) signaling. Methods The expression of RANKL, JAK2, STAT3, and SOCS3 proteins was assessed by western blot analysis, real-time PCR and ELISA in IL-6 combined with soluble IL-6 receptor (sIL-6R)-stimulated rheumatoid arthritis (RA)-FLS with or without tacrolimus treatment. The effects of tacrolimus on synovial inflammation and bone erosion were assessed using mice with arthritis induced by K/BxN serum. Immunofluorescent staining was performed to identify the effect of tacrolimus on RANKL and SOCS3. The tartrate-resistant acid phosphatase staining assay was performed to assess the effect of tacrolimus on osteoclast differentiation. Results We found that RANKL expression in RA FLS is regulated by the IL-6/sIL-6R/JAK2/STAT3/SOCS3 pathway. Inhibitory effects of tacrolimus on RANKL expression in a serum-induced arthritis mice model were identified. Tacrolimus inhibits RANKL expression in IL-6/sIL-6R-stimulated FLS by suppressing STAT3. Among negative regulators of the JAK/STAT pathway, such as CIS1, SOCS1, and SOCS3, only SOCS3 is significantly induced by tacrolimus. As compared to dexamethasone and methotrexate, tacrolimus more potently suppresses RANKL expression in FLS. By up-regulating SOCS3, tacrolimus down-regulates activation of the JAK-STAT pathway by IL-6/sIL-6R trans-signaling, thus decreasing RANKL expression in FLS. Conclusions These data suggest that tacrolimus might affect the RANKL expression in IL-6 stimulated FLS through STAT3 suppression, together with up-regulation of SOCS3. PMID:23406906

  14. New alternative in treatment of callus.

    PubMed

    Akdemir, Ovunc; Bilkay, Ufuk; Tiftikcioglu, Yigit Ozer; Ozek, Cüneyt; Yan, Hede; Zhang, Feng; Akin, Yalcin

    2011-02-01

    The pathological transformation of the skin into a thick and hard callus due to repetitive trauma or friction is commonly known as corn. Although a variety of medical and operative treatment choices have been proposed, an ideal treatment method is yet to be defined. Effectiveness of tangential excision together with topical cantharidin has been evaluated. We used Canthacur-PS as an adjunct to excision in an outpatient setting. Canthacur-PS is a commercially available topical solution that includes 1% cantharidin, 30% salicylic acid and 5% podophyllin. The treatment has been applied to 72 patients. We found that 65 patients (90.3%) had corn on their feet and seven patients (9.7%) on their hands. Thick, hard and hyperkeratotic skin area was scraped with the help of a no. 15 blade. The solution was applied on and around the periphery (up to 1–2 mm) of the lesion with a cotton swab, and kept closed for 5 days with an antibiotic dressing. All the patients had been followed up for at least 1 year and evaluated by clinical examination and patient satisfaction query. One session of treatment succeeded in 57 (79.2%) corn patients. Two sessions in nine corn patients (12.5%), three sessions in five corn patients (6.9%) and four sessions in one patient (1.4%) were needed. Only one recurrence (1.4%) was seen. No scar formation or other side-effects were seen. Our findings show that this treatment method is a simple, minimally invasive and reliable treatment for calluses. © 2010 Japanese Dermatological Association.

  15. Oxybutynin as an alternative treatment for hyperhidrosis*

    PubMed Central

    Delort, Sergio; Marchi, Evaldo; Corrêa, Marcos Antônio

    2017-01-01

    Hyperhidrosis is the excessive production of sweating, which can be primary and focal or secondary to various pathologies. The exact cause of primary focal hyperhidrosis is still unknown, although a genetic basis is recognized, and its prevalence varies from 1% to 2.8%. The most affected sites are the armpits, palms, soles and face. It causes much discomfort, affects the quality of life, and is estimated to be undervalued by health professionals. Many treatment options are proposed, both clinical and surgical. The aim of this review is to focus on the treatment of hyperhidrosis with oxybutynin, an anticholinergic drug originally used to control overactive bladder. PMID:28538882

  16. Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

    PubMed Central

    Shokati, Touraj; Bodenberger, Nicholas; Gadpaille, Holly; Schniedewind, Björn; Vinks, Alexander A.; Jiang, Wenlei; Alloway, Rita R.; Christians, Uwe

    2015-01-01

    The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United States. Tacrolimus is a narrow therapeutic index drug and as such requires therapeutic drug monitoring and dose adjustment based on its whole blood trough concentrations. To facilitate home therapeutic drug and adherence monitoring, the collection of dried blood spots is an attractive concept. After a finger stick, the patient collects a blood drop on filter paper at home. After the blood is dried, it is mailed to the analytical laboratory where tacrolimus is quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in combination with a simple manual protein precipitation step and online column extraction. For tacrolimus analysis, a 6-mm disc is punched from the saturated center of the blood spot. The blood spot is homogenized using a bullet blender and then proteins are precipitated with methanol/0.2 M ZnSO4 containing the internal standard D2,13C-tacrolimus. After vortexing and centrifugation, 100 µl of supernatant is injected into an online extraction column and washed with 5 ml/min of 0.1 formic acid/acetonitrile (7:3, v:v) for 1 min. Hereafter, the switching valve is activated and the analytes are back-flushed onto the analytical column (and separated using a 0.1% formic acid/acetonitrile gradient). Tacrolimus is quantified in the positive multi reaction mode (MRM) using a tandem mass spectrometer. The assay is linear from 1 to 50 ng/ml. Inter-assay variability (3.6%-6.1%) and accuracy (91.7%-101.6%) as assessed over 20 days meet acceptance criteria. Average extraction recovery is 95.5%. There are no relevant carry-over, matrix interferences and matrix effects. Tacrolimus is stable in dried blood spots at RT and at +4 °C for 1 week. Extracted samples in the autosampler are stable at +4 °C for at least 72 hr. PMID:26575262

  17. Selecting forest residue treatment alternatives using goal programming.

    Treesearch

    Bruce B. Bare; Brian F. Anholt

    1976-01-01

    The use of goal programing for selecting forest residue treatment alternatives within a multiple goal framework is described. The basic features of goal programing are reviewed and illustrated with a hypothetical problem involving the selection of residue treatments for 10 cutting units. Twelve residue-regeneration treatment combinations are evaluated by using physical...

  18. Treatment, promotion, commotion: Antibiotic alternatives in food-producing animals

    USDA-ARS?s Scientific Manuscript database

    Alternatives to antibiotics in animal agriculture are urgently needed but present a complex problem because of their various uses: disease treatment, disease prevention, and feed efficiency improvement. Numerous antibiotic alternatives, such as feed amended with pre- and probiotics, have been propos...

  19. Performance Tests of Alternative Ballast Water Treatment Systems

    DOT National Transportation Integrated Search

    2001-08-01

    This report summarizes the results of the U.S. Coast Guard (USCG) assessment of ballast water treatment system alternatives to ballast water exchange as a means of reducing the probability of aquatice nuisance species (ANS) transfer. The audits inclu...

  20. Synthesis of wood treatment alternatives for timber railroad structures.

    DOT National Transportation Integrated Search

    2011-12-01

    A wealth of information exists on various wood preservatives, treatment techniques, curing practices, and other engineered : controls, along with alternative materials for replacement. This study was initiated to review and synthesize available : inf...

  1. Proven Alternatives for Aboveground Treatment of Arsenic in Groundwater

    EPA Pesticide Factsheets

    This issue paper, developed for EPA's Engineering Forum, identifies and summarizes experiences with proven aboveground treatment alternatives for arsenic in groundwater, and provides information on their relative effectiveness and cost.

  2. 21 CFR 862.1678 - Tacrolimus test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tacrolimus test system. 862.1678 Section 862.1678 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... quantitatively determine tacrolimus concentrations as an aid in the management of transplant patients receiving...

  3. Application of Biodegradable Nanoparticles in Liver Targeting of Tacrolimus

    NASA Astrophysics Data System (ADS)

    Affifi, Nagia N.; Heikal, Ola A.; Hanafi, Rasha S.; Tammam, Salma N.

    2011-06-01

    Tacrolimus is a potent immunosuppressant used in liver transplantation to avoid graft rejection. Tacrolimus has a narrow therapeutic index and variable pharmacokinetics, making dose adjustment and therapeutic drug monitoring a complicated task. Increasing the occurrence of adverse effects, especially nephrotoxicity are another concerns. In graft rejection, antigen presentation occurs in the graft and lymphatics. Therefore, by targeting tacrolimus to the liver and spleen, graft survival could be achieved with a decrease in nephrotoxicity. Poly(lactide) tacrolimus nanoparticles (PLA-TAC-NP) were formulated and characterized with the aim of targeting tacrolimus to the liver and spleen and therefore decreasing its nephrotoxicity. To evaluate the targeting efficiency of PLA-TAC-NP, rats were divided into two groups. They were intravenously injected either PLA-TAC-NP or free tacrolimus. At assigned time intervals, blood, liver, spleen and kidney samples were collected from each rat. Drug extraction and HPLC analysis were used to evaluate tacrolimus tissue distribution and consequently the targeting efficiency of the prepared PLA-TAC-NP. PLA-TAC-NP proved their success in targeting liver and spleen, by showing significantly higher drug amounts compared to the rats injected with free tacrolimus. PLA-TAC-NP increased tacrolimus concentration in the liver 24 fold and in the spleen 1.94 fold whereas tacrolimus concentration in the kidneys decreased by 7.12 fold. Transmission electron microscopy (TEM) was used to examine a liver section, obtained from a rat that has received PLA-TAC-NP. TEM images showed PLA-TAC-NP in a Kupffer cell and in the liver sinusoids. Therefore, PLA-TAC-NP are promising drug delivery systems for achieving localized immunosuppression and minimizing nephrotoxicity in liver transplant patients.

  4. Living proof and the pseudoscience of alternative cancer treatments.

    PubMed

    Vickers, Andrew J; Cassileth, Barrie R

    2008-01-01

    Michael Gearin-Tosh was an English professor at Oxford University who was diagnosed with multiple myeloma in 1994. He rejected conventional chemotherapeutic approaches and turned to a variety of alternative cancer treatments, particularly those involving nutritional supplements and dietary change. In 2002, Dr. Gearin-Tosh published a book, Living Proof: A Medical Mutiny, recounting his experiences. The book gained significant public and media attention. One chapter was written by Carmen Wheatley, an advocate of alternative cancer treatments. In distinction to Dr. Gearin-Tosh's personal story, Dr. Wheatley makes general claims about cancer treatment that are supposedly based on the research literature. This appears to provide scientific validation for a highly unconventional program of cancer care. However, the scientific case made for alternative cancer treatments in Living Proof does not bear serious examination. There are numerous inaccuracies, omissions, and misrepresentations. Many important claims are either entirely unsubstantiated or not supported by the literature cited. In conclusion, a highly publicized book gives the impression that alternative cancer treatments are supported by scientific research. It also suggests that little progress has been made in the conventional treatment of myeloma. This is highly misleading and may lead to cancer patients rejecting effective treatments.

  5. Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.

    PubMed

    Pieterse, Reneé; Todorov, Svetoslav D

    2010-07-01

    Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease.

  6. Bacteriocins – Exploring Alternatives to Antibiotics in Mastitis Treatment

    PubMed Central

    Pieterse, Reneé; Todorov, Svetoslav D.

    2010-01-01

    Mastitis is considered to be the most costly disease affecting the dairy industry. Management strategies involve the extensive use of antibiotics to treat and prevent this disease. Prophylactic dosages of antibiotics used in mastitis control programmes could select for strains with resistance to antibiotics. In addition, a strong drive towards reducing antibiotic residues in animal food products has lead to research in finding alternative antimicrobial agents. In this review we have focus on the pathogenesis of the mastitis in dairy cows, existing antibiotic treatments and possible alternative for application of bacteriocins from lactic acid bacteria in the treatment and prevention of this disease. PMID:24031528

  7. [Use of alternative medicine in the treatment of allergic diseases].

    PubMed

    Félix Berumen, José Alfredo; González Díaz, Sandra Nora; Canseco González, Carlos; Arias Cruz, Alfredo

    2004-01-01

    The alternative medicine and the complementary medicine are forms of treatment very spread and frequently demanded by patients with allergic diseases. According to recent studies, homeopathy, acupuncture and herbal medicine are the most commonly used types of alternative medicine. To know the frequency in the use of different types of alternative medicine for the treatment of allergic diseases in patients attended at the Centro Regional de Alergia e Immunologia Clínica of the Hospital Universitario de Monterrey, Nuevo León. A transversal, descriptive and observational study was done by the use of questionnaires applied to patients and/or patients' relatives attended in this Center. This survey included questions to focus the investigation in the use of a Iternative medicine for the treatment of any allergic disease. The data analysis was done by descriptive statistics. Four hundred one questionnaires were applied. The average age of the patients was of 14 years (range from 1 to 73 years). Fourty-seven percent (189 patients) were female and 58.2% (212 patients) were male. The diagnoses included: allergic rhinitis in 215 patients (53.6), asthma in 97 (24.2%), rhinitis and asthma in 73 (18.2) and atopic dermatitis in 16 (4%). Out of the patients 34.4% (138) had used at least one type of alternative medicine for the treatment of their allergic disease. Homeopathy was the most commonly used type of alternative medicine (78.2%), followed by the natural medicine (31.5%). Alternative medicine for the treatment of allergic diseases is frequent in patients who attend to this center. Homeopathy and the natural medicine are the most used.

  8. [An alternative to aortopexy in the treatment of severe tracheomalacia].

    PubMed

    Sánchez Martín , R; Matute Cárdenas , J A; Barrientos Fernández , G; Romero Ruiz , R; García-Casillas, M A; Vázquez Estévez , J

    2000-09-01

    The classic treatment of severe tracheomalacia is aortopexy. In the 1980s endoscopic insertion of the Palmaz stent, originally designed for use in the treatment of vascular stenosis, began to be used in the treatment of relapsing or residual tracheomalacia. We present a patient with severe tracheomalacia who had previously undergone surgery for esophageal atresia with distal tracheoesophageal fistula in which aortopexy was contraindicated due to a complex congenital heart disease. Treatment consisted of endoscopic insertion of a Palmaz stent. This stent provides an effective alternative to conventional surgery, although each case should be individually evaluated.

  9. Advances in developing alternative treatments for postharvest pest control

    USDA-ARS?s Scientific Manuscript database

    USDA-ARS made two significant advances in the last 10 years in the development of alternative treatments for postharvest pest control: oxygenated phosphine fumigation and nitric oxide fumigation. Oxygenated phosphine is phosphine fumigation in an oxygen enriched atmosphere. It is significantly more...

  10. Adult Heart Transplantation Under Tacrolimus (FK506) Immunosuppression: Histopathologic Observations and Comparison to a Cyclosporine-based Regimen with Lympholytic (ATG) Induction

    PubMed Central

    Tsamandas, Athanassios C.; Pham, Si M.; Seaberg, Eric C.; Pappo, Orit; Kormos, Robert L.; Kawai, Akihiko; Griffith, Bartley P.; Zeevi, Adriana; Duquesnoy, Rene; Fung, John J.; Starzl, Thomas E.; Demetris, Anthony J.

    2011-01-01

    Background Tacrolimus (FK506) is an effective immunosuppressant for human heart transplantation, but information about its effects on cardiac allograft and nonallograft kidney and liver histopathologic study is limited. Methods We therefore reviewed 1145 endomyocardial biopsy specimens and eight autopsy results from 80 heart transplant recipients who received tacrolimus as baseline immunosuppression. These were compared with 619 endomyocardial biopsy specimens and four autopsy results from 51 patients treated with cyclosporine-based immunosuppression with lympholytic induction (CLI) by use of rabbit anti-thymocyte globulin. Twenty-one histologic features including the International Society for Heart and Lung Transplantation histopathologic grade were retrospectively assessed without knowledge of the treatment regimen. The lymphocyte growth index on biopsy specimens obtained from these patients was also compared. Results In general, there were no qualitative differences in the histopathologic appearance of various allograft syndromes between tacrolimus- and CLI-treated patients. Thus histopathologic criteria used to diagnose various graft syndromes are applicable under tacrolimus immunosuppression. However, early (between 10 and 30 days) after transplantation, biopsy specimens from patients treated with tacrolimus showed a significantly higher percentage of inflamed fragments (p = 0.02), the inflammation tended to be more severe (p = 0.09), and the rejection grade tended to be slightly higher (p = 0.08). In contrast, during the late transplantation period (275 to 548 days), biopsy specimens from patients treated with CLI showed a significantly higher percentage of inflamed fragments (p = 0.03), more severe inflammation (p = 0.03), higher rejection grades (p = 0.01), and a higher frequency of Quilty lesions (p = 0.05). Although overall freedom from any grade 3A or higher rejection was greater in the CLI-treated arm, tacrolimus was successfully used to treat

  11. The atraumatic restorative treatment approach: an "atraumatic" alternative.

    PubMed

    Carvalho, Thiago-Saads; Ribeiro, Talitha-Rodrigues; Bönecker, Marcelo; Pinheiro, Elayne-Cristina-Morais; Colares, Viviane

    2009-12-01

    Fear and anxiety are part of all human experiences and they may contribute directly to a patient's behavior. The Atraumatic Restorative Treatment (ART) is a technique that may be an alternative approach in treating special care patients or those who suffer fear or anxiety. the aim of this paper is to review the ART technique as an alternative to reduce pain and fear during dental treatment. A search for the term "atraumatic restorative treatment" was carried out in the MEDLINE search engine. References, from the last 10 years, containing at least one of the terms: "psychological aspects", "discomfort", "fear", "anxiety" or "pain", were selected. A total of 120 references were found, from which only 17 fit the criteria. All authors agreed that the ART promotes less discomfort for patients, contributing to a reduction of anxiety and fear during the dental treatment. Results also indicated that ART minimizes pain reported by patients. The ART approach can be considered as having favorable characteristics for the patient, promoting an "atraumatic" treatment. This technique may be indicated for patients who suffer from fear or anxiety towards dental treatments and whose behavior may cause the treatment to become unfeasible or even impossible altogether.

  12. Mechanisms of lower maintenance dose of tacrolimus in obese patients.

    PubMed

    Sawamoto, Kazuki; Huong, Tran T; Sugimoto, Natsumi; Mizutani, Yuka; Sai, Yoshimichi; Miyamoto, Ken-ichi

    2014-01-01

    A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (<18.5), normal (≥ 18.5 and <25) or overweight/obese (≥ 25). The average maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.

  13. Plasma cell cheilitis, successfully treated with topical 0.03% tacrolimus ointment.

    PubMed

    Jin, Seon Pil; Cho, Kwang Hyun; Huh, Chang Hun

    2010-05-01

    Plasma cell cheilitis is a rare, idiopathic mucosal condition. The treatment of plasma cell cheilitis is often disappointing. It is often resistant to various topical treatments. We present a 65-year-old woman who had a painful, eroded area on her lower lip, which responded poorly to various topical treatments. A biopsy revealed a band-like infiltration composed mainly of plasma cells in the dermis. She was diagnosed as having plasma cell cheilitis, and was successfully treated with 0.03% topical tacrolimus ointment.

  14. Costs and Effectiveness of Treatment Alternatives for Proximal Caries Lesions

    PubMed Central

    Schwendicke, Falk; Meyer-Lueckel, Hendrik; Stolpe, Michael; Dörfer, Christof Edmund; Paris, Sebastian

    2014-01-01

    Objectives Invasive therapy of proximal caries lesions initiates a cascade of re-treatment cycles with increasing loss of dental hard tissue. Non- and micro-invasive treatment aim at delaying this cascade and may thus reduce both the health and economic burden of such lesions. This study compared the costs and effectiveness of alternative treatments of proximal caries lesions. Methods A Markov-process model was used to simulate the events following the treatment of a proximal posterior lesion (E2/D1) in a 20-year-old patient in Germany. We compared three interventions (non-invasive; micro-invasive using resin infiltration; invasive using composite restoration). We calculated the risk of complications of initial and possible follow-up treatments and modelled time-dependent non-linear transition probabilities. Costs were calculated based on item-fee catalogues in Germany. Monte-Carlo-microsimulations were performed to compare cost-effectiveness of non- versus micro-invasive treatment and to analyse lifetime costs of all three treatments. Results Micro-invasive treatment was both more costly and more effective than non-invasive therapy, with ceiling-value-thresholds for willingness-to-pay between 16.73 € for E2 and 1.57 € for D1 lesions. Invasive treatment was the most costly strategy. Calculated costs and effectiveness were sensitive to lesion stage, patient’s age, discounting rate and assumed initial treatment costs. Conclusions Non- and micro-invasive treatments have lower long-term costs than invasive therapy of proximal lesions. Micro-invasive therapy had the highest cost-effectiveness for treating D1 lesions in young patients. Decision makers with a willingness-to-pay over 16.73 € and 1.57 € for E2 and D1 lesions, respectively, will find micro-invasive treatment more cost-effective than non-invasive therapy. PMID:24475208

  15. Alternating treatments design: one strategy for comparing the effects of two treatments in a single subject.

    PubMed Central

    Barlow, D H; Hayes, S C

    1979-01-01

    A little used and often confused design, capable of comparing two treatments within a single subject, has been termed, variously, a multielement baseline design, a multiple schedule design, and a randomization design. The background of these terms is reviewed, and a new, more descriptive term, Alternating Treatments Design, is proposed. Critical differences between this design and a Simultaneous Treatment Design are outlined, and experimental questions answerable by each design are noted. Potential problems with multiple treatment interference in this procedure are divided into sequential confounding, carryover effects, and alternation effects and the importance of these issues vis-a-vis other single-case experimental designs is considered. Methods of minimizing multiple treatment interference as well as methods of studying these effects are outlined. Finally, appropriate uses of Alternating Treatments Designs are described and discussed in the context of recent examples. PMID:489478

  16. An Alternative Surgical Method for Treatment of Osteoid Osteoma

    PubMed Central

    Gökalp, Mehmet Ata; Gözen, Abdurrahim; Ünsal, Seyyid Şerif; Önder, Haci; Güner, Savaş

    2016-01-01

    Background An osteoid osteoma is a benign bone tumor that tends to be <1 cm in size. The tumor is characterized by night-time pain that may be relieved by aspirin or other non-steroidal anti-inflammatory drugs. Osteoid osteoma can be treated with various conservative and surgical methods, but these have some risks and difficulties. The purpose of the present study was to present an alternative treatment method for osteoid osteoma and the results we obtained. Material/Methods In the period from 2010 to 2014, 10 patients with osteoid osteoma underwent nidus excision by using a safe alternative method in an operating room (OR) with no computed tomography (CT). The localization of the tumor was determined by use of a CT-guided Kirschner wire in the radiology unit, then, in the OR the surgical intervention was performed without removing the Kirschner wire. Results Following the alternative intervention, all the patients were completely relieved of pain. In the follow-up, no recurrence or complication occurred. Conclusions The presented alternative method for treating osteoid osteoma is an efficient and practical procedure for surgeons working in clinics that lack specialized equipment. PMID:26898923

  17. Alternative treatment technology information center computer database system

    SciTech Connect

    Sullivan, D.

    1995-10-01

    The Alternative Treatment Technology Information Center (ATTIC) computer database system was developed pursuant to the 1986 Superfund law amendments. It provides up-to-date information on innovative treatment technologies to clean up hazardous waste sites. ATTIC v2.0 provides access to several independent databases as well as a mechanism for retrieving full-text documents of key literature. It can be accessed with a personal computer and modem 24 hours a day, and there are no user fees. ATTIC provides {open_quotes}one-stop shopping{close_quotes} for information on alternative treatment options by accessing several databases: (1) treatment technology database; this contains abstracts from the literature on all typesmore » of treatment technologies, including biological, chemical, physical, and thermal methods. The best literature as viewed by experts is highlighted. (2) treatability study database; this provides performance information on technologies to remove contaminants from wastewaters and soils. It is derived from treatability studies. This database is available through ATTIC or separately as a disk that can be mailed to you. (3) underground storage tank database; this presents information on underground storage tank corrective actions, surface spills, emergency response, and remedial actions. (4) oil/chemical spill database; this provides abstracts on treatment and disposal of spilled oil and chemicals. In addition to these separate databases, ATTIC allows immediate access to other disk-based systems such as the Vendor Information System for Innovative Treatment Technologies (VISITT) and the Bioremediation in the Field Search System (BFSS). The user may download these programs to their own PC via a high-speed modem. Also via modem, users are able to download entire documents through the ATTIC system. Currently, about fifty publications are available, including Superfund Innovative Technology Evaluation (SITE) program documents.« less

  18. Technoeconomic aspects of alternative municipal solid wastes treatment methods.

    PubMed

    Economopoulos, Alexander P

    2010-04-01

    This paper considers selected treatment technologies for comingled domestic and similar wastes and provides technoeconomic data and information, useful for the development of strategic management plans. For this purpose, treatment technologies of interest are reviewed and representative flow diagrams, along with material and energy balances, are presented for the typical composition of wastes in Greece; possible difficulties in the use of treatment products, along with their management implications, are discussed, and; cost functions are developed, allowing assessment of the initial capital investment and annual operating costs. Based on the latter, cost functions are developed for predicting the normalized treatment costs of alternative methods (in euro/t of MSW treated), as function of the quantity of MSW processed by plants built and operated (a) by municipality associations, and (b) by private enterprises. Finally, the alternative technologies considered are evaluated on the basis of their cost aspects, product utilization and compatibility with the EU waste framework Directive 2008/98. Copyright 2009 Elsevier Ltd. All rights reserved.

  19. Complementary and alternative medicine for treatment of irritable bowel syndrome.

    PubMed

    Shen, Yi-Hao A; Nahas, Richard

    2009-02-01

    To review the evidence supporting selected complementary and alternative medicine approaches used in the treatment of irritable bowel syndrome (IBS). MEDLINE (from January 1966), EMBASE (from January 1980), and the Cochrane Database of Systematic Reviews were searched until March 2008, combining the terms irritable bowel syndrome or irritable colon with complementary therapies, alternative medicine, acupuncture, fiber, peppermint oil, herbal, traditional, yoga, massage, meditation, mind, relaxation, probiotic, hypnotherapy, psychotherapy, cognitive therapy, or behavior therapy. Results were screened to include only clinical trials, systematic reviews, and meta-analyses. Level I evidence was available for most interventions. Soluble fibre improves constipation and global IBS symptoms. Peppermint oil alleviates IBS symptoms, including abdominal pain. Probiotic trials show overall benefit for IBS but there is little evidence supporting the use of any specific strain. Hypnotherapy and cognitive-behavioural therapy are also effective therapeutic options for appropriate patients. Certain herbal formulas are supported by limited evidence, but safety is a potential concern. All interventions are supported by systematic reviews or meta-analyses. Several complementary and alternative therapies can be recommended as part of an evidence-based approach to the treatment of IBS; these might provide patients with satisfactory relief and improve the therapeutic alliance.

  20. Personalized tacrolimus doses determined by CYP3A5 genotype for induction and maintenance phases of kidney transplantation.

    PubMed

    Vannaprasaht, Suda; Reungjui, Sirirat; Supanya, Darika; Sirivongs, Dhavee; Pongskul, Cholatip; Avihingsanon, Yingyos; Tassaneeyakul, Wichittra

    2013-11-01

    required for the induction and maintenance phases and MDR1 polymorphism. Determination of the CYP3A5 genotype would be helpful in the design of adequate immunosuppressive treatment and in lowering toxicity by predicting the doses of tacrolimus required for the induction and maintenance phases in individual kidney transplant recipients. © 2013 Elsevier HS Journals, Inc. All rights reserved.

  1. In Vitro Interactions between Tacrolimus and Azoles against Candida albicans Determined by Different Methods▿

    PubMed Central

    Sun, Shujuan; Li, Yan; Guo, Qiongjie; Shi, Changwen; Yu, Jinlong; Ma, Lin

    2008-01-01

    Combination therapy could be of use for the treatment of fungal infections, especially those caused by drug-resistant fungi. However, the methods and approaches used for data generation and result interpretation need further optimizing. The fractional inhibitory concentration index (FICI) is the most commonly used method, but it has several drawbacks in characterizing antifungal drug interaction. Alternatively, some new methods can be used such as the ΔE model (difference between the predicted and measured fungal growth percentages) and the response surface approach, which uses the concentration-effect relationship over the whole concentration range instead of just the MIC. In the present study, in vitro interactions between tacrolimus (FK506) and three azoles—fluconazole (FLC), itraconazole (ITR), and voriconazole (VRC)-against Candida albicans were evaluated by the checkerboard microdilution method and time-killing test. The intensity of the interactions was determined by visual reading and the spectrophotometric method in a checkerboard assay, and the nature of the interactions was assessed by nonparametric models of FICI and ΔE. Colony counting and colorimetric viable detection methods (2,3-bis {2-methoxy-4-nitro-5-[(sulfenylamino) carbonyl]-2H-tetrazolium hydroxide} [XTT] reduction test) were used for evaluating the combination antifungal effects over time. Synergistic and indifferent effects were found for the combination of FK506 and azoles against azole-sensitive strains, while strong synergy was found against azole-resistant strains analyzed by FICI. The ΔE model gave more consistent results with FICI. The positive interactions were also confirmed by the time-killing test. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and azoles to augment activity against resistant C. albicans. PMID:18056277

  2. Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis

    PubMed Central

    Whitmore, Kristene E

    2002-01-01

    The management of interstitial cystitis (IC) is predominantly the reduction of the symptoms of frequency, urgency, and pain. Multimodal treatment approaches for IC are helpful in customizing therapy for individual patients. Complementary and alternative therapies are a quintessential addition to the therapeutic armamentarium and frequently include dietary modification, nutraceuticals, bladder training, neuromodulation, stress reduction, and sex therapy. Dietary modification involves elimination of bladder irritants, fluid regulation, and a bowel regimen. Nutraceuticals studied for the treatment of IC include calcium glycerophosphate, L-arginine, mucopolysaccharides, bioflavinoids, and Chinese herbs. Bladder training is effective after pain reduction. The neuromodulation of high-tone pelvic-floor muscle dysfunction is achieved with physical therapy and acupuncture. Stress reduction and sex therapy are best administered by a qualified stress manager and sex therapist. Multimodal, nonconventional management may add efficacy to the treatment of IC. PMID:16986031

  3. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.

  4. Candidiasis: predisposing factors, prevention, diagnosis and alternative treatment.

    PubMed

    Martins, Natália; Ferreira, Isabel C F R; Barros, Lillian; Silva, Sónia; Henriques, Mariana

    2014-06-01

    Candidiasis is the most common opportunistic yeast infection. Candida species and other microorganisms are involved in this complicated fungal infection, but Candida albicans continues to be the most prevalent. In the past two decades, it has been observed an abnormal overgrowth in the gastrointestinal, urinary and respiratory tracts, not only in immunocompromised patients, but also related to nosocomial infections and even in healthy individuals. There is a widely variety of causal factors that contribute to yeast infection which means that candidiasis is a good example of a multifactorial syndrome. Due to rapid increase in the incidence in these infections, this is the subject of numerous studies. Recently, the focus of attention is the treatment and, above all, the prevention of those complications. The diagnosis of candidiasis could become quite complicated. Prevention is the most effective "treatment," much more than eradication of the yeast with antifungal agents. There are several aspects to consider in the daily routine that can provide a strength protection. However, a therapeutic approach is necessary when the infection is established, and therefore, other alternatives should be explored. This review provides an overview on predisposition factors, prevention and diagnosis of candidiasis, highlighting alternative approaches for candidiasis treatment.

  5. Complementary and Alternative Medicine for Treatment of Food Allergy.

    PubMed

    Li, Xiu-Min

    2018-02-01

    The prevalence of food allergy is increasing. Food allergy can be life threatening and there is no approved treatment available. Allergen avoidance and rescue medication remain the sole management tools. Complementary and alternative medicine (CAM) use is common in the United States. However, research into safety and efficacy for food allergy is limited. Continued scientific research into food allergy herbal formula 2 (FAHF-2), refined methods of formulation, purified compounds, and other modalities are needed. Traditional Chinese medicine is the main component of CAM in the United States. Conventional doctors, CAM practitioners, and patients' families must collaborate to comanage these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Intravenous tacrolimus and cyclosporine induced anaphylaxis: what is next?

    PubMed Central

    Kang, Sung-Yoon; Sohn, Kyoung-Hee; Lee, Jeong-Ok; Kim, Sae-Hoon; Cho, Sang-Heon

    2015-01-01

    Tacrolimus and cyclosporine have been used in various formulations, but their hypersensitivity reactions are rare in practice. Castor oil derivatives are nonionic surfactants used in aqueous preparations of hydrophobic active pharmaceutical ingredients. Castor oil derivatives that can be used as additives to tacrolimus and cyclosporine may play a role in the development of hypersensitivity reactions, especially anaphylaxis. Various immunologic and nonimmunologic mechanisms have been implicated in hypersensitivity reactions induced by castor oil derivatives. Physicians should be aware that not only the drug itself, but also its additives or metabolites could induce hypersensitivity reactions. We report a case of anaphylaxis caused by vitamin K (phytonadine), serotonin antagonist (granisetron), intravenous tacrolimus, and cyclosporine. Interestingly, the patient tolerated oral cyclosporine, which did not contain Cremophor EL or polysorbate 80. PMID:26240796

  7. A case of vesicular cutaneous lupus erythematosus in a Border collie successfully treated with topical tacrolimus and nicotinamide-tetracycline.

    PubMed

    Lehner, Georg M; Linek, Monika

    2013-12-01

    Canine vesicular cutaneous lupus erythematosus (VCLE) is an autoimmune skin disease of the Shetland sheepdog and rough collie, which manifests as an erosive dermatitis of sparsely haired skin of the ventrum and concave pinnae. Reported treatment consists of immunosuppression with glucocorticoids alone or in combination with azathioprine, but successful treatment is unpredictable. To report on the treatment of VCLE in a Border collie dog with topical 0.1% tacrolimus and nicotinamide in combination with tetracycline. An 8-year-old male neutered Border collie was presented with multiple coalescing erosions on the ventral abdomen, groin and axillae and ulceration on the oral commissures. Clinical presentation, routine diagnostics, histology and immunohistochemistry were consistent with VCLE. Remission was achieved with topical 0.1% tacrolimus and combination therapy of nicotinamide and tetracycline. This dog responded well to treatment with topical 0.1% tacrolimus, nicotinamide-tetracycline and sun avoidance. Complete remission was achieved after 2.5 months, and the dog was lesion free during a 1 year follow-up period. © 2013 ESVD and ACVD.

  8. Limited interaction between tacrolimus and P-glycoprotein in the rat small intestine.

    PubMed

    Saitoh, Hiroshi; Saikachi, Yuko; Kobayashi, Mikako; Yamaguchi, Michiko; Oda, Masako; Yuhki, Yoshimitsu; Achiwa, Kazuhito; Tadano, Koji; Takahashi, Yasushi; Aungst, Bruce J

    2006-05-01

    The significance of intestinal P-glycoprotein (P-gp) in determining the oral bioavailability of tacrolimus has been still controversial. In this study, we reevaluated the interaction of tacrolimus with P-gp in the rat small intestine, by evaluating its absorption from the rat small intestine and its modulating effect on the absorption of known P-gp substrates (digoxin, methylprednisolone, and vinblastine). Intestinal absorption of tacrolimus itself was as extensive as other P-gp modulators such as cyclosporine and verapamil. While cyclosporine and verapamil significantly increased the absorption of methylprednisolone and vinblastine through potent inhibition of intestinal P-gp, tacrolimus failed to achieve this. When cyclosporine and tacrolimus were intravenously administered to rats, digoxin absorption was significantly increased by cyclosporine but not by tacrolimus. When tacrolimus was coadministered with clotrimazole, a specific CYP3A inhibitor, into the rat small intestine, the area under the curve of tacrolimus blood concentrations increased more than seven-fold compared with that of tacrolimus alone. Our present results strongly suggest that the interaction between tacrolimus and P-gp is limited in the rat small intestine and that extensive metabolism by CYP3A enzymes is more responsible for the low oral bioavailability of tacrolimus. It was considered that the extensive absorption of cyclosporine and verapamil was closely associated with their potent ability to inhibit intestinal P-gp.

  9. Potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus

    PubMed Central

    Ha, Dong-Ho; Pathak, Shiva; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon; Park, Jun-Beom

    2016-01-01

    The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus. Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres were prepared using electrospraying technique. In vitro release study of tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres was performed in phosphate-buffered saline (pH 7.4). Gingiva-derived stem cells were isolated and incubated with tacrolimus or tacrolimus-loaded microspheres. Release study of the microspheres revealed prolonged release profiles of tacrolimus without any significant initial burst release. The microsphere itself did not affect the morphology of the mesenchymal stem cells, and cell morphology was retained after incubation with microspheres loaded with tacrolimus at 1 μg/mL to 10 μg/mL. Cultures grown in the presence of microspheres loaded with tacrolimus at 1 μg/mL showed the highest mineralization. Alkaline phosphatase activity increased with an increase in incubation time. The highest expression of pSmad1/5 was achieved in the group receiving tacrolimus 0.1 μg/mL every third day, and the highest expression of osteocalcin was achieved in the group receiving 1 μg/mL every third day. Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Microspheres loaded with tacrolimus may be applied for increased osteoblastic differentiation. PMID:27721434

  10. Safety and efficacy of conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation: randomized controlled trial in adult renal transplantation.

    PubMed

    Oh, Chang-Kwon; Huh, Kyu Ha; Lee, Jong Soo; Cho, Hong Rae; Kim, Yu Seun

    2014-09-01

    The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.

  11. Complementary and alternative medicine for the treatment of multiple sclerosis

    PubMed Central

    Yadav, Vijayshree; Shinto, Lynne; Bourdette, Dennis

    2010-01-01

    Multiple sclerosis (MS) is a chronic disabling disease of the CNS that affects people during early adulthood. Despite several US FDA-approved medications, the treatment options in MS are limited. Many people with MS explore complementary and alternative medicine (CAM) treatments to help control their MS and treat their symptoms. Surveys suggest that up to 70% of people with MS have tried one or more CAM treatment for their MS. People with MS using CAM generally report deriving some benefit from the therapies. The CAM therapies most frequently used include diet, omega-3 fatty acids and antioxidants. There is very limited research evaluating the safety and effectiveness of CAM in MS. The most promising among CAM therapies that warrant further investigation are a low-fat diet, omega-3 fatty acids, lipoic acid and vitamin D supplementation as potential anti-inflammatory and neuroprotective agents in both relapsing and progressive forms of MS. There is very limited research evaluating the safety and effectiveness of CAM in MS. However, in recent years, the NIH and the National MS Society have been actively supporting the research in this very important area. PMID:20441425

  12. Kinesiotaping as an alternative treatment method for carpal tunnel syndrome.

    PubMed

    Geler Külcü, Duygu; Bursali, Canan; Aktaş, İlknur; Bozkurt Alp, Selin; Ünlü Özkan, Feyza; Akpinar, Pınar

    2016-06-23

    Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. Conservative treatment choices are not always satisfactory. The aim of this study was to investigate the effect of kinesiotaping (KT) on pain level, grip strength, and functional status compared with that of placebo KT and orthotic device (OD) in patients with CTS. In this randomized, placebo-controlled study, participants were allocated into one of three groups: an experimental KT group (Group 1), a placebo KT group (Group 2), and an OD group (Group 3). Visual analogue scale (VAS) and Douleur Neuropathique 4 (DN4) scores, dynamometric grip strength measures, and the Boston CTS questionnaire (BQ) were the outcome measures. All groups significantly improved in terms of VAS scores (P < 0.05), DN4 scores (P < 0.05), and BQ scores (P < 0.05). Grip strength improved in Group 3 (P = 0.001). There was a significant difference among the groups with respect to BQ scores (P < 0.05). KT application for the treatment of CTS should be an alternative treatment choice.

  13. Complementary and alternative medicine treatments among stroke patients in India.

    PubMed

    Pandian, Jeyaraj Durai; Toor, Gagan; Arora, Rajni; Kaur, Paramdeep; Dheeraj, K V; Bhullar, Ranjeet Singh; Sylaja, Padmawati N

    2012-01-01

    Complementary and alternative medicine (CAM) is commonly used by persons with stroke throughout the world, particularly in Asia. The objectives of this study were to determine the frequency of CAM use and the factors that predict the use of CAM in stroke patients. This study was carried out in the stroke units of Christian Medical College, Ludhiana, and Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India, from June 2010 to December 2010. Participants were interviewed using a structured questionnaire (≥ 6 months post stroke). Outcomes were assessed using a modified Rankin Scale (mRS). Three hundred fourteen stroke patients were interviewed; mean age was 57.4 ± 12.9 years, and 230 (73.2%) patients were men. Of 314 patients, 114 (36.3%) had used the following CAM treatments: ayurvedic massage, 67 (59.3%); intravenous fluids, 22 (19.5%); herbal medicines, 17 (15%); homeopathy, 15 (13.3%); witchcraft, 3 (2.7%); acupuncture, 3 (2.7%); opium intake, 10 (8.8%); and other nonconventional treatments, 10 (8.8%). Patients with severe stroke (P < .0001), limb weakness (P < .0001), dysphagia (P = .02), dyslipidemia (P = .007), hypertension (P = .03), or hemorrhagic stroke (P<.0001) and patients with poor outcome (mRS >2;P < .0001) often used CAM treatments. More than one-third of the patients in this study opted for CAM. Presence of limb weakness, dysphagia, dyslipidemia, hypertension, hemorrhagic stroke, severe stroke, and poor outcome predicted the use of CAM.

  14. Multiple-objective evaluation of wastewater treatment plant control alternatives.

    PubMed

    Flores-Alsina, Xavier; Gallego, Alejandro; Feijoo, Gumersindo; Rodriguez-Roda, Ignasi

    2010-05-01

    Besides the evaluation of the environmental issues, the correct assessment of wastewater treatment plants (WWTP) should take into account several objectives such as: economic e.g. operation costs; technical e.g. risk of suffering microbiology-related TSS separation problems; or legal e.g. accomplishment with the effluent standards in terms of the different pollution loads. For this reason, the main objective of this paper is to show the benefits of complementing the environmental assessment carried out by life cycle assessment with economical, technical and legal criteria. Using a preliminary version of the BSM2 as a case study, different combinations of controllers are implemented, simulated and evaluated. In the following step, the resulting multi-criteria matrix is mined using multivariate statistical techniques. The results showed that the presence of an external carbon source addition, the type of aeration system and the TSS controller are the key elements creating the differences amongst the alternatives. Also, it was possible to characterize the different control strategies according to a set of aggregated criteria. Additionally, the existing synergies amongst different objectives and their consequent trade-offs were identified. Finally, it was discovered that from the initial extensive list of evaluation criteria, only a small set of five are really discriminant, being useful to differentiate within the generated alternatives. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Treatment alternatives of congenital hand differences with thumb hypoplasia involvement.

    PubMed

    Papadogeorgou, Ellada V; Soucacos, Panayotis N

    2008-01-01

    Congenital thumb hypoplasia is a complex and heterogeneous congenital difference that is detrimental to hand function. Apart from its' classic form, which is now considered to be part of radial dysplasia, it can occur as part of other congenital anomalies including, syndactyly, symbrachydactyly, atypical cleft hand, bifid thumb, triphalangeal thumb, mirror hand, constriction band syndrome, as well as generalized anomalies and syndromes. Management is aimed primarily at restoring basic hand function, specifically, power grasp and precision pinch, and secondarily to improve cosmoses, which inevitably is going to be impaired. Several treatment alternatives have been proposed to manage the specific disabling condition and include, 1st web space reconstruction and opponensplasty, pollicization, toe-to-hand transfer, distraction lengthening, free toe phalangeal transfer or the use of allograft, stabilization of the metacarpophalangeal joint, and surgery of "spare parts." The purpose of this study is to evaluate the various alternatives available today and propose an algorithm applicable for the appropriate management of thumb deficiency, based on their specific characteristics. Copyright 2008 Wiley-Liss, Inc. Microsurgery, 2008.

  16. Pollution Impact and Alternative Treatment for Produced Water

    NASA Astrophysics Data System (ADS)

    Hedar, Yusran; Budiyono

    2018-02-01

    Oil and gas exploration and production are two of the activities that potentially cause pollution and environmental damage. The largest waste generated from this activity is produced water. Produced water contains hazardous pollutants of both organic and inorganic materials, so that the produced water of oil and gas production cannot be discharged directly to the environment. Uncontrolled discharge can lead to the environmental damage, killing the life of water and plants. The produced water needs to be handled and fulfill the quality standards before being discharged to the environment. Several studies to reduce the contaminants in the produced water were conducted by researchers. Among them were gravity based separation - flotation, separation technique based on filtration, and biological process treatment. Therefore, some of these methods can be used as an alternative waste handling of produced water.

  17. Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

    PubMed Central

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G.

    2014-01-01

    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement. PMID:24639902

  18. Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

    PubMed

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

    2014-01-01

    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  19. Immunomodulation and safety of topical calcineurin inhibitors for the treatment of atopic dermatitis.

    PubMed

    Hultsch, Thomas; Kapp, Alexander; Spergel, Jonathan

    2005-01-01

    Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin condition that primarily affects children. Topical corticosteroids have been the mainstay of treatment since the late 1950s. While providing excellent short-term efficacy, topical corticosteroid usage is limited by potential adverse effects, including impairment of the function and viability of Langerhans cells/dendritic cells. The recently introduced topical calcineurin inhibitors pimecrolimus cream 1% (Elidel) and tacrolimus ointment 0.03 and 0.1% (Protopic) exhibit a more selective mechanism of action and do not affect Langerhans cells/dendritic cells. For the immune system of young children 'learning' to mount a balanced Th1/Th2 response, this selective effect has particular benefits. In clinical experience, topical calcineurin inhibitors have been shown to be a safe and effective alternative to topical corticosteroids in almost 7 million patients (>5 million on pimecrolimus; >1.7 million on tacrolimus). Topical pimecrolimus is primarily used in children with mild and moderate AD, whereas tacrolimus is used preferentially in more severe cases. None of the topical calcineurin inhibitors have been associated with systemic immunosuppression-related malignancies known to occur following long-term sustained systemic immunosuppression with oral immunosuppressants (e.g., tacrolimus, cyclosporine A, and corticosteroids) in transplant patients. Preclinical and clinical data suggest a greater skin selectivity and larger safety margin for topical pimecrolimus. (c) 2005 S. Karger AG, Basel

  20. Current Pharmaceutical Treatments and Alternative Therapies of Parkinson's Disease

    PubMed Central

    Dong, Jie; Cui, Yanhua; Li, Song; Le, Weidong

    2016-01-01

    Over the decades, pharmaceutical treatments, particularly dopaminergic (DAergic) drugs have been considered as the main therapy against motor symptoms of Parkinson's disease (PD). It is proposed that DAergic drugs in combination with other medications, such as monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, anticholinergics and other newly developed non-DAergic drugs can make a better control of motor symptoms or alleviate levodopa-induced motor complications. Moreover, non-motor symptoms of PD, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances caused by intrinsic PD pathology or drug-induced side effects, are gaining increasing attention and urgently need to be taken care of due to their impact on quality of life. Currently, neuroprotective therapies have been investigated extensively in pre-clinical studies, and some of them have been subjected to clinical trials. Furthermore, non-pharmaceutical treatments, including deep brain stimulation (DBS), gene therapy, cell replacement therapy and some complementary managements, such as Tai chi, Yoga, traditional herbs and molecular targeted therapies have also been considered as effective alternative therapies to classical pharmaceutics. This review will provide us updated information regarding the current drugs and non-drugs therapies for PD. PMID:26585523

  1. Gut Microbiota and Tacrolimus Dosing in Kidney Transplantation

    PubMed Central

    Lee, John R.; Muthukumar, Thangamani; Dadhania, Darshana; Taur, Ying; Jenq, Robert R.; Toussaint, Nora C.; Ling, Lilan; Pamer, Eric; Suthanthiran, Manikkam

    2015-01-01

    Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2±1.1 mg/day vs. 3.8±0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6±2.4 mg/day vs. 3.3±1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient±standard error of 1.0±0.6 (P=0.08) after multivariable linear regression. Our novel

  2. Radiation Synovectomy: an effective alternative treatment for inflamed small joints.

    PubMed

    Karavida, N; Notopoulos, A

    2010-01-01

    An inflamed painful joint is one of the most common indications for the patient to be referred to a rheumatologist or an orthopedician. In relation to the aetiology, the therapeutic approach might be systemic, local or a combination of them in some cases, always with the thought of balancing risk with benefit for the patient. In all cases, independently of the cause, the goal of therapy is to improve the quality of life through the reduction of pain, improvement of mobility and preservation of function. Nuclear Medicine has to offer Radiosynoviorthesis, an effective alternative procedure for treating inflamed small joints. Various radionuclides are available for radiosynoviorthesis. Their selection depends on the size of the joint to be treated. Small joints are mainly treated with [169Er] erbium under a fluoroscopic or sonographic guidance, usually with a simultaneous instillation of a corticoid. Candidates for radiosynoviorthesis should have been under a six-month systemic treatment without encouraging results or should have undergone at least one unsuccessful intra-articular injection of a long acting glucocorticoid. Since 1973, when [169Er] erbium was firstly suggested as a therapeutic agent for radiosynoviorthesis of the finger joints, there has been quite enough experience in its' application. It has been found to be cost effective in providing long term relief of pain and deformity of the inflamed joints in comparison to other therapeutic approaches. Additionally, there is no radiation risk and can be performed on an out patient basis. Therefore it can stand as an effective alternative procedure for treating early stages of chronic synovitis in RA (rheumatoid arthritis) patients, with minor damage of the cartilage and the adjacent bones, and for synovitis secondary to inflammatory arthropathies.

  3. Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.

    PubMed

    Egashira, Kanoko; Sasaki, Hitoshi; Higuchi, Shun; Ieiri, Ichiro

    2012-01-01

    Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.

  4. Alternative foaming agents for topical treatment of ulcerative colitis.

    PubMed

    Asama, Martin; Hall, Alex; Qi, Yijun; Moreau, Branden; Walthier, Heidi; Schaschwary, Matthew; Bristow, Blaine; Wang, Qun

    2018-05-01

    Approximately 907,000 Americans currently suffer from ulcerative colitis, a condition characterized by inflammation of the large intestine or rectum. Treatment of this disease often includes anti-inflammatory medication or immunosuppressants. Here foams are an attractive delivery platform, offering relatively high bioavailability, low systemic exposure, and improved patient comfort. However, the surfactants that generate these foams may adversely affect the diseased mucosa. Therefore, this project evaluated two alternative surfactants for use in topical drug delivery platforms: sodium caseinate and l-α-phosphatidylcholine. Both were compared to the biocompatible surfactant Pluronic ® F-127 using stability and density tests, and biocompatibility tests performed on mini-guts. Sodium caseinate foams were less stable but denser than Pluronic ® foams; however, they exhibited an unexpectedly low shelf-life. l-α-phosphatidylcholine was an unsuccessful primary foaming agent owing to poor foamability at low concentrations. Mini-gut growth rates were not significantly altered by surfactants, while morphology and an MTT assay identified Pluronic ® as the most biocompatible surfactant at higher concentrations. These results clarify the possible challenges that the tested surfactants may present in topical delivery platforms and show the relevance of permeability to tissue-surfactant interaction tests. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1448-1456, 2018. © 2017 Wiley Periodicals, Inc.

  5. Alternating magnetic field optimization for IONP hyperthermia cancer treatment

    NASA Astrophysics Data System (ADS)

    Kastner, Elliot J.; Reeves, Russell; Bennett, William; Misra, Aditi; Petryk, Jim D.; Petryk, Alicia A.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) have therapeutic potential to deliver a thermal dose to tumors when activated in an alternating magnetic field (AMF). Through various targeting methods such as antibody labeling or injection site choice, delivery of IONPs to tumors yields enhanced treatment accuracy and efficacy. Despite this advantage, delivery an AMF, which is sufficient to result in clinically relevant IONP heating, can result in nonspecific tissue heating via the generation of eddy currents and tissue permeated by local electric fields (joule heating). The production of eddy current heating is a function of tissue size, geometry and composition as well as coil design and operation. The purpose of this research is to increase the level of energy deposited into the IONPs versus the non-target tissue (power ratio/PR)1 in order to improve target heating and reduce nonspecific tissue damage. We propose to improve the PR using two primary concepts: (1) reduce power deposition into non-target tissue by manipulating the fields and eddy current flow and (2) enhance heat removal from non-target tissue. We have shown that controlling tissue placement within the AMF field, accounting for tissue geometry, utilizing external cooling devices, and modifying the field properties can decrease non-target heating by more than 50%, at clinically relevant AMF levels, thereby allowing for an increase in thermal dose to the tumor and increasing the therapeutic ratio.

  6. Pharmacokinetics of prolonged-release tacrolimus and implications for use in solid organ transplant recipients.

    PubMed

    Tanzi, Maria G; Undre, Nasrullah; Keirns, James; Fitzsimmons, William E; Brown, Malcolm; First, M Roy

    2016-08-01

    Prolonged-release tacrolimus was developed as a once-daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax ) for a given dose compared with immediate-release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged-release tacrolimus in healthy subjects, in transplant recipients converted from immediate-release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate-release formulation, prolonged-release tacrolimus shows a strong correlation between trough concentration (Cmin ) and area under the 24-hour time-concentration curve (AUC24 ), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged-release tacrolimus. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Focal metatarsal fistulae syndrome affecting a greyhound dog successfully treated with topical 0.1% tacrolimus ointment.

    PubMed

    Scholz, Fiona M; Muse, Russell; Burrows, Amanda K

    2015-12-01

    Metatarsal fistulation is an uncommon cutaneous condition reported almost exclusively in German shepherd dogs and their cross-breeds. To the best of the authors' knowledge this is the first reported case of focal metatarsal fistulae syndrome affecting a greyhound. Remission was obtained within 6 weeks of commencing treatment using compounded 0.1% tacrolimus ointment twice daily and the dog remained stable for another 6 months with twice weekly application before treatment was discontinued. The dog remained in remission at the time of writing, which is 1 year after treatment withdrawal. © 2015 ESVD and ACVD.

  8. Tacrolimus interaction with nafcillin resulting in significant decreases in tacrolimus concentrations: A case report.

    PubMed

    Wungwattana, Minkey; Savic, Marizela

    2017-04-01

    Tacrolimus (TAC) is subject to many drug interactions as a result of its metabolism primarily via CYP450 isoenzyme 3A4. Numerous case reports of TAC and CYP3A4 inducers and inhibitors have been described including antimicrobials, calcium channel antagonists, and antiepileptic drugs. We present the case of a 13-year-old patient with cystic fibrosis and a history of liver transplantation, where subtherapeutic TAC concentrations were suspected to be a result of concomitant TAC and nafcillin (NAF) therapy. The observed drug interaction occurred on two separate hospital admissions, during both of which the patient exhibited therapeutic TAC concentrations prior to exposure to NAF, a CYP3A4 inducer. Upon discontinuation of NAF, TAC concentrations recovered in both instances. This case represents a drug-drug interaction between TAC and NAF that has not previously been reported to our knowledge. Despite the lack of existing reports of interaction between these two agents, this case highlights the importance of therapeutic drug monitoring and assessing for any potential drug-drug or drug-food interactions in patients receiving TAC therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. 40 CFR 268.46 - Alternative treatment standards based on HTMR.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Alternative treatment standards based on HTMR. 268.46 Section 268.46 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND DISPOSAL RESTRICTIONS Treatment Standards § 268.46 Alternative treatment...

  10. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    PubMed

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  11. Integration of alternative feedstreams for biomass treatment and utilization

    DOEpatents

    Hennessey, Susan Marie [Avondale, PA; Friend, Julie [Claymont, DE; Dunson, Jr., James B.; Tucker, III, Melvin P.; Elander, Richard T [Evergreen, CO; Hames, Bonnie [Westminster, CO

    2011-03-22

    The present invention provides a method for treating biomass composed of integrated feedstocks to produce fermentable sugars. One aspect of the methods described herein includes a pretreatment step wherein biomass is integrated with an alternative feedstream and the resulting integrated feedstock, at relatively high concentrations, is treated with a low concentration of ammonia relative to the dry weight of biomass. In another aspect, a high solids concentration of pretreated biomass is integrated with an alternative feedstream for saccharifiaction.

  12. Alternative Splicing as a Target for Cancer Treatment.

    PubMed

    Martinez-Montiel, Nancy; Rosas-Murrieta, Nora Hilda; Anaya Ruiz, Maricruz; Monjaraz-Guzman, Eduardo; Martinez-Contreras, Rebeca

    2018-02-11

    Alternative splicing is a key mechanism determinant for gene expression in metazoan. During alternative splicing, non-coding sequences are removed to generate different mature messenger RNAs due to a combination of sequence elements and cellular factors that contribute to splicing regulation. A different combination of splicing sites, exonic or intronic sequences, mutually exclusive exons or retained introns could be selected during alternative splicing to generate different mature mRNAs that could in turn produce distinct protein products. Alternative splicing is the main source of protein diversity responsible for 90% of human gene expression, and it has recently become a hallmark for cancer with a full potential as a prognostic and therapeutic tool. Currently, more than 15,000 alternative splicing events have been associated to different aspects of cancer biology, including cell proliferation and invasion, apoptosis resistance and susceptibility to different chemotherapeutic drugs. Here, we present well established and newly discovered splicing events that occur in different cancer-related genes, their modification by several approaches and the current status of key tools developed to target alternative splicing with diagnostic and therapeutic purposes.

  13. Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats.

    PubMed

    Tamura, Shigeki; Ohike, Atsuo; Ibuki, Rinta; Amidon, Gordon L; Yamashita, Shinji

    2002-03-01

    The objective of this study is to investigate the role of P-glycoprotein (P-gp), a membrane efflux pump associated with multidrug resistance (MDR) and a known substrate for tacrolimus, in determining the regional intestinal permeability of tacrolimus in rats. Thus, isolated segments of rat jejunum, ileum, or colon were perfused with tacrolimus solutions containing polyethoxylated hydrogenated castor oil 60 surfactant, and with or without verapamil, a P-gp substrate used to reverse the MDR phenotype. The results indicated that the intrinsic permeability of tacrolimus in the jejunum, calculated on the basis of the concentration of non-micellized free tacrolimus, was quite high ( approximately 1.4 x 10(-4) cm/s). The apparent permeability (P(app)) in the jejunum was unaffected by the presence of verapamil; however, the P(app) in the ileum and the colon increased significantly in the presence of verapamil and were similar to the values observed in the jejunum. The results suggest that systemic absorption of tacrolimus from the gastrointestinal tract could be significantly affected by P-gp efflux mechanisms. It is also possible that differences in P-gp function at various intestinal sites in a subject or at a given intestinal site in various subjects could lead to large intra- and interindividual variability in bioavailability of tacrolimus following oral administration. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association .

  14. ENVIRONMENTAL POLLUTION CONTROL ALTERNATIVES: DRINKING WATER TREATMENT FOR SMALL COMMUNITIES

    EPA Science Inventory

    This document provides information for small system owners, operators, managers, and local decision makers, such as town officials, regarding drinking water treatment requirements and the treatment technologies suitable for small systems. t is not intended to be a comprehensive m...

  15. Relative bioavailability of single doses of prolonged-release tacrolimus administered as a suspension, orally or via a nasogastric tube, compared with intact capsules: a phase 1 study in healthy participants.

    PubMed

    Undre, Nasrullah; Dickinson, James

    2017-04-04

    Tacrolimus, an immunosuppressant widely used in solid organ transplantation, is available as a prolonged-release capsule for once-daily oral administration. In the immediate postsurgical period, if patients cannot take intact capsules orally, tacrolimus therapy is often initiated as a suspension of the capsule contents, delivered orally or via a nasogastric tube. This study evaluated the relative bioavailability of prolonged-release tacrolimus suspension versus intact capsules in healthy participants. A phase 1, open-label, single-dose, cross-over study. A single clinical research unit. In total, 20 male participants, 18-55 years old, entered and completed the study. All participants received nasogastric administration of tacrolimus 10 mg suspension in treatment period 1, with randomisation to oral administration of suspension or intact capsules in periods 2 and 3. Blood concentration-time profile over 144 hours was used to estimate pharmacokinetic parameters. Primary end point: relative bioavailability of prolonged-release intact capsule versus oral or nasogastric administration of prolonged-release tacrolimus suspension (area under the concentration-time curve (AUC) from time 0 to infinity post-tacrolimus dose (AUC 0-∞ ); AUC measured until the last quantifiable concentration (AUC 0-tz ); maximum observed concentration (C max ); time to C max (T max )). Tolerability was assessed throughout the study. Relative bioavailability of prolonged-release tacrolimus suspension administered orally was similar to intact capsules, with a ratio of least-square means for AUC 0-tz and AUC 0-∞ of 1.05 (90% CI 0.96 to 1.14). Bioavailability was lower with suspension administered via a nasogastric tube versus intact capsules (17%; ratio 0.83; CI 0.76 to 0.92). C max was higher for oral and nasogastric suspension (30% and 28%, respectively), and median T max was shorter (difference 1.0 and 1.5 hours postdose, respectively) versus intact capsules (2.0 hours). Single 10

  16. Simulations of alternative mechanical thinning treatment programs on western timberland

    Treesearch

    Karen L. Abt; Jeffrey P. Prestemon; Kenneth E. Skog; R. James Barbour; Miles A, Hemstrom; Robert J. Huggett

    2011-01-01

    We used the Economics of Biomass Removals model to evaluate the required treatment acreages, volumes removed, treatment costs and product revenues from national forest and other ownerships. We used three distinct treatment prescriptions to achieve two hazard reduction goals for treatable timberlands in the Western United States. The two hazard reduction goals were to...

  17. ALTERNATIVE OXIDANT AND DISINFECTANT TREATMENT STRATEGIES FOR CONTROLLING TRIHALOMETHANE FORMATION

    EPA Science Inventory

    To comply with the maximum contaminant level (MCL) for total trihalomethanes (TTHM), many utilities have modified their pre-oxidation and disinfection practices by switching to alternative oxidants and disinfectants in place of free chlorine. To evaluate the impact of these chang...

  18. Involvement of CYP 3A5 In the Interaction Between Tacrolimus and Nicardipine: A Case Report.

    PubMed

    Sassi, Mouna B; Gaies, Emna; Salouage, Issam; Trabelsi, Sameh; Lakhal, Mohamed; Klouz, Anis

    2015-01-01

    Tacrolimus is a calcineurin inhibitor primarily metabolized by CYP3A4 and secondarily by CYP3A5. Several drugs can modify tacrolimus blood levels as calcium channel blockers (CCBs). Interaction with nicardipine was reported in some cases. A man with a history of malignant arterial hypertension treated with nicardipine, underwent kidney transplantation. After transplantation, he was treated with tacrolimus, mycophenolate mofetil and corticoids. Therapeutic drug monitoring of tacrolimus was done regularly showing a mean trough concentration (C0) of 24.39 ng/mL with some concentrations reaching 52 ng/mL. After changing nicardipine by prazosine, the first tacrolimus C0 after stopping nicardipine was 3.2 ng/mL. Increase of tacrolimus trough concentrations is due to the inhibition of CYP3A4. Very high levels of tacrolimus suggest the non expression of CYP3A5. Thus, because of the possible lack of the secondary pathway, therapeutic drug monitoring of tacrolimus is highly recommended at the introduction of CCBs and also at its stopping.

  19. Different Influences on Tacrolimus Pharmacokinetics by Coadministrations of Zhi Ke and Zhi Shi in Rats

    PubMed Central

    Lin, Shiuan-Pey; Wu, Ping-Ping; Hou, Yu-Chi; Tsai, Shang-Yuan; Wang, Meng-Ju; Fang, Shih-Hua; Chao, Pei-Dawn Lee

    2011-01-01

    Tacrolimus, an immunosuppressant with narrow therapeutic window, has been used widely in transplant patients. Grapefruit juice and pomelo have been reported to increase the blood levels of tacrolimus. Zhi Ke and Zhi Shi, the ripe peels and unripe fruits of Citrus aurantium which is chemotaxonomically related to grapefruit and pomelo, are in wide use in clinical Chinese medicine. To investigate the possible interaction of these two Citrus herbs with tacrolimus, male Sprague-Dawley rats were orally given tacrolimus (1.5 mg/kg) with and without Zhi Ke and Zhi Shi decoctions in a cross-over design. Blood samples were withdrawn via cardiopuncture at specific time and quantitated by a microparticle enzyme immunoassay. In addition, to explore the mechanism of interaction, LS 180 cell line was used for the transport study of rhodamine 123, a typical substrate of P-glycoprotein (P-gp). The results showed that Zhi Shi significantly decreased the C max and AUC0−t of tacrolimus by 72.4% and 72.0%, respectively, whereas Zhi Ke did not affect tacrolimus pharmacokinetics. LS 180 cell line study indicated that Zhi Shi increased the efflux activity of P-gp, enabling us to explain the decreased oral bioavailability of tacrolimus caused by Zhi Shi. Hence, we suggest that Zhi Shi be contraindicated for transplant patients treated with tacrolimus to reduce the risk of allograft rejection. PMID:21318106

  20. Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.

    PubMed

    Cho, Jung Hyun; Kim, Yong-Il; Kim, Dong-Wuk; Yousaf, Abid Mehmood; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2014-04-11

    The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Brief Report: Alternative Approaches to the Development of Effective Treatments for Autism.

    ERIC Educational Resources Information Center

    Rimland, Bernard; Baker, Sidney M.

    1996-01-01

    The most widely used "alternative" biomedical treatments for autism are reviewed, including: nutritional supplements, especially megadose vitamin B6 and magnesium; treatment of food allergies and intolerances; treatment of microbial infections; and treatment of immune system dysfunction. The Defeat Autism Now! project is briefly…

  2. Initial response of understory vegetation to three alternative thinning treatments

    Treesearch

    Liane R. Davis; Klaus J. Puettmann

    2009-01-01

    This study compares initial understory vegetation response among three thinning treatments and a control in 30 - to 50-year-old even-aged Pseudotsuga menziesii (Mirbel) Franco (Douglas-fir) stands. It was conducted on four sites on the western slope of the central Oregon Cascades. Treatments included a control (no thinning), a light thinning, and...

  3. Acceptability of Alternative Treatments for Deviant Child Behavior.

    ERIC Educational Resources Information Center

    Kazdin, Alan E.

    1980-01-01

    Cases of deviant child behavior were described to 88 undergraduate students along with four different treatments (reinforcement of incompatible behavior, time out from reinforcement, drug therapy, and electric shock). Reinforcement of incompatible behavior was more acceptable than other treatments which followed, in order, time out from…

  4. Alternative ponderosa pine restoration treatments in the western United States

    Treesearch

    James McIver; Phillip Weatherspoon; Carl Edminster

    2001-01-01

    Compared to presettlement times, many ponderosa pine forests of the United States are now more dense and have greater quantities of fuels. Widespread treatments are needed in these forests to restore ecological integrity and to reduce the risk of uncharacteristically severe fires. Among possible restorative treatments, however, the appropriate balance among cuttings,...

  5. Improved prediction of tacrolimus concentrations early after kidney transplantation using theory-based pharmacokinetic modelling.

    PubMed

    Størset, Elisabet; Holford, Nick; Hennig, Stefanie; Bergmann, Troels K; Bergan, Stein; Bremer, Sara; Åsberg, Anders; Midtvedt, Karsten; Staatz, Christine E

    2014-09-01

    The aim was to develop a theory-based population pharmacokinetic model of tacrolimus in adult kidney transplant recipients and to externally evaluate this model and two previous empirical models. Data were obtained from 242 patients with 3100 tacrolimus whole blood concentrations. External evaluation was performed by examining model predictive performance using Bayesian forecasting. Pharmacokinetic disposition parameters were estimated based on tacrolimus plasma concentrations, predicted from whole blood concentrations, haematocrit and literature values for tacrolimus binding to red blood cells. Disposition parameters were allometrically scaled to fat free mass. Tacrolimus whole blood clearance/bioavailability standardized to haematocrit of 45% and fat free mass of 60 kg was estimated to be 16.1 l h−1 [95% CI 12.6, 18.0 l h−1]. Tacrolimus clearance was 30% higher (95% CI 13, 46%) and bioavailability 18% lower (95% CI 2, 29%) in CYP3A5 expressers compared with non-expressers. An Emax model described decreasing tacrolimus bioavailability with increasing prednisolone dose. The theory-based model was superior to the empirical models during external evaluation displaying a median prediction error of −1.2% (95% CI −3.0, 0.1%). Based on simulation, Bayesian forecasting led to 65% (95% CI 62, 68%) of patients achieving a tacrolimus average steady-state concentration within a suggested acceptable range. A theory-based population pharmacokinetic model was superior to two empirical models for prediction of tacrolimus concentrations and seemed suitable for Bayesian prediction of tacrolimus doses early after kidney transplantation.

  6. Alternative approaches to conventional treatment of acute uncomplicated urinary tract infection in women.

    PubMed

    Foxman, Betsy; Buxton, Miatta

    2013-04-01

    The increasing resistance of uropathogens to antibiotics and recognition of the generally self-limiting nature of uncomplicated urinary tract infection (UTI) suggest that it is time to reconsider empirical treatment of UTI using antibiotics. Identifying new and effective strategies to prevent recurrences and alternative treatment strategies are a high priority. We review the recent literature regarding the effects of functional food products, probiotics, vaccines, and alternative treatments on treating and preventing UTI.

  7. Alternative aggregates and materials for high friction surface treatments : [summary].

    DOT National Transportation Integrated Search

    2016-07-01

    Researchers at the Texas A&M Transportation Institute studied the materials and practices that best eliminate premature HFST failures and reduce overall HFST costs, while maintaining or improving treatment life and friction performance.

  8. Alternative aggregates and materials for high friction surface treatments.

    DOT National Transportation Integrated Search

    2016-05-01

    The State of Florida has used high friction surface treatments (HFSTs) since 2006 to reduce wet weather crashes on : tight curves and intersections and to maintain bridge decks; however, the Florida Department of Transportation : (FDOT) has reported ...

  9. [Behavior and cognitive treatments for insomnia. An alternative to pharmacotherapy].

    PubMed

    Baillargeon, L

    1997-02-01

    To familiarize family physicians with cognitive and behavioural treatments for insomnia. MEDLINE was searched from 1983 to 1995 and Psychlit from 1974 to 1995 using the key words "behaviour therapy," "cognitive therapy," "phototherapy," and "insomnia." We chose randomized trials and meta-analyses on the treatment of insomnia. Information was extracted on time-lag before sleep, frequency and duration of wakeful periods during the night, consumption of hynotics, and subjects' own assessment of their sleep before and after treatment. The most effective interventions were relaxation training, sleep restriction, and stimulus control. Practising good sleeping habits was only somewhat effective and should always be used in conjunction with other interventions. Stimulus control for insomnia has been demonstrated to be effective when used by primary care physicians. Other nonpharmacologic treatments should be evaluated in a similar manner.

  10. Proven Alternatives for Aboveground Treatment of Arsenic in Groundwater

    DTIC Science & Technology

    2002-10-01

    Contaminant of Concern by Mediaa Media Number of Sites Groundwater 380 Soil 372 Sediment 154 Surface Water 86 Debris 77 Sludge 45 Solid Waste 30 Leachate ...issue paper does not address three technologies that have been used to treat water containing arsenic: • Biological treatment • Phytoremediation ...arsenic in water, and no aboveground treatments of groundwater conducted at full scale were found. Phytoremediation and electrokinetics are not

  11. Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus.

    PubMed

    Fazal, Muhammad Asim; Idrees, Muhammad Khalid; Akhtar, Syed Fazal

    2014-05-01

    To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy. The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3 mg/kg) and group B was treated with tacrolimus (0.1 mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5 ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses. Of the 182 patients, 144 (79.1%) were males and 38 (20.9%) were females. The overall mean age was 30.18 +/- 9.57 years, and the mean weight was 54.41 +/- 11.144 kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54 (59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy. The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication.

  12. Alemtuzumab induction with tacrolimus monotherapy in de novo renal transplantation.

    PubMed

    Villanueva, M E; Muñoz, A S; Casasola, C C; Africa, J B; Danguilan, R A; Ona, E T

    2008-09-01

    Alemtuzumab is increasingly being used as induction therapy for kidney transplantation, allowing immunosuppression minimization. This study examined the efficacy of alemtuzumab induction followed by low-dose tacrolimus monotherapy in standard risk primary kidney transplant patients. This retrospective cohort of primary standard risk renal transplant recipients were given alemtuzumab induction and low-dose tacrolimus maintenance immunosuppression (target trough 7 to 10 ng/mL for the first 6 months and 5 to 7 ng/mL thereafter). Serum creatinine values, acute rejection episodes, and graft survival were noted at week 1 as well as months 3, 6, 12, and 18. At the time of analysis, 47 patients were at 6 months, 28 at 12 months, and 6 patients at 18 months from transplant. Mean follow-up was 12.53 months (range, 6 to 23). Mean serum creatinine was 1.47 +/- 0.65 mg/dL at 3 months, 1.56 +/- 0.84 at 6 months, 1.45 +/- 0.37 at 12 months, and 1.74 +/- 0.35 at 18 months. The 1-year clinical acute rejection rate was 21% (6/28), occurring at 0 to 3 months in 2 (33%), 4 to 6 months in 1 (17%), and >6 months in 3 patients (50%). Biopsy-proven acute rejection was 14% (4/28). The episodes were classified as borderline in one, Banff 2A in two, and Banff 3 in one patients. One patient had both acute cellular and acute humoral rejection; half responded to steroid pulse therapy. The 1-year patient survival rate was 90%. The 1-year death-censored graft survival rate was 98%. Alemtuzumab induction with tacrolimus monotherapy is an acceptable option in standard risk patients. BPAR was 14%, but renal function remained satisfactory at 18 months posttransplant.

  13. Is biological treatment a viable alternative for micropollutant removal in drinking water treatment processes?

    PubMed

    Benner, Jessica; Helbling, Damian E; Kohler, Hans-Peter E; Wittebol, Janneke; Kaiser, Elena; Prasse, Carsten; Ternes, Thomas A; Albers, Christian N; Aamand, Jens; Horemans, Benjamin; Springael, Dirk; Walravens, Eddy; Boon, Nico

    2013-10-15

    In western societies, clean and safe drinking water is often taken for granted, but there are threats to drinking water resources that should not be underestimated. Contamination of drinking water sources by anthropogenic chemicals is one threat that is particularly widespread in industrialized nations. Recently, a significant amount of attention has been given to the occurrence of micropollutants in the urban water cycle. Micropollutants are bioactive and/or persistent chemicals originating from diverse sources that are frequently detected in water resources in the pg/L to μg/L range. The aim of this review is to critically evaluate the viability of biological treatment processes as a means to remove micropollutants from drinking water resources. We first place the micropollutant problem in context by providing a comprehensive summary of the reported occurrence of micropollutants in raw water used directly for drinking water production and in finished drinking water. We then present a critical discussion on conventional and advanced drinking water treatment processes and their contribution to micropollutant removal. Finally, we propose biological treatment and bioaugmentation as a potential targeted, cost-effective, and sustainable alternative to existing processes while critically examining the technical limitations and scientific challenges that need to be addressed prior to implementation. This review will serve as a valuable source of data and literature for water utilities, water researchers, policy makers, and environmental consultants. Meanwhile this review will open the door to meaningful discussion on the feasibility and application of biological treatment and bioaugmentation in drinking water treatment processes to protect the public from exposure to micropollutants. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. [Alternative splicing regulation: implications in cancer diagnosis and treatment].

    PubMed

    Martínez-Montiel, Nancy; Rosas-Murrieta, Nora; Martínez-Contreras, Rebeca

    2015-04-08

    The accurate expression of the genetic information is regulated by processes like mRNA splicing, proposed after the discoveries of Phil Sharp and Richard Roberts, who demonstrated the existence of intronic sequences, present in almost every structural eukaryotic gene, which should be precisely removed. This intron removal is called "splicing", which generates different proteins from a single mRNA, with different or even antagonistic functions. We currently know that alternative splicing is the most important source of protein diversity, given that 70% of the human genes undergo splicing and that mutations causing defects in this process could originate up to 50% of genetic diseases, including cancer. When these defects occur in genes involved in cell adhesion, proliferation and cell cycle regulation, there is an impact on cancer progression, rising the opportunity to diagnose and treat some types of cancer according to a particular splicing profile. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  15. Pharmacogenetics of tacrolimus and sirolimus in renal transplant patients: from retrospective analyses to prospective studies.

    PubMed

    Anglicheau, D; Legendre, C; Thervet, E

    2007-09-01

    The promises of pharmacogenetics are to elucidate the inherited basis of differences between individual responses to drugs in order to identify the right drug and dose for each patient. The recent identification of genetic polymorphisms in drug-metabolizing enzymes and drug transporters led to the hypothesis that genetic factors may be implicated in the interindividual variability of the pharmacokinetic or pharmacodynamic characteristics of immunosuppressive drugs, major side effects, and efficacy. The purpose of this study was to provide a short overview of recent results obtained in the field of pharmacogenetics of tacrolimus and sirolimus, both substrates of the cytochrome P450 3A (CYP3A) enzymes and of the efflux pump P-glycoprotein, the product of the Multidrug Resistance-1 (MDR1) genes. A number of retrospective studies that demonstrated a link between the polymorphisms governing the CYP3A5 protein expression, with more conflicting results with the MDR1 gene polymorphisms, related to the daily dose necessary to achieve adequate blood tacrolimus levels. The CYP3A5 polymorphisms have also been associated with sirolimus pharmacokinetics. One challenge is to investigate the combined effect of a number of different polymorphisms in various genes to define genetic backgrounds with different pharmacokinetic profiles using high throughput technologies. Another challenge is to move toward prospective randomized studies to explore whether a pharmacogenetic approach, taking into account a limited number of polymorphisms prior to drug treatment, could be used on an individual basis to guide initial dosing of a given drug. The last challenge is based on "target" pharmacogenetics to investigate the role of the polymorphisms of other genes implicated in the efficacy and/or safety of the drug.

  16. Complementary and alternative medicine treatments for low back pain.

    PubMed

    Marlowe, Dan

    2012-09-01

    Complementary and alternative medicine, often referred to as integrated medicine, is often used for the treatment of low back pain. This article presents 6 therapies (ie, behavioral treatment, acupuncture, manipulation, prolotherapy, neuroreflexotherapy, and herbal treatments), which are discussed in terms of the specifics of the modality, as well as the empirical evidence related to their effectiveness. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Alternative prosthodontic-based treatment of a patient with hypocalcified type Amelogenesis Imperfecta.

    PubMed

    Jivanescu, Anca; Miglionico, Antonio; Barua, Souman; Hategan, Simona Ioana

    2017-07-01

    The Amelogenesis Imperfecta is associated with malocclusion and usually requires an interdisciplinary treatment. Due to the patient's refusal of orthodontic treatment, prosthodontics-based treatments alternative was considered and planned. The patient was treated with zirconia-based fixed partial dentures, which resulted in improved occlusion, better oral health, and improved esthetic appearance.

  18. An Alternating Treatment Comparison of Minimal and Maximal Opposition Sound Selection in Turkish Phonological Disorders

    ERIC Educational Resources Information Center

    Topbas, Seyhun; Unal, Ozlem

    2010-01-01

    A single-subject alternating treatment design in combination with a staggered multiple baseline model across subjects was implemented with two 6:0 year-old girls, monozygotic twins, who were referred to a university clinic for evaluation and treatment. The treatment programme was structured according to variants of "minimal pair contrast…

  19. Use of Complementary and Alternative Medicine (CAM) Treatments by Parents of Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Christon, Lillian M.; Mackintosh, Virginia H.; Myers, Barbara J.

    2010-01-01

    Parents of children with autism spectrum disorders (ASDs) may elect to use complementary and alternative medicine (CAM) treatments with their children in place of, or in addition to, conventional treatments. CAM treatments are controversial and understudied and, for most, the efficacy has not been established. The current study (n = 248) examined…

  20. Propolis as an alternative treatment for cutaneous warts.

    PubMed

    Zedan, Hatem; Hofny, Eman R M; Ismail, Sahar A

    2009-11-01

    Warts are common problems affecting adults and children. Multiple treatment options are available, but no single therapy stands out as uniformly effective. Propolis and Echinacea are relatively safe immunomodulators with antiviral properties. The purpose of this study was to assess the efficacy of Propolis and Echinacea in treating different types of warts. In a single-blind, randomized, 3-months trial, 135 patients with different types of warts received oral Propolis, Echinacea, or placebo. In patients with plane and common warts treated with Propolis, cure was achieved in 75% and 73% of patients, respectively. These results were significantly better than those associated with Echinacea treatment or placebo. We conclude that Propolis is an effective and safe immunomodulating therapy for plane and common warts.

  1. What if endoscopic hemostasis fails? Alternative treatment strategies: interventional radiology.

    PubMed

    Nanavati, Sujal M

    2014-12-01

    Since the 1960s, interventional radiology has played a role in the management of gastrointestinal bleeding. What began primarily as a diagnostic modality has evolved into much more of a therapeutic tool. And although the frequency of gastrointestinal bleeding has diminished thanks to management by pharmacologic and endoscopic methods, the need for additional invasive interventions still exists. Transcatheter angiography and intervention is a fundamental step in the algorithm for the treatment of gastrointestinal bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Randomized Comparison of Topical Betamethasone Valerate Foam, Intralesional Triamcinolone Acetonide and Tacrolimus Ointment in Management of Localized Alopecia Areata

    PubMed Central

    Kuldeep, CM; Singhal, Himanshu; Khare, Ashok Kumar; Mittal, Asit; Gupta, Lalit K; Garg, Anubhav

    2011-01-01

    Background: Alopecia areata (AA) is a common, non-scarring, patchy loss of hair at scalp and elsewhere. Its pathogenesis is uncertain; however, auto-immunity has been exemplified in various studies. Familial incidence of AA is 10-42%, but in monozygotic twins is 50%. Local steroids (topical / intra-lesional) are very effective in treatment of localized AA. Aim: To compare hair regrowth and side effects of topical betamethasone valerate foam, intralesional triamcinolone acetonide and tacrolimus ointment in management of localized AA. Materials and Methods: 105 patients of localized AA were initially registered but 27 were drop out. So, 78 patients allocated at random in group A (28), B (25) and C (25) were prescribed topical betamethasone valerate foam (0.1%) twice daily, intralesional triamcinolone acetonide (10mg/ml) every 3 weeks and tacrolimus ointment (0.1%) twice daily, respectively, for 12 weeks. They were followed for next12 weeks. Hair re-growth was calculated using “HRG Scale”; scale I- (0-25%), S II-(26-50%), S III - (51-75%) and S IV- (75-100%). Results: Hair re-growth started by 3 weeks in group B (Scale I: P<0.03), turned satisfactory at 6 weeks in group A and B (Scale I: P<0.005, Scale IV: P<0.001)), good at 9 weeks (Scale I: P<0.0005, Scale IV: P<0.00015), and better by 12 weeks of treatment (Scale I: P<0.000021, Scale IV: P<0.000009) in both A and B groups. At the end of 12 weeks follow-up hair re-growth (>75%, HRG IV) was the best in group B (15 of 25, 60%), followed by A (15 of 28, 53.6%) and lastly group-C (Nil of 25, 0%) patients. Few patients reported mild pain and atrophy at injection sites, pruritus and burning with betamethasone valerate foam and tacrolimus. Conclusion: Intralesional triamcinolone acetonide is the best, betamethasone valerate foam is better than tacrolimus in management of localized AA. PMID:21769231

  3. Trends in the biosynthesis and production of the immunosuppressant tacrolimus (FK506).

    PubMed

    Barreiro, Carlos; Martínez-Castro, Miriam

    2014-01-01

    The current off-patent state of tacrolimus (FK506) has opened the hunting season for new generic pharmaceutical formulations of this immunosuppressant. This fact has boosted the scientific and industrial research on tacrolimus for the last 5 years in order to improve its production. The fast discovery of tacrolimus producer strains has generated a huge number of producers, which presents the biosynthetic cluster of FK506 as a high promiscuous genetic region. For the first time, the current state-of-the-art on the tacrolimus biosynthesis, production improvements and drug purification is reviewed. On one hand, all the genes involved in the tacrolimus biosynthesis, in addition to the traditional PKS/NRPS, as well as their regulation are analysed. On the other hand, tacrolimus direct and indirect precursors are reviewed as a straight manner to improve the final yield, which is a current trend in the field. Twenty years of industrial and scientific improvements on tacrolimus production are summarised, whereas future trends are also drafted.

  4. Guidance: Demonstrating Compliance with the Land Disposal Restrictions (LDR) Alternative Soil Treatment Standards

    EPA Pesticide Factsheets

    This guidance provides suggestions and perspectives on how members of the regulated community, states, and the public can demonstrate compliance with the alternative treatment standards for certain contaminated soils that will be land disposed.

  5. SELENIUM TREATMENT/REMOVAL ALTERNATIVES DEMONSTRATION PROJECT - MINE WASTE TECHNOLOGY PROGRAM ACTIVITY III, PROJECT 20

    EPA Science Inventory

    This document is the final report for EPA's Mine WAste Technology Program (MWTP) Activity III, Project 20--Selenium Treatment/Removal Alternatives Demonstration project. Selenium contamination originates from many sources including mining operations, mineral processing, abandoned...

  6. Approval of Alternative Test Method for Puerto Nuevo Wastewater Treatment Plant, San Juan, Puerto Rico Memorandum

    EPA Pesticide Factsheets

    This December 2008 memorandum is from Conniesue Oldham of the Measurement Technology Group to Marcus E. Kantz in EPA Region 2. This memorandum is regarding a request to use an alternative test method at the Puerto Neuvo wastewater treatment plant

  7. Use of Topical Tacrolimus and Topical Pimecrolimus in Four European Countries: A Multicentre Database Cohort Study.

    PubMed

    Kuiper, Josephina G; van Herk-Sukel, Myrthe P P; Castellsague, Jordi; Pottegård, Anton; Berglind, Ingegärd Anveden; Dedman, Daniel; Gutierrez, Lia; Calingaert, Brian; Hallas, Jesper; Sundström, Anders; Gallagher, Arlene M; Kaye, James A; Pardo, Carolina; Rothman, Kenneth J; Perez-Gutthann, Susana

    2018-05-07

    Despite the concerns about a potential increased risk of skin cancer and lymphoma with the use of topical tacrolimus and pimecrolimus, no population-based studies have given an overview of the use of these drugs in Europe. To assess the use of topical tacrolimus and pimecrolimus in children and adults in Europe. Multicentre database cohort study comprising data from the Netherlands, Denmark, Sweden and the UK. We analysed users of topical tacrolimus and pimecrolimus starting from the date of first availability (between 2002 and 2003) or start establishment of the prescription database in Sweden (2006) through 2011. Use was assessed separately for children (≤ 18 years) and adults. 32,052 children and 104,902 adults were treated with topical tacrolimus, and 32,125 children and 58,280 adults were treated with topical pimecrolimus. The number of users increased rapidly after first availability, especially for topical tacrolimus. Topical tacrolimus was more frequently used in all countries except Denmark. For both drugs, there was a decrease in users after 2004 in the Netherlands and Denmark and after 2005 in the UK, especially among children. This decrease was largest in Denmark. The decrease in the number of users was temporary for topical tacrolimus, while use remained relatively low for topical pimecrolimus. The number of topical tacrolimus and pimecrolimus users increased rapidly after regulatory approval. A transient reduction in topical tacrolimus use and a persistent reduction in topical pimecrolimus use was seen after 2004 in the Netherlands and Denmark and after 2005 in the UK.

  8. Tacrolimus placental transfer at delivery and neonatal exposure through breast milk.

    PubMed

    Zheng, Songmao; Easterling, Thomas R; Hays, Karen; Umans, Jason G; Miodovnik, Menachem; Clark, Shannon; Calamia, Justina C; Thummel, Kenneth E; Shen, Danny D; Davis, Connie L; Hebert, Mary F

    2013-12-01

    The current investigation aims to provide new insights into fetal exposure to tacrolimus in utero by evaluating maternal and umbilical cord blood (venous and arterial), plasma and unbound concentrations at delivery. This study also presents a case report of tacrolimus excretion via breast milk. Maternal and umbilical cord (venous and arterial) samples were obtained at delivery from eight solid organ allograft recipients to measure tacrolimus and metabolite bound and unbound concentrations in blood and plasma. Tacrolimus pharmacokinetics in breast milk were assessed in one subject. Mean (±SD) tacrolimus concentrations at the time of delivery in umbilical cord venous blood (6.6 ± 1.8 ng ml(-1)) were 71 ± 18% (range 45-99%) of maternal concentrations (9.0 ± 3.4 ng ml(-1)). The mean umbilical cord venous plasma (0.09 ± 0.04 ng ml(-1)) and unbound drug concentrations (0.003 ± 0.001 ng ml(-1)) were approximately one fifth of the respective maternal concentrations. Arterial umbilical cord blood concentrations of tacrolimus were 100 ± 12% of umbilical venous concentrations. In addition, infant exposure to tacrolimus through the breast milk was less than 0.3% of the mother's weight-adjusted dose. Differences between maternal and umbilical cord tacrolimus concentrations may be explained in part by placental P-gp function, greater red blood cell partitioning and higher haematocrit levels in venous cord blood. The neonatal drug exposure to tacrolimus via breast milk is very low and likely does not represent a health risk to the breastfeeding infant. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

  9. [Calcitonin as an alternative treatment for root resorption].

    PubMed

    Pierce, A; Berg, J O; Lindskog, S

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

  10. Alternative approaches to treatment of Central Sleep Apnea

    PubMed Central

    2013-01-01

    Synopsis Divergent approaches to treatment of hypocapnic central sleep apnea syndromes reflect the difficulties in taming a hyperactive respiratory chemoreflex. As both sleep fragmentation and a narrow CO2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable non-rapid eye movement (NREM) sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO2-based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient dyssynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO2 manipulation directly stabilize respiratory control by moving CO2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent and Winx may be less likely to trigger central apneas or periodic breathing in those with a narrow CO2 reserve. An oral appliance can meaningfully reduce positive pressure requirements and thus enable treatment of complex apnea. Novel pharmacological approaches may target mediators of carotid body glomus cell excitation, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is not always successful, and multi-modality therapy might need to be considered. Phenotyping of sleep apnea beyond conventional scoring approaches is the key to optimal management. PMID:24772053

  11. Alternative approaches to treatment of Central Sleep Apnea.

    PubMed

    Thomas, Robert Joseph

    2014-03-01

    Divergent approaches to treatment of hypocapnic central sleep apnea syndromes reflect the difficulties in taming a hyperactive respiratory chemoreflex. As both sleep fragmentation and a narrow CO 2 reserve or increased loop gain drive the disease, sedatives (to induce longer periods of stable non-rapid eye movement (NREM) sleep and reduce the destabilizing effects of arousals in NREM sleep) and CO 2 -based stabilization approaches are logical. Adaptive ventilation reduces mean hyperventilation yet can induce ventilator-patient dyssynchrony, while enhanced expiratory rebreathing space (EERS, dead space during positive pressure therapy) and CO 2 manipulation directly stabilize respiratory control by moving CO 2 above the apnea threshold. Carbonic anhydrase inhibition can provide further adjunctive benefits. Provent and Winx may be less likely to trigger central apneas or periodic breathing in those with a narrow CO 2 reserve. An oral appliance can meaningfully reduce positive pressure requirements and thus enable treatment of complex apnea. Novel pharmacological approaches may target mediators of carotid body glomus cell excitation, such as the balance between gas neurotransmitters. In complex apnea patients, single mode therapy is not always successful, and multi-modality therapy might need to be considered. Phenotyping of sleep apnea beyond conventional scoring approaches is the key to optimal management.

  12. Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

    PubMed

    Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

    2016-10-01

    Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Is exercise an alternative treatment for chronic insomnia?

    PubMed Central

    Passos, Giselle Soares; Poyares, Dalva Lucia Rollemberg; Santana, Marcos Gonçalves; Tufik, Sergio; de Mello, Marco Túlio

    2012-01-01

    The purposes of this systematic/critical review are: 1) to identify studies on the effects of exercise on chronic insomnia and sleep complaints in middle-aged and older adults and to compare the results of exercise with those obtained with hypnotic medications and 2) to discuss potential mechanisms by which exercise could promote sleep in insomniac patients. We identified studies from 1983 through 2011 using MEDLINE, SCOPUS and Web of Science. For systematic analyses, only studies assessing the chronic effects of exercise on sleep in people with sleep complaints or chronic insomnia were considered. We used the following keywords when searching for articles: insomnia, sleep, sleep complaints, exercise and physical activity. For a critical review, studies were selected on the effects of exercise and possible mechanisms that may explain the effects of exercise on insomnia. We identified five studies that met our inclusion criteria for systematic review. Exercise training is effective at decreasing sleep complaints and insomnia. Aerobic exercise has been more extensively studied, and its effects are similar to those observed after hypnotic medication use. Mechanisms are proposed to explain the effects of exercise on insomnia. There is additional documented evidence on the antidepressant and anti-anxiety effects of exercise. Exercise is effective to decrease sleep complaints and to treat chronic insomnia. Exercise presented similar results when compared with hypnotics; however, prospective studies comparing the effects of exercise with medical and non-medical treatments are warranted before including exercise as a first-line treatment for chronic insomnia are necessary. PMID:22760906

  14. The enduring effects of psychodynamic treatments vis-a-vis alternative treatments: A multilevel longitudinal meta-analysis

    NASA Astrophysics Data System (ADS)

    Kivlighan, D. Martin, III

    Although evidence suggests that the benefits of psychodynamic treatments are sustained over time, presently it is unclear whether these sustained benefits are superior to non-psychodynamic treatments. Additionally, the extant literature comparing the sustained benefits of psychodynamic treatments compared to alternative treatments is limited with methodological shortcomings. The purpose of the current study was to conduct a rigorous test of the growth of the benefits of psychodynamic treatments relative to alternative treatments across distinct domains of change (i.e., all outcome measures, targeted outcome measures, non-targeted outcome measures, and personality outcome measures). To do so, the study employed strict inclusion criteria to identify randomized clinical trials that directly compared at least one bona fide psychodynamic treatment and one bona fide non-psychodynamic treatment. Hierarchical linear modeling (Raudenbush, Bryk, Cheong & Congdon, du Toit, 2011) was used to longitudinally model the impact of psychodynamic treatments compared to non-psychodynamic treatments at post-treatment and to compare the growth (i.e., slope) of effects beyond treatment completion. Findings from the present meta-analysis indicated that psychodynamic treatments and non-psychodynamic treatments were equally efficacious at post-treatment and at follow-up for combined outcomes ( k = 20), targeted outcomes (k =19), non-targeted outcomes (k =17), and personality outcomes (k =6). Clinical implications, directions for future research, and limitations are discussed.

  15. Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.

    PubMed

    Miles, Clifford D; Skorupa, Jill Y; Sandoz, John P; Rigley, Theodore H; Nielsen, Kathleen J; Stevens, R Brian

    2011-01-01

    Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications. © 2010 John Wiley & Sons A/S.

  16. A Review of Indigo Naturalis as an Alternative Treatment for Nail Psoriasis.

    PubMed

    McDermott, Laura; Madan, Raman; Rupani, Reena; Siegel, Daniel

    2016-03-01

    Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

  17. De novo use of generic tacrolimus in liver transplantation - a single center experience with one-yr follow-up.

    PubMed

    Dannhorn, E; Cheung, M; Rodrigues, S; Cooper, H; Thorburn, D; Patch, D; Burroughs, A K; O'Beirne, J

    2014-12-01

    Use of generic tacrolimus in liver transplantation (LT) could result in cost savings. Generic tacrolimus has been shown to be bioequivalent to innovator tacrolimus in healthy volunteers and renal transplant patients. There are limited data on the de novo use of generic tacrolimus in LT. This study aimed to determine whether the de novo use of generic tacrolimus (Adoport, Sandoz,UK) was associated with differences in outcomes, safety, and cost compared with innovator tacrolimus (Prograf, Astellas, Japan). Patients were studied before and after a programmatic change from de novo IS with Prograf to Adoport. Outcomes, tacrolimus levels, doses, and costs were compared for the first-yr post-LT. Ninety-four patients were studied, 46 Prograf, 48 Adoport. No significant differences in rejection, cytomegalovirus infection, acute kidney injury, sepsis, or graft loss were observed between groups. Tacrolimus costs were significantly reduced with the de novo use of Adoport. Day 14 dose normalized levels in Adoport patients showed significant variation but at the day 30 and one yr, there were no significant differences in the doses or levels of tacrolimus between groups. Adoport is safe and effective compared to Prograf when used de novo in LT patients. Tacrolimus costs were significantly reduced by the use of Adoport. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial

    PubMed Central

    Vinks, Alexander A.; Fukuda, Tsuyoshi; King, Eileen C.; Zou, Yuanshu; Jiang, Wenlei; Klawitter, Jelena; Christians, Uwe

    2017-01-01

    Background Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, “brand”) product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. Methods and findings From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within

  19. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

    PubMed

    Alloway, Rita R; Vinks, Alexander A; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; King, Eileen C; Zou, Yuanshu; Jiang, Wenlei; Woodle, E Steve; Tremblay, Simon; Klawitter, Jelena; Klawitter, Jost; Christians, Uwe

    2017-11-01

    Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration

  20. Evaluating alternative fuel treatment strategies to reduce wildfire losses in a Mediterranean area

    Treesearch

    Michele Salis; Maurizio Laconi; Alan A. Ager; Fermin J. Alcasena; Bachisio Arca; Olga Lozano; Ana Fernandes de Oliveira; Donatella Spano

    2016-01-01

    The goal of this work is to evaluate by a modeling approach the effectiveness of alternative fuel treatment strategies to reduce potential losses from wildfires in Mediterranean areas. We compared strategic fuel treatments located near specific human values vs random locations, and treated 3, 9 and 15% of a 68,000 ha study area located in Sardinia, Italy. The...

  1. Simultaneous Synthesis of Treatment Effects and Mapping to a Common Scale: An Alternative to Standardisation

    ERIC Educational Resources Information Center

    Ades, A. E.; Lu, Guobing; Dias, Sofia; Mayo-Wilson, Evan; Kounali, Daphne

    2015-01-01

    Objective: Trials often may report several similar outcomes measured on different test instruments. We explored a method for synthesising treatment effect information both within and between trials and for reporting treatment effects on a common scale as an alternative to standardisation Study design: We applied a procedure that simultaneously…

  2. Combination of Surgical Drainage and Renal Artery Embolization: An Alternative Treatment for Xanthogranulomatous Pyelonephritis

    SciTech Connect

    Upasani, Anand, E-mail: anand.upasani@gosh.nhs.uk; Barnacle, Alex, E-mail: alex.barnacle@gosh.nhs.uk; Roebuck, Derek, E-mail: derek.roebuck@gosh.nhs.uk

    Conventionally, xanthogranulomatous pyelonephritis is treated with antibiotics and drainage of abscess followed by nephrectomy for definitive treatment. Surgical excision of the affected kidney carries risk of significant complications. An alternative treatment modality is described in the form of embolization of the renal artery to devascularise the renal parenchyma and ablate the renal tissue, thus avoiding a major surgical procedure and the significant risks involved.

  3. Effects of ecological restoration alternative treatments on nonnative plant species establishment (P-53)

    Treesearch

    Michael T. Stoddard; Christopher M. McGlone; Peter Z. Fule

    2008-01-01

    Disturbances generated by forest restoration treatments have the potential for enhancing the establishment of nonnative species thereby impeding long-term native plant recovery. In a ponderosa pine forest next to the Fort Valley Experimental Forest, Arizona, we examined the establishment of nonnative species after three alternative treatments with different intensities...

  4. Effects of ecological restoration alternative treatments on nonnative plant species establishment

    Treesearch

    Michael T. Stoddard; Christopher M. McGlone; Peter Z. Fule

    2008-01-01

    Disturbances generated by forest restoration treatments have the potential for enhancing the establishment of nonnative species thereby impeding long-term native plant recovery. In a ponderosa pine forest next to the Fort Valley Experimental Forest, Arizona, we examined the establishment of nonnative species after three alternative treatments with different intensities...

  5. Alternative/Complementary Approaches to Treatment of Children with Autism Spectrum Disorders.

    ERIC Educational Resources Information Center

    Levy, Susan E.; Hyman, Susan L.

    2002-01-01

    This article reviews common complementary or alternative medicine (CAM) treatments used to address symptoms of autistic spectrum disorders, including vitamin supplements, medications, antibiotics, antifungals, diet strategies, chelation/mercury detoxification, and nonbiologic treatments. Strategies that professionals may use in assessing the…

  6. Beneficial effects of topical tacrolimus on recalcitrant erosions of pemphigus vulgaris.

    PubMed

    Gach, J E; Ilchyshyn, A

    2004-05-01

    We report a case of pemphigus vulgaris in which a recalcitrant area of erosion on the cheek cleared only when topical tacrolimus was used in addition to a regime of systemic therapy consisting of cyclophosphamide and prednisolone. Clinical improvement occurred within 10 days of applying topical tacrolimus with healing of erosions and reduction in pain and burning sensations. Topical tacrolimus may inhibit local activation of T lymphocytes through altered expression of cytokines such as interleukin-1, -4 and -5, tumour necrosis factor-alpha and interferon-gamma. Some of these cytokines may also contribute directly to increasing keratinocyte fragility in the aetiology of pemphigus vulgaris erosions. This case illustrates that topical tacrolimus may be a useful adjunct in the management of patients with pemphigus vulgaris.

  7. Advantage of Rapamycin Over Mycophenolate Mofetil When Used With Tacrolimus for Simultaneous Pancreas Kidney Transplants: Randomized, Single-Center Trial at 10 Years

    PubMed Central

    Ciancio, G.; Sageshima, J.; Chen, L.; Gaynor, J. J.; Hanson, L.; Tueros, L.; Montenora-Velarde, E.; Gomez, C.; Kupin, W.; Guerra, G.; Mattiazzi, A.; Fornoni, A.; Pugliese, A.; Roth, D.; Wolf, M.; Burke, G. W.

    2015-01-01

    Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent. PMID:22946986

  8. “Living proof” and the pseudo-science of alternative cancer treatments

    PubMed Central

    Vickers, Andrew J.; Cassileth, Barrie R.

    2008-01-01

    Michael Gearin-Tosh was an English Professor at Oxford University who was diagnosed with multiple myeloma in 1994. He rejected conventional chemotherapeutic approaches and turned to a variety of alternative cancer treatments, particularly those involving nutritional supplements and dietary change. In 2002, Dr Gearin-Tosh published a book, “Living Proof”, recounting his experiences. The book gained significant public and media attention. One chapter was written by Carmen Wheatley, an advocate of alternative cancer treatments. In distinction to Dr Gearin-Tosh’s personal story, Dr Wheatley makes general claims about cancer treatment that are supposedly based on the research literature. This appears to provide scientific validation for a highly unconventional program of cancer care. However, the scientific case made for alternative cancer treatments in “Living Proof” does not bear serious examination. There are numerous inaccuracies, omissions and misrepresentations. Many important claims are either entirely unsubstantiated or not supported by the literature cited. In conclusion, a highly publicized book gives the impression that alternative cancer treatments are supported by scientific research. It also suggests that little progress has been made in the conventional treatment of myeloma. This is highly misleading and may lead to cancer patients rejecting effective treatments. PMID:18302909

  9. The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation

    PubMed Central

    Thölking, Gerold; Fortmann, Christian; Koch, Raphael; Gerth, Hans Ulrich; Pabst, Dirk; Pavenstädt, Hermann; Kabar, Iyad; Hüsing, Anna; Wolters, Heiner

    2014-01-01

    The effective calcineurin inhibitor (CNI) tacrolimus (Tac) is an integral part of the standard immunosuppressive regimen after renal transplantation (RTx). However, as a potent CNI it has nephrotoxic potential leading to impaired renal function in some cases. Therefore, it is of high clinical impact to identify factors which can predict who is endangered to develop CNI toxicity. We hypothesized that the Tac metabolism rate expressed as the blood concentration normalized by the dose (C/D ratio) is such a simple predictor. Therefore, we analyzed the impact of the C/D ratio on kidney function after RTx. Renal function was analyzed 1, 2, 3, 6, 12 and 24 months after RTx in 248 patients with an immunosuppressive regimen including basiliximab, tacrolimus, mycophenolate mofetil and prednisolone. According to keep the approach simple, patients were split into three C/D groups: fast, intermediate and slow metabolizers. Notably, compared with slow metabolizers fast metabolizers of Tac showed significantly lower estimated glomerular filtration rate (eGFR) values at all the time points analyzed. Moreover, fast metabolizers underwent more indication renal biopsies (p = 0.006) which revealed a higher incidence of CNI nephrotoxicity (p = 0.015) and BK nephropathy (p = 0.024) in this group. We herein identified the C/D ratio as an easy calculable risk factor for the development of CNI nephrotoxicity and BK nephropathy after RTx. We propose that the simple C/D ratio should be taken into account early in patient’s risk management strategies. PMID:25340655

  10. Alternative Approaches to Conventional Treatment of Acute Uncomplicated Urinary Tract Infection in Women

    PubMed Central

    Foxman, Betsy; Buxton, Miatta

    2013-01-01

    The increasing resistance of uropathogens to antibiotics, and recognition of generally self-limiting nature of uncomplicated urinary tract infection (UTI) suggests that it is time to reconsider empirical treatment of UTI using antibiotics. Identifying new and effective strategies to prevent recurrences and alterative treatment strategies are a high priority. We review the recent literature regarding the effects of functional food products, probiotics, vaccines, and alternative treatments on treating and preventing UTI. PMID:23378124

  11. Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.

    PubMed

    Rostaing, Lionel; Bunnapradist, Suphamai; Grinyó, Josep M; Ciechanowski, Kazimierz; Denny, Jason E; Silva, Helio Tedesco; Budde, Klemens

    2016-04-01

    1-year data from this trial showed the noninferiority of a novel once-daily extended-release tacrolimus (LCPT; Envarsus XR) to immediate-release tacrolimus (IR-Tac) twice daily after kidney transplantation. Final 24-month analysis of a 2-armed, parallel-group, randomized, double-blind, double-dummy, multicenter, phase 3 trial. 543 de novo kidney recipients randomly assigned to LCPT (n=268) or IR-Tac (n=275); 507 (93.4%) completed the 24-month study. LCPT tablets once daily at 0.17 mg/kg/d or IR-Tac twice daily at 0.1 mg/kg/d; subsequent doses were adjusted to maintain target trough ranges (first 30 days, 6-11 ng/mL; thereafter, 4-11 ng/mL). The intervention was 24 months; the study was double blinded for the entirety. Treatment failure (death, transplant failure, biopsy-proven acute rejection, or loss to follow up) within 24 months. Safety end points included adverse events, serious adverse events, new-onset diabetes, kidney function, opportunistic infections, and malignancies. Pharmacokinetic measures included total daily dose (TDD) of study drugs and tacrolimus trough levels. 24-month treatment failure was LCPT, 23.1%; IR-Tac, 27.3% (treatment difference, -4.14% [95% CI, -11.38% to +3.17%], well below the +10% noninferiority criterion defined for the primary 12-month end point). Subgroup analyses showed fewer treatment failures for LCPT versus IR-Tac among black, older, and female recipients. Safety was similar between groups. From month 1, TDD was lower for LCPT; the difference increased over time. At month 24, mean TDD for LCPT was 24% lower than for the IR-Tac group (P<0.001), but troughs were similar (means at 24 months: LCPT, 5.47 ± 0.17 ng/mL; IR-Tac, 5.8 ± 0.30 ng/mL; P=0.4). Trial participant eligibility criteria may limit the generalizability of results to the global population of de novo kidney transplant recipients. Results suggest that once-daily LCPT in de novo kidney transplantation has comparable efficacy and safety profile to that of IR

  12. The cost effectiveness of tacrolimus versus microemulsified cyclosporin: a 10-year model of renal transplantation outcomes.

    PubMed

    Orme, Michelle E; Jurewicz, Wieslaw A; Kumar, Nagappan; McKechnie, Tracy L

    2003-01-01

    In 1983, the launch of cyclosporin was a significant clinical advance for organ transplant recipients. Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion (cyclosporin ME) and tacrolimus. This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation. A model was developed to project the costs and outcomes over a 10-year period following transplantation. The model was based on the results of a prospective, randomised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus, which was conducted by the Welsh Transplantation Research Group (median follow-up: 2.7 years). The short-term costs and outcomes were the averages from the actual head-to-head trial data. From this, the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3, 5 and 10 years post transplant, as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit. PERSPECTIVE AND YEAR OF COST DATA: The analysis was conducted from the perspective of a UK transplant unit. Costs were at 1999 prices (pounds sterling 1 = dollars US 1.42 = Euro 1.5) and costs and outcomes were discounted at 6% and 1.5%, respectively. The model estimated that 10 years after transplantation, the proportion of patients surviving was 56% of the cyclosporin ME cohort and 64% of the tacrolimus cohort. The cumulative cost of maintenance therapy at 10 years was pounds sterling 23204 per patient maintained on cyclosporin ME versus pounds sterling 23803 per patient on tacrolimus. The cost per survivor at 10 years was pounds sterling 37000 (tacrolimus) versus pounds sterling 41000 (cyclosporin ME) and the cost per patient with a functioning graft was pounds sterling 39000 versus pounds sterling 45000

  13. Complementary alternative treatments used by patients with cancer in eastern Turkey.

    PubMed

    Gözüm, Sebahat; Tezel, Ayfer; Koc, Mehmet

    2003-06-01

    Interest in complementary-alternative medicine therapies is growing rapidly in Turkey. Therefore, the purpose of this research was to determine the types and prevalence of alternative therapies used by the patients with a diagnosis of cancer, and to determine factors influencing the choices of their therapies in Erzurum, Turkey. Approximately 10-minute face-to-face interviews were conducted with each subject in the radiation oncology department. The factors associated with the use of alternative therapies after a diagnosis of cancer were assessed by chi-square analysis. The findings indicated that complementary-alternative medicine therapies were used by 41.1% of the subjects after their diagnosis, and that all of the alternatives they used were herbs. The most commonly used herb was stinging nettle leaf (urtica dioica) or seed of nettle. Almost all (93.2%) of the herbs used were nettle. In general, especially the women and the younger patients of both genders were more likely to be using alternative therapies. There was no difference in demographic and cancer characteristics between users of alternative therapy and nonusers. More than the half of the patients using alternative therapies (54.5%) reportedly did not discuss the use of herbs with their healthcare professionals. Most of the patients using stinging nettle and other herbs therapies reported that they had heard about the use of herbs from friends or relatives (52.3%), or from the other patients in this clinic (43.2%). This study found that there is a high prevalence of alternative therapies used by patients with cancer in eastern Turkey. The use of these alternative therapies requires that nursing professionals rethink staff competency, patient assessment, and patient-focused care. Communication between patients and healthcare professionals should initiate dialogues on this topic for a better understanding of patient choices with regard to treatment options.

  14. Renal Cell Carcinoma: Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review.

    PubMed

    Prins, Fieke M; Kerkmeijer, Linda G W; Pronk, Anne A; Vonken, Evert-Jan P A; Meijer, Richard P; Bex, Axel; Barendrecht, Maurits M

    2017-10-01

    The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery, alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance, radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future.

  15. Complementary and alternative medicine treatments for children with autism spectrum disorders.

    PubMed

    Levy, Susan E; Hyman, Susan L

    2008-10-01

    Complementary and alternative medical (CAM) treatments are commonly used for children with autism spectrum disorders. This review discusses the evidence supporting the most frequently used treatments, including categories of mind-body medicine, energy medicine, and biologically based, manipulative, and body-based practices, with the latter two treatments the most commonly selected by families. Clinical providers need to understand the evidence for efficacy (or lack thereof) and potential side effects. Some CAM practices have evidence to reject their use, such as secretin, whereas others have emerging evidence to support their use, such as melatonin. Most treatments have not been adequately studied and do not have evidence to support their use.

  16. Elbasvir/Grazoprevir, an Alternative in Antiviral Hepatitis C Therapy in Patients under Amiodarone Treatment

    PubMed Central

    Weiss, Lina; Wustmann, Kerstin; Semmo, Mariam; Schwerzmann, Markus; Semmo, Nasser

    2018-01-01

    A sofosbuvir/ledipasvir combination is part of a first-line treatment of hepatitis C. However, in patients concurrently treated with amiodarone, cardiac side effects have been described, resulting in an official warning in 2015 by the American Food and Drug Administration and the European Medicines Agency when combining those substances. This deprived numerous hepatitis C patients with concurrent cardiovascular problems of receiving this highly effective treatment. Here we present a treatment alternative with an elbasvir/grazoprevir regimen, based on our successful treatment of a patient under concurrent amiodarone therapy. Our observations indicate that patients treated with amiodarone can finally benefit from effective antiviral therapy. PMID:29606942

  17. The role of complementary and alternative medicine in the treatment of eating disorders: A systematic review.

    PubMed

    Fogarty, Sarah; Smith, Caroline A; Hay, Phillipa

    2016-04-01

    This systematic review critically appraises the role of complementary and alternative medicine in the treatment of those with an eating disorder. Sixteen studies were included in the review. The results of this review show that the role of complementary and alternative medicine in the treatment of those with an eating disorder is unclear and further studies should be conducted. A potential role was found for massage and bright light therapy for depression in those with Bulimia Nervosa and a potential role for acupuncture and relaxation therapy, in the treatment of State Anxiety, for those with an eating disorder. The role of these complementary therapies in treating eating disorders should only be provided as an adjunctive treatment only. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Population pharmacokinetic and pharmacogenetic analysis of tacrolimus in paediatric liver transplant patients

    PubMed Central

    Abdel Jalil, Mariam H; Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael D; McElnay, James C

    2014-01-01

    Aims To build a population pharmacokinetic model that describes the apparent clearance of tacrolimus and the potential demographic, clinical and genetically controlled factors that could lead to inter-patient pharmacokinetic variability within children following liver transplantation. Methods The present study retrospectively examined tacrolimus whole blood pre-dose concentrations (n = 628) of 43 children during their first year post-liver transplantation. Population pharmacokinetic analysis was performed using the non-linear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance and influential covariates. Results The final model identified time post-transplantation and CYP3A5*1 allele as influential covariates on tacrolimus apparent clearance according to the following equation: where TVCL is the typical value for apparent clearance, TPT is time post-transplantation in days and the CYP3A5 is 1 where *1 allele is present and 0 otherwise. The population estimate and inter-individual variability (%CV) of tacrolimus apparent clearance were found to be 0.977 l h−1 kg−1 (95% CI 0.958, 0.996) and 40.0%, respectively, while the residual variability between the observed and predicted concentrations was 35.4%. Conclusion Tacrolimus apparent clearance was influenced by time post-transplantation and CYP3A5 genotypes. The results of this study, once confirmed by a large scale prospective study, can be used in conjunction with therapeutic drug monitoring to recommend tacrolimus dose adjustments that take into account not only body weight but also genetic and time-related changes in tacrolimus clearance. PMID:23738951

  19. Friction Surface Treatment Selection: Aggregate Properties, Surface Characteristics, Alternative Treatments, and Safety Effects

    DOT National Transportation Integrated Search

    2017-07-01

    This study aimed to evaluate the long term performance of the selected surface friction treatments, including high friction surface treatment (HFST) using calcined bauxite and steel slag, and conventional friction surfacing, in particular pavement pr...

  20. A Strategy for Making Decisions and Evaluating Alternative Juvenile Offender Treatment Programs: Compensating for Missing Information.

    ERIC Educational Resources Information Center

    Roberts, Albert R.; Schervish, Phillip

    1988-01-01

    National survey data on the cost-effectiveness and cost-benefits of 11 different juvenile offender treatment program types are reviewed. Best-worst-midpoint, threshold, and convergency analyses are applied to these studies. Meaningful ways of dealing with missing information when evaluating alternative juvenile justice policies and programs are…

  1. Alternatives to Incarceration: Prevention or Treatment. Monograph on Youth in the 1990s. Issue #4.

    ERIC Educational Resources Information Center

    Richards, Anthony, Ed.; Bocarro, Jason, Ed.

    The articles in this collection address various definitions, viewpoints, and treatments for youth at risk and youth offenders. Articles not only examine alternatives to incarceration, but also provide examples of value-forming experiences beneficial to all young people. The articles and authors are: (1) "Introduction" (Anthony Richards); (2) "The…

  2. Amoxicillin and Ceftriaxone as Treatment Alternatives to Penicillin for Maternal Syphilis.

    PubMed

    Katanami, Yuichi; Hashimoto, Takehiro; Takaya, Saho; Yamamoto, Kei; Kutsuna, Satoshi; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Ohmagari, Norio

    2017-05-01

    There is no proven alternative to penicillin for treatment of maternal syphilis. We report 2 case-patients with maternal syphilis who were successfully treated without penicillin. We used amoxicillin and probenecid for the first case-patient and amoxicillin, probenecid, and ceftriaxone for the second case-patient.

  3. Old and New Controversies in the Alternative Treatment of Attention-Deficit Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Rojas, Neal L.; Chan, Eugenia

    2005-01-01

    Use of complementary and alternative medicine (CAM) for treatment of attention-deficit hyperactivity disorder (ADHD) has become widespread in both referral and primary care populations. We review the purported mechanism of action and available evidence for selected CAM therapies for ADHD. Enduring controversies, such as elimination of artificial…

  4. Imagining the Alternatives to Life Prolonging Treatments: Elders' Beliefs about the Dying Experience

    ERIC Educational Resources Information Center

    Winter, Laraine; Parker, Barbara; Schneider, Melissa

    2007-01-01

    Deciding for or against a life-prolonging treatment represents a choice between prolonged life and death. When the death alternative is not described, individuals must supply their own assumptions. How do people imagine the experience of dying? The authors asked 40 elderly people open-ended questions about dying without 4 common life-prolonging…

  5. Donor CYP3A5 genotype influences tacrolimus disposition on the first day after paediatric liver transplantation.

    PubMed

    Calvo, Pier Luigi; Serpe, Loredana; Brunati, Andrea; Nonnato, Antonello; Bongioanni, Daniela; Olio, Dominic Dell'; Pinon, Michele; Ferretti, Carlo; Tandoi, Francesco; Carbonaro, Giulia; Salizzoni, Mauro; Amoroso, Antonio; Romagnoli, Renato; Canaparo, Roberto

    2017-06-01

    The aim of the present study was to investigate the influence of the cytochrome P450 (CYP) 3A4/5 genotype in paediatric liver transplant recipients and donors, and the contribution of age and gender to tacrolimus disposition on the first day after transplantation. The contribution of the CYP3A4/5 genotype in paediatric liver transplant recipients and donors to the tacrolimus blood trough concentrations (C 0 ) and the tacrolimus concentration/weight-adjusted dose ratio on day 1 was evaluated in 67 liver-transplanted children: 33 boys and 34 girls, mean age 4.5 years. Donor CYP3A5 genotype appears to be significantly associated with tacrolimus disposition on the first day after liver transplantation (P < 0.0002). Other physiological factors, such as recipient age and donor gender may also play a role and lead to significant differences in tacrolimus C 0 and tacrolimus concentration/weight-adjusted dose ratio on day 1. However, according to the general linear model, only recipient age appears to be independently associated with tacrolimus disposition on the first day after liver transplantation (P < 0.03). Indeed, there was a faster tacrolimus metabolism in children under 6 years of age (P < 0.02). Donor CYP3A5 genotype, recipient age and, to a lesser extent, donor gender appear to be associated with tacrolimus disposition on day 1 after transplant. This suggests that increasing the starting tacrolimus doses in paediatric patients under 6 years of age who receive a graft from a male extensive metabolizer may enhance the possibility of their tacrolimus levels reaching the therapeutic range sooner. © 2017 The British Pharmacological Society.

  6. Differences in Peripheral Blood Lymphocytes between Brand-Name and Generic Tacrolimus Used in Stable Liver Transplant Recipients.

    PubMed

    Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Sinn, Dong Hyun; Choi, Gyu-Seong; Park, Jae Berm; Kang, Eun-Suk; Lee, Suk-Koo

    2017-01-01

    In this study, peripheral blood lymphocytes were compared between a brand-name and a generic tacrolimus group in stable liver transplant recipients. Sixteen patients who underwent ABO-compatible living donor liver transplants between 2012 and 2013 and had stable graft function were included in this study. Ten patients received brand-name tacrolimus and 6 patients received generic tacrolimus. CD3, CD4, CD8, γδ, CD4+FoxP3+, and CD3-CD56+ T cells were analyzed in peripheral blood obtained preoperatively and 4, 8, 12, and 24 weeks after liver transplantation. Categorical variables were compared using a χ2 test or Fisher exact test, and continuous variables were compared using the Mann-Whitney U test. Regarding the baseline and perioperative characteristics, there were no statistically significant differences between the 2 groups. Immunosuppression also was not different. Subtype analysis of T-cell populations carried out in parallel showed similar levels of CD3, CD4, CD8, and γδT cells with brand-name tacrolimus and generic tacrolimus in stable liver transplant recipients. However, the levels of CD4+Foxp3+ and CD3-CD56+ T cells were higher in the brand-name tacrolimus group than in the generic tacrolimus group 8 weeks after transplantation (p < 0.05). The level of CD4+Foxp3+ T cells was higher in the brand-name tacrolimus group than in the generic tacrolimus group after transplantation. This finding showed that brand-name tacrolimus could have more potential immunosuppressive activity than generic tacrolimus regarding the contribution of CD4+Foxp3+ T cells to graft tolerance in liver transplant recipients. © 2017 S. Karger AG, Basel.

  7. The Blackfeet Indian culture camp: Auditioning an alternative indigenous treatment for substance use disorders.

    PubMed

    Gone, Joseph P; Calf Looking, Patrick E

    2015-05-01

    American Indian and Alaska Native (AIAN) communities experience alarming health disparities, including high rates of substance use disorders (SUDs). Psychological services for AIANs, including SUDs treatment, are primarily funded by the federal Indian Health Service and typically administered by tribal governments. Tribal administration of SUDs treatment programs has routinely involved either inclusion of traditional cultural practices into program activities or adaptation of conventional treatment approaches to distinctive community sensibilities. In this article, we investigate a third possibility: the collaborative, community-based development of an alternative indigenous intervention that was implemented as a form of SUDs treatment in its own right and on its own terms. Specifically, in July of 2012, we undertook a trial implementation of a seasonal cultural immersion camp based on traditional Pikuni Blackfeet Indian cultural practices for 4 male clients from the reservation's federally funded SUDs treatment program. Given a variety of logistical and methodological constraints, the pilot offering of the culture camp primarily served as a demonstration of "proof of concept" for this alternative indigenous intervention. In presenting and reflecting on this effort, we consider many challenges associated with alternative indigenous treatment models, especially those associated with formal outcome evaluation. Indeed, we suggest that the motivation for developing local indigenous alternatives for AIAN SUDs treatment may work at cross-purposes to the rigorous assessment of therapeutic efficacy for such interventions. Nevertheless, we conclude that these efforts afford ample opportunities for expanding the existing knowledge base concerning the delivery of community-based psychological services for AIANs. (c) 2015 APA, all rights reserved).

  8. Comparative LCA of decentralized wastewater treatment alternatives for non-potable urban reuse.

    PubMed

    Opher, Tamar; Friedler, Eran

    2016-11-01

    Municipal wastewater (WW) effluent represents a reliable and significant source for reclaimed water, very much needed nowadays. Water reclamation and reuse has become an attractive option for conserving and extending available water sources. The decentralized approach to domestic WW treatment benefits from the advantages of source separation, which makes available simple small-scale systems and on-site reuse, which can be constructed on a short time schedule and occasionally upgraded with new technological developments. In this study we perform a Life Cycle Assessment to compare between the environmental impacts of four alternatives for a hypothetical city's water-wastewater service system. The baseline alternative is the most common, centralized approach for WW treatment, in which WW is conveyed to and treated in a large wastewater treatment plant (WWTP) and is then discharged to a stream. The three alternatives represent different scales of distribution of the WW treatment phase, along with urban irrigation and domestic non-potable water reuse (toilet flushing). The first alternative includes centralized treatment at a WWTP, with part of the reclaimed WW (RWW) supplied back to the urban consumers. The second and third alternatives implement de-centralized greywater (GW) treatment with local reuse, one at cluster level (320 households) and one at building level (40 households). Life cycle impact assessment results show a consistent disadvantage of the prevailing centralized approach under local conditions in Israel, where seawater desalination is the marginal source of water supply. The alternative of source separation and GW reuse at cluster level seems to be the most preferable one, though its environmental performance is only slightly better than GW reuse at building level. Centralized WW treatment with urban reuse of WWTP effluents is not advantageous over decentralized treatment of GW because the supply of RWW back to consumers is very costly in materials and

  9. Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

    PubMed Central

    Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

    2013-01-01

    Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

  10. An exploratory study of alternative configurations of governing boards of substance abuse treatment centers

    PubMed Central

    Blum, Terry C.; Roman, Paul M.

    2011-01-01

    Boards of directors are the ultimate governing authorities for most organizations providing substance abuse treatment. A governing board may establish policies, monitor and improve operations, and represent a treatment organization to the public. This paper explores alternative configurations of governing boards in a national sample of 500 substance abuse treatment centers. The study proceeds from the premise that boards may be configured with varying levels of engagement in five aspects of internal management and external connections in treatment center operating environments. Based on interviews with treatment center administrative directors, four clusters emerge, describing boards that are: (1) active and balanced across internal and external domains; (2) active boundary spanners concentrating primarily on external relationships; (3) focused primarily on internal organizational management; and (4) relatively inactive. In post hoc analysis, we found that placement in these clusters is associated with treatment center attributes such as rate of growth and financial results, use of evidence based practices and provision of integrated care. PMID:21489737

  11. Optimization of wastewater treatment alternative selection by hierarchy grey relational analysis.

    PubMed

    Zeng, Guangming; Jiang, Ru; Huang, Guohe; Xu, Min; Li, Jianbing

    2007-01-01

    This paper describes an innovative systematic approach, namely hierarchy grey relational analysis for optimal selection of wastewater treatment alternatives, based on the application of analytic hierarchy process (AHP) and grey relational analysis (GRA). It can be applied for complicated multicriteria decision-making to obtain scientific and reasonable results. The effectiveness of this approach was verified through a real case study. Four wastewater treatment alternatives (A(2)/O, triple oxidation ditch, anaerobic single oxidation ditch and SBR) were evaluated and compared against multiple economic, technical and administrative performance criteria, including capital cost, operation and maintenance (O and M) cost, land area, removal of nitrogenous and phosphorous pollutants, sludge disposal effect, stability of plant operation, maturity of technology and professional skills required for O and M. The result illustrated that the anaerobic single oxidation ditch was the optimal scheme and would obtain the maximum general benefits for the wastewater treatment plant to be constructed.

  12. Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

    PubMed Central

    Provenzani, Alessio; Santeusanio, Andrew; Mathis, Erin; Notarbartolo, Monica; Labbozzetta, Manuela; Poma, Paola; Provenzani, Ambra; Polidori, Carlo; Vizzini, Giovanni; Polidori, Piera; D’Alessandro, Natale

    2013-01-01

    The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolimus; also, unlike phenotypic tests, the genotype is a stable characteristic that needs to be determined only once for any given gene. However, prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that medication. At present, research has been able to reliably show that the CYP3A5 genotype, but not the CYP3A4 or ABCB1 ones, can modify the pharmacokinetics of tacrolimus. However, it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and toxicity. For these reasons, pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing. PMID:24409044

  13. Investigation of bioaerosols released from swine farms using conventional and alternative waste treatment and management technologies

    USGS Publications Warehouse

    Ko, G.; Simmons, O. D.; Likirdopulos, C.A.; Worley-Davis, L.; Williams, M.; Sobsey, M.D.

    2008-01-01

    Microbial air pollution from concentrated animal feeding operations (CAFOs) has raised concerns about potential public health and environmental impacts. We investigated the levels of bioaerosols released from two swine farms using conventional lagoon-sprayfield technology and ten farms using alternative waste treatment and management technologies in the United States. In total, 424 microbial air samples taken at the 12 CAFOs were analyzed for several indicator and pathogenic microorganisms, including culturable bacteria and fungi, fecal coliform, Escherichia coli, Clostridium perfringens, bacteriophage, and Salmonella. At all of the investigated farms, bacterial concentrations at the downwind boundary were higher than those at the upwind boundary, suggesting that the farms are sources of microbial air contamination. In addition, fecal indicator microorganisms were found more frequently near barns and treatment technology sites than upwind or downwind of the farms. Approximately 4.5% (19/424), 1.2% (5/424), 22.2% (94/424), and 12.3% (53/424) of samples were positive for fecal coliform, E. coli, Clostridium, and total coliphage, respectively. Based on statistical comparison of airborne fecal indicator concentrations at alternative treatment technology farms compared to control farms with conventional technology, three alternative waste treatment technologies appear to perform better at reducing the airborne release of fecal indicator microorganisms during on-farm treatment and management processes. These results demonstrate that airborne microbial contaminants are released from swine farms and pose possible exposure risks to farm workers and nearby neighbors. However, the release of airborne microorganisms appears to decrease significantly through the use of certain alternative waste management and treatment technologies. ?? 2008 American Chemical Society.

  14. Understanding antimicrobial stewardship: Disease severity treatment thresholds and antimicrobial alternatives among organic and conventional calf producers.

    PubMed

    Habing, Greg; Djordjevic, Catherine; Schuenemann, Gustavo M; Lakritz, Jeff

    2016-08-01

    Reductions in livestock antimicrobial use (AMU) can be achieved through identification of effective antimicrobial alternatives as well as accurate and stringent identification of cases requiring antimicrobial therapy. Objective measurements of selectivity that incorporate appropriate case definitions are necessary to understand the need and potential for reductions in AMU through judicious use. The objective of this study was to measure selectivity using a novel disease severity treatment threshold for calf diarrhea, and identify predictors of more selective application of antimicrobials among conventional dairy producers. A second objective of this study was to describe the usage frequency and perceptions of efficacy of common antimicrobial alternatives among conventional and organic producers. The cross-sectional survey was mailed to Michigan and Ohio, USA dairy producers and contained questions on AMU attitudes, AMU practices, veterinary-written protocols, and antimicrobial alternatives. The treatment threshold, defined based on the case severity where the producer would normally apply antimicrobials, was identified with a series of descriptions with increasing severity, and ordinal multivariable logistic regression was used to determine the association between the treatment threshold and individual or herd characteristics. The response rate was 49% (727/1488). Overall, 42% of conventional producers reported any veterinary-written treatment protocol, and 27% (113/412) of conventional producers had a veterinary-written protocol for the treatment of diarrhea that included a case identification. The majority (58%, 253/437) of conventional producers, but a minority (7%) of organic producers disagreed that antibiotic use in agriculture led to resistant bacterial infections in people. Among conventional producers, the proportion of producers applying antimicrobials for therapy increased from 13% to 67% with increasing case severity. The treatment threshold was low

  15. TAC-TIC use of tacrolimus-based regimens in lupus nephritis

    PubMed Central

    Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

    2016-01-01

    Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

  16. Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

    PubMed

    Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

    2000-12-01

    We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

  17. Age-dependent metabolic and immunosuppressive effects of Tacrolimus

    PubMed Central

    Krenzien, Felix; Quante, Markus; Heinbokel, Timm; Seyda, Midas; Minami, Koichiro; Uehara, Hirohito; Biefer, Hector Rodriguez Cetina; Schuitenmaker, Jeroen M.; Gabardi, Steven; Splith, Katrin; Schmelzle, Moritz; Petrides, Athena K.; Azuma, Haruhito; Pratschke, Johann; Li, Xian C.; ElKhal, Abdallah; Tullius, Stefan G.

    2016-01-01

    Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor Tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T-cells. Old recipient mice exhibited prolonged skin graft survival when compared to young animals following TAC administration. More importantly, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce pro-inflammatory IFN-γ cytokine production and promote IL-10 production in old CD4+ T-cells. In addition, TAC administration decreased IL-2 secretion in old CD4+ T-cells more effectively while inhibiting the proliferation of CD4+ T-cells in old mice. Both, TAC treated murine and human CD4+ T-cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca2+-influx, two critical pathways in T-cell activation. Of note, depletion of CD8+ T-cells did not alter allograft survival outcome in old TAC treated mice, suggesting that TAC age-specific effects were mainly CD4+ T-cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4+ T-cell mediated. The suppression of calcineurin levels and Ca2+-influx in both, old murine and human T-cells emphasizes on the clinical relevance of age-specific effects when utilizing TAC. PMID:27754593

  18. Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.

    PubMed

    Krenzien, F; Quante, M; Heinbokel, T; Seyda, M; Minami, K; Uehara, H; Biefer, H R C; Schuitenmaker, J M; Gabardi, S; Splith, K; Schmelzle, M; Petrides, A K; Azuma, H; Pratschke, J; Li, X C; ElKhal, A; Tullius, S G

    2017-05-01

    Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T cells. Old recipient mice exhibited prolonged skin graft survival compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4 + T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4 + T cells more effectively while inhibiting the proliferation of CD4 + T cells in old mice. Both TAC-treated murine and human CD4 + T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca 2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8 + T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4 + T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4 + T cell mediated. The suppression of calcineurin levels and Ca 2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Glucose Gel as a Potential Alternative Treatment to Infant Formula for Neonatal Hypoglycaemia in Australia.

    PubMed

    Barber, Raenee L; Ekin, Amy E; Sivakumar, Pushparani; Howard, Kay; O'Sullivan, Therese A

    2018-04-27

    Infant formula is often used as a treatment for neonatal hypoglycaemia in Australia; however, there are concerns that this may jeopardise mother-baby bonding and breastfeeding. Successful use of glucose gel as an alternative treatment for hypoglycaemia has been reported. We wanted to investigate in a pilot study whether the use of glucose gel has the potential to quickly and safely restore normoglycaemia in the infants of diabetic mothers in an Australian setting. Infants with asymptomatic hypoglycaemia were treated with glucose gel ( n = 36) and compared to a historical group of infants which had been treated with infant formula ( n = 24). Within 15 min of the first treatment, the gel group had a mean blood glucose level (BGL) of 2.6 mmol/L, and 2.7 mmol/L 30 min after the second treatment. This was lower than the BGL after the first treatment for the formula group, which rose to a mean of 2.8 then to 3.2 mmol/L after the second treatment ( p = 0.003). In successfully treated infants, administration of the gel resulted in normoglycaemia within 30 min. The likelihood of special care nursery admission was not significantly different between the groups, although we had a small sample size, and our findings should be interpreted with caution. These pilot results provide support for further investigations into the use of glucose gel as an alternative treatment to infant formula.

  20. Successful management of angiolymphoid hyperplasia with eosinophilia in a split-face trial of topical tacrolimus and timolol solution.

    PubMed

    Chacon, Anna; Mercer, Jessica

    2016-08-01

    Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, benign condition characterized by multiple benign angiomatous nodules or plaques. Cutaneous lesions can be painful, pruritic, pulsatile, or potentially disfiguring resulting in significant morbidity. ALHE is a pathologic diagnosis featuring proliferations of capillary-sized vessels with epithelioid endothelial cells surrounded by larger, thick-walled vessels and accompanying eosinophils and lymphocytes. Surgery is generally required, however the skin lesions often recur after excision. ALHE is notoriously difficult to treat and many physicians would prefer a non-invasive treatment of choice. We report a case of ALHE that was successfully treated with the novel use of topical tacrolimus in a split-face trial with topical timolol solution.

  1. [The therapeutic drug monitoring network server of tacrolimus for Chinese renal transplant patients].

    PubMed

    Deng, Chen-Hui; Zhang, Guan-Min; Bi, Shan-Shan; Zhou, Tian-Yan; Lu, Wei

    2011-07-01

    This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.

  2. A rare but important adverse effect of tacrolimus in a heart transplant recipient: diabetic ketoacidosis.

    PubMed

    Öztürk, Zeynelabidin; Gönç, E Nazlı; Akcan, Leman; Kesici, Selman; Ertuğrul, İlker; Bayrakçı, Benan

    2015-01-01

    Heart transplantation indications in pediatric population include congenital heart diseases, cardiomyopathies and retransplants. Cardiomyopathy is the primary indication for 11 to 17 years of age. The surveillance after transplantation is a very important issue because of both the rejection risk and the adverse effects due to medications after transplantation. Immunosuppressive agents that are commonly used after heart transplantations have several toxicities. Here we present an adolescent patient diagnosed with dilated cardiomyopathy, performed heart transplantation, treated with tacrolimus and suffered from diabetic ketoacidosis due to tacrolimus. After the diagnosis was made the appropriate fluid and insulin therapy was started immediately and ketoacidosis resolved in the first 24 hours of the therapy. The diagnosis revised as new onset diabetes mellitus after transplantation and the tacrolimus dosage titrated to therapeutic level. After glycemic control the patient discharged with rapid acting insulin, three times daily, before meals; and long acting insulin once daily at night. In ten month follow up time the insulin dosages were progressively reduced.

  3. Solid state compatibility study and characterization of a novel degradation product of tacrolimus in formulation.

    PubMed

    Rozman Peterka, Tanja; Grahek, Rok; Hren, Jure; Bastarda, Andrej; Bergles, Jure; Urleb, Uroš

    2015-06-10

    Tacrolimus is macrolide drug that is widely used as a potent immunosuppressant. In the present work compatibility testing was conducted on physical mixtures of tacrolimus with excipients and on compatibility mixtures prepared by the simulation of manufacturing process used for the final drug product preparation. Increase in one major degradation product was detected in the presence of magnesium stearate based upon UHPLC analysis. The degradation product was isolated by preparative HPLC and its structure was elucidated by NMR and MS studies. Mechanism of the formation of this degradation product is proposed based on complementary degradation studies in a solution and structural elucidation data. The structure was proven to be alpha-hydroxy acid which is formed from the parent tacrolimus molecule through a benzilic acid type rearrangement reaction in the presence of divalent metallic cations. Degradation is facilitated at higher pH values. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Longer treatment with alternative non-drug reinforcement fails to reduce resurgence of cocaine or alcohol seeking in rats.

    PubMed

    Nall, Rusty W; Craig, Andrew R; Browning, Kaitlyn O; Shahan, Timothy A

    2018-04-02

    Provision of alternative non-drug reinforcement is among the most effective methods for treating substance use disorders. However, when alternative reinforcers become unavailable during treatment interruptions or upon cessation of treatment, relapse often occurs. Relapse following the loss of alternative reinforcement is known as resurgence. One factor that could reduce resurgence is longer duration of treatment with alternative reinforcement, but the available data are mixed. Further, the effects of length of treatment have previously only been examined with food seeking. The present experiments directly examined if duration of treatment impacted the magnitude of resurgence of cocaine or alcohol seeking in rats. First, rats were trained to self-administer cocaine (Experiment 1) or alcohol (Experiment 2) by performing a target behavior. Second, target behavior was extinguished and performing an alternative behavior produced an alternative non-drug (i.e., food) reinforcer. Finally, resurgence was assessed following removal of alternative reinforcement after either 5 or 20 sessions of treatment. Treatment duration did not differentially affect resurgence of cocaine seeking in Experiment 1 or Alcohol seeking in Experiment 2. These results suggest that extended treatment with alternative non-drug reinforcement may not decrease propensity to relapse. Further, these results may have implications for treatment of substance use disorders and for theories of resurgence. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Cryosurgery as an effective alternative for treatment of oral lesions in children.

    PubMed

    Rezende, Karla Mayra; Moraes, Paulo de Camargo; Oliveira, Luciana Butini; Thomaz, Luiz Alexandre; Junqueira, José Luiz Cintra; Bönecker, Marcelo

    2014-01-01

    Children can exhibit a wide variety of oral pathologies, such as oral lesions, bone lesions, tumors, cysts and cutaneous lesions. Different techniques have been described for the treatment of these lesions, but all of them are invasive. This paper presents a series of cases that demonstrate the clinical efficacy of cryosurgery as an alternative to invasive surgical treatments of the most common oral lesions in children. This technique has been well tolerated by patients due to the absence of anesthesia, rapid healing and minimal bleeding. Cryotherapy has many applications in oral medicine and is an extremely useful alternative in patients to whom surgery is contraindicated due to age or medical history. It is a simple procedure to perform, minimally invasive, low-cost and very effective in pediatric dentistry clinic.

  6. Imagining the alternatives to life prolonging treatments: elders' beliefs about the dying experience.

    PubMed

    Winter, Laraine; Parker, Barbara; Schneider, Melissa

    2007-08-01

    Deciding for or against a life-prolonging treatment represents a choice between prolonged life and death. When the death alternative is not described, individuals must supply their own assumptions. How do people imagine the experience of dying? We asked 40 elderly people open-ended questions about dying without 4 common life-prolonging treatments, eliciting beliefs about pain, length of time, loneliness, and palliative care. Beliefs were diverse, loneliness was commonly assumed, and palliation was rarely mentioned spontaneously. Results underscore needs for improved understanding of the dying process and palliative care and for fuller communication between patients and healthcare providers.

  7. Alternatives to vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections.

    PubMed

    Micek, Scott T

    2007-09-15

    Vancomycin remains the reference standard for the treatment of systemic infection caused by methicillin-resistant Staphylococcus aureus (MRSA). However, as a result of limited tissue distribution, as well as the emergence of isolates with reduced susceptibility and in vitro resistance to vancomycin, the need for alternative therapies that target MRSA has become apparent. New treatment options for invasive MRSA infections include linezolid, daptomycin, tigecycline, and quinupristin/dalfopristin. Additionally, a number of new anti-MRSA compounds are in development, including novel glycopeptides (dalbavancin, telavancin, and oritavancin), ceftobiprole, and iclaprim. The present article will review clinical issues surrounding the newly marketed and investigational agents with activity against MRSA.

  8. Interstitial laser coagulation of benign prostatic hyperplasia: a minimally invasive treatment alternative

    NASA Astrophysics Data System (ADS)

    Ordonez, Robert F.; Mittemeyer, Bernhard T.; Aronoff, David R.; de Riese, Werner T. W.

    2003-06-01

    The use of minimally invasive treatments for benign prostatic hyperplasia (BPH) have been introduced into the medical community. Over the last decade several minimally invasive treatment techniques have been approved for use. In particular, interstitial laser coagulation (ILC) has shown pomise as an alternative to the current gold standard, transurethral resection of prostate (TURP). Studies show ILC to have equal efficacy as TURP while causing less side effects. Future technical advances as well as increased physician experience with ILC could lead to the replacement of TURP as the gold standard in trestment of BPH.

  9. A Review of Complementary and Alternative Treatments for Autism Spectrum Disorders

    PubMed Central

    Lofthouse, Nicholas; Hendren, Robert; Hurt, Elizabeth; Arnold, L. Eugene; Butter, Eric

    2012-01-01

    Given the severe and chronic problems associated with Autism Spectrum Disorders (ASD) and the limitations of available treatments, there exists a large public health need for additional interventions. As more parents are inquiring about complementary and alternative treatments (CATs), both parents and practitioners require up-to-date information about them and whether and how to integrate them into treatment. After presenting data on CAT usage patterns for ASD, we review 13 ingestible (i.e., orally administered) and 6 noningestible (i.e., externally administered) CATs for ASD. For each CAT we briefly describe its definition; rationale for use; current research support, limitations, and future directions; safety issues; and whether we currently recommend, not recommend, or find it acceptable for the treatment of ASD. We conclude this paper with recommendations for future research and ten clinical recommendations for practitioners. PMID:23243505

  10. Alternatives to CPAP in the treatment of the obstructive sleep apnea syndrome.

    PubMed

    Bloch, Konrad E

    2006-04-29

    The obstructive sleep apnoea syndrome (OSAS) results in excessive daytime sleepiness, impaired quality of life, and is associated with an increased risk of traffic accidents and cardiovascular disease. Nasal continuous positive airway pressure (CPAP), the standard treatment for OSAS provides immediate relief of symptoms and has only minor side effects. Nevertheless, an alternative treatment is needed if CPAP is not feasible for medical or psychological reasons. Removable oral appliances that advance the mandible when fitted to the teeth during sleep also improve nocturnal breathing disturbances, symptoms, quality of life, vigilance and blood pressure in OSAS patients. Their long-term effectiveness and side effects require further study. In morbidly obese patients suffering from OSAS bariatric surgery should be considered as a treatment that reduces obesity and at the same time improves OSAS. In selected patients including those with adeno-tonsillar hypertrophy, and cranio-facial malformations various surgical techniques that enlarge the upper airway may be a treatment option for OSAS.

  11. Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone.

    PubMed

    Ebisumoto, Koji; Okami, Kenji; Hamada, Masashi; Maki, Daisuke; Sakai, Akihiro; Saito, Kosuke; Shimizu, Fukuko; Kaneda, Shoji; Iida, Masahiro

    2018-06-01

    The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Do labeled versus unlabeled treatments of alternatives' names influence stated choice outputs? Results from a mode choice study.

    PubMed

    Jin, Wen; Jiang, Hai; Liu, Yimin; Klampfl, Erica

    2017-01-01

    Discrete choice experiments have been widely applied to elicit behavioral preferences in the literature. In many of these experiments, the alternatives are named alternatives, meaning that they are naturally associated with specific names. For example, in a mode choice study, the alternatives can be associated with names such as car, taxi, bus, and subway. A fundamental issue that arises in stated choice experiments is whether to treat the alternatives' names as labels (that is, labeled treatment), or as attributes (that is, unlabeled treatment) in the design as well as the presentation phases of the choice sets. In this research, we investigate the impact of labeled versus unlabeled treatments of alternatives' names on the outcome of stated choice experiments, a question that has not been thoroughly investigated in the literature. Using results from a mode choice study, we find that the labeled or the unlabeled treatment of alternatives' names in either the design or the presentation phase of the choice experiment does not statistically affect the estimates of the coefficient parameters. We then proceed to measure the influence toward the willingness-to-pay (WTP) estimates. By using a random-effects model to relate the conditional WTP estimates to the socioeconomic characteristics of the individuals and the labeled versus unlabeled treatments of alternatives' names, we find that: a) Given the treatment of alternatives' names in the presentation phase, the treatment of alternatives' names in the design phase does not statistically affect the estimates of the WTP measures; and b) Given the treatment of alternatives' names in the design phase, the labeled treatment of alternatives' names in the presentation phase causes the corresponding WTP estimates to be slightly higher.

  13. Early add-on treatment vs alternative monotherapy in patients with partial epilepsy.

    PubMed

    Semah, Franck; Thomas, Pierre; Coulbaut, Safia; Derambure, Philippe

    2014-06-01

    The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug (AED); alternative monotherapy vs early add-on treatment. We conducted an open, cluster-randomised, prospective, controlled trial in patients with persistent partial seizures, despite treatment with one AED, who were never administered any other AEDs. Neurologists were randomised to two strategies: in group A, an alternative monotherapy with a second AED was employed; in group B, add-on treatment with a second AED was employed. The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment. The secondary outcomes were: (i) the percentage of patients achieving a 50% reduction in the number of seizures at six months; (ii) the quality of life based on the Quality Of Life In Epilepsy scale; and (iii) tolerability. A total of 143 neurologists were included and randomised, and 264 patients were evaluated. At six months, the primary outcome was 51% in group A and 45% in group B (p=0.34). The percentage of patients achieving a 50% reduction in the number of seizures at six months was 76% in group A and 84% in group B (p=0.53). The quality of life and the tolerability did not significantly differ between the two groups. Alternative monotherapy or early treatment initiation with another AED drug resulted in similar efficacy, and the side effects associated with monotherapy and combined therapies were similar, which suggests that individual susceptibility is more important than the number and burden of AEDs used.

  14. Incidence and risk factors for the metabolic syndrome and posttransplant diabetes in renal transplant recipients taking tacrolimus.

    PubMed

    Pérez-Flores, I; Sánchez-Fructuoso, A; Calvo, N; Valga, E F; Barrientos, A

    2010-10-01

    We investigated the incidence and risk factors for the metabolic syndrome (MS) and posttransplant diabetes mellitus (PTDM) among renal transplant recipients on tacrolimus-based immunosuppressive regimens during the first year posttransplant. In addition, we studied the relationship between MS and PTDM with transplant renal function at 1 year. We included the 100 patients who received a renal transplant in our unit between January 2007 and June 2008, collecting demographic, clinical and biochemical characteristics at 1, 6, and 12 months posttransplantation. We excluded 15% of patients with pretransplantation diabetes. MS was defined according to the National Cholesterol Education Program criteria and PTDM according to World Health Organization criteria. Insulin resistance at one year posttransplant was measured using the homeostasis model assessment (HOMA) index. Insulin therapy was required in 46% of patients during the first hospitalization and hyperglycemia was present in 65% of the cases. The incidence of PTDM decreased throughout the first year posttransplant, namely, 44%, 24%, and 13% at 1, 6, and 12 months, respectively. The incidence of MS increased to 33%, 48% and 50% at 1, 6, and 12 months, respectively. Age, body mass index, plasma fasting glucose levels at 1 month posttransplant, and pretransplant fasting triglyceridemia predicted PTDM. Rejection and in-patient hyperglycemia predicted MS. PTDM and MS were closely correlated (P=.004). The HOMA index was higher among patients with MS than other subjects at 1 year posttransplant: 3.2 (1.2) versus 2.3 (0.9; P=.035). Neither PTDM nor MS was associated with impaired plasma creatinine levels at 1 year after kidney transplantation. There was an high incidence of PTDM and MS among kidney transplant recipients treated with tacrolimus as the main immunosuppressive agent. The HOMA index was a good test of insulin resistance in this population. Screening and treatment of risk factors may avoid the development of

  15. [Factors determining the selection of treatment options of complementary and alternative medicine].

    PubMed

    Zörgő, Szilvia; Purebl, György; Zana, Ágnes

    2016-04-10

    Complementary and alternative medicine have undoubtedly been gaining ground on the healthcare market, thus the vital question arises why patients choose these treatments, oftentimes at the cost of discontinuing the Western medical therapy. The aim of the authors was to investigate and scrutinize factors leading to the utilization of various alternative medical services. The basis of this qualitative research was medical anthropological fieldwork conducted at a clinic of Traditional Chinese Medicine including participant observation (355 hours), unstructured interviews with patients (n = 93) and in-depth interviews (n = 14). Patients of alternative medical systems often do not receive a diagnosis, explanation or cure for their illness from Western medicine, or they do not agree with what they are offered. In other instances, patients choose alternative medicine because it exhibits a philosophical congruence with their already existing explanatory model, that is, previous concepts of world, man or illness. A particular therapy is always part of a cultural system and it is embedded in a specific psycho-social context, hence choice of therapy must be interpreted in accordance with this perspective.

  16. Development of a Simple and Rapid Method to Measure the Free Fraction of Tacrolimus in Plasma Using Ultrafiltration and LC-MS/MS.

    PubMed

    Stienstra, Nicolaas A; Sikma, Maaike A; van Dapperen, Anouk L; de Lange, Dylan W; van Maarseveen, Erik M

    2016-12-01

    Tacrolimus is an immunosuppressant mainly used in the prophylaxis of solid organ transplant rejection. Therapeutic drug monitoring of tacrolimus is essential for avoiding toxicity related to overexposure and transplant rejection from underexposure. Previous studies suggest that unbound tacrolimus concentrations in the plasma may serve as a better predictor of tacrolimus-associated nephrotoxicity and neurotoxicity compared to tacrolimus concentration in whole blood. Monitoring the plasma concentrations of unbound tacrolimus might be of interest in preventing tacrolimus-related toxicity. Therefore, the aim was to develop a method for the measurement of total and unbound tacrolimus concentrations in plasma. The sample preparation for the determination of the plasma concentrations of unbound tacrolimus consisted of an easy-to-use ultrafiltration method followed by solid-phase extraction. To determine the total concentration of tacrolimus in plasma, a simple method based on protein precipitation was developed. The extracts were injected into a Thermo Scientific HyPurity C18 column using gradient elution. The analytes were detected by liquid chromatography-tandem mass spectrometry with positive ionization. The method was validated over a linear range of 1.00-200 ng/L for unbound tacrolimus concentrations in plasma and 100-3200 ng/L for total plasma concentrations. The lower limit of quantification was 1.00 ng/L in ultrafiltrate and 100 ng/L in plasma. The inaccuracy and imprecision for the determination of unbound tacrolimus concentrations in ultrafiltrate and plasma showed a maximum coefficients of variation (CV) of 11.7% and a maximum bias of 3.8%. A rapid and easy method based on ultrafiltration and liquid chromatography-tandem mass spectrometry was established to measure the total and unbound tacrolimus concentrations in plasma. This method can facilitate further investigations on the relationship between plasma concentrations of unbound tacrolimus and clinical

  17. Use of traditional herbal medicine as an alternative in dental treatment in Mexican dentistry: a review.

    PubMed

    Cruz Martínez, Cindy; Diaz Gómez, Martha; Oh, Myung Sook

    2017-12-01

    Herbal therapies are used worldwide to treat health conditions. In Mexico, generations have used them to treat gingivitis, periodontitis, mouth infections, and discoloured teeth. However, few studies have collected scientific evidence on their effects. This study aimed at searching and compiling scientific evidence of alternative oral and dental treatments using medicinal herbs from Mexico. We collected various Mexican medicinal plants used in the dental treatment from the database of the Institute of Biology at the National Autonomous University of Mexico. To correlate with existing scientific evidence, we used the PubMed database with the key term '(scientific name) and (oral or dental)'. Mexico has various medical herbs with antibacterial and antimicrobial properties, according to ancestral medicinal books and healers. Despite a paucity of experimental research demonstrating the antibacterial, antimicrobial, and antiplaque effects of these Mexican plants, they could still be useful as an alternative treatment of several periodontal diseases or as anticariogenic agents. However, the number of studies supporting their uses and effects remains insufficient. It is important for the health of consumers to scientifically demonstrate the real effects of natural medicine, as well as clarify and establish their possible therapeutic applications. Through this bibliographical revision, we found papers that testify or refute their ancestral uses, and conclude that the use of plants to treat oral conditions or to add to the dental pharmacological arsenal should be based on experimental studies verifying their suitability for dental treatments.

  18. Assessment of wastewater treatment alternatives for small communities: An analytic network process approach.

    PubMed

    Molinos-Senante, María; Gómez, Trinidad; Caballero, Rafael; Hernández-Sancho, Francesc; Sala-Garrido, Ramón

    2015-11-01

    The selection of the most appropriate wastewater treatment (WWT) technology is a complex problem since many alternatives are available and many criteria are involved in the decision-making process. To deal with this challenge, the analytic network process (ANP) is applied for the first time to rank a set of seven WWT technology set-ups for secondary treatment in small communities. A major advantage of ANP is that it incorporates interdependent relationships between elements. Results illustrated that extensive technologies, constructed wetlands and pond systems are the most preferred alternatives by WWT experts. The sensitivity analysis performed verified that the ranking of WWT alternatives is very stable since constructed wetlands are almost always placed in the first position. This paper showed that ANP analysis is suitable to deal with complex decision-making problems, such as the selection of the most appropriate WWT system contributing to better understand the multiple interdependences among elements involved in the assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Tacrolimus has immunosuppressive effects on heavy/light chain pairs and free light chains in patients after heart transplantation: A relationship with infection.

    PubMed

    Lavríková, Petra; Sečník, Peter; Kubíček, Zdenek; Jabor, Antonín; Hošková, Lenka; Franeková, Janka

    2018-06-15

    The aim of the study was to investigate the relationship between tacrolimus (TAC) immunosuppressive treatment and serum concentrations of immunoglobulin heavy/light chain pairs (sHLC) and free light chains (sFLC) in patients after heart transplantation (HTX) and to use these biomarkers to predict the risk of infection in these patients. A total of 88 patients with an immunosuppressive regimen involving tacrolimus who underwent HTX were analyzed over 24 months of follow-up. sFLC and sHLC levels were determined before and at three time points after HTX. TAC concentrations were determined at several time points after HTX, and mean TAC concentrations and areas under the curve (AUCs) of TAC concentration were calculated. Relevant clinical data were obtained from patients' medical records. A larger AUC of TAC was associated with decreases in the concentrations of IgG total (p < 0.05); similarly, cumulative AUC of TAC during 18 post-transplant months correlated inversely with sHLC IgG kappa (r = -0.228, p < 0.05) and IgG total (r = -0.352, p < 0.05). Concentrations of sFLC kappa, sFLC lambda, sHLC IgG kappa, and sHLC IgG total were significantly lower in infected patients (in the 9th month after HTX, all p < 0.05). Combined criteria for increased AUC (greater than the median of 12.9 mg·d/l) and decreased sFLC kappa (less than the median of 12.5 mg/l) correlated with the presence of infection (p < 0.03) in the 9th month after HTX. Ratio of concentration of TAC to sFLC kappa or lambda was significantly higher in infected patients (both p < 0.05). Intensive treatment with tacrolimus after HTX is possibly reflected by decreases in sFLC and sHLC (mainly sHLC IgG). Patients with decreased concentrations of these biomarkers are at increased risk for infection, primarily in the 9th month after HTX, when the concentrations of tacrolimus were the highest. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Declining conventional cancer treatment and using complementary and alternative medicine: a problem or a challenge?

    PubMed

    Verhoef, M J; Rose, M S; White, M; Balneaves, L G

    2008-08-01

    Several studies have shown that a small but significant percentage of cancer patients decline one or more conventional cancer treatments and use complementary and alternative medicine (CAM) instead. Here, drawing on the literature and on our own ongoing research, we describe why cancer patients decide to decline conventional cancer treatments, who those patients are, and the response by physicians to patients who make such decisions. Poor doctor-patient communication, the emotional impact of the cancer diagnosis, perceived severity of conventional treatment side effects, a high need for decision-making control, and strong beliefs in holistic healing appear to affect the decision by patients to decline some or all conventional cancer treatments. Many patients indicate that they value ongoing follow-up care from their oncologists provided that the oncologists respect their beliefs. Patients declining conventional treatments have a strong sense of internal control and prefer to make the final treatment decisions after considering the opinions of their doctors. Few studies have looked at the response by physicians to patients making such a decision. Where research has been done, it found that a tendency by doctors to dichotomize patient decisions as rational or irrational may interfere with the ability of the doctors to respond with sensitivity and understanding. Declining conventional treatment is not necessarily an indicator of distrust of the medical system, but rather a reflection of many personal factors. Accepting and respecting such decisions may be instrumental in "keeping the door open."

  1. The role of information search in seeking alternative treatment for back pain: a qualitative analysis

    PubMed Central

    2014-01-01

    Background Health consumers have moved away from a reliance on medical practitioner advice to more independent decision processes and so their information search processes have subsequently widened. This study examined how persons with back pain searched for alternative treatment types and service providers. That is, what information do they seek and how; what sources do they use and why; and by what means do they search for it? Methods 12 persons with back pain were interviewed. The method used was convergent interviewing. This involved a series of semi-structured questions to obtain open-ended answers. The interviewer analysed the responses and refined the questions after each interview, to converge on the dominant factors influencing decisions about treatment patterns. Results Persons with back pain mainly search their memories and use word of mouth (their doctor and friends) for information about potential treatments and service providers. Their search is generally limited due to personal, provider-related and information-supply reasons. However, they did want in-depth information about the alternative treatments and providers in an attempt to establish apriori their efficacy in treating their specific back problems. They searched different sources depending on the type of information they required. Conclusions The findings differ from previous studies about the types of information health consumers require when searching for information about alternative or mainstream healthcare services. The results have identified for the first time that limited information availability was only one of three categories of reasons identified about why persons with back pain do not search for more information particularly from external non-personal sources. PMID:24725300

  2. Clinical and genetic factors affecting tacrolimus trough levels and drug-related outcomes in Korean kidney transplant recipients.

    PubMed

    Kim, In-Wha; Moon, Yoo Jin; Ji, Eunhee; Kim, Kyung Im; Han, Nayoung; Kim, Sung Ju; Shin, Wan Gyoon; Ha, Jongwon; Yoon, Jeong-Hyun; Lee, Hye Suk; Oh, Jung Mi

    2012-05-01

    The purpose of this study was to characterize the effects of clinical and genetic variables on the pharmacokinetics and complications of tacrolimus during the first year after kidney transplantation. One hundred and thirty-two Korean kidney recipients who received tacrolimus were genotyped for ABCB1 (exons 12, 21, and 26) and CYP3A5 (intron 3). Tacrolimus trough levels, dose, or dose-adjusted trough levels and complications were compared among patients during the early stage (3, 7, 14, 30, and 90 days) and up to 1 year according to the genotypes. A donor source-adjusted linear mixed model with multilevel analysis adjusting for age, body weight, hematocrit, and serum creatinine showed that CYP3A5 genotype is associated with dose-adjusted level of tacrolimus (p < 0.001). The influence of ABCB1 polymorphisms on the pharmacokinetics or complications of tacrolimus was less certain in our study. The incidence of acute rejections was significantly higher in recipients of cadaveric donor kidney (p < 0.05). A generalized estimating equation model analysis showed that alopecia and hyperlipidemia were associated with dose-adjusted level of tacrolimus (p < 0.001). Genotype of CYP3A5 variants along with significant clinical covariates may be useful in individualizing tacrolimus therapy in kidney transplantation patients.

  3. Review of Efficacy of Complementary and Alternative Medicine Treatments for Menopausal Symptoms.

    PubMed

    Moore, Thea R; Franks, Rachel B; Fox, Carol

    2017-05-01

    Complementary and alternative medicine (CAM) treatments have been used for thousands of years around the world. There has been increased interest in utilizing CAM for menopausal symptoms since the release of results of the Women's Health Initiative elucidated long-term adverse effects associated with hormone therapy. Women looking for more natural or safer means to treat hot flushes, night sweats, and other menopausal symptoms often turn to CAM such as yoga, phytoestrogens, or black cohosh. Yet there have been few well-conducted studies looking at the efficacy of these treatments. This review examines randomized clinical trials, systematic reviews, and meta-analyses evaluating the effectiveness of commonly used CAM for the treatment of menopausal symptoms. © 2017 by the American College of Nurse-Midwives.

  4. Old and new controversies in the alternative treatment of attention-deficit hyperactivity disorder.

    PubMed

    Rojas, Neal L; Chan, Eugenia

    2005-01-01

    Use of complementary and alternative medicine (CAM) for treatment of attention-deficit hyperactivity disorder (ADHD) has become widespread in both referral and primary care populations. We review the purported mechanism of action and available evidence for selected CAM therapies for ADHD. Enduring controversies, such as elimination of artificial food additives, colors, and/or preservatives; the effect of sugar on behavior in children; and the use of EEG biofeedback, have been well studied but lack support as effective sole treatments for ADHD. The initial evidence for some emerging CAM therapies, such as essential fatty acid supplementation, yoga, massage, homeopathy, and green outdoor spaces, suggests potential benefits as part of an overall ADHD treatment plan. More rigorously designed studies are needed to evaluate their effectiveness as single therapy for ADHD. Copyright 2005 Wiley-Liss, Inc.

  5. Meditation over medication for irritable bowel syndrome? On exercise and alternative treatments for irritable bowel syndrome.

    PubMed

    Asare, Fredrick; Störsrud, Stine; Simrén, Magnus

    2012-08-01

    Complimentary alternative treatment regimens are widely used in irritable bowel syndrome (IBS), but the evidence supporting their use varies. For psychological treatment options, such as cognitive behavioral therapy, mindfulness, gut-directed hypnotherapy, and psychodynamic therapy, the evidence supporting their use in IBS patients is strong, but the availability limits their use in clinical practice. Dietary interventions are commonly included in the management of IBS patients, but these are primarily based on studies assessing physiological function in relation to dietary components, and to a lesser degree upon research examining the role of dietary components in the therapeutic management of IBS. Several probiotic products improve a range of symptoms in IBS patients. Physical activity is of benefit for health in general and recent data implicates its usefulness also for IBS patients. Acupuncture does not seem to have an effect beyond placebo in IBS. A beneficial effect of some herbal treatments has been reported.

  6. Perspectives of complementary and alternative medicine (CAM) practitioners in the support and treatment of infertility.

    PubMed

    O'Reilly, Erin; Sevigny, Marika; Sabarre, Kelley-Anne; Phillips, Karen P

    2014-10-14

    Infertility patients are increasingly using complementary and alternative medicine (CAM) to supplement or replace conventional fertility treatments. The objective of this study was to determine the roles of CAM practitioners in the support and treatment of infertility. Ten semi-structured interviews were conducted in Ottawa, Canada in 2011 with CAM practitioners who specialized in naturopathy, acupuncture, traditional Chinese medicine, hypnotherapy and integrated medicine. CAM practitioners played an active role in both treatment and support of infertility, using a holistic, interdisciplinary and individualized approach. CAM practitioners recognized biological but also environmental and psychosomatic determinants of infertility. Participants were receptive to working with physicians, however little collaboration was described. Integrated infertility patient care through both collaboration with CAM practitioners and incorporation of CAM's holistic, individualized and interdisciplinary approaches would greatly benefit infertility patients.

  7. On-site sanitation: a viable alternative to modern wastewater treatment plants.

    PubMed

    Lamichhane, K M

    2007-01-01

    Rapid population growth and urbanization are exerting excessive pressure on soil and water resources. To address these problems this paper proposes a cheap and sustainable alternative sanitation system, which accelerates nutrient recycling ("closing the loop"): ecological sanitation (ecosan) is a potential alternative to conventional sanitation systems that replenishes the organic matter and nutrients of the soil that are taken off as the crop harvest. A comparison is made of the environmental and the operation and maintenance costs between a modern wastewater treatment plant and on-site sanitation. An elevated double box urine diverting toilet ("ecotoilet") is proposed and its advantages and disadvantages over a system with a centrally controlled modern WWTP are discussed. Bagmati Area Sewerage Project in Kathmandu is taken as an example of modern WWTP and ecosan being practiced in a village in Nepal is taken as an example of ecotoilet for the comparison.

  8. Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

    PubMed

    TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

    2015-07-01

    DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

  9. Erratic tacrolimus exposure, assessed using the standard deviation of trough blood levels, predicts chronic lung allograft dysfunction and survival.

    PubMed

    Gallagher, Harry M; Sarwar, Ghulam; Tse, Tracy; Sladden, Timothy M; Hii, Esmond; Yerkovich, Stephanie T; Hopkins, Peter M; Chambers, Daniel C

    2015-11-01

    Erratic tacrolimus blood levels are associated with liver and kidney graft failure. We hypothesized that erratic tacrolimus exposure would similarly compromise lung transplant outcomes. This study assessed the effect of tacrolimus mean and standard deviation (SD) levels on the risk of chronic lung allograft dysfunction (CLAD) and death after lung transplantation. We retrospectively reviewed 110 lung transplant recipients who received tacrolimus-based immunosuppression. Cox proportional hazard modeling was used to investigate the effect of tacrolimus mean and SD levels on survival and CLAD. At census, 48 patients (44%) had developed CLAD and 37 (34%) had died. Tacrolimus SD was highest for the first 6 post-transplant months (median, 4.01; interquartile range [IQR], 3.04-4.98 months) before stabilizing at 2.84 μg/liter (IQR, 2.16-4.13 μg/liter) between 6 and 12 months. The SD then remained the same (median, 2.85; IQR, 2.00-3.77 μg/liter) between 12 and 24 months. A high mean tacrolimus level 6 to 12 months post-transplant independently reduced the risk of CLAD (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.63-0.86; p < 0.001) but not death (HR, 0.96; 95% CI, 0.83-1.12; p = 0.65). In contrast, a high tacrolimus SD between 6 and 12 months independently increased the risk of CLAD (HR, 1.46; 95% CI, 1.23-1.73; p < 0.001) and death (HR, 1.27; 95% CI, 1.08-1.51; p = 0.005). Erratic tacrolimus levels are a risk factor for poor lung transplant outcomes. Identifying and modifying factors that contribute to this variability may significantly improve outcomes. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  10. Perspectives on Home-based Healthcare as an Alternative to Hospital Admission After Emergency Treatment.

    PubMed

    Stuck, Amy; Crowley, Christopher; Martinez, Tracy; Wittgrove, Alan; Brennan, Jesse J; Chan, Theodore C; Castillo, Edward M

    2017-06-01

    The study objective was to explore emergency physicians' (EP) awareness, willingness, and prior experience regarding transitioning patients to home-based healthcare following emergency department (ED) evaluation and treatment; and to explore patient selection criteria, processes, and services that would facilitate use of home-based healthcare as an alternative to hospitalization. We provided a five-question survey to 52 EPs, gauging previous experience referring patients to home-based healthcare, patient selection, and motivators and challenges when considering home-based options as an alternative to admission. In addition, we conducted three focus groups and four interviews. Of participating EPs, 92% completed the survey, 38% reported ordering home-based healthcare from the ED as an alternative to admission, 90% ranked cellulitis among the top three medical conditions for home-based healthcare, 90% ranked "reduce unnecessary hospitalizations and observation stays" among their top three perceived motivators for using home-based care, and 77% ranked "no existing process in place to refer to home-based care" among their top three perceived barriers. Focus group and interview themes included the need for alternatives to admission; the longer-term benefits of home-based healthcare; the need for streamlined transition processes; and the need for highly qualified home-care staff capable of responding the same day or within 24 hours. The study found that EPs are receptive to referring patients for home-based healthcare following ED treatment and believe people with certain diagnoses are likely to benefit, with the dominant barrier being the absence of an efficient referral process.

  11. Perspectives on Home-based Healthcare as an Alternative to Hospital Admission After Emergency Treatment

    PubMed Central

    Stuck, Amy; Crowley, Christopher; Martinez, Tracy; Wittgrove, Alan; Brennan, Jesse J.; Chan, Theodore C.; Castillo, Edward M.

    2017-01-01

    Introduction The study objective was to explore emergency physicians’ (EP) awareness, willingness, and prior experience regarding transitioning patients to home-based healthcare following emergency department (ED) evaluation and treatment; and to explore patient selection criteria, processes, and services that would facilitate use of home-based healthcare as an alternative to hospitalization. Methods We provided a five-question survey to 52 EPs, gauging previous experience referring patients to home-based healthcare, patient selection, and motivators and challenges when considering home-based options as an alternative to admission. In addition, we conducted three focus groups and four interviews. Results Of participating EPs, 92% completed the survey, 38% reported ordering home-based healthcare from the ED as an alternative to admission, 90% ranked cellulitis among the top three medical conditions for home-based healthcare, 90% ranked “reduce unnecessary hospitalizations and observation stays” among their top three perceived motivators for using home-based care, and 77% ranked “no existing process in place to refer to home-based care” among their top three perceived barriers. Focus group and interview themes included the need for alternatives to admission; the longer-term benefits of home-based healthcare; the need for streamlined transition processes; and the need for highly qualified home-care staff capable of responding the same day or within 24 hours. Conclusion The study found that EPs are receptive to referring patients for home-based healthcare following ED treatment and believe people with certain diagnoses are likely to benefit, with the dominant barrier being the absence of an efficient referral process. PMID:28611899

  12. Population pharmacokinetics of tacrolimus in paediatric systemic lupus erythematosus based on real-world study.

    PubMed

    Wang, D-D; Lu, J-M; Li, Q; Li, Z-P

    2018-05-15

    Different population pharmacokinetics (PPK) models of tacrolimus have been established in various populations. However, the tacrolimus PPK model in paediatric systemic lupus erythematosus (PSLE) is still undefined. This study aimed to establish the tacrolimus PPK model in Chinese PSLE. A total of nineteen Chinese patients with PSLE from real-world study were characterized with nonlinear mixed-effects modelling (NONMEM). The impact of demographic features, biological characteristics, and concomitant medications was evaluated. Model validation was assessed by bootstrap and prediction-corrected visual predictive check (VPC). A one-compartment model with first-order absorption and elimination was determined to be the most suitable model in PSLE. The typical values of apparent oral clearance (CL/F) and the apparent volume of distribution (V/F) in the final model were 2.05 L/h and 309 L, respectively. Methylprednisolone and simvastatin were included as significant. The first validated tacrolimus PPK model in patients with PSLE is presented. © 2018 John Wiley & Sons Ltd.

  13. Effects of tacrolimus and erythropoietin in experimental spinal cord lesion in rats: functional and histological evaluation

    PubMed Central

    de Mesquita Coutinho, P R; Cristante, A F; de Barros Filho, T E P; Ferreira, R; dos Santos, G B

    2016-01-01

    Study design: Experimental study with rats. Objective: To evaluate functional and histological effects of tacrolimus (FK 506) and erythropoietin (EPO) after experimental spinal cord contusion injury (SCI). Setting: Brazil. Methods: Wistar rats (n=60) were submitted to SCI with the NYU Impactor system. The control group received saline; the EPO group received EPO; the group EPO+FK 506 received EPO associated with tacrolimus and the group FK 506 received tacrolimus only. The Sham group underwent SCI, but did not receive any drug. Locomotor function was evaluated after SCI by BBB (Basso, Beattie and Bresnahan) weekly and by the motor-evoked potential test in 42 days. The spinal cord was histologically evaluated. Results: There was a significant difference between treated and the control groups from the seventh day on for BBB scores, with no difference between the groups EPO and EPO+FK 506 by the end of the study. There were significant differences between groups for necrosis and bleeding, but not for hiperemia, degeneration and cellular infiltrate. Axon neuron count was different between all groups (P=0.001), between EPO+FK 506 and FK 506 (P=0.011) and between EPO+FK 506 and Sham (P=0.002). Amplitude was significantly different between all groups except between control and sham. For latency, there was no difference. Conclusions: This study did not reveal significant differences in the recovery of locomotor function, or in the histological and electrophysiological analysis in animals treated with EPO and tacrolimus after thoracic SCI. PMID:26481712

  14. Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction.

    PubMed

    Grünewald, Volker; Höfner, Klaus; Thon, Walter F.; Kuczyk, Markus A.; Jonas, Udo

    1999-01-01

    Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.

  15. Alternatives to connective tissue graft in the treatment of localized gingival recessions: A systematic review.

    PubMed

    Amine, K; El Amrani, Y; Chemlali, S; Kissa, J

    2018-02-01

    The aim of this Systematic Review (SR) was to assess the clinical efficacy of alternatives procedures; Acellular Dermal Matrix (ADM), Xenogeneic Collagen Matrix (XCM), Enamel Matrix Derivative (EMD) and Platelet Rich Fibrin (PRF), compared to conventional procedures in the treatment of localized gingival recessions. Electronic searches were performed to identify randomized clinical trials (RCTs) on treatment of single gingival recession with at least 6 months of follow-up. Applying guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA). The risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Eighteen randomized controlled trials (RCTs) with a total of 390 treated patients (606 recessions) were included. This systematic review showed that: Coronally Advanced Flap (CAF) in conjunction with ADM was significantly better than CAF alone, while the comparison between CAF+ADM and CTG was affected by large uncertainty. The CAF+EMD was significantly better than CAF alone, whereas the comparison between CAF+EMD and CTG was affected by large uncertainty. No significant difference was recorded when comparing CAF+XCM with CAF alone, and the comparison between CAF+XCM and CTG was affected by large uncertainty. The comparison between PRF and others technique was affected by large uncertainty. ADM, XCM and EMD assisted to CAF might be considered alternatives of CTG in the treatment of Miller class I and II gingival recession. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. LONG-TERM OUTCOME OF THE DIFFERENT TREATMENT ALTERNATIVES FOR RECURRENT AND PERSISTENT CUSHING DISEASE.

    PubMed

    Espinosa-de-Los-Monteros, Ana Laura; Sosa-Eroza, Ernesto; Espinosa, Etual; Mendoza, Victoria; Arreola, Rocio; Mercado, Moises

    2017-07-01

    Treatment alternatives for persistent and recurrent Cushing disease (CD) include pituitary surgical re-intervention, radiation therapy (RT), pharmacotherapy, and bilateral adrenalectomy (BA). The decision of which of these alternatives is better suited for the individual patient rests on clinical judgment and the availability of resources. This retrospective cohort study was performed at a referral center to evaluate the long-term efficacy of different secondary interventions for persistent and recurrent CD. We evaluated the hospital charts of 84 patients (77 female, median age 34 years, median follow up 6.3 years) with CD diagnosed, treated, and followed at our multidisciplinary clinic according to a pre-established protocol. Of the 81 patients who were initially treated with transsphenoidal surgery (TSS), 61.7% had a long-lasting remission, 16% had persistent disease, and 22% achieved remission but relapsed during follow-up. The most frequently used secondary treatment was pituitary re-intervention, followed by ketoconazole, RT, and BA. Early remissions were observed in 66.6% of the re-operated and in 58.3% of the radiated patients; long-lasting remission was achieved in 33.3% and 41.6% of these patients, respectively. Nelson syndrome developed in 41.6% of the patients who underwent BA. Upon last follow-up, 88% of all the patients are in remission, and 9.5% are biochemically controlled with ketoconazole. The efficacy of treatment alternatives for recurrent or persistent CD varies considerably among patients and multiple interventions are often required to achieve long-lasting remission. ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CBG = cabergoline; CD = Cushing disease; CV = coefficient of variation; DXM = dexamethasone; IQR = interquartile range; RT = radiation therapy; SRS = stereotactic radiosurgery; TSS = transsphenoidal surgery; UFC = urinary free cortisol; ULN = upper limit of normal.

  17. Alternative pre-approved and novel therapies for the treatment of anthrax.

    PubMed

    Head, Breanne M; Rubinstein, Ethan; Meyers, Adrienne F A

    2016-11-03

    Bacillus anthracis, the causative agent of anthrax, is a spore forming and toxin producing rod-shaped bacterium that is classified as a category A bioterror agent. This pathogenic microbe can be transmitted to both animals and humans. Clinical presentation depends on the route of entry (direct contact, ingestion, injection or aerosolization) with symptoms ranging from isolated skin infections to more severe manifestations such as cardiac or pulmonary shock, meningitis, and death. To date, anthrax is treatable if antibiotics are administered promptly and continued for 60 days. However, if treatment is delayed or administered improperly, the patient's chances of survival are decreased drastically. In addition, antibiotics are ineffective against the harmful anthrax toxins and spores. Therefore, alternative therapeutics are essential. In this review article, we explore and discuss advances that have been made in anthrax therapy with a primary focus on alternative pre-approved and novel antibiotics as well as anti-toxin therapies. A literature search was conducted using the University of Manitoba search engine. Using this search engine allowed access to a greater variety of journals/articles that would have otherwise been restricted for general use. In order to be considered for discussion for this review, all articles must have been published later than 2009. The alternative pre-approved antibiotics demonstrated high efficacy against B. anthracis both in vitro and in vivo. In addition, the safety profile and clinical pharmacology of these drugs were already known. Compounds that targeted underexploited bacterial processes (DNA replication, RNA synthesis, and cell division) were also very effective in combatting B. anthracis. In addition, these novel compounds prevented bacterial resistance. Targeting B. anthracis virulence, more specifically the anthrax toxins, increased the length of which treatment could be administered. Several novel and pre-existing antibiotics

  18. Development of an Alternative Treatment Scheme for Sr/TRU Removal: Permanganate Treatment of AN-107 Waste

    SciTech Connect

    RT Hallen; SA Bryan; FV Hoopes

    A number of Hanford tanks received waste containing organic complexants, which increase the volubility of Sr-90 and transuranic (TRU) elements. Wastes from these tanks require additional pretreatment to remove Sr-90 and TRU for immobilization as low activity waste (Waste Envelope C). The baseline pretreatment process for Sr/TRU removal was isotopic exchange and precipitation with added strontium and iron. However, studies at both Battelle and Savannah River Technology Center (SRTC) have shown that the Sr/Fe precipitates were very difficult to filter. This was a result of the formation of poor filtering iron solids. An alternate treatment technology was needed for Sr/TRUmore » removal. Battelle had demonstrated that permanganate treatment was effective for decontaminating waste samples from Hanford Tank SY-101 and proposed that permanganate be examined as an alternative Sr/TRU removal scheme for complexant-containing tank wastes such as AW107. Battelle conducted preliminary small-scale experiments to determine the effectiveness of permanganate treatment with AN-107 waste samples that had been archived at Battelle from earlier studies. Three series of experiments were performed to evaluate conditions that provided adequate Sr/TRU decontamination using permanganate treatment. The final series included experiments with actual AN-107 diluted feed that had been obtained specifically for BNFL process testing. Conditions that provided adequate Sr/TRU decontamination were identified. A free hydroxide concentration of 0.5M provided adequate decontamination with added Sr of 0.05M and permanganate of 0.03M for archived AN-107. The best results were obtained when reagents were added in the sequence Sr followed by permanganate with the waste at ambient temperature. The reaction conditions for Sr/TRU removal will be further evaluated with a 1-L batch of archived AN-107, which will provide a large enough volume of waste to conduct crossflow filtration studies (Hallen et al. 2000

  19. Rifampicin for Idiopathic Granulomatous Lobular Mastitis: A Promising Alternative for Treatment.

    PubMed

    Farouk, Omar; Abdelkhalek, Mohamed; Abdallah, Ahmed; Shata, Ahmed; Senbel, Ahmed; Attia, Essam; Elghaffar, Mohamed Abd; Mesbah, Mahmoud; Soliman, Nermine; Amin, Maha; El-Tantawy, Dina

    2017-05-01

    Idiopathic granulomatous lobular mastitis (IGLM) is a chronic, non-caseating, inflammatory breast disease of obscure aetiology characterized by multiple masses, abscesses and sinus formation. There is no standard treatment to date, but surgical procedures and systemic corticosteroids are effective in its treatment despite high recurrence rates. This prospective study including 30 patients with IGLM between November 2012 and May 2016 aimed to investigate the possibility of administration of Rifampicin (300 mg twice daily for a period of 6-9 months) as an alternative therapy for both surgery and corticosteroids in patients with IGLM. All patients were diagnosed by core needle biopsy. All patients were of reproductive age and had a history of breast feeding, which is the most important predisposing factor for IGLM. The mean age was 31.6 ± 5.8 years (range 23-42 years). Eighteen patients (60%) were treated by Rifampicin for 6 months, whereas 12 patients (40%) were treated for 9 months. Twelve months after the beginning of therapy, all patients showed complete clinical and ultrasonographic responses. No serious side effects were reported to stop the treatment course. The median follow-up after finishing the course of treatment was 15.5 months (average 3-35 months) with no episodes of disease relapse. Rifampicin is effective in the treatment of patients with IGLM with complete clinical and ultrasonographic response after 6-9 months and could be used as a solo medical therapy alternative to both surgery and corticosteroids.

  20. Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

    PubMed

    Nieuwenhuis, Klaske; de Laat, Peter C J; Janmohamed, Sherief R; Madern, Gerard C; Oranje, Arnold P

    2013-01-01

    Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated. © 2012 Wiley Periodicals, Inc.

  1. Cost variability of suggested generic treatment alternatives under the Medicare Part D benefit.

    PubMed

    Patel, Rajul A; Walberg, Mark P; Tong, Emily; Tan, Florence; Rummel, Ashley E; Woelfel, Joseph A; Carr-Lopez, Sian M; Galal, Suzanne M

    2014-03-01

    The substitution of generic treatment alternatives for brand-name drugs is a strategy that can help lower Medicare beneficiary out-of-pocket costs. Beginning in 2011, Medicare beneficiaries reaching the coverage gap received a 50% discount on the full drug cost of brand-name medications and a 7% discount on generic medications filled during the gap. This discount will increase until 2020, when beneficiaries will be responsible for 25% of total drug costs during the coverage gap. To examine the cost variability of brand and generic drugs within 4 therapeutic classes before and during the coverage gap for each 2011 California stand-alone prescription drug plan (PDP) and prospective coverage gap costs in 2020 to determine the effects on beneficiary out-of-pocket drug costs. Equivalent doses of brand and generic drugs in the following 4 pharmacological classes were examined: angiotensin II receptor blockers (ARBs), bisphosphonates, HMG-CoA reductase inhibitors (statins), and proton pump inhibitors (PPIs). The full drug cost and patient copay/coinsurance amounts during initial coverage and the coverage gap of each drug was recorded based on information retrieved from the Medicare website. These drug cost data were recorded for 28 California PDPs. The highest cost difference between a brand medication and a Centers for Medicare Medicaid Services (CMS)-suggested generic treatment alternative varied between $110.53 and $195.49 at full cost and between $51.37 and $82.35 in the coverage gap. The lowest cost difference varied between $38.45 and $76.93 at full cost and between -$4.11 and $18.52 during the gap. Medicare beneficiaries can realize significant out-of-pocket cost savings for their drugs by taking CMS-suggested generic treatment alternatives. However, due to larger discounts on brand medications made available through recent changes reducing the coverage gap, the potential dollar savings by taking suggested generic treatment alternatives during the gap is less

  2. Hyperbaric oxygen therapy with topical negative pressure: an alternative treatment for the refractory sternal wound infection.

    PubMed

    Sun, I-Feng; Lee, Su-Shin; Chiu, Chaw-Chi; Lin, Sin-Daw; Lai, Chung-Sheng

    2008-01-01

    Sternal osteomyelitis is a potentially lethal complication after cardiac surgery. It may be the cause of postoperative morbidity and mortality. We present a case of deep sternal wound infection after sternotomy. The patient received three treatments of surgical debridement, irrigation, topical negative pressure (TNP) dressing, and hyperbaric oxygen (HBO) therapy. Forty-five HBO therapy sessions were administered. After nine weeks, the sternal wound was healed and completely epithelialized. This conservative therapy can be an alternative and inexpensive method for the difficult sternal wound infection patient.

  3. An alternating treatment comparison of oral and total communications training programs with echolalic autistic children.

    PubMed Central

    Barrera, R D; Sulzer-Azaroff, B

    1983-01-01

    An alternating treatment comparison was conducted of the relative effectiveness of oral and total communication training models for teaching expressive labeling skills to three echolalic autistic children. The results of this comparison demonstrated that total communication proved to be the most successful approach with each of the subjects. In addition, the replication of these findings both within and across subjects suggest that total communication may be, in general, the most effective of these two training models for teaching basic vocal language skills to echolalic children. A number of hypotheses are presented that may provide a basis for the demonstrated effect. PMID:6654770

  4. Sirolimus and tacrolimus rather than cyclosporine A cause bone loss in healthy adult male rats.

    PubMed

    Rubert, Mercedes; Montero, Mercedes; Guede, David; Caeiro, Jose-Ramón; Martín-Fernández, Marta; Díaz-Curiel, Manuel; de la Piedra, Concepción

    2015-06-01

    The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on bone mass, femoral microstructure, femoral biomechanical properties, and bone remodeling in healthy adult male rats. Forty-eight 5-month-old male Wistar rats were used. CsA (2 mg/kg/day), FK-506 (3 mg/kg/day), RAPA (1.25 mg/kg/day), or water (0.5 ml/rat/day, control group) were administered orally for 3 months. After sacrifice, mean values of immunosuppressants in blood were: CsA (670.4 ng/ml), FK-506 (19.2 ng/ml), and RAPA (4.8 ng/ml). Levels of biochemical parameters were normal in all groups. Femoral BMD was decreased in FK-506 and RAPA groups and lumbar BMD in FK-506 group. Trabecular volume fraction (BV/TV) decreased only in FK-506 group. RAPA and CsA affected femoral cortical structure, but FK-506 did not. FK-506 produced an increase in bone remodeling, and CsA a decrease. FK-506 group showed a decrease in biomechanical parameters relative to all groups. RAPA group showed a decrease in ultimate stress vs control group, and CsA group presented an increase in biomechanical parameters versus control group. We found that administration of both RAPA and FK-506 as monotherapy for healthy rats produced osteopenia. CsA treatment only produces slight damages in the cortical zone of the femur.

  5. Nano-liposomal dry powder inhaler of tacrolimus: preparation, characterization, and pulmonary pharmacokinetics.

    PubMed

    Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

    2007-01-01

    The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% +/- 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 +/- 0.8 microm, maximum fine particle fraction (FPF) of 71.1 +/- 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 +/- 0.1 microm, and geometric standard deviation (GSD) 1.7 +/- 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi's Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection.

  6. Nano-liposomal dry powder inhaler of tacrolimus: Preparation, characterization, and pulmonary pharmacokinetics

    PubMed Central

    Chougule, Mahavir; Padhi, Bijay; Misra, Ambikanandan

    2007-01-01

    The studies were undertaken to evaluate feasibility of pulmonary delivery of liposomaly encapsulated tacrolimus dry powder inhaler for prolonged drug retention in lungs as rescue therapy to prevent refractory rejection of lungs after transplantation. Tacrolimus encapsulated liposomes were prepared by thin film evaporation technique and liposomal dispersion was passed through high pressure homogenizer. Tacrolimus nano-liposomes (NLs) were separated by centrifugation and characterized. NLs were dispersed in phosphate buffer saline (PBS) pH 7.4 containing different additives like lactose, sucrose, and trehalose, and L-leucine as antiadherent. The dispersion was spray dried and spray dried powders were characterized. In vitro and in vivo pulmonary deposition was performed using Andersen Cascade Impactor and intratracheal instillation in rats respectively. NLs were found to have average size of 140 nm, 96% ± 1.5% drug entrapment, and zeta potential of 1.107 mV. Trehalose based formulation was found to have low density, good flowability, particle size of 9.46 ± 0.8 μm, maximum fine particle fraction (FPF) of 71.1 ± 2.5%, mean mass aerodynamic diameter (MMAD) 2.2 ± 0.1 μm, and geometric standard deviation (GSD) 1.7 ± 0.2. Developed formulations were found to have in vitro prolonged drug release up to 18 hours, following Higuchi’s Controlled Release model. In vivo studies revealed maximal residence of tacrolimus within lungs of 24 hours, suggesting slow clearance from the lungs. The investigation provides a practical approach for direct delivery of tacrolimus encapsulated in NLs for controlled and prolonged retention at the site of action. It may play a promising role as rescue therapy in reducing the risk of acute rejection and chronic rejection. PMID:18203434

  7. Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.

    PubMed

    Chen, W-Y; Lee, C-Y; Lin, P-Y; Hsieh, C-E; Ko, C-J; Lin, K-H; Lin, C-C; Ming, Y-Z; Chen, Y-L

    2017-03-01

    Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients. In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach. Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups. Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Artificial neural network model for predicting the bioavailability of tacrolimus in patients with renal transplantation

    PubMed Central

    Thishya, Kalluri; Vattam, Kiran Kumar; Naushad, Shaik Mohammad; Raju, Shree Bhushan

    2018-01-01

    The objective of the current study was to explore the role of ABCB1 and CYP3A5 genetic polymorphisms in predicting the bioavailability of tacrolimus and the risk for post-transplant diabetes. Artificial neural network (ANN) and logistic regression (LR) models were used to predict the bioavailability of tacrolimus and risk for post-transplant diabetes, respectively. The five-fold cross-validation of ANN model showed good correlation with the experimental data of bioavailability (r2 = 0.93–0.96). Younger age, male gender, optimal body mass index were shown to exhibit lower bioavailability of tacrolimus. ABCB1 1236 C>T and 2677G>T/A showed inverse association while CYP3A5*3 showed a positive association with the bioavailability of tacrolimus. Gender bias was observed in the association with ABCB1 3435 C>T polymorphism. CYP3A5*3 was shown to interact synergistically in increasing the bioavailability in combination with ABCB1 1236 TT or 2677GG genotypes. LR model showed an independent association of ABCB1 2677 G>T/A with post transplant diabetes (OR: 4.83, 95% CI: 1.22–19.03). Multifactor dimensionality reduction analysis (MDR) revealed that synergistic interactions between CYP3A5*3 and ABCB1 2677 G>T/A as the determinants of risk for post-transplant diabetes. To conclude, the ANN and MDR models explore both individual and synergistic effects of variables in modulating the bioavailability of tacrolimus and risk for post-transplant diabetes. PMID:29621269

  9. The Chinese approach to complementary and alternative medicine treatment for interstitial cystitis/bladder pain syndrome.

    PubMed

    Pang, Ran; Ali, Abdullah

    2015-12-01

    Management of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a challenge due to poor understanding on its etiology. Complementary and alternative medicine (CAM), as an optional treatment, has been widely used, because no definitive conventional therapy is available. The different domain of CAM provides miscellaneous treatments for IC/BPS, which mainly include dietary modification, nutraceuticals, bladder training, biofeedback, yoga, massage, physical therapy, Qigong, traditional Chinese medicine and acupuncture. Clinical evidence has shown that each therapy can certainly benefit a portion of IC/BPS patients. However, the target patient group of each therapy has not been well studied and randomized, controlled trials are needed to further confirm the efficacy and reliability of CAM on managing IC/BPS. Despite these limitations, CAM therapeutic characteristics including non-invasive and effectiveness for specific patients allow clinicians and patients to realize multimodal and individualized therapy for IC/BPS.

  10. The Chinese approach to complementary and alternative medicine treatment for interstitial cystitis/bladder pain syndrome

    PubMed Central

    Ali, Abdullah

    2015-01-01

    Management of interstitial cystitis/bladder pain syndrome (IC/BPS) remains a challenge due to poor understanding on its etiology. Complementary and alternative medicine (CAM), as an optional treatment, has been widely used, because no definitive conventional therapy is available. The different domain of CAM provides miscellaneous treatments for IC/BPS, which mainly include dietary modification, nutraceuticals, bladder training, biofeedback, yoga, massage, physical therapy, Qigong, traditional Chinese medicine and acupuncture. Clinical evidence has shown that each therapy can certainly benefit a portion of IC/BPS patients. However, the target patient group of each therapy has not been well studied and randomized, controlled trials are needed to further confirm the efficacy and reliability of CAM on managing IC/BPS. Despite these limitations, CAM therapeutic characteristics including non-invasive and effectiveness for specific patients allow clinicians and patients to realize multimodal and individualized therapy for IC/BPS. PMID:26816867

  11. [Biotechnological therapies for the treatment of back pain: alternatives to corticosteroids].

    PubMed

    Moser, C; Thiel, H-J; Grönemeyer, D

    2013-12-01

    In recent years, it is increasingly clear that back pain is not only caused by biomechanical problems. Currently, biologically-based local therapy concepts for the treatment of affected spinal regions as an alternative to the standard treatment with steroids are in development or in early stages of clinical application. The common features of these new therapies are to intervene in the regulation of homeostasis at various key points at the affected region and specifically to suppress or block catabolic influences as well as to provide with anti-inflammatory substances and growth factors. These include on one hand the genetically produced Biologicals such as TNF-α inhibitors and cytokine antagonists and on the other hand therapies with autologous blood preparations (Autologous Conditioned Serum [ACS], and Platelet Rich Plasma formulations [PRP]). This article presents the individual methods, gives an overview of developments and results of various studies and discusses current recommendations.

  12. Parents' Views and Experiences about Complementary and Alternative Medicine Treatments for Their Children with Autistic Spectrum Disorder

    ERIC Educational Resources Information Center

    Senel, Hatice Gunayer

    2010-01-01

    Use of complementary and alternative medicine (CAM) treatments have been increasing for children with autistic spectrum disorder (ASD). In this study, 38 Turkish parents of children with ASD were surveyed related with their use of CAM treatments, experiences, and views for each treatment. They mentioned "Vitamins and minerals",…

  13. Errors of Omission and Commission during Alternative Reinforcement of Compliance: The Effects of Varying Levels of Treatment Integrity

    ERIC Educational Resources Information Center

    Leon, Yanerys; Wilder, David A.; Majdalany, Lina; Myers, Kristin; Saini, Valdeep

    2014-01-01

    We conducted two experiments to evaluate the effects of errors of omission and commission during alternative reinforcement of compliance in young children. In Experiment 1, we evaluated errors of omission by examining two levels of integrity during alternative reinforcement (20 and 60%) for child compliance following no treatment (baseline) versus…

  14. [Hometreatment- an effective alternative to inpatient treatment in child and adolescent psychiatry?].

    PubMed

    Boege, Isabel; Schepker, Renate; Herpertz-Dahlmann, Beate; Vloet, Timo D

    2015-11-01

    In many countries hometreatment (HT) offers a cost-effective alternative to hospitalization for children and adolescents with mental health problems requiring intensive mental healthcare. However, the database on HT varies as HT may refer to different models and settings of intensive outpatient treatment. In Germany HT is not used routinely in mental healthcare in child and adolescent psychiatry, therefore the data on HT in Germany, especially in child and adolescent psychiatry, are scarce although funding for studies investigating the effectiveness of HT is available. This review represents a comprehensive search in electronic databases (1980-2014) of literature on HT. It provides as well an overview of the underlying concepts of and the present evidence for HT. In addition, the evidence base on HT for specific child and adolescent mental health disorders is reviewed. Future prospects for the development of HT in Germany facing the upcoming change in health service commissioning (PEPP = «pauschalierendes Entgeltsystem in Psychiatric und Psychosomatik>) are discussed, as HT in child and adolescent psychiatry, when accurately indicated, can be a valid alternative to inpatient treatment.

  15. [Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

    PubMed

    Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

    2007-04-02

    There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

  16. Complementary and alternative medicine for the treatment and diagnosis of asthma and allergic diseases.

    PubMed

    Passalacqua, G; Compalati, E; Schiappoli, M; Senna, G

    2005-03-01

    The use of Complementary/Alternative Medicines (CAM) is largely diffused and constantly increasing, especially in the field of allergic diseases and asthma. Homeopathy, acupuncture and phytotherapy are the most frequently utilised treatments, whereas complementary diagnostic techniques are mainly used in the field of food allergy-intolerance. Looking at the literature, the majority of clinical trials with CAMS are of low methodological quality, thus difficult to interpret. There are very few studies performed in a rigorously controlled fashion, and those studies provided inconclusive results. In asthma, none of the CAM have thus far been proved more effective than placebo or equally effective as standard treatments. Some herbal products, containing active principles, have displayed some clinical effect, but the herbal remedies are usually not standardised and not quantified, thus carry the risk of toxic effects or interactions. None of the alternative diagnostic techniques (electrodermal testing, kinesiology, leukocytotoxic test, iridology, hair analysis) have been proved able to distinguish between healthy and allergic subjects or to diagnose sensitizations. Therefore these tests must not be used, since they can lead to delayed or incorrect diagnosis and therapy.

  17. Modeling economic implications of alternative treatment strategies for acute bacterial skin and skin structure infections.

    PubMed

    Revankar, Nikhil; Ward, Alexandra J; Pelligra, Christopher G; Kongnakorn, Thitima; Fan, Weihong; LaPensee, Kenneth T

    2014-10-01

    The economic implications from the US Medicare perspective of adopting alternative treatment strategies for acute bacterial skin and skin structure infections (ABSSSIs) are substantial. The objective of this study is to describe a modeling framework that explores the impact of decisions related to both the location of care and switching to different antibiotics at discharge. A discrete event simulation (DES) was developed to model the treatment pathway of each patient through various locations (emergency department [ED], inpatient, and outpatient) and the treatments prescribed (empiric antibiotic, switching to a different antibiotic at discharge, or a second antibiotic). Costs are reported in 2012 USD. The mean number of days on antibiotic in a cohort assigned to a full course of vancomycin was 11.2 days, with 64% of the treatment course being administered in the outpatient setting. Mean total costs per patient were $8671, with inpatient care accounting for 58% of the costs accrued. The majority of outpatient costs were associated with parenteral administration rather than drug acquisition or monitoring. Scenarios modifying the treatment pathway to increase the proportion of patients receiving the first dose in the ED, and then managing them in the outpatient setting or prescribing an oral antibiotic at discharge to avoid the cost associated with administering parenteral therapy, therefore have a major impact and lower the typical cost per patient by 11-20%. Since vancomycin is commonly used as empiric therapy in clinical practice, based on these analyses, a shift in treatment practice could result in substantial savings from the Medicare perspective. The choice of antibiotic and location of care influence the costs and resource use associated with the management of ABSSSIs. The DES framework presented here can provide insight into the potential economic implications of decisions that modify the treatment pathway.

  18. Dose-dense paclitaxel with carboplatin for advanced ovarian cancer: a feasible treatment alternative.

    PubMed

    Glaze, Sarah; Teitelbaum, Lisa; Chu, Pamela; Ghatage, Prafull; Nation, Jill; Nelson, Gregg

    2013-01-01

    Epithelial ovarian cancer is the leading cause of death from gynaecologic cancers in the Western world. If possible, initial cytoreductive surgery is the treatment of choice, followed by adjuvant chemotherapy, usually with a platinum/taxane combination. Increased survival has been recently reported in women who were given adjuvant chemotherapy weekly rather than at three-week intervals, which has been the standard. At our centre, we have been treating patients with advanced ovarian cancer with a dose-dense protocol since March 2010. Treatment is given in an outpatient setting on days 1, 8, and 15 of a 21-day cycle for six cycles. Carboplatin for an AUC of 5 mg/mL/min and paclitaxel 80mg/m² are given on day 1, followed by paclitaxel 80mg/m² on days 8 and 15. Our objective was to determine whether this protocol is a feasible alternative treatment in our population and whether or not the toxicity profile is acceptable. We performed a chart review of 46 patients undergoing treatment with dose-dense chemotherapy for advanced ovarian cancer. Demographic information, patient characteristics, adverse events, and treatment endpoints were recorded. Sixty-one percent of women completed the six-cycle protocol as planned with minimal interruption, which is comparable to the only previously reported trial using this regimen. The most common side effects of treatment were fatigue, neuropathy, and neutropenia. Supplementation with regular magnesium and granulocyte colony-stimulating factor reduced delays. Dose-dense paclitaxel with carboplatin chemotherapy for the treatment of advanced ovarian cancer shows promise in terms of progression-free and overall survival. We have shown this protocol to be practical and feasible in our population.

  19. Distinct deleterious effects of cyclosporine and tacrolimus and combined tacrolimus-sirolimus on endothelial cells: protective effect of defibrotide.

    PubMed

    Carmona, Alba; Díaz-Ricart, Maribel; Palomo, Marta; Molina, Patricia; Pino, Marc; Rovira, Montserrat; Escolar, Ginés; Carreras, Enric

    2013-10-01

    Endothelial dysfunction seems to be a key factor in the development of several complications observed early after hematopoietic stem cell transplantation (HSCT). The conditioning regimen and many other factors associated with the procedure are responsible for this endothelial damage. The effects of immunosuppressive agents on endothelial function have not been explored in detail. We evaluated the effects of 3 drugs commonly used in HSCT: 2 calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus (TAC), and an inhibitor of mTOR, sirolimus (SIR). We also evaluated the effect of the combination of TAC and SIR (TAC+SIR), which is used increasingly in clinical practice. Microvascular endothelial cells (HMEC-1) were exposed to these drugs to evaluate changes in (1) intercellular adhesion molecule (ICAM)-1 expression on the cell surface, assessed by immunofluorescence labeling and expressed as the mean gray value (MGV); (2) reactivity of the extracellular matrix (ECM) toward platelets, upon exposure of the ECM to circulating blood; and (3) whole-blood clot formation, assessed by thromboelastometry. Studies were conducted in the absence and presence of defibrotide (DF) to assess its possible protective effect. The exposure of HMEC-1 to CSA and TAC+SIR significantly increased the expression of ICAM-1 (157.5 ± 11.6 and 153.4 ± 9.5 MGV, respectively, versus 105.7 ± 6.5 MGV in controls [both P < .05]). TAC applied alone increased ICAM-1 slightly (120.3 ± 8.2 MGV), and SIR had no effect (108.9 ± 7.4 MGV). ECM reactivity increased significantly only in response to CSA (surface covered by platelets of 41.2% ± 5.4% versus 30.1% ± 2.0%, P < .05). DF attenuated all these changes. No significant changes in the viscoelastic properties of clot formation were observed in any condition with blood samples incubated in vitro. In conclusion, CSA and TAC+SIR had a proinflammatory effect, but only CSA exhibited an additional prothrombotic effect. Interestingly, DF exerted clear

  20. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial.

    PubMed

    Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H L; Brown, Malcolm W; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R J

    2017-08-01

    ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m), acute rejection and graft and patient survival. The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan-Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients receiving corticosteroids tapered over 10

  1. Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women?

    PubMed

    Mazaro-Costa, Renata; Andersen, Monica L; Hachul, Helena; Tufik, Sergio

    2010-11-01

    Female sexual dysfunction (FSD) is a complex and multifactorial condition. An increased incidence of FSD is especially associated with the decline of estrogen. Thus, menopause is a critical phase for FSD complaints. In this context, medicinal plants may be a therapeutic option. To identify and describe the popular and clinical uses of medicinal plants for FSD treatment in climacteric women. We highlighted the majority of the plants commonly involved with the female reproductive system including: Angelica sinensis, Cimicifuga racemosa, Ferula hermonis, Ginkgo biloba, Humulus lupulus, Lepidium meyenii, Tribulus terrestris, Trifolium pratense, and Vitex agnus-castus. This study is a narrative review of studies of plants that are possible alternative treatments for FSD. The species described have clinical and popular uses in different cultures as well as medical indications for female reproductive disturbances, mainly in climacteric women. We have also analyzed the evidence level of clinical studies. The main outcome assessed is the efficacy of plants in improving the symptoms of FSD. There is little evidence from the literature to recommend the use of medicinal plants when treating FSD. The majority of studies with a strong level of evidence are associated with the treatment of the vasomotor symptoms of menopause. Ferula hermonis, Angelica sinensis, and Gingko biloba may be suggested for arousal disorder studies. Cimicifuga racemosa, Trifolium pratense, and Vitex agnus-castus may be recommended for several FSD. Humulus lupulus and Tribulus terrestris may help with desire disorder studies. Lepidium meyenii should be studied further. Studies of these plants indicate that they may be useful as a possible alternative and/or complementary approach for studies aimed at the treatment of FSD. At this time, however, this review cannot recommend a plant that has a strong enough level of evidence for treatment of FSD. Thus, there is a need for clinical (double-blinded and

  2. Economic feasibility study for new technological alternatives in wastewater treatment processes: a review.

    PubMed

    Molinos-Senante, María; Hernández-Sancho, Francesc; Sala-Garrido, Ramón

    2012-01-01

    The concept of sustainability involves the integration of economic, environmental, and social aspects and this also applies in the field of wastewater treatment. Economic feasibility studies are a key tool for selecting the most appropriate option from a set of technological proposals. Moreover, these studies are needed to assess the viability of transferring new technologies from pilot-scale to full-scale. In traditional economic feasibility studies, the benefits that have no market price, such as environmental benefits, are not considered and are therefore underestimated. To overcome this limitation, we propose a new methodology to assess the economic viability of wastewater treatment technologies that considers internal and external impacts. The estimation of the costs is based on the use of cost functions. To quantify the environmental benefits from wastewater treatment, the distance function methodology is proposed to estimate the shadow price of each pollutant removed in the wastewater treatment. The application of this methodological approach by decision makers enables the calculation of the true costs and benefits associated with each alternative technology. The proposed methodology is presented as a useful tool to support decision making.

  3. Alternative Treatment in Prostate Pain Syndrome Based on Iranian Traditional Medicine

    PubMed Central

    Latifi, Seied Amirhossein; Kamalinejad, Mohammad; Minaiee, Bagher; Bahrami, Mohsen; Gooran, Shahram; Nikbakht Nasrabadi, Alireza

    2014-01-01

    Introduction: Unknown etiology and pathophysiology of prostate pain syndrome (PPS) has led to a lack of proper and competent treatment in modern medicine. According to the guidelines of European Association of Urology (EAU), use of complementary treatments is recommended for PPS. In this preliminary study, analyzing the signs and symptoms of PPS from the viewpoint of Iranian traditional medicine (ITM) was helpful in selecting the appropriate alternative treatment. Case Presentation: Two male patients diagnosed with PPS were evaluated and treated according to the ITM. Each patient took 15 mL oxymel 45 minutes after lunch and dinner. For each patient, four clinical visits were made with one week intervals and the validated Farsi version of international prostate symptom score (IPSS) and numeric pain rating score (NPRS) were completed for them. Conclusions: Considering the fact that other major pathological causes are ruled out, many of the symptoms and signs observed in these patients were similar to those associated with flatulency-related diseases in ITM. Selecting treatment with oxymel was based on this view and led to improvements in the digestive and urinary symptoms according to Farsi version of the IPSS and NPRS. PMID:25237573

  4. Complementary and alternative medicine for prevention and treatment of the common cold

    PubMed Central

    Nahas, Richard; Balla, Agneta

    2011-01-01

    Abstract Objective To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults. Quality of Evidence MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included. Main Message For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold. Conclusion Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research. PMID:21322286

  5. Beliefs and perceptions of women with newly diagnosed breast cancer who refused conventional treatment in favor of alternative therapies.

    PubMed

    Citrin, Dennis L; Bloom, Diane L; Grutsch, James F; Mortensen, Sara J; Lis, Christopher G

    2012-01-01

    Although breast cancer is a highly treatable disease, some women reject conventional treatment opting for unproven "alternative therapy" that may contribute to poor health outcomes. This study sought to understand why some women make this decision and to identify messages that might lead to greater acceptance of evidence-based treatment. This study explored treatment decision making through in-depth interviews with 60 breast cancer patients identified by their treating oncologists. Thirty refused some or all conventional treatment, opting for alternative therapies, whereas 30 accepted both conventional and alternative treatments. All completed the Beck Anxiety Inventory and the Rotter Locus of Control scale. Negative first experiences with "uncaring, insensitive, and unnecessarily harsh" oncologists, fear of side effects, and belief in the efficacy of alternative therapies were key factors in the decision to reject potentially life-prolonging conventional therapy. Refusers differed from controls in their perceptions of the value of conventional treatment, believing that chemotherapy and radiotherapy were riskier (p < .0073) and less beneficial (p < .0001) than did controls. Controls perceived alternative medicine alone as riskier than did refusers because its value for treating cancer is unproven (p < .0001). Refusers believed they could heal themselves naturally from cancer with simple holistic methods like raw fruits, vegetables, and supplements. According to interviewees, a compassionate approach to cancer care plus physicians who acknowledge their fears, communicate hope, educate them about their options, and allow them time to come to terms with their diagnosis before starting treatment might have led them to better treatment choices.

  6. Tacrolimus hydrate ointment inhibits skin plasma extravasation in rats induced by topical m-xylene but not capsaicin.

    PubMed

    Goto, Shiho; Kondo, Fumio; Ikai, Yoshitomo; Miyake, Mio; Futamura, Masaki; Ito, Komei; Sakamoto, Tatsuo

    2009-04-17

    Tacrolimus ointment is used to treat various chronic inflammatory skin diseases. However, the effect of this ointment on acute neurogenic inflammation in the skin remains to be fully elucidated. Topical capsaicin and m-xylene produce tachykinin release from sensory nerves in the skin, resulting in skin plasma leakage. We investigated the effect of tacrolimus ointment (0.1%) on skin microvascular leakage induced by topical capsaicin (10 mM) and m-xylene (neat), and intracutaneous compound 48/80 (c48/80) (10 microg/ml, 50 microl/site) in two groups of rats pretreated with excessive capsaicin or its vehicle. The amount of leaked Evans blue dye reflected skin plasma leakage. Capsaicin, m-xylene or c48/80 was applied to the shaved abdomens of rats 8 h after topical application of tacrolimus ointment or its base. Desensitization with capsaicin reduced the skin response to capsaicin and m-xylene by 100% and 65%, respectively, but not to c48/80. Tacrolimus ointment significantly inhibited the skin response induced by m-xylene and c48/80, regardless of pretreatment with capsaicin. However, topical tacrolimus did not influence the skin response induced by capsaicin. We also evaluated whether topical capsaicin and m-xylene, and intracutaneous c48/80 cause mast cell degranulation in skin treated with tacrolimus. Mast cell degranulation was microscopically assessed. Topical tacrolimus only significantly suppressed degranulation induced by m-xylene and c48/80. Our data shows that tacrolimus ointment partially inhibits plasma leakage and mast cell degranulation in rat skin induced by m-xylene and c48/80 but not capsaicin, suggesting that the inhibitory effect is not associated with a reduction in neurogenic-mediated mechanisms.

  7. A randomized, crossover pharmacokinetic study comparing generic tacrolimus vs. the reference formulation in subpopulations of kidney transplant patients.

    PubMed

    Bloom, R D; Trofe-Clark, J; Wiland, A; Alloway, R R

    2013-01-01

    An exploratory, post hoc analysis was performed using data from a prospective, multicenter, open-label, randomized, two-period (14 d per period), two-sequence, crossover, steady-state pharmacokinetic study comparing generic tacrolimus (Sandoz) vs. reference tacrolimus in stable renal transplant patients receiving their pre-study twice-daily dose. Pharmacokinetic parameters were compared in 68 patients according to gender, African American ethnicity, the presence or absence of diabetes, and use of steroids. The ratios of tacrolimus AUC0-12 h , Cmax , and C12 with generic vs. reference tacrolimus were calculated using the geometric mean (GM) of dose-normalized values at days 14 and 28. Mean (SD) tacrolimus dose at baseline was 5.7 (4.2) mg/d. There were no consistent differences in dose-normalized AUC0-12 h , C12 , Cmax, or tmax between the generic and reference preparations within subpopulations. The 90% confidence intervals (CI) for the ratios of dose-normalized AUC0-12 h and C12 with generic vs. reference tacrolimus were within 80-125% for all subpopulations, as were 90% CIs for Cmax other than for females, African Americans, and non-diabetics, which is not unexpected given the wide variability of tacrolimus Cmax and the small subpopulation sizes. These exploratory results suggest that this generic tacrolimus preparation would be expected to offer comparable bioavailability to the reference drug in these patient subpopulations. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Tacrolimus potently inhibits human osteoclastogenesis induced by IL-17 from human monocytes alone and suppresses human Th17 differentiation.

    PubMed

    Yago, Toru; Nanke, Yuki; Kawamoto, Manabu; Yamanaka, Hisashi; Kotake, Shigeru

    2012-08-01

    Tacrolimus (FK506, Prograf®) is an orally available, T cell specific and anti-inflammatory agent that has been proposed as a therapeutic drug in rheumatoid arthritis (RA) patients. It has been known that T cells have a critical role in the pathogenesis of RA. Recent studies suggest that Th17 cells, which mainly produce IL-17, are involved in many autoimmune inflammatory disease including RA. The present study was undertaken to assess the effect of tacrolimus on IL-17-induced human osteoclastogenesis and human Th17 differentiation. Human CD14(+) monocytes were cultured in the presence of macrophage-colony stimulating factor (M-CSF) and IL-17. From day 4, tacrolimus was added to these cultures. Osteoclasts were immunohistologically stained for vitronectin receptor 10days later. IL-17 production from activated T cells stimulated with IL-23 was measured by enzyme-linked immunosorbent assay (ELISA). Th17 differentiation from naïve T cells was assayed by flow cytometry. Tacrolimus potently inhibited IL-17-induced osteoclastogenesis from human monocytes and osteoclast activation. Addition of tacrolimus also reduced production of IL-17 in human activated T cells stimulated with IL-23. Interestingly, the population of human IL-17(+)IFN-γ(-) CD4 T cells or IL-17(+)TNF-α(+) CD4 T cells were decreased by adding of tacrolimus. The present study demonstrates that the inhibitory effect of tacrolimus on IL-17-induced osteoclastogenesis from human monocytes. Tacrolimus also inhibited expression of IL-17 or TNF-α by reducing the proportion of Th17, suggesting that therapeutic effect on Th17-associated disease such as RA, inflammatory bowel disease, multiple sclerosis, psoriasis, or allograft rejection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Use of Complementary and Alternative Medicine Treatments by Patients with Obstructive Sleep Apnea Hypopnea Syndrome

    PubMed Central

    Sood, Amit; Narayanan, Sujata; Wahner-Roedler, Dietlind L.; Knudsen, Kayla; Sood, Richa; Loehrer, Laura L.; Hanson, Andrew C.; Kuzniar, Tomasz J.; Olson, Eric J.

    2007-01-01

    Study Objectives: To assess the proportion of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) reporting previous or current use and interest in future use of complementary and alternative medicine (CAM) therapies. Design: Cross-sectional, point-of-care, anonymous survey. Setting: Sleep disorders center at a Midwest tertiary care center. Participants: Six hundred forty-six consecutive patients undergoing polysomnography. Measurements: The survey instrument comprised 45 items specifically related to CAM therapies, in addition to obtaining baseline data. Results: Response rate was 81% (522/646). A total of 406/522 (78%) patients were diagnosed with OSAHS. Mean age ± SD was 57 ± 14 years, and 267 participants (66%) were men. Overall, 237 (58%) participants reported ever using CAM. Ever and current CAM use specifically for improving sleep was reported by 20% and 7% of the participants, respectively. Twenty-six percent of participants reported ever using biologic products, and 52% reported ever using nonbiologic CAM treatments. A high proportion (58%) of the participants showed interest in future CAM use for improving sleep. Conclusion: A high proportion of patients with OSAHS report previous or current use, and interest in future use, of CAM treatments. This underscores the need to conduct further research in this field. Citation: Sood A; Narayanan S; Wahner-Roedler DL; Knudsen K; Sood R; Loehrer LL; Hanson AC; Kuzniar TJ; Olson EJ. Use of complementary and alternative medicine treatments by patients with obstructive sleep apnea hypopnea syndrome. J Clin Sleep Med 2007;3(6):575-579. PMID:17993037

  10. Trick or treat? Australian newspaper portrayal of complementary and alternative medicine for the treatment of cancer.

    PubMed

    Mercurio, Reegan; Eliott, Jaklin Ardath

    2011-01-01

    Many cancer patients within developed nations cite the media as informing their decisions to use complementary and alternative medicine (CAM). The present study describes (1) Australian newspaper coverage of CAM use for cancer between 1998 and 2007; (2) trends in reporting frequency and characteristics; and (3) how the Australian press framed stories on CAM use for cancer. This study is a content analysis featuring quantitative and qualitative techniques, the latter guided by 'media framing', of targeted newspaper articles. One hundred nineteen articles focused on CAM use for the treatment of cancer were identified. Quantitative analysis found that biologically based CAMs were most frequently described and breast cancer most mentioned. Two thirds of all articles described CAM use in the context of a cure, with approximately half of these opposing this reason for use. Potential benefits of CAM were discussed more frequently than potential risks, and information on costs and how to access CAM were uncommon. Recommendations included advice to use complementary, not alternative therapies, yet advice to discuss CAM with a medical doctor was rare. Qualitative analysis found six CAM cancer-related frames, four in support of CAM use for cancer treatment. The dominant frame constructed CAM as legitimate tools to assist biomedicine (even to cure), with others depicting CAM as normal and necessary or as addressing limitations of biomedicine. Negative frames depicted CAM as questionable and risky practices and the industry/practitioners as possessing malevolent intent. These findings have implications for biomedical practitioners attempting to determine, respect and assist patient choices about their treatment.

  11. Environmental comparison of alternative treatments for sewage sludge: An Italian case study.

    PubMed

    Lombardi, Lidia; Nocita, Cristina; Bettazzi, Elena; Fibbi, Donatella; Carnevale, Ennio

    2017-11-01

    A Life Cycle Assessment (LCA) was applied to compare different alternatives for sewage sludge treatment: such as land spreading, composting, incineration, landfill and wet oxidation. The LCA system boundaries include mechanical dewatering, the alternative treatment, transport, and final disposal/recovery of residues. Cases of recovered materials produced as outputs from the systems, were resolved by expanding the system boundaries to include avoided primary productions. The impact assessment was calculated using the CML-IA baseline method. Results showed that the incineration of sewage sludge with electricity production and solid residues recovery collects the lowest impact indicator values in the categories human toxicity, fresh water aquatic ecotoxicity, acidification and eutrophication, while it has the highest values for the categories global warming and ozone layer depletion. Land spreading has the lowest values for the categories abiotic depletion, fossil fuel depletion, global warming, ozone layer depletion and photochemical oxidation, while it collects the highest values for terrestrial ecotoxicity and eutrophication. Wet oxidation has just one of the best indicators (terrestrial ecotoxicity) and three of the worst ones (abiotic depletion, human toxicity and fresh water aquatic ecotoxicity). Composting process shows intermediate results. Landfill has the worst performances in global warming, photochemical oxidation and acidification. Results indicate that if the aim is to reduce the effect of the common practice of sludge land spreading on human and ecosystem toxicity, on acidification and on eutrophication, incineration with energy recovery would clearly improve the environmental performance of those indicators, but an increase in resource depletion and global warming is unavoidable. However, these conclusions are strictly linked to the effective recovery of solid residues from incineration, as the results are shown to be very sensitive with respect to

  12. Development of extended-release solid dispersion granules of tacrolimus: evaluation of release mechanism and human oral bioavailability.

    PubMed

    Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken-Ichi; Sako, Kazuhiro; Hakomori, Tadashi; Higaki, Kazutaka

    2017-12-01

    We aimed to prepare a once-daily modified-release oral formulation of tacrolimus by utilizing an extended-release granules (ERG). Extended-release granules were prepared using ethylcellulose (EC), hydroxypropylmethylcellulose (HPMC) and lactose via a solvent evaporation method with ethanol. Physicochemical and biopharmaceutical studies were performed to determine the formulation with optimum release profile of tacrolimus from ERG. Tacrolimus existed in an amorphous state in ERG. Tacrolimus release from ERG was attenuated by EC and facilitated by lactose, suggesting that drug release kinetics could adequately be regulated by these components. Those release profiles were consistent with Higuchi's equation, suggesting a diffusion-type release mechanism. Smooth surface of ERG changed to the structure with pores after the release test, likely derived from the dissolution of HPMC and lactose. But ERG structure formed by EC was still maintained after the release test, leading to the longer maintenance of diffusion-type release. Two ERG formulations selected by blood concentration simulation successfully provided long-term retention of tacrolimus in blood in a human absorption study. We successfully developed the formulation exhibiting a significant reduction in C max , the longer mean residence time and AUC close to that of an immediate-release tacrolimus formulation, being preferred from the viewpoint of safe and effective immunosuppressant pharmacotherapy. © 2017 Royal Pharmaceutical Society.

  13. Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: a Retrospective Study.

    PubMed

    Strohbehn, Garth W; Pan, Warren W; Petrilli, Christopher M; Heidemann, Lauren; Larson, Sophia; Aaronson, Keith D; Johnson, Matt; Ellies, Tammy; Heung, Michael

    2018-04-30

    Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the pre-analytical phase of the inpatient tacrolimus TDM process at their institution. Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted and time distribution plots for each step in the inpatient TDM process were generated. Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 +/- 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within one hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

  14. Design and physicochemical characterization of advanced spray-dried tacrolimus multifunctional particles for inhalation

    PubMed Central

    Wu, Xiao; Hayes, Don; Zwischenberger, Joseph B; Kuhn, Robert J; Mansour, Heidi M

    2013-01-01

    The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary

  15. Novel Virtual Environment for Alternative Treatment of Children with Cerebral Palsy

    PubMed Central

    de Oliveira, Juliana M.; Fernandes, Rafael Carneiro G.; Pinto, Cristtiano S.; Pinheiro, Plácido R.; Ribeiro, Sidarta

    2016-01-01

    Cerebral palsy is a severe condition usually caused by decreased brain oxygenation during pregnancy, at birth or soon after birth. Conventional treatments for cerebral palsy are often tiresome and expensive, leading patients to quit treatment. In this paper, we describe a virtual environment for patients to engage in a playful therapeutic game for neuropsychomotor rehabilitation, based on the experience of the occupational therapy program of the Nucleus for Integrated Medical Assistance (NAMI) at the University of Fortaleza, Brazil. Integration between patient and virtual environment occurs through the hand motion sensor “Leap Motion,” plus the electroencephalographic sensor “MindWave,” responsible for measuring attention levels during task execution. To evaluate the virtual environment, eight clinical experts on cerebral palsy were subjected to a questionnaire regarding the potential of the experimental virtual environment to promote cognitive and motor rehabilitation, as well as the potential of the treatment to enhance risks and/or negatively influence the patient's development. Based on the very positive appraisal of the experts, we propose that the experimental virtual environment is a promising alternative tool for the rehabilitation of children with cerebral palsy. PMID:27403154

  16. Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

    PubMed

    Hautvast, R W; DeJongste, M J; ter Horst, G J; Blanksma, P K; Lie, K I

    1996-07-01

    The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

  17. Oncologists' experiences of discussing complementary and alternative treatment options with their cancer patients. A qualitative analysis.

    PubMed

    Corina, Güthlin; Christine, Holmberg; Klein, Gudrun

    2016-09-01

    The rising use of complementary and alternative medicine (CAM) means oncologists are increasingly asked by patients to discuss CAM treatment options. However, no formal training or established standards are available on the subject. The aim of this paper was to investigate real-world discussions of CAM treatments. In particular, we wanted to learn about the values, norms and defining features that characterise oncologist-patient discussions on CAM. Semi-standardised interviews with 17 oncologists were analysed using interpretation pattern analysis combined with thematic analysis. Advice on CAM is seen by oncologists as an important service they provide to their patients, even though their knowledge of the subject is often limited. Many interviewees mentioned an apparent lack of scientific proof, especially when their aim was to warn patients against the use of CAM. Discussions on CAM tend to reflect the idea that CAM belongs 'to another world', and judging by the interviews with oncologists, this notion appears to be shared by patients and oncologists alike. Oncologists require reliable information on CAM and would profit from training in the communication of CAM treatment options to patients. Knowing scientific data on CAM would also lower barriers stemming from the view that CAM belongs 'to another world'. Under- and postgraduate education programmes should include training on how to respond to requests addressing possible CAM options.

  18. ALTERNATIVE MEDICINE PRODUCTS AS A NOVEL TREATMENT STRATEGY FOR INFLAMMATORY BOWEL DISEASE

    PubMed Central

    Jackson, Lindsey N.; Zhou, Yuning; Qiu, Suimin; Wang, Qingding; Evers, B. Mark

    2008-01-01

    Inflammatory bowel disease (IBD) affects the mucosal lining of the gastrointestinal tract; the etiology is unknown and treatment is directed at systemic immunosuppression. Natural products, including medicinal herbs, have provided approximately half of the drugs developed for clinical use over the past 20 years. The purpose of our current study was to determine the effects of a novel combination of herbal extracts on intestinal inflammation using a murine model of IBD. Female Swiss-Webster mice were randomized to receive normal water or 5% dextran sulfate sodium (DSS) drinking water to induce colitis. Mice were treated with either a novel combination of herbal aqueous extracts or vehicle control per os (po) or per rectum (pr) every 24h for 7-8d. Disease activity index score (DAI) was determined daily; mice were sacrificed and colons analyzed by H&E staining, MPO assay, and cytokine (TNF-α, IL-6) ELISAs. Mice treated with the combination of herbal extracts, either po or pr, had significantly less rectal bleeding and lower DAI scores when compared to the vehicle-treated group. Moreover, colonic ulceration, leukocytic infiltration, and cytokine levels (TNF-α and IL-6) were decreased in the colons of herbal-treated mice, reflected by H&E staining, MPO assay, and cytokine ELISA. Treatment with the combination of medicinal herbs decreases leukocyte infiltration and mucosal ulceration, ameliorating the course of acute colonic inflammation. This herbal remedy may prove to be a novel and safe therapeutic alternative in the treatment of IBD. PMID:19051360

  19. Evaluating sphingosine and its analogues as potential alternatives for aggressive lymphoma treatment.

    PubMed

    Bode, Constantin; Berlin, Max; Röstel, Franziska; Teichmann, Bianca; Gräler, Markus H

    2014-01-01

    Ceramide (Cer) and sphingosine (Sph) interfere with critical cellular functions relevant for cancer progression and cell survival. While Cer has already been investigated as a potential drug target for lymphoma treatment, information about the potency of sphingosine is scarce. The aim of this study therefore was to evaluate Sph and its synthetic stereoisomer L-threo-sphingosine (Lt-Sph) as potential treatment options for aggressive lymphomas. Diffuse large B cell lymphoma (DLBCL) cell lines were incubated with Sph and Lt-Sph and consequently analysed by flow cytometry (FACS), enzyme-linked immunosorbent assay (ELISA), liquid chromatography coupled to triple-quadrupole mass spectrometry (LC/MS/MS), electron microscopy, and Western blot. Sph induced cell death and blocked cell growth independently of S1P receptors in different DLBCL cell lines. Three different modes of Sph-mediated cell death were observed: Apoptosis, autophagy, and protein kinase C (PKC) inhibition. Generation of pro-apoptotic Cer accounted only for a minor portion of the apoptotic rate. Sph and its analogues could evolve as alternative treatment options for aggressive lymphomas via PKC inhibition, apoptosis, and autophagy. These physiological responses induced by different intracellular signalling cascades (phosphorylation of JNK, PARP cleavage, LC3-II accumulation) identify Sph and analogues as potent cell death inducing agents. © 2014 S. Karger AG, Basel.

  20. Demagnetization Treatment of Remanent Composite Microspheres Studied by Alternating Current Susceptibility Measurements

    PubMed Central

    van Berkum, Susanne; Erné, Ben H.

    2013-01-01

    The magnetic remanence of silica microspheres with a low concentration of embedded cobalt ferrite nanoparticles is studied after demagnetization and remagnetization treatments. When the microspheres are dispersed in a liquid, alternating current (AC) magnetic susceptibility spectra reveal a constant characteristic frequency, corresponding to the rotational diffusion of the microparticles; this depends only on particle size and liquid viscosity, making the particles suitable as a rheological probe and indicating that interactions between the microspheres are weak. On the macroscopic scale, a sample with the dry microparticles is magnetically remanent after treatment in a saturating field, and after a demagnetization treatment, the remanence goes down to zero. The AC susceptibility of a liquid dispersion, however, characterizes the remanence on the scale of the individual microparticles, which does not become zero after demagnetization. The reason is that an individual microparticle contains only a relatively small number of magnetic units, so that even if they can be reoriented magnetically at random, the average vector sum of the nanoparticle dipoles is not negligible on the scale of the microparticle. In contrast, on the macroscopic scale, the demagnetization procedure randomizes the orientations of a macroscopic number of magnetic units, resulting in a remanent magnetization that is negligible compared to the saturation magnetization of the entire sample. PMID:24009021

  1. The UASB reactor as an alternative for the septic tank for on-site sewage treatment.

    PubMed

    Coelho, A L S S; do Nascimento, M B H; Cavalcanti, P F F; van Haandel, A C

    2003-01-01

    Although septic tanks are amply used for on site sewage treatment, these units have serious drawbacks: the removal efficiency of organic material and suspended solids is low, the units are costly and occupy a large area and operational cost is high due to the need for periodic desludging. In this paper an innovative variant of the UASB reactor is proposed as an alternative for the septic tank. This alternative has several important advantages in comparison with the conventional septic tank: (1) Although the volume of the UASB reactor was about 4 times smaller than the septic tank, its effluent quality was superior, even though small sludge particles were present, (2) desludging of the UASB reactor is unnecessary and even counterproductive, as the sludge mass guarantees proper performance, (3) the UASB reactor is easily transportable (compact and light) and therefore can be produced in series, strongly reducing construction costs and (4) since the concentration of colloids in the UASB effluent is much smaller than in the ST effluent, it is expected that the infiltration of the effluent will be much less problematic.

  2. The role of the Internet in cancer patients' engagement with complementary and alternative treatments.

    PubMed

    Broom, Alex; Tovey, Philip

    2008-04-01

    This article draws on a study of 80 National Health Service cancer patients and their experiences of using the Internet within disease and treatment processes. It focuses on the role the Internet plays in the context of potential or actual engagement with complementary and alternative medicine (CAM). The results depart from previous conceptualizations of the Internet as a major source of CAM knowledge, and second, as a major pathway to patient CAM usage. Moreover, the results highlight significant anxiety as patients attempt to process vast amounts of complex biomedical diagnostic and prognostic information online. For patients attempting to embrace alternative therapeutic models of cancer care, exposure to prognostic data may pose considerable risks to individual well-being and engagement with healing practices. On the basis of these results we problematize social theorizations of the Internet as contributing to such things as: the democratization of knowledge; the deprofessionalization of medicine; and patient empowerment. We emphasize, instead, the potential role of the Internet in reinforcing biomedicine's paradigmatic dominance in cancer care.

  3. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

    PubMed

    Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

    2018-04-19

    We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Noncontingent reinforcement without extinction plus differential reinforcement of alternative behavior during treatment of problem behavior.

    PubMed

    Fritz, Jennifer N; Jackson, Lynsey M; Stiefler, Nicole A; Wimberly, Barbara S; Richardson, Amy R

    2017-07-01

    The effects of noncontingent reinforcement (NCR) without extinction during treatment of problem behavior maintained by social positive reinforcement were evaluated for five individuals diagnosed with autism spectrum disorder. A continuous NCR schedule was gradually thinned to a fixed-time 5-min schedule. If problem behavior increased during NCR schedule thinning, a continuous NCR schedule was reinstated and NCR schedule thinning was repeated with differential reinforcement of alternative behavior (DRA) included. Results showed an immediate decrease in all participants' problem behavior during continuous NCR, and problem behavior maintained at low levels during NCR schedule thinning for three participants. Problem behavior increased and maintained at higher rates during NCR schedule thinning for two other participants; however, the addition of DRA to the intervention resulted in decreased problem behavior and increased mands. © 2017 Society for the Experimental Analysis of Behavior.

  5. INVO procedure: minimally invasive IVF as an alternative treatment option for infertile couples.

    PubMed

    Lucena, Elkin; Saa, Angela M; Navarro, Doris E; Pulido, Carlos; Lombana, Oscar; Moran, Abby

    2012-01-01

    Intravaginal culture (IVC), also called INVO (intravaginal culture of oocytes), is an assisted reproduction procedure where oocyte fertilization and early embryo development are carried out within a gas permeable air-free plastic device, placed into the maternal vaginal cavity for incubation. In the present study we assessed the outcome of the INVO procedure, using the recently designed INVOcell device, in combination with a mild ovarian stimulation protocol. A total of 125 cycles were performed. On average 6.5 oocytes per cycle were retrieved, and a mean of 4.2 were placed per INVOcell device. The cleavage rate obtained after the INVO culture was 63%. The procedure yielded 40%, 31.2%, and 24% of clinical pregnancy, live birth, and single live birth rates per cycle, respectively. Our results suggest that the INVO procedure is an effective alternative treatment option in assisted reproduction that shows comparable results to those reported for existing IVF techniques.

  6. INVO Procedure: Minimally Invasive IVF as an Alternative Treatment Option for Infertile Couples

    PubMed Central

    Lucena, Elkin; Saa, Angela M.; Navarro, Doris E.; Pulido, Carlos; Lombana, Oscar; Moran, Abby

    2012-01-01

    Intravaginal culture (IVC), also called INVO (intravaginal culture of oocytes), is an assisted reproduction procedure where oocyte fertilization and early embryo development are carried out within a gas permeable air-free plastic device, placed into the maternal vaginal cavity for incubation. In the present study we assessed the outcome of the INVO procedure, using the recently designed INVOcell device, in combination with a mild ovarian stimulation protocol. A total of 125 cycles were performed. On average 6.5 oocytes per cycle were retrieved, and a mean of 4.2 were placed per INVOcell device. The cleavage rate obtained after the INVO culture was 63%. The procedure yielded 40%, 31.2%, and 24% of clinical pregnancy, live birth, and single live birth rates per cycle, respectively. Our results suggest that the INVO procedure is an effective alternative treatment option in assisted reproduction that shows comparable results to those reported for existing IVF techniques. PMID:22645435

  7. Characteristics of venom allergic reactions in Turkish beekeepers and alternative treatment modalities.

    PubMed

    Çelıksoy, Mehmet Halil; Sancak, Recep; Söğüt, Ayhan; Güner, Sükrü Nail; Korkmaz, Ali

    2014-07-01

    The objective of this work was to determine the characteristics of allergic reactions that may occur after a bee sting and alternative treatment methods in Turkish beekeepers. A written questionnaire was administered to beekeepers from the Ordu, Samsun, Sinop, Amasya, and Çorum provinces located in the Central Black Sea Region of Turkey. The study included 301 beekeepers, 295 (98%) of whom were male. Their mean age was 48.2 ± 11.5 years. The mean beekeeping duration was 15.3 ± 10.5 years. A total of 270 participants (89.9%) had a history of bee stings in the previous 12 months. Systemic reactions, large local reactions, and local reactions were seen in 21 (6.9%), 193 (64.1%), and 12 (4.0%) beekeepers, respectively. The face was the most frequently stung body site, and swelling generally occurred in the eyelids. The size of the swellings decreased within 12 to 24 hours in 259 (86.1%) beekeepers. The size of the swellings was 1 × 2 cm in diameter in 157 (52.2%) beekeepers. Natural protection against bee stings had developed by 12 months in 140 (46.5%) beekeepers. In total, 61.5% of the beekeepers applied alternative treatments (eg, garlic, onion water, yogurt), whereas 14.0% (3/21) were admitted to a hospital with a systemic reaction. In total, 10.6% and 14.2% of beekeepers were aware of adrenaline auto-injector and venom immunotherapy, respectively. This study indicates insufficient knowledge and attitudes among Turkish beekeepers regarding bee sting reactions. © 2014 ARS-AAOA, LLC.

  8. Use of complementary and alternative medicine for treatment among African-Americans: a multivariate analysis.

    PubMed

    Barner, Jamie C; Bohman, Thomas M; Brown, Carolyn M; Richards, Kristin M

    2010-09-01

    The use of complementary and alternative medicine (CAM) is substantial among African-Americans; however, research on characteristics of African-Americans who use CAM to treat specific conditions is scarce. To determine what predisposing, enabling, need, and disease-state factors are related to CAM use for treatment among a nationally representative sample of African-Americans. A cross-sectional study design was employed using the 2002 National Health Interview Survey (NHIS). A nationwide representative sample of adult (> or =18 years) African-Americans who used CAM in the past 12 months (n=16,113,651 weighted; n=2,952 unweighted) was included. The Andersen Health Care Utilization Model served as the framework with CAM use for treatment as the main outcome measure. Independent variables included the following: predisposing (eg, age, gender, and education); enabling (eg, income, employment, and access to care); need (eg, health status, physician visits, and prescription medication use); and disease state (ie, most prevalent conditions among African-Americans) factors. Multivariate logistic regression was used to address the study objective. Approximately 1 in 5 (20.2%) who used CAM in the past 12 months used CAM to treat a specific condition. Ten of the 15 CAM modalities were used primarily for treatment by African-Americans. CAM for treatment was significantly (P<.05) associated with the following factors: graduate education, smaller family size, higher income, region (northeast, midwest, west more likely than south), depression/anxiety, more physician visits, less likely to engage in preventive care, more frequent exercise behavior, more activities of daily living (ADL) limitations, and neck pain. Twenty percent of African-Americans who used CAM in the past year were treating a specific condition. Alternative medical systems, manipulative and body-based therapies, and folk medicine, prayer, biofeedback, and energy/Reiki were used most often. Health care

  9. Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids.

    PubMed

    Mourad, Michel; Mourad, Georges; Wallemacq, Pierre; Garrigue, Valérie; Van Bellingen, Christophe; Van Kerckhove, Valérie; De Meyer, Martine; Malaise, Jacques; Eddour, Djamila Chaib; Lison, Dominique; Squifflet, Jean Paul; Haufroid, Vincent

    2005-10-15

    CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.

  10. Complementary and alternative medicine for the treatment of bronchiolitis in infants: A systematic review.

    PubMed

    Kua, Kok Pim; Lee, Shaun Wen Huey

    2017-01-01

    Bronchiolitis is a common cause of hospitalization among infants. The limited effectiveness of conventional medication has prompted the use of complementary and alternative medicine (CAM) as alternative or adjunctive therapy for the management of bronchiolitis. To determine the effectiveness and safety of CAM for the treatment of bronchiolitis in infants aged less than 2 years. A systematic electronic search was performed in Medline, Embase, CINAHL, AMED, and Cochrane Central Register of Controlled Trials (CENTRAL) from their respective inception to June 30, 2016 for studies evaluating CAM as an intervention to treat bronchiolitis in infants (1 month to 2 years of age). The CAM could be any form of treatment defined by the National Center for Complementary and Integrative Health (NCCIH) and was utilized either as a single agent or adjunctive therapy. The predefined primary outcome was length of hospital stay. Secondary outcomes were time to resolution of bronchiolitis symptoms, adverse events, and all other clinical outcomes reported by the included studies. The review identified 11 studies (8 randomized controlled trials and 3 cohort studies) examining four herbal preparations and four supplements used either as adjunctive or alternative therapy for bronchiolitis in 904 infants. Most studies were of moderate quality. Among six studies reporting on length of stay, a significant benefit was found for Chinese herbal medicine compared to ribavirin in one cohort study (n = 66) and vitamin D compared to placebo in one randomized controlled trial (n = 89). Studies of Chinese herbal medicine (4 studies, n = 365), vitamin D (1 study, n = 89), N-acetylcysteine (1 study, n = 100), and magnesium (2 studies, n = 176) showed some benefits with respect to clinical severity scores, oxygen saturation, and other symptoms, although data were sparse for any single intervention and the outcomes assessed and reported varied across studies. Only five studies reported on adverse events

  11. Alternative treatments for adults with attention-deficit hyperactivity disorder (ADHD).

    PubMed

    Arnold, L E

    2001-06-01

    A previous review of alternative treatments (Tx) of ADHD--those other than psychoactive medication and behavioral/psychosocial Tx--was supplemented with an additional literature search focused on adults with ADHD. Twenty-four alternative Tx were identified, ranging in scientific documentation from discrediting controlled studies through mere hypotheses to positive controlled double-blind clinical trials. Many of them are applicable only to a specific subgroup. Although oligoantigenic (few-foods) diets have convincing double-blind evidence of efficacy for a properly selected subgroup of children, they do not appear promising for adults. Enzyme-potentiated desensitization, relaxation/EMG biofeedback, and deleading also have controlled evidence of efficacy. Iron supplementation, magnesium supplementation, Chinese herbals, EEG biofeedback, massage, meditation, mirror feedback, channel-specific perceptual training, and vestibular stimulation all have promising prospective pilot data, many of these tests reasonably controlled. Single-vitamin megadosage has some intriguing pilot trial data. Zinc supplementation is hypothetically supported by systematic case-control data, but no systematic clinical trial. Laser acupuncture has promising unpublished pilot data and may be more applicable to adults than children. Essential fatty acid supplementation has promising systematic case-control data, but clinical trials are equivocal. RDA vitamin supplementation, non-Chinese herbals, homeopathic remedies, and antifungal therapy have no systematic data in ADHD. Megadose multivitamin combinations are probably ineffective for most patients and are possibly dangerous. Simple sugar restriction seems ineffective. Amino acid supplementation is mildly effective in the short term, but not beyond 2-3 months. Thyroid treatment is effective in the presence of documented thyroid abnormality. Some alternative Tx of ADHD are effective or probably effective, but mainly for certain patients. In some

  12. Ecological effects of alternative fuel-reduction treatments: highlights of the National Fire and Fire Surrogate study (FFS)

    Treesearch

    James D. McIver; Scott L. Stephens; James K. Agee; Jamie Barbour; Ralph E. J. Boerner; Carl B. Edminster; Karen L. Erickson; Kerry L. Farris; Christopher J. Fettig; Carl E. Fiedler; Sally Haase; Stephen C. Hart; Jon E. Keeley; Eric E. Knapp; John F. Lehmkuhl; Jason J. Moghaddas; William Otrosina; Kenneth W. Outcalt; Dylan W. Schwilk; Carl N. Skinner; Thomas A. Waldrop; C. Phillip Weatherspoon; Daniel A. Yaussy; Andrew Youngblood; Steve Zack

    2012-01-01

    The 12-site National Fire and Fire Surrogate study (FFS) was a multivariate experiment that evaluated ecological consequences of alternative fuel-reduction treatments in seasonally dry forests of the US. Each site was a replicated experiment with a common design that compared an un-manipulated control, prescribed fire, mechanical and mechanical + fire treatments....

  13. A Behavioral Perspective of Childhood Trauma and Attachment Issues: Toward Alternative Treatment Approaches for Children with a History of Abuse

    ERIC Educational Resources Information Center

    Prather, Walter; Golden, Jeannie A.

    2009-01-01

    Attachment theory provides a useful conceptual framework for understanding trauma and the treatment of children who have been abused. This article examines childhood trauma and attachment issues from the perspective of behavior analysis, and provides a theoretical basis for two alternative treatment models for previously abused children and their…

  14. A synopsis of short-term response to alternative restoration treatments in Sagebrush-Steppe: The SageSTEP Project

    Treesearch

    James McIver; Mark Brunson; Steve Bunting; Jeanne Chambers; Paul Doescher; James Grace; April Hulet; Dale Johnson; Steve Knick; Richard Miller; Mike Pellant; Fred Pierson; David Pyke; Benjamin Rau; Kim Rollins; Bruce Roundy; Eugene Schupp; Robin Tausch; Jason Williams

    2014-01-01

    The Sagebrush Steppe Treatment Evaluation Project (SageSTEP) is an integrated long-term study that evaluates ecological effects of alternative treatments designed to reduce woody fuels and to stimulate the herbaceous understory of sagebrush steppe communities of the Intermountain West. This synopsis summarizes results through 3 yr posttreatment. Woody vegetation...

  15. Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds.

    PubMed

    McLaughlin, Patricia J; Cain, Jarrett D; Titunick, Michelle B; Sassani, Joseph W; Zagon, Ian S

    2017-09-01

    Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex ® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.

  16. Management of acute cough by Zataria multiflora Boiss as an alternative treatment.

    PubMed

    Mahboubi, Mohaddese

    2018-01-01

    Cough, as a defensive reflux mechanism, removes foreign objects and secretions from bronchi and bronchioles of airways. Zataria multiflora is a popular plant for treatment of cough in Iranian traditional medicine. The aim of this review was to evaluate the potency of Z. multiflora as an alternative treatment in management of acute cough and its possible mechanisms of action. Here the authors compiled information about Z. multiflora in the treatment of cough from all accessible resources and books. The results of this investigation showed that there were five clinical studies that evaluated the efficacy of Z. multiflora essential oil or extract alone (n = 1), in combination with Althaea officinalis (n = 2) or Foeniculum vulgare essential oil (n = 1), in the form of syrup (n = 3), oral drop (n = 1) and soft capsule (n = 1), for the treatment of acute cough in comparison with placebo or synthetic drugs (bromhexine, dextromethorphan and clobutinol). All clinical studies confirmed the efficacy of Z. multiflora in the amelioration of acute cough in pediatric (n = 1) and adult patients (n = 4) without any adverse effects. Different mechanisms, such as anti-inflammatory, analgesic, antimicrobial, relaxant and immune-enhancement, may be responsible for the efficacy of Z. multiflora in cough relief. Other clinical trials can be performed with Z. multiflora in combination with ivy leaf extract or primrose root extract on patients with cough. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  17. Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to Prednisone.

    PubMed

    Liu, Chanchan; Gui, Mengcui; Cao, Yayun; Lin, Jing; Li, Yue; Ji, Suqiong; Bu, Bitao

    2017-12-01

    Myasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. Children with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. Fourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P < 0.05), the symptoms were evaluated by the quantitative myasthenia gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P < 0.05, P < 0.05, and P < 0.01, respectively). More importantly, ten (76.9%) patients had completely discontinued prednisone, and the major side effects were nearly reversed. The mean titer of antiacetylcholine receptor antibodies significantly dropped from 1.96±2.62 nmol/L to 0.70±1.04 nmol/L (P < 0.05). No severe adverse events were reported. Our results suggest that tacrolimus is a promising agent for children with refractory myasthenia gravis. Randomized clinical trials are needed to confirm the observation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values.

    PubMed

    Rigo-Bonnin, Raül; Blanco-Font, Aurora; Canalias, Francesca

    2018-05-08

    Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results. The aim of this study was to estimate measurement uncertainty of whole blood mass concentration tacrolimus values obtained by UHPLC-MS/MS using two top-down approaches: the single laboratory validation approach and the proficiency testing approach. For the single laboratory validation approach, we estimated the uncertainties associated to the intermediate imprecision (using long-term internal quality control data) and the bias (utilizing a certified reference material). Next, we combined them together with the uncertainties related to the calibrators-assigned values to obtain a combined uncertainty for, finally, to calculate the expanded uncertainty. For the proficiency testing approach, the uncertainty was estimated in a similar way that the single laboratory validation approach but considering data from internal and external quality control schemes to estimate the uncertainty related to the bias. The estimated expanded uncertainty for single laboratory validation, proficiency testing using internal and external quality control schemes were 11.8%, 13.2%, and 13.0%, respectively. After performing the two top-down approaches, we observed that their uncertainty results were quite similar. This fact would confirm that either two approaches could be used to estimate the measurement uncertainty of whole blood mass concentration tacrolimus values in clinical laboratories. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Using Supercritical Fluid Technology (SFT) in Preparation of Tacrolimus Solid Dispersions.

    PubMed

    Obaidat, Rana M; Tashtoush, Bassam M; Awad, Alaa Abu; Al Bustami, Rana T

    2017-02-01

    Tacrolimus is an immunosuppressant agent that suffers from poor and variable bioavailability. This can be related to limited solubility and dissolution. The main objective of this study is to use SFT to prepare solid dispersions of tacrolimus in order to enhance its dissolution. SFT was selected since it offers several advantages over conventional techniques such as efficiency and stability. Several solid dispersions of tacrolimus were prepared using SFT to enhance its dissolution. The selected polymers included soluplus, PVP, HPMC, and porous chitosan. TPGS was used as a surfactant additive with chitosan, HPMC, and PVP. Soluplus dispersions were used to study the effect of processing parameters (time, temperature, and pressure) on loading efficiency (LE) and dissolution of the preparation. Physicochemical characterization was performed using DSC, X-ray diffraction, FTIR analysis, SEM, and in vitro drug release. Stability testing was evaluated after 3 months for selected dispersions. Significant improvement for the release profile was achieved for the prepared dispersions. Better release achieved in the soluplus dispersions which reached maximum cumulative release equal to 98.76% after 24 h. Drug precipitated in its amorphous form in all prepared dispersions except those prepared from chitosan. All dispersions were physically stable except for PVP preparations that contained TPGS which started to re-crystallize after one month. Prepared dispersions were proved to be affected by supercritical processing parameters. In conclusion, SFT was successfully used to prepare dispersions of tacrolimus that exhibited higher dissolution than raw drug. Dissolution rate and stability are affected by the type of the polymer.

  20. Comparison of alternative flue gas dry treatment technologies in waste-to-energy processes.

    PubMed

    Dal Pozzo, Alessandro; Antonioni, Giacomo; Guglielmi, Daniele; Stramigioli, Carlo; Cozzani, Valerio

    2016-05-01

    Acid gases such as HCl and SO2 are harmful both for human health and ecosystem integrity, hence their removal is a key step of the flue gas treatment of Waste-to-Energy (WtE) plants. Methods based on the injection of dry sorbents are among the Best Available Techniques for acid gas removal. In particular, systems based on double reaction and filtration stages represent nowadays an effective technology for emission control. The aim of the present study is the simulation of a reference two-stage (2S) dry treatment system performance and its comparison to three benchmarking alternatives based on single stage sodium bicarbonate injection. A modelling procedure was applied in order to identify the optimal operating configuration of the 2S system for different reference waste compositions, and to determine the total annual cost of operation. Taking into account both operating and capital costs, the 2S system appears the most cost-effective solution for medium to high chlorine content wastes. A Monte Carlo sensitivity analysis was carried out to assess the robustness of the results. Copyright © 2016. Published by Elsevier Ltd.

  1. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  2. Laser-mediated Photodynamic Therapy: An Alternative Treatment for Actinic Keratosis?

    PubMed

    Kessels, Janneke P H M; Nelemans, Patty J; Mosterd, Klara; Kelleners-Smeets, Nicole W J; Krekels, Gertruud A M; Ostertag, Judith U

    2016-03-01

    Photodynamic therapy (PDT) with light emitting diode (LED) illumination is a frequently used treatment modality for actinic keratosis (AK) with excellent cosmetic outcome. A major disadvantage, however, is the high pain score. Pulsed dye laser (PDL) illumination has been suggested, but the long-term efficacy of this treatment is unknown. In this split-face study we prospectively treated 61 patients with AK, with both LED-PDT and PDL-PDT. The mean change in the number of lesions between the end of follow-up and start of therapy was -4.25 (95% confidence interval (95% CI) -5.07; -3.43) for LED-PDT and -3.88 (95% CI -4,76; -2.99) for PDL-PDT, with a non-significant difference (p = 0.258) of -0.46 (95% CI -1.28; 0.35). The percentage decrease from baseline in the total number of AK was 55.8% and 47.8%, respectively, at 12-month follow-up. Visual analogue scale pain score was lower after PDL (mean 2.64) compared with LED illumination (mean 6.47). These findings indicate that PDL-PDT is an effective alternative illumination source fo.

  3. Hepatotoxic microcystin removal using pumice embedded monolithic composite cryogel as an alternative water treatment method.

    PubMed

    Gurbuz, Fatma; Ceylan, Şeyda; Odabaşı, Mehmet; Codd, Geoffrey A

    2016-03-01

    Microcystins are the most commonly encountered water-borne cyanotoxins which present short- and long-term risks to human health. Guidelines at international and national level, and legislation in some countries, have been introduced for the effective health risk management of these potent hepatotoxic, tumour-promoters. The stable cyclic structure of microcystins and their common production by cyanobacteria in waterbodies at times of high total dissolved organic carbon content presents challenges to drinking water treatment facilities, with conventional, advanced and novel strategies under evaluation. Here, we have studied the removal of microcystins using three different forms of pumice particles (PPs), which are embedded into macroporous cryogel columns. Macroporous composite cryogel columns (MCCs) are a new generation of separation media designed to face this challenging task. Three different MCCs were prepared by adding plain PPs, Cu(2+)-attached PPs and Fe(3+)-attached PPs to reaction media before the cryogelation step. Column studies showed that MCCs could be successfully used as an alternative water treatment method for successful microcystin removal. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Treatment of PVC using an alternative low energy ion bombardment procedure

    NASA Astrophysics Data System (ADS)

    Rangel, Elidiane C.; dos Santos, Nazir M.; Bortoleto, José Roberto R.; Durrant, Steven F.; Schreiner, Wido H.; Honda, Roberto Y.; Rangel, Rita de Cássia C.; Cruz, Nilson C.

    2011-12-01

    In many applications, polymers have progressively substituted traditional materials such as ceramics, glasses, and metals. Nevertheless, the use of polymeric materials is still limited by their surface properties. Frequently, selective modifications are necessary to suit the surface to a given application. Amongst the most common treatments, plasma immersion ion implantation (PIII) has attracted the attention of many researchers owing to its versatility and practicality. This method, however, requires a power supply to provide high voltage (tens of kV) negative pulses, with a controlled duty cycle, width and frequency. Owing to this, the implementation of PIII on the industrial scale can become economically inviable. In this work, an alternative plasma treatment that enables low energy ion bombardment without the need of a high voltage pulse generator is presented. To evaluate the efficiency of the treatment of polymers, polyvinylchloride, PVC, specimens were exposed to 5 Pa argon plasmas for 3600 s, at excitation powers, P, of between 10 and 125 W. Through contact angle and atomic force microscopy data, the influence of P on the wettability, surface free energy and roughness of the samples was studied. Surface chemical composition was measured by X-ray photoelectron spectroscopy, XPS. To evaluate the effect of aging under atmospheric conditions, contact angle and XPS measurements were performed one and 1334 days after the treatment. The plasma potential and ion density around the driven electrode were determined from Langmuir probe measurements while the self-bias potential was derived with the aid of an oscilloscope. From these data it was possible to estimate the mean energy of ions bombarding the PVC surface. Chlorine, carbon and oxygen contamination were detected on the surface of the as-received PVC. Upon exposure to the plasma, the proportion of chlorine was observed to decrease while that of oxygen increased. Consequently, the wettability and surface energy

  5. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years.

    PubMed

    Gonwa, Thomas; Johnson, Christopher; Ahsan, Nasimul; Alfrey, Edward J; Halloran, Philip; Stegall, Mark; Hardy, Mark; Metzger, Robert; Shield, Charles; Rocher, Leslie; Scandling, John; Sorensen, John; Mulloy, Laura; Light, Jimmy; Corwin, Claudia; Danovitch, Gabriel; Wachs, Michael; VanVeldhuisen, Paul; Leonhardt, Maryanne; Fitzsimmons, William E

    2003-06-27

    Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), or cyclosporine (Neoral; CsA) + MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years. The results at 3 years corroborate and extend the findings of the 2-year results. Patients with DGF treated with TAC+MMF experienced an increase in 3-year allograft survival compared with patients receiving CsA+MMF (84.1% vs. 49.9%, P=0.02). Patients randomized to either treatment arm containing TAC exhibited numerically superior kidney function when compared with CsA. During the 3 years, new-onset insulin dependence occurred in 6, 3, and 11 patients in the TAC+MMF, CsA+MMF, and TAC+AZA treatment arms, respectively. Furthermore, patients randomized to TAC+MMF received significantly lower doses of MMF as compared with those who received CsA+MMF. All three immunosuppressive regimens provided excellent safety and efficacy. However, the best results overall were achieved with TAC+MMF. The combination may provide particular benefit to kidney allograft recipients with DGF. In patients who experienced DGF, graft survival was better at 3 years in those patients receiving TAC in combination with either MMF or AZA as compared with the patients receiving CsA with MMF.

  6. Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models

    PubMed Central

    Shen, Xiujin; Jiang, Hong; Ying, Meike; Xie, Zhoutao; Li, Xiayu; Wang, Haibing; Zhao, Jie; Lin, Chuan; Wang, Yucheng; Feng, Shi; Shen, Jia; Weng, Chunhua; Lin, Weiqiang; Wang, Huiping; Zhou, Qin; Bi, Yan; Li, Meng; Wang, Lingyan; Zhu, Tongyu; Huang, Xiaoru; Lan, Hui-Yao; Zhou, Jing; Chen, Jianghua

    2016-01-01

    Podocyte injury and the appearance of proteinuria are features of minimal-change disease (MCD). Cyclosporin A (CsA) and tacrolimus (FK506) has been reported to reduce proteinuria in patients with nephrotic syndrome, but mechanisms remain unknown. We, therefore, investigated the protective mechanisms of CsA and FK506 on proteinuria in a rat model of MCD induced by puromycin aminonucleoside (PAN) and in vitro cultured mouse podocytes. Our results showed that CsA and FK506 treatment decreased proteinuria via a mechanism associated to a reduction in the foot-process fusion and desmin, and a recovery of synaptopodin and podocin. In PAN-treated mouse podocytes, pre-incubation with CsA and FK506 restored the distribution of the actin cytoskeleton, increased the expression of synaptopodin and podocin, improved podocyte viability, and reduced the migrating activities of podocytes. Treatment with CsA and FK506 also inhibited PAN-induced podocytes apoptosis, which was associated with the induction of Bcl-xL and inhibition of Bax, cleaved caspase 3, and cleaved PARP expression. Further studies revealed that CsA and FK506 inhibited PAN-induced p38 and JNK signaling, thereby protecting podocytes from PAN-induced injury. In conclusion, CsA and FK506 inhibit proteinuria by protecting against PAN-induced podocyte injury, which may be associated with inhibition of the MAPK signaling pathway. PMID:27580845

  7. Dried blood spot measurement: application in tacrolimus monitoring using limited sampling strategy and abbreviated AUC estimation.

    PubMed

    Cheung, Chi Yuen; van der Heijden, Jaques; Hoogtanders, Karin; Christiaans, Maarten; Liu, Yan Lun; Chan, Yiu Han; Choi, Koon Shing; van de Plas, Afke; Shek, Chi Chung; Chau, Ka Foon; Li, Chun Sang; van Hooff, Johannes; Stolk, Leo

    2008-02-01

    Dried blood spot (DBS) sampling and high-performance liquid chromatography tandem-mass spectrometry have been developed in monitoring tacrolimus levels. Our center favors the use of limited sampling strategy and abbreviated formula to estimate the area under concentration-time curve (AUC(0-12)). However, it is inconvenient for patients because they have to wait in the center for blood sampling. We investigated the application of DBS method in tacrolimus level monitoring using limited sampling strategy and abbreviated AUC estimation approach. Duplicate venous samples were obtained at each time point (C(0), C(2), and C(4)). To determine the stability of blood samples, one venous sample was sent to our laboratory immediately. The other duplicate venous samples, together with simultaneous fingerprick blood samples, were sent to the University of Maastricht in the Netherlands. Thirty six patients were recruited and 108 sets of blood samples were collected. There was a highly significant relationship between AUC(0-12), estimated from venous blood samples, and fingerprick blood samples (r(2) = 0.96, P < 0.0001). Moreover, there was an excellent correlation between whole blood venous tacrolimus levels in the two centers (r(2) = 0.97; P < 0.0001). The blood samples were stable after long-distance transport. DBS sampling can be used in centers using limited sampling and abbreviated AUC(0-12) strategy as drug monitoring.

  8. Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation.

    PubMed

    Fukazawa, Kyota; Nishida, Seigo; Aguina, Luz; Pretto, Ernesto

    2011-01-01

    Central pontine myelinolysis (CPM) is the most detrimental neurologic complication after liver transplantation. The incidence of CPM after liver transplantation ascends to 17%. Although the precise etiology and pathogenesis of CPM is largely unknown, a growing literature implicates a possible role of immunosuppressive agents, such as Cyclosporine (incidence 30%) on its development. Other immunosuppressive agents also can cause CPM but the frequency of these cases is less compared to Cyclosporine. There is only one case report for Tacrolimus (FK506)-associated speech disorder, which might be an atypical presentation of CPM, and no case reports for Rapamycin. We present a case of Tacrolimus induced CPM. A 62-year-old woman who underwent liver transplantation developed clinical symptoms with radiologic evidence consistent with CPM 7 days after liver transplant. Since the electrolytes in this patient remained normal from her admission, the hypothesis of inmunossupressor neurotoxicity was established and the therapy was switched, resulting in an evident clinical and radiological improvement of her condition in the following days. Five months later, the patient's only neurological deficit was slight dysarthria and a follow-up MRI showed no abnormalities. This case provides evidence of Tacrolimus-associated CPM after transplantation, which presented with a classic "lock-in syndrome" with radiographic confirmation.

  9. Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate.

    PubMed

    Park, Young-Joon; Ryu, Dong-Sung; Li, Dong Xun; Quan, Qi Zhe; Oh, Dong Hoon; Kim, Jong Oh; Seo, Youn Gee; Lee, Young-Im; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2009-06-01

    To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.

  10. Physical and microbiological stability of an extemporaneous tacrolimus suspension for paediatric use.

    PubMed

    Han, J; Beeton, A; Long, P F; Wong, I; Tuleu, C

    2006-04-01

    An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. Suspensions (0.5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22-26 degrees C and evaluated weekly. The volume mean diameter d((4,3)) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.

  11. Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

    NASA Astrophysics Data System (ADS)

    Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

    2017-02-01

    Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

  12. Perceived treatment effectiveness, medication compliance, and complementary and alternative medicine use among veterans with bipolar disorder.

    PubMed

    Jarman, Christopher N; Perron, Brian E; Kilbourne, Amy M; Teh, Carrie Farmer

    2010-03-01

    Recent research shows a high rate of complementary and alternative medicine (CAM) use among persons with mental disorders, although correlates and patterns of CAM use are relatively unknown. This study tested whether CAM use is associated with perceived effectiveness of conventional treatment (i.e., psychotropic medication and psychotherapy) and medication compliance among persons with bipolar disorder. Patients with bipolar disorder (n = 435) were included as part of a naturalistic cohort study. Measures of CAM utilization, medication compliance, and perceptions of the effectiveness of psychotropic medications and psychotherapy were based on previously established questionnaires. Associations were tested using bivariate and multivariate analyses. Bivariate analyses showed that patients who did not perceive psychotherapy as effective at improving social, family, or job functioning reported greater CAM use. However, medication compliance was not significantly associated with use of CAM. Patients who used oral (e.g., herbal therapies) or cognitive (e.g., meditation) CAM were more likely to report that their medications were not effective at relieving manic or depressive symptoms. Users of cognitive CAM were more likely to report that their medications did not help with social, job, or family functioning, and that they did not prevent recurrences of manic or depressive episodes. None of the bivariate associations remained significant in multivariate analyses. Prior research has suggested that persons who are dissatisfied with treatment for medical conditions are more likely to use CAM therapies. However, the results of this study do not show CAM therapies to be associated with perceived effectiveness of treatments for mental health problems among this sample of persons with serious mental illnesses. This suggests that motivations for CAM use may vary by population and condition. Because few correlates of CAM use among persons with serious mental illnesses are known

  13. Seasonal pathogen removal by alternative on-site wastewater treatment systems.

    PubMed

    Pundsack, J; Axler, R; Hicks, R; Henneck, J; Nordman, D; McCarthy, B

    2001-01-01

    Subsurface-flow constructed wetlands, sand filters, and peat filters near Duluth, Minnesota, were studied to determine their seasonal performance for removing pathogens from wastewater. Influent was a high-strength septic tank effluent (mean values of 5-day biochemical oxygen demand, total nitrogen, and total phosphorus were 294, 96, and 15 mg/L, respectively) at the Natural Resources Research Institute's alternative treatment system test facility in northern Minnesota. Each treatment system was inoculated with cultures of Salmonella choleraesuis (serotype typhimurium) for 5 to 7 consecutive days in summer and winter during 1998 to 1999. After the seeding, outflow samples were taken until Salmonella counts were sustained at background levels. The removal of Salmonella was calculated for each system, although the exact removal mechanisms were not determined. During the summer, the wetlands removed 99.6 to 99.999 4% (2.4 to 5.3 log10 reduction) of the culturable Salmonella. The sand filters demonstrated a greater than 7 log10 removal of Salmonella cells, whereas the peat filters were responsible for a greater than 8 log10 loss of cells. Fewer Salomonella cells were removed by all of these systems during the winter, although the pattern of removal was similar to their summer operation. During the winter, the wetlands and sand filters removed greater than 1 log10 of culturable cells, but the peat filters were responsible for a greater than 5 log10 loss of cells. Fecal coliform removal patterns reflected those for Salmonella by treatment systems for summer and winter periods. Based on Salmonella and fecal coliform removal, the peat filters operated most effectively followed by the sand filters and the constructed wetlands.

  14. Regenerative medicine provides alternative strategies for the treatment of anal incontinence.

    PubMed

    Gräs, Søren; Tolstrup, Cæcilie Krogsgaard; Lose, Gunnar

    2017-03-01

    Anal incontinence is a common disorder but current treatment modalities are not ideal and the development of new treatments is needed. The aim of this review was to identify the existing knowledge of regenerative medicine strategies in the form of cellular therapies or bioengineering as a treatment for anal incontinence caused by anal sphincter defects. PubMed was searched for preclinical and clinical studies in English published from January 2005 to January 2016. Animal studies have demonstrated that cellular therapy in the form of local injections of culture-expanded skeletal myogenic cells stimulates repair of both acute and 2 - 4-week-old anal sphincter injuries. The results from a small clinical trial with ten patients and a case report support the preclinical findings. Animal studies have also demonstrated that local injections of mesenchymal stem cells stimulate repair of sphincter injuries, and a complex bioengineering strategy for creation and implantation of an intrinsically innervated internal anal sphincter construct has been successfully developed in a series of animal studies. Cellular therapies with myogenic cells and mesenchymal stem cells and the use of bioengineering technology to create an anal sphincter are new potential strategies to treat anal incontinence caused by anal sphincter defects, but the clinical evidence is extremely limited. The use of culture-expanded autologous skeletal myogenic cells has been most intensively investigated and several clinical trials were ongoing at the time of this report. The cost-effectiveness of such a therapy is an issue and muscle fragmentation is suggested as a simple alternative.

  15. [Treatment adherence and use of complementary and alternative medicine in patients with inflammatory bowel disease].

    PubMed

    Lakatos, László; Czeglédi, Zsófia; Dávid, Gyula; Kispál, Zsófi; Kiss, Lajos S; Palatka, Károly; Kristóf, Tünde; Molnár, Tamás; Salamon, Agnes; Demeter, Pál; Miheller, Pál; Szamosi, Tamás; Banai, János; Papp, Mária; Bene, László; Kovács, Agota; Rácz, István; Lakatos, Péter László

    2010-02-14

    Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence the use of CAM in Hungarian patients with IBD. A total of 655 consecutive IBD patients (Crohn's disease [CD]: 344, age: 38.2 + or - 12.9 years; ulcerative colitis [UC]: 311, age: 44.9 + or - 15.3 years) were interviewed during the visit at specialists by self-administered questionnaire including demographic and disease-related data, as well as items analyzing the extent of non-adherence and CAM use. Patients taking more then 80% of each prescribed medicine were classified as adherent. The overall rate of self reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use was not different between CD and UC. The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tee (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy. Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship.

  16. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases.

    PubMed

    Langhorst, J; Wulfert, H; Lauche, R; Klose, P; Cramer, H; Dobos, G J; Korzenik, J

    2015-01-01

    We performed a systematic review for Complementary and Alternative Medicine [CAM] as defined by the National Institute of Health in Inflammatory Bowel Disease [IBD], ie Crohn's disease [CD] and ulcerative colitis [UC], with the exception of dietary and nutritional supplements, and manipulative therapies. A computerized search of databases [Cochrane Library, Pubmed/Medline, PsychINFO, and Scopus] through March 2014 was performed. We screened the reference sections of original studies and systematic reviews in English language for CAM in IBD, CD and UC. Randomized controlled trials [RCT] and controlled trials [CT] were referred and assessed using the Cochrane risk of bias tool. A total of: 26 RCT and 3 CT for herbal medicine, eg aloe-vera gel, andrographis paniculata, artemisia absinthium, barley foodstuff, boswellia serrata, cannabis, curcumin, evening primrose oil, Myrrhinil intest®, plantago ovata, silymarin, sophora, tormentil, wheatgrass-juice and wormwood; 1 RCT for trichuris suis ovata; 7 RCT for mind/body interventions such as lifestyle modification, hypnotherapy, relaxation training and mindfulness; and 2 RCT in acupuncture; were found. Risk of bias was quite heterogeneous. Best evidence was found for herbal therapy, ie plantago ovata and curcumin in UC maintenance therapy, wormwood in CD, mind/body therapy and self-intervention in UC, and acupuncture in UC and CD. Complementary and alternative therapies might be effective for the treatment of inflammatory bowel diseases; however, given the low number of trials and the heterogeneous methodological quality of trials, further in-depth research is necessary. Copyright © 2014 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. Hypericin-photodynamic therapy (PDT) using an alternative treatment regime suitable for multi-fraction PDT.

    PubMed

    Thong, Patricia Soo-Ping; Watt, Frank; Ren, Min Qin; Tan, Puay Hoon; Soo, Khee Chee; Olivo, Malini

    2006-01-02

    Photodynamic therapy (PDT) outcome depends on the conditions under which it is carried out. Maintaining the tumour tissue oxygen level is important for PDT efficacy and using a low fluence rate can improve outcome. In this work we studied the response of human nasopharyngeal carcinoma tumours in murine models to hypericin-PDT carried out under low fluence and fluence rate. A drug-light interval (DLI) of 1h or 6h was used for 1h-PDT and 6h-PDT, respectively. Evan's blue test was used to assess necrosis and TUNEL staining for apoptosis. Nuclear microscopy was used to quantify elemental concentrations in tumours. Serum vascular endothelial growth factor (VEGF) levels were also determined. TUNEL results showed that 6h-PDT induced significantly more apoptosis compared to 1h-PDT (p<0.01). This was supported by nuclear microscopy showing an increase in calcium and a decrease in zinc levels (both known triggers of apoptosis) in 6h-PDT tumours compared to non-PDT tumours (p<0.05). These results further imply a zinc-mediated pathway in hypericin-PDT induced apoptosis. 6h-PDT also resulted in a significant increase in copper concentrations compared to non-PDT tumours (p<0.05). Serum VEGF levels measured after 6h-PDT were lower than those obtained after 1h-PDT. Overall tumour response to hypericin-PDT under low fluence and fluence rate and using a 6h DLI showed increased apoptosis and lower serum VEGF levels. This treatment regime is suitable for the alternative approach of multi-fraction PDT in which the tumour can be exposed to multiple PDT fractions for complete tumour response. This alternative approach might yield improved outcome.

  18. De novo use of a generic formulation of tacrolimus versus reference tacrolimus in kidney transplantation: evaluation of the clinical results, histology in protocol biopsies, and immunological monitoring.

    PubMed

    Melilli, Edoardo; Crespo, Elena; Sandoval, Diego; Manonelles, Anna; Sala, Neus; Mast, Richard; Padulles, Ariadna; Grinyo, Josep M; Bestard, Oriol; Cruzado, Josep Maria

    2015-11-01

    The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor-specific antibody) was found between the two groups. © 2015 Steunstichting ESOT.

  19. SLUDGE TREATMENT PROJECT PHASE 1 SLUDGE STORAGE OPTIONS ASSESSMENT OF T PLANT VERSUS ALTERNATE STORAGE FACILITY

    SciTech Connect

    RUTHERFORD WW; GEUTHER WJ; STRANKMAN MR

    2009-04-29

    The CH2M HILL Plateau Remediation Company (CHPRC) has recommended to the U.S. Department of Energy (DOE) a two phase approach for removal and storage (Phase 1) and treatment and packaging for offsite shipment (Phase 2) of the sludge currently stored within the 105-K West Basin. This two phased strategy enables early removal of sludge from the 105-K West Basin by 2015, allowing remediation of historical unplanned releases of waste and closure of the 100-K Area. In Phase 1, the sludge currently stored in the Engineered Containers and Settler Tanks within the 105-K West Basin will be transferred into sludge transportmore » and storage containers (STSCs). The STSCs will be transported to an interim storage facility. In Phase 2, sludge will be processed (treated) to meet shipping and disposal requirements and the sludge will be packaged for final disposal at a geologic repository. The purpose of this study is to evaluate two alternatives for interim Phase 1 storage of K Basin sludge. The cost, schedule, and risks for sludge storage at a newly-constructed Alternate Storage Facility (ASF) are compared to those at T Plant, which has been used previously for sludge storage. Based on the results of the assessment, T Plant is recommended for Phase 1 interim storage of sludge. Key elements that support this recommendation are the following: (1) T Plant has a proven process for storing sludge; (2) T Plant storage can be implemented at a lower incremental cost than the ASF; and (3) T Plant storage has a more favorable schedule profile, which provides more float, than the ASF. Underpinning the recommendation of T Plant for sludge storage is the assumption that T Plant has a durable, extended mission independent of the K Basin sludge interim storage mission. If this assumption cannot be validated and the operating costs of T Plant are borne by the Sludge Treatment Project, the conclusions and recommendations of this study would change. The following decision-making strategy

  20. [Effects of ciclosporin and tacrolimus on replication of hepatitis B virus in vitro: a comparative study].

    PubMed

    Xia, Wei-liang; Xie, Hai-yang; Shen, Yan; Wu, Li-ming; Zhang, Feng; Zheng, Shu-sen

    2006-01-10

    To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506) on replication of hepatitis B virus (HBV) in vitro. HBV genome permanently transfected human liver cancer cells of the line HepG2.2.15 were cultured. CsA and FK506 at different concentrations were added into the culture fluid so as to identify the nontoxic concentrations by MTT method. Then the HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic concentrations respectively for 4 days. ELISA was used to detect the HB surface antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative replication level of HBV DNA was detected by slot blot analysis. MTT method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0 microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group, the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/- 9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%, 11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P > 0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic concentrations showed no significant inhibitory effect on the levels of HBsAg, HBeAg, and HBV DNA. CsA dose-dependently inhibits the HBV replication in vitro, and FK506 does not exercise similar effects.

  1. Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment.

    PubMed

    Wu, Haotian; Olmsted, Alexandra; Cantonwine, David E; Shahsavari, Shahin; Rahil, Tayyab; Sites, Cynthia; Pilsner, J Richard

    2017-02-01

    Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment. Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015. In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males. Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Environmental Manipulations as an Effective Alternative Treatment to Reduce Endometriosis Progression.

    PubMed

    Torres-Reverón, Annelyn; Rivera, Leslie L; Flores, Idhaliz; Appleyard, Caroline B

    2017-01-01

    Treatments for endometriosis include pharmacological or surgical procedures that produce significant side effects. We aimed to determine how environmental enrichment (EE) could impact the progression of endometriosis using the autotransplantation rat model. Female rats were exposed to EE (endo-EE: toys and nesting materials, 4 rats per cage, larger area enclosure) or no enrichment (endo-NE: 2 rats per cage) starting on postnatal day 21. After 8 weeks, sham surgery or surgical endometriosis was induced by suturing uterine horn tissue next to the intestinal mesentery, then allowed to progress for 60 days during which EE or NE continued. At the time of killing, we measured anxiety behaviors, collected endometriotic vesicles and uterus, and processed for quantitative real-time polymerase chain reaction for corticotropin-releasing hormone (CRH), urocortin-1, CRH receptors type 1 and type 2, and glucocorticoid receptor (GR). Endometriosis did not affect anxiety-like behaviors, yet rats in enriched conditions showed lower basal anxiety behaviors than the nonenriched group. Importantly, the endo-EE group showed a 28% reduction in the number of endometriosis vesicles and the vesicles were significantly smaller compared to the endo-NE group. Endometriosis increased CRH and GR only in the vesicles of endo-NE, and this increase was dampened in the endo-EE. However, urocortin 1 was increased in the vesicles of the endo-EE group, suggesting different pathways of activation of CRH receptors in this group. Our results suggest that the use of multimodal complementary therapies that reduce stress in endometriosis could be an effective and safe treatment alternative, with minimal side effects.

  3. Laser ablation therapy: An alternative treatment for medically resistant mesial temporal lobe epilepsy after age 50.

    PubMed

    Waseem, Hena; Osborn, Katie E; Schoenberg, Mike R; Kelley, Valerie; Bozorg, Ali; Cabello, Daniel; Benbadis, Selim R; Vale, Fernando L

    2015-10-01

    Selective anterior mesial temporal lobe (AMTL) resection is considered a safe and effective treatment for medically refractory mesial temporal lobe epilepsy (MTLE). However, as with any open surgical procedure, older patients (aged 50+) face greater risks. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has shown recent potential as an alternative treatment for MTLE. As a less invasive procedure, MRgLITT could be particularly beneficial to older patients. To our knowledge, no study has evaluated the safety and efficacy of MRgLITT in this population. Seven consecutive patients (aged 50+) undergoing MRgLITT for MTLE were followed prospectively to assess surgical time, complications, postoperative pain control, length of stay (LOS), operating room (OR) charges, total hospitalization charges, and seizure outcome. Five of these patients were assessed at the 1-year follow-up for seizure outcome. These data were compared with data taken from 7 consecutive patients (aged 50+) undergoing AMTL resection. Both groups were of comparable age (mean: 60.7 (MRgLITT) vs. 53 (AMTL)). One AMTL resection patient had a complication of aseptic meningitis. One MRgLITT patient experienced an early postoperative seizure, and two MRgLITT patients had a partial visual field deficit. Seizure-freedom rates were comparable (80% (MRgLITT) and 100% (AMTL) (p>0.05)) beyond 1year postsurgery (mean follow-up: 1.0years (MRgLITT) vs. 1.8years (AMTL)). Mean LOS was shorter in the MRgLITT group (1.3days vs. 2.6days (p<0.05)). Neuropsychological outcomes were comparable. Short-term follow-up suggests that MRgLITT is safe and provides outcomes comparable to AMTL resection in this population. It also decreases pain medication requirement and reduces LOS. Further studies are necessary to assess the long-term efficacy of the procedure. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. A narrative review of medical, chiropractic, and alternative health practices in the treatment of primary dysmenorrhea

    PubMed Central

    Spears, Lolita G.

    2005-01-01

    Abstract Objective Primary dysmenorrhea and related issues are discussed as they influence the gynecological and social health of females during adolescence, adulthood, and senior maturity. Health practitioners are exposed to multiple approaches towards the management of menstrual pain. Clinical and social viewpoints target the causation, development, diagnosis, manifestation and management of primary dysmenorrhea. This narrative review includes the topic of the doctor-patient relationship in efforts of cultivating effectively communicative health practitioners. Controversial topics related to primary dysmenorrhea and the quality of life for women are addressed. Data Sources A search for literature reviews, case studies, laboratory research, and clinical trials from 1985–2004 was performed using the MEDLINE database. Sources of additional information included textbooks, national organizational literature and contemporary articles. Discussion Menstrual pain is a prevalent experience yet it is socially taboo for conversation; as such, it poses a hindrance to its management. The communication between the doctor and patient is a critical barrier point between establishing a diagnosis and determining an appropriate treatment plan. A multi-disciple treatment plan varies as much as patients themselves vary in personal experiences, needs, and preferences. Conclusions Medicinal prophylactics, physical therapeutics, non-acidic diets, herbal supplements, eastern therapies and the chiropractic manual adjustments of the spine are effective methods for the management of primary dysmenorrhea. The non-invasive management of primary dysmenorrhea includes the chiropractic adjustment with complimentary modalities, and other alternative health care practices. Medicinal prophylactics are invasive and pose a higher risk to long-term chemical exposure, side effects or irreversible conditions. PMID:19674650

  5. Metoclopramide for Acute Migraine Treatment in the Emergency Department: An Effective Alternative to Opioids.

    PubMed

    Najjar, Mejdi; Hall, Tyler; Estupinan, Blanca

    2017-04-20

    In light of recent warnings by the United States (US) Surgeon General and Centers for Disease Control (CDC) guidelines for recommending more prudent use of opioid narcotics, the search for a non-opioid alternative for aborting acute migraines is particularly relevant. The CDC also estimates the prevalence of opioid dependence may be as high as 26% among patients prescribed opioids for chronic pain, not due to cancer, in the primary care setting. Given such staggering data, it is imperative that we, as caretakers, not foster opioid dependence but rather continue to investigate non-opioid therapies for the management of acute migraines in the emergent care settings. Our literature review demonstrates that metoclopramide should be used more frequently as first-line therapy for an acute migraine over opioids. The use of opioids specifically has been discouraged as migraine treatment by the American Headache Society citing "insufficient evidence" as the main reason. Metoclopramide, specifically using the 10 mg dose, has been cited as "highly likely to be effective" by the same guidelines. Another major issue with opioids is the growing potential for abuse, thus minimizing the use of these drugs for only special circumstances would be beneficial overall.

  6. [COCONUT OIL: NON-ALTERNATIVE DRUG TREATMENT AGAINST ALZHEIMER´S DISEASE].

    PubMed

    Hu Yang, Iván; De la Rubia Ortí, Jose Enrique; Selvi Sabater, Pablo; Sancho Castillo, Sandra; Rochina, Mariano Julián; Manresa Ramón, Noemí; Montoya-Castilla, Inmaculada

    2015-12-01

    Alzheimer's dementia is the most prevalent nowadays. As for treatment, there is no definitive cure drug, thus new therapies are needed. In this regard the medium chain triglycerides are a direct source of cellular energy and can be a nonpharmacological alternative to the neuronal death for lack of it, that occurs in Alzheimer patients. to evaluate the impact of coconut oil in the development of Alzheimer's dementia, in any degree of dementia. Also determine whether this improvement influences within variables such as sex and suffering or not Type II Diabetes Mellitus. a prospective study was conducted in patients with Alzheimer's dementia, with a control and an intervention group which was administered 40 ml/day of extra virgin coconut oil. The parameters evaluated were the mini test scores Lobo cognitive test, pre and post intervention in both groups. it was observed in subjects taking the product, a statistically significant increase in test score MECWOLF and therefore an improvement in cognitive status, improving especially women's, those without diabetes mellitus type II, and severe patients. this study, although preliminary, demonstrated the positive influence of coconut oil at the cognitive level of patients with Alzheimer's, this improvement being dependent on sex, presence or absence of diabetes and degree of dementia. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  7. Rhodomyrtus tomentosa (Aiton) Hassk. leaf extract: An alternative approach for the treatment of staphylococcal bovine mastitis.

    PubMed

    Mordmuang, Auemphon; Voravuthikunchai, Supayang Piyawan

    2015-10-01

    Antibiotic residues in dairy products as well as emergence of antimicrobial resistance in foodborne pathogens have been recognized as global public health concerns. The present work was aimed to study a potent antibacterial extract from natural product as an alternative treatment for staphylococcal bovine mastitis. Staphylococcal isolates (n=44) were isolated from milk samples freshly squeezed from individual cows. All staphylococcal isolates were resistant to ampicillin, ciprofloxacin, erythromycin, gentamicin, penicillin, except vancomycin. Rhodomyrtus tomentosa leaf ethanolic extract was accessed for its antibacterial activity and anti-inflammatory potential. The extract exhibited profound antibacterial activity against all of staphylococcal isolates with MIC and MBC values ranged from 16-64 μg/ml and 64->128 μg/ml, respectively. Moreover, the extract also exerted anti-protein denaturation and human red blood cell membrane stabilizing activity. The results support the use of R. tomentosa extract that could be applied to cure bovine mastitis and to reduce inflammatory injury caused by the bacterial infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Alternatives to lithium and divalproex in the maintenance treatment of bipolar disorder.

    PubMed

    Gnanadesikan, Mukund; Freeman, Marlene P; Gelenberg, Alan J

    2003-06-01

    The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

  9. Native ureteropyelostomy in the treatment of obstructive uropathy in adult renal transplant. Experience and technical alternatives.

    PubMed

    Trilla, E; Lorente, D; Salvador, C; Planas, J; Placer, J; Celma, A; Cantarell, C; Moreso, F; Seron, D; Morote, J

    2014-10-01

    To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  10. An alternative method in mandibular fracture treatment: bone graft use instead of a plate.

    PubMed

    Alagöz, Murat Sahin; Uysal, Ahmet Cagri; Sensoz, Omer

    2008-03-01

    In the treatment of the mandibular fractures, one of the main principles is to use the least amount of foreign material. We present an alternative technique that the bone grafts harvested from the fracture borders or from the iliac crest were used instead of plates and the fixation was done with screws. In the study including 24 mandible fractures, the bone grafts harvested from the fracture borders were used in the 10 favorable fractures and the bone grafts harvested from the iliac crest were used in the 14 unfavorable fractures. In the combined mandible fractures, four fractures were fixated with titanium plates and the other side with the bone graft. The patients, who were followed up for 12 to 20 months, were evaluated with macroscopic occlusion, panoramic graphs, and three-dimensional computerized tomographs. The advantage of this technique of fixation with the autogenous tissue is reduced infection rates and reduced operation costs. In the pediatric patients, the second session operation of plate removal is not necessary.

  11. Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment.

    PubMed

    Martínez-Montiel, Nancy; Rosas-Murrieta, Nora Hilda; Martínez-Montiel, Mónica; Gaspariano-Cholula, Mayra Patricia; Martínez-Contreras, Rebeca D

    2016-01-01

    In eukaryotes, genes are frequently interrupted with noncoding sequences named introns. Alternative splicing is a nuclear mechanism by which these introns are removed and flanking coding regions named exons are joined together to generate a message that will be translated in the cytoplasm. This mechanism is catalyzed by a complex machinery known as the spliceosome, which is conformed by more than 300 proteins and ribonucleoproteins that activate and regulate the precision of gene expression when assembled. It has been proposed that several genetic diseases are related to defects in the splicing process, including cancer. For this reason, natural products that show the ability to regulate splicing have attracted enormous attention due to its potential use for cancer treatment. Some microbial metabolites have shown the ability to inhibit gene splicing and the molecular mechanism responsible for this inhibition is being studied for future applications. Here, we summarize the main types of natural products that have been characterized as splicing inhibitors, the recent advances regarding molecular and cellular effects related to these molecules, and the applications reported so far in cancer therapeutics.

  12. Noncitrus alkaline fruit: a dietary alternative for the treatment of hypocitraturic stone formers.

    PubMed

    Baia, Leandro da Cunha; Baxmann, Alessandra Calábria; Moreira, Silvia Regina; Holmes, Ross Philip; Heilberg, Ita Pfeferman

    2012-09-01

    Fruits and vegetables are natural suppliers of potassium, bicarbonate, or bicarbonate precursors such as citrate, malate and others-hence, possessing potential effects on citraturia. We aimed to compare the acute effects of a noncitrus (melon) fruit vs citric ones (orange and lime) on citraturia and other lithogenic parameters. Two-hour urine samples were collected from 30 hypocitraturic stone-forming patients after an overnight fast and 2, 4, and 6 hours after the consumption of 385 mL (13 oz) of either freshly squeezed orange juice (n=10), freshly blended melon juice (n=10), or freshly squeezed lime juice (n=10). Urinary citrate, potassium, pH, and other lithogenic parameters were determined and net gastrointestinal alkali absorption (NGIA) was calculated. Potential renal acid load (PRAL) and pH from juices were determined. Significant and comparable increases of mean urinary citrate were observed in all groups, whereas mean urinary potassium, pH, and NGIA were significantly increased only after consumption of melon and orange juices. The pH of melon juice was higher and the PRAL value was more negative compared with orange juice, indicating a higher alkalinity. These findings suggested that melon, a noncitrus source of potassium, citrate, and malate, yielded an increase in urinary citrate excretion equivalent to that provided by orange, and hence represents another dietary alternative for the treatment of hypocitraturic stone-formers. Despite its low potassium content, lime also produced comparable increases in citraturia possibly because of its high citric acid content.

  13. Environmental assessment of alternative treatment schemes for energy and nutrient recovery from livestock manure.

    PubMed

    Pedizzi, C; Noya, I; Sarli, J; González-García, S; Lema, J M; Moreira, M T; Carballa, M

    2018-04-20

    The application of livestock manure on agricultural land is being restricted due to its significant content of phosphorus (P) and nitrogen (N), leading to eutrophication. At the same time, the growing demand for N and P mineral fertilizers is increasing their production costs and causing the depletion of natural phosphate rock deposits. In the present work, seven technologically feasible treatment schemes for energy (biogas) and nutrient recovery (e.g., struvite precipitation) and/or removal (e.g., partial nitritation/anammox) were evaluated from an environmental perspective. In general, while approaches based solely on energy recovery and use of digestate as fertilizer are commonly limited by community regulations, strategies pursuing the generation of high-quality struvite are not environmentally sound alternatives. In contrast, schemes that include further solid/liquid separation of the digestate improved the environmental profile, and their combination with an additional N-removal stage would lead to the most environmental-friendly framework. However, the preferred scenario was identified to be highly dependent on the particular conditions of each site, integrating environmental, social and economic criteria. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Tacrolimus loaded biocompatible lecithin-based microemulsions with improved skin penetration: Structure characterization and in vitro/in vivo performances.

    PubMed

    Savić, Vedrana; Todosijević, Marija; Ilić, Tanja; Lukić, Milica; Mitsou, Evgenia; Papadimitriou, Vassiliki; Avramiotis, Spyridon; Marković, Bojan; Cekić, Nebojša; Savić, Snežana

    2017-08-30

    In order to improve skin penetration of tacrolimus we aimed to develop potentially non-irritant, lecithin-based microemulsions containing ethanol, isopropanol and/or propylene glycol as cosurfactants, varying caprylic/capric triglycerides and propylene glycol monocaprylate as oil phase. The influence of excipients on the size of microemulsion region in pseudo-ternary phase diagrams and their ability to form different types of microemulsions was evaluated. The comprehensive physicochemical characterization of microemulsions and the evaluation of their structure was performed, while the localization of tacrolimus in microemulsions was further investigated using electron paramagnetic resonance spectroscopy. Moreover, stability studies proved no change in tacrolimus content during one year of storage at room temperature. In addition, in vivo skin performance indicated no skin irritation potential of blank microemulsions, whereas in vitro release testing using Franz diffusion cells showed superior release rate of tacrolimus from microemulsions (0.98±0.10 and 0.92±0.11μg/cm 2 /h for two bicontinuous and 1.00±0.24μg/cm 2 /h for oil-in-water microemulsion) compared to referent Protopic ointment (0.15±0.08μg/cm 2 /h). Furthermore, ex vivo penetration assessed through porcine ear skin using tape stripping, confirmed superiority of two microemulsions related to the reference, implying developed microemulsions as promising carriers for dermal delivery of tacrolimus. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Sirolimus Associated with Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial.

    PubMed

    Kojima, Cristiane Akemi; Nga, Hong Si; Takase, Henrique Mochida; Bravin, Ariane Moyses; Martinez Garcia, Márcia de Fátima Faraldo; Garcia, Paula Dalsoglio; Contti, Mariana Moraes; de Andrade, Luis Gustavo Modelli

    2018-06-01

    There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimus-mycophenolate (23 patients). Cytomegalovirus infection rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

  16. Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored

    PubMed Central

    López, René; Arriagada, Elizabeth; Carrasco, René; Gallardo, Natalia; Lorca, Eduardo

    2017-01-01

    Background. Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods. Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results. Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL (p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion. Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians. PMID:28246556

  17. Switching Stable Kidney Transplant Recipients to a Generic Tacrolimus Is Feasible and Safe, but It Must Be Monitored.

    PubMed

    González, Fernando; López, René; Arriagada, Elizabeth; Carrasco, René; Gallardo, Natalia; Lorca, Eduardo

    2017-01-01

    Background . Tacrolimus is the primary immunosuppressive drug used in kidney transplant patients. Replacing brand name products with generics is a controversial issue that we studied after a Chilean Ministry of Health mandate to implement such a switch. Methods . Forty-one stable Prograf (Astellas) receiving kidney transplant patients were switched to a generic tacrolimus (Sandoz) in a 1 : 1 dose ratio and were followed up for up to 8 months. All other drugs were maintained as per normal practice. Results . Neither tacrolimus doses nor their trough blood levels changed significantly after the switch, but serum creatinine did: 1.62 ± 0.90 versus 1.75 ± 0.92 mg/dL ( p < 0.001). At the same time, five graft biopsies were performed, and two of them showed cellular acute rejection. There were nine infectious episodes treated satisfactorily with proper therapies. No patient or graft was lost during the follow-up time period. Conclusion . Switching from brand name tacrolimus to a generic tacrolimus (Sandoz) is feasible and appears to be safe, but it must be monitored carefully by treating physicians.

  18. Local Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance Induction Protocol

    DTIC Science & Technology

    2016-10-01

    Chimerism Vascularized Composite Allograft Tolerance Induction Protocol PRINCIPAL INVESTIGATORS: Dr. Curtis L. Cetrulo CONTRACTING ORGANIZATION...Tacrolimus (FK506) Delivery for Prevention of Acute Rejection in the Nonhuman Primate Delayed Mixed Chimerism Vascularized Composite Allograft Tolerance...tacrolimus, FK506, vascularized composite allografts , immune rejection, preclinical, transplant, nonhuman primate model, degradable polymer, tyrosine

  19. TU-AB-BRB-01: Coverage Evaluation and Probabilistic Treatment Planning as a Margin Alternative

    SciTech Connect

    Siebers, J.

    The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV-to-CTV and CTV-to-PTV margins during the planning process to design a PTV-conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter- and intra-fractional positional variations, tissue motions, and initial contouring uncertainties. Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage-based planning objectives. Themore » treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP-evaluation for the underlying CTVs and OARs to design an optimal treated volume. This symposium will describe CP-evaluation methods as well as various robust planning techniques including use of probability-weighted dose distributions, probability-weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter-fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra-fractional organ motion. Clinical examples will be used to inter-compare robust and margin-based planning, highlighting advantages of robust-plans in terms of target and normal tissue coverage. Robust-planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning. Learning Objectives: To

  20. Evaluation of healthcare waste treatment/disposal alternatives by using multi-criteria decision-making techniques.

    PubMed

    Özkan, Aysun

    2013-02-01

    Healthcare waste should be managed carefully because of infected, pathological, etc. content especially in developing countries. Applied management systems must be the most appropriate solution from a technical, environmental, economic and social point of view. The main objective of this study was to analyse the current status of healthcare waste management in Turkey, and to investigate the most appropriate treatment/disposal option by using different decision-making techniques. For this purpose, five different healthcare waste treatment/disposal alternatives including incineration, microwaving, on-site sterilization, off-site sterilization and landfill were evaluated according to two multi-criteria decision-making techniques: analytic network process (ANP) and ELECTRE. In this context, benefits, costs and risks for the alternatives were taken into consideration. Furthermore, the prioritization and ranking of the alternatives were determined and compared for both methods. According to the comparisons, the off-site sterilization technique was found to be the most appropriate solution in both cases.

  1. Frozen Elephant Trunk and Antegrade Visceral Debranching in the Surgical Treatment of Type B Aortic Dissection: An Alternative Method

    PubMed Central

    Tuncer, Altug; Akbulut, Mustafa; Adademir, Taylan; Tas, Serpil; Ak, Adnan; Arslan, Özgür; Erden, Benay; Şişmanoğlu, Mesut

    2016-01-01

    Intervention is inevitable in complicated Type B aortic dissections. Classical surgical procedures and endovascular interventions are far from ideal treatments due to their high risk of periprocedural complications and mortality. There is often a need for alternative method in cases of difficult anatomy. We present the combined use of frozen elephant trunk and antegrade visceral debranching methods in the treatment of a 54-year-old male patient with complicated Type B aortic dissection. PMID:28516092

  2. Non-surgical alternative in the treatment of skeletal Class III problems.

    PubMed

    Jefferson, Y

    1995-01-01

    The dental profession is not static, but dynamic. New research findings, along with medical and technological advances, necessitate constant re-examination of treatment philosophies and techniques. What were acceptable treatment techniques in the past may not necessarily be the most effective and best techniques for our patients today. Currently, many practitioners feel that the only treatment for the correction of a skeletal Class III abnormality is via orthognathic surgery in older patients. In some cases it may be the only treatment option. But in most cases today, there are more conservative, non-surgical treatment alternatives in correcting Class III problems in younger aged children. In treating facial-skeletal problems, it must be emphasized that the human face is a biological masterpiece of form and function. Its importance has been documented in arts and sciences since the beginning of modern civilization. It is important enough so that individuals who are blessed with attractive features are afforded greater opportunities in our society. Attractive faces are associated with intelligence, honesty and good work ethics. With the advent of orthognathic surgery, functional appliance, functional regulator, and myofunctional therapy, the dental profession has the capability of leveling out the playing field for many individuals in our society. It does so by being able to correct problems closely associated with the human psyche--the human face. The ability to change facial features brings tremendous prestige to our profession. Along with this prestige comes greater responsibility. Our ability to change facial features entails greater understanding of facial balance and harmony. Ricketts states that the face must conform to stringent proportions known as the "divine proportion" in order for it to be esthetically pleasing. Also, our ability to move facial-skeletal structures entails greater understanding of the biomechanics of the human face. Without this

  3. Long-term influence of alternative forest management treatments on total ecosystem and wood product carbon storage

    Treesearch

    Joshua J. Puhlick; Aaron R. Weiskittel; Ivan J. Fernandez; Shawn Fraver; Laura S. Kenefic; Robert S. Seymour; Randall K. Kolka; Lindsey E. Rustad; John C. Brissette

    2016-01-01

    Developing strategies for reducing atmospheric CO2 is one of the foremost challenges facing natural resource professionals today. The goal of this study was to evaluate total ecosystem and harvested wood product carbon (C) stocks among alternative forest management treatments (selection cutting, shelterwood cutting, commercial clearcutting, and...

  4. Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.

    PubMed

    Jeng, Long-Bin; Lee, Sung Gyu; Soin, Arvinder Singh; Lee, Wei-Chen; Suh, Kyung-Suk; Joo, Dong Jin; Uemoto, Shinji; Joh, Jaewon; Yoshizumi, Tomoharu; Yang, Horng-Ren; Song, Gi-Won; Lopez, Patricia; Kochuparampil, Jossy; Sips, Carole; Kaneko, Shuhei; Levy, Gary

    2018-06-01

    In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P < .001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P < .001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1 mL/min/1.73 m 2 , P = .108), and in patients continuing randomized treatment (-8.0 vs. -13.3 mL/min/1.73 m 2 , P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

    PubMed

    de Abreu, Letícia Coli Louvisse; Todaro, Valerio; Sathler, Plinio Cunha; da Silva, Luiz Cláudio Rodrigues Pereira; do Carmo, Flávia Almada; Costa, Cleonice Marques; Toma, Helena Keiko; Castro, Helena Carla; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

    2016-12-01

    The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.

  6. Inpatients' Preferences, Beliefs, and Stated Willingness to Pay for Complementary and Alternative Medicine Treatments.

    PubMed

    Montross-Thomas, Lori P; Meier, Emily A; Reynolds-Norolahi, Kimberly; Raskin, Erin E; Slater, Daniel; Mills, Paul J; MacElhern, Lauray; Kallenberg, Gene

    2017-04-01

    Research demonstrates the benefits of complementary and alternative medicine (CAM) in myriad environments. Yet, the majority of CAM services are offered in outpatient settings. Incorporating CAM into hospital settings may lead to increased patient comfort, well-being, and overall satisfaction with hospital admissions. Few studies have examined CAM services among inpatients. Therefore, this study assessed inpatients' preferences and beliefs regarding CAM, as well as their stated willingness to pay for these services. Adult patients (n = 100), ranging in age from 19-95 years (M = 53 years; SD = 19.2 years), were recruited during their hospitalization in the University of California, San Diego, Healthcare System. The inpatients completed a brief individual interview to gather their perspectives on common CAM services, including acupuncture, aromatherapy, art therapy, guided imagery, healthy food, humor therapy, massage therapy, music therapy, pet therapy, Reiki, and stress management. Inpatients were asked which CAM therapies they perceived as being potentially the most helpful, their willingness to pay for those therapies, and their perceived beliefs regarding the use of those therapies. Inpatients most commonly perceived healthy food (85%), massage therapy (82%), and humor therapy (70%) to be the most helpful, and were most willing to pay for healthy food (71%), massage therapy (70%), and stress management (48%). Inpatients most commonly believed CAM treatments would provide relaxation (88%), increase well-being (86%), and increase their overall satisfaction with the hospitalization (85%). This study suggests that CAM services may be a beneficial addition to hospitals, as demonstrated by inpatients' interest and stated willingness to pay for these services. These findings may help organizational leaders when making choices regarding the development of CAM services within hospitals, particularly since a significant percentage of inpatients reported that

  7. Inhaled sildenafil as an alternative to oral sildenafil in the treatment of pulmonary arterial hypertension (PAH).

    PubMed

    Rashid, Jahidur; Patel, Brijeshkumar; Nozik-Grayck, Eva; McMurtry, Ivan F; Stenmark, Kurt R; Ahsan, Fakhrul

    2017-03-28

    The practice of treating PAH patients with oral or intravenous sildenafil suffers from the limitations of short dosing intervals, peripheral vasodilation, unwanted side effects, and restricted use in pediatric patients. In this study, we sought to test the hypothesis that inhalable poly(lactic-co-glycolic acid) (PLGA) particles of sildenafil prolong the release of the drug, produce pulmonary specific vasodilation, reduce the systemic exposure of the drug, and may be used as an alternative to oral sildenafil in the treatment of PAH. Thus, we prepared porous PLGA particles of sildenafil using a water-in-oil-in-water double emulsion solvent evaporation method with polyethyleneimine (PEI) as a porosigen and characterized the formulations for surface morphology, respirability, in-vitro drug release, and evaluated for in vivo absorption, alveolar macrophage uptake, and safety. PEI increased the particle porosity, drug entrapment, and produced drug release for 36h. Fluorescent particles showed reduced uptake by alveolar macrophages. The polymeric particles were safe to rat pulmonary arterial smooth muscle cell and to the lungs, as evidenced by the cytotoxicity assay and analyses of the injury markers in the bronchoalveolar lavage fluid, respectively. Intratracheally administered sildenafil particles elicited more pulmonary specific and sustained vasodilation in SUGEN-5416/hypoxia-induced PAH rats than oral, intravenous, or intratracheal plain sildenafil did, when administered at the same dose. Overall, true to the hypothesis, this study shows that inhaled PLGA particles of sildenafil can be administered, as a substitute for oral form of sildenafil, at a reduced dose and longer dosing interval. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Efficacy of tacrolimus/mycophenolate mofetil as acute graft-versus-host disease prophylaxis and the impact of subtherapeutic tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation.

    PubMed

    Offer, Katharine; Kolb, Michelle; Jin, Zhezhen; Bhatia, Monica; Kung, Andrew L; George, Diane; Garvin, James H; Robinson, Chalitha; Sosna, Jean; Karamehmet, Esra; Satwani, Prakash

    2015-03-01

    Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Stability of tacrolimus injection diluted in 0.9% sodium chloride injection and stored in Excel bags.

    PubMed

    Myers, Alan L; Zhang, Yanping; Kawedia, Jitesh D; Shank, Brandon R; Deaver, Melissa A; Kramer, Mark A

    2016-12-15

    The chemical stability and physical compatibility of tacrolimus i.v. infusion solutions prepared in Excel bags and stored at 23 or 4 °C for up to nine days were studied. Tacrolimus admixtures (2, 4, and 8 μg/mL) were prepared in Excel bags using 0.9% sodium chloride injection and stored at 23 °C without protection from light or at 4 °C in the dark. Test samples were withdrawn from triplicate bag solutions immediately after preparation and at predetermined time intervals (1, 3, 5, 7, and 9 days). Chemical stability was assessed by measuring tacrolimus concentrations using a validated stability-indicating high-performance liquid chromatography assay. The physical stability of the admixtures was assessed by visual examination and by measuring turbidity, particle size, and drug content. All test solutions stored at 23 or 4 °C had a no greater than 6% loss of the initial tacrolimus concentration throughout the nine-day study period. All test samples of tacrolimus admixtures, under both storage conditions, were without precipitation and remained clear initially and throughout the nine-day observation period. Changes in turbidities were minor; measured particulates remained few in number in all samples throughout the study. Extemporaneously prepared infusion solutions of tacrolimus 2, 4, and 8 μg/mL in 0.9% sodium chloride injection in Excel bags were chemically and physically stable for at least nine days when stored at room temperature (23 °C) without protection from light and when stored in a refrigerator (4 °C) in the dark. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  10. Chemotherapy induces alternative transcription and splicing: Facts and hopes for cancer treatment.

    PubMed

    Lambert, Charles A; Garbacki, Nancy; Colige, Alain C

    2017-10-01

    Alternative promoter usage, alternative splicing and alternative cleavage/polyadenylation (referred here as to alternative transcription and splicing) are main instruments to diversify the transcriptome from a limited set of genes. There is a good deal of evidence that chemotherapeutic drugs affect these processes, but the therapeutic incidence of these effects is poorly documented. The scope of this study is to review the impact of chemotherapy on alternative transcription and splicing and to discuss potential implications in cancer therapy. A literature survey identified >2200 events induced by chemotherapeutic drugs. The molecular pathways involved in these regulations are briefly discussed. The GO terms associated with the alternative transcripts are mainly related to cell cycle/division, mRNA processing, DNA repair, macromolecules catabolism and chromatin. A large fraction (43%) of transcripts are also related to the new hallmarks of cancer, mostly genetic instability and replicative immortality. Finally, we ask the question of the impact of alternative transcription and splicing on drug efficacy and of the possible curative benefit of combining chemotherapy and pharmaceutical regulation of this process. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Conversion from cyclosporine to tacrolimus improves renal function and lipid profile after cardiac transplantation.

    PubMed

    Garlicki, Mirosław; Czub, Paweł; Labuś, Krzysztof; Ehrlich, Marek P; Rdzanek, Hanna

    2006-01-01

    Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. The impact on renal function after conversion from cyclosporine (CsA) to tacrolimus (TAC) is reported. Fifteen patients (men age 42 +/- 11 years) after cardiac transplantation (HTX) were switched from CsA to TAC (mean time after HTX 21 +/- 6 months). There were 13 male and 2 female patients. Mean cholesterol and LDL level at the time of conversion were 217 +/- 65 ml/dl and and 136 +/- 51 mg/100 ml respectively. Indication for HTX was ischemic cardiomyopathy (CMP) in 8, congenital in 3 and dilatative CMP in the remaining 4 patients. Mean tacrolimus level (microg/dl) at 1, 3, 6 and 12 months were 8.6 +/- 3.3, 8.6 +/- 1.4, 9.2 +/- 2.8 and 9.8 +/- 2.5 respectively. There was a statistically significant improvement in creatinine levels at 1, 3, 6 and 12 months after conversion from baseline 1.9 +/- 0.7 mg/dl to 1.4 +/- 0.5 mg/dl, 1.4 +/- 0.4 mg/dl, 1.3 +/- 0.4 mg/dl and 1.2 +/- 0.4 mg/dl, respectively (p < 0.05). Furthermore, TAC decreased cholesterol as well as LDL-levels during this one-year time frame. This study shows that conversion from CsA to tacrolimus after orthotopic heart transplantation improves renal function.

  12. Safety and efficacy of the switch to generic mycophenolate mofetil and tacrolimus in heart transplant patients.

    PubMed

    Söderlund, Carl; Rådegran, Göran

    2015-07-01

    Generic immunosuppressants may offer economic advantages, but their use is still controversial. At our center, 55 heart transplant patients were switched from CellCept(®) to Myfenax Teva(®) (MT) (n = 51, 18% female, 8.1 ± 6.6 yr post-transplantation) and/or Prograf(®) to Tacrolimus Sandoz(®) (TS) (n = 17, 41% female, 6.6 ± 5.8 yr post-transplantation). We conducted an acute monitoring and a retrospective follow-up with regard to safety and efficacy. Acute cellular rejections (ACRs) on endomyocardial biopsies (EMBs) four wk after the MT switch were specifically compared to a matched retrospective control group. Tacrolimus C0 levels (TS switch) as well as hemoglobin, leukocytes, and thrombocytes (MT switch) did not change (p = NS) during the three wk after each respective switch (8.7 ± 2.9 vs. 8.4 ± 1.9 μg/L, 129.1 ± 12.6 vs. 130.1 ± 12.8 g/L, 6.3 vs. 6.2 × 10(9) /L, and 217.4 ± 56.6 vs. 219.3 ± 61.8 × 10(9) /L, respectively). 0% of the EMBs in the MT switch vs. 3% of the EMBs in the control group showed ACR>grade 1R (p = NS). After six months, survival was 96% (MT switch) and 100% (TS switch), and the frequency of severe ACR was low. Safety parameters measured at the next annual follow-up were also stable following each switch. Switching to MT and/or TS several years after heart transplantation appeared safe in the short-term perspective, showing no detectable changes in tacrolimus C0 levels, safety or efficacy, during an average follow-up of six months. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Complementary and alternative medicine use for treatment and prevention of late-life mood and cognitive disorders

    PubMed Central

    Lavretsky, Helen

    2009-01-01

    Late-life mood disorders and cognitive aging are the most common reasons for using complementary and alternative therapies. The amount of rigorous scientific data to support the efficacy of complementary therapies in the treatment of depression or cognitive impairment is extremely limited. The areas with the most evidence for beneficial effects are exercise, herbal therapy (Hypericum perforatum), the use of fish oil, and, to a lesser extent, acupuncture and relaxation therapies. There is a need for further research involving randomized, controlled trials to investigate the efficacy of complementary and alternative therapies in the treatment of depression and cognitive impairment in late-life. This research may lead to the development of effective treatment and preventive approaches for these serious conditions. PMID:19956796

  14. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor.

    PubMed

    Panizza, Pedro Sergio Brito; de Albuquerque Cavalcanti, Conrado Furtado; Yamaguchi, Nise Hitomi; Leite, Claudia Costa; Cerri, Giovanni Guido; de Menezes, Marcos Roberto

    2016-02-01

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

  15. Percutaneous CT-Guided Cryoablation as an Alternative Treatment for an Extensive Pelvic Bone Giant Cell Tumor

    SciTech Connect

    Panizza, Pedro Sergio Brito; Albuquerque Cavalcanti, Conrado Furtado de; Yamaguchi, Nise Hitomi

    2016-02-15

    A giant cell tumor (GCT) is an intermediate grade, locally aggressive neoplasia. Despite advances in surgical and clinical treatments, cases located on the spine and pelvic bones remain a significant challenge. Failure of clinical treatment with denosumab and patient refusal of surgical procedures (hemipelvectomy) led to the use of cryoablation. We report the use of percutaneous CT-guided cryoablation as an alternative treatment, shown to be a minimally invasive, safe, and effective option for a GCT with extensive involvement of the pelvic bones and allowed structural and functional preservation of the involved bones.

  16. Evaluating transportation systems management & operations (TSM&O) benefits to alternative intersection treatments.

    DOT National Transportation Integrated Search

    2015-12-01

    This research provides a comprehensive review and assessment of current alternative intersection methods : which successfully eliminate the left-turn phase. With increasing traffic and limited resources, the Florida : Department of Transportati...

  17. Erosive pustular dermatosis of the scalp successfully treated with oral prednisone and topical tacrolimus*

    PubMed Central

    Zahdi, Mariana Ribas; Seidel, Gabriela Bestani; Soares, Vanessa Cristina; de Freitas, Camila Fernanda Novak Pinheiro; Mulinari-Brenner, Fabiane Andrade

    2013-01-01

    Erosive pustular dermatosis of the scalp is a rare inflammatory disorder of the scalp, affecting elderly patients after local trauma and leading to scarring or cicatricial alopecia. Case Report: An elderly female patient complained of painful pustules on the parietal region bilaterally with progressive enlargement and ulceration. A biopsy suggested erosive pustular dermatosis of the scalp and the patient was treated with prednisone 40 mg/day and 0.1% topical tacrolimus. After 10 weeks complete closure of the eroded areas was observed and a stable scarring alopecia developed. PMID:24173187

  18. Complementary and Alternative Medicine in the Treatment of Chronic Pelvic Pain in Women: What Is the Evidence?

    PubMed

    Paiva, Sara; Carneiro, Márcia Mendonça

    2013-01-01

    Chronic pelvic pain (CPP) is defined as pain of at least 6 months' duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.

  19. Efficacy of Alkaline Hydrolysis as an Alternative Method for Treatment and Disposal of Infectious Animal Waste.

    PubMed

    Kaye, Gordon; Weber, Peter; Evans, Ann; Venezia, Richard

    1998-05-01

    The efficacy of alkaline hydrolysis as an alternative for incineration or autoclaving during treatment and disposal of infectious waste was evaluated by testing for the destruction of samples of pure cultures of selected infectious microorganisms during digestion of 114 to 136-kg loads of animal carcasses in an animal tissue digestor at the Albany Medical College. Ten milliliter samples of pure cultures of each microorganism were divided among 3 dialysis bags made from narrow diameter dialysis tubing, and each of these bags was placed inside another dialysis bag made from larger diameter dialysis tubing. Each double-bagged sample was suspended from the cover of the carcass basket of the tissue digestor so that it was completely covered by hot alkaline digestion solution during the carcass digestion process. The following organisms were required by the New York State Department of Health as representative pathogens for testing sterilization capabilities of the procedure: Staphylococcus aureus, Mycobacterium fortuitum, Candida albicans, Bacillus subtilis, Pseudomonas aeruginosa, Aspergillus fumigatus, Mycobacterium bovis BCG, MS-2 bacteriophage, and Giardia muris. Animal carcasses included pigs, sheep, rabbits, dogs, rats, mice, and guinea pigs. The tissue digestor was operated at 110 to 120 C and approximately 15 lb/in2 (gauge) for 18 h before the system was allowed to cool to 50 C and dialysis bags were retrieved and submitted for microbial culture. None of the samples obtained from the dialysis bags after the digestion process yielded indicator bacteria or yeast. Giardia cysts were completely destroyed; only small fragments of what appeared to be cyst wall could be recognized with light microscopic examination. No plaque-forming units were detected with MS-2 bacteriophage after digestion. Samples of the hydrolyzate also did not yield growth on culture media. Animal carcasses were completely solubilized and digested, with only the inorganic components of the bones

  20. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

    PubMed

    Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

    2017-09-01

    Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

  1. Toward Enhancing Treatment for Pregnant Smokers: Laying the Groundwork for the Use of Complementary and Alternative Medicine Approaches.

    PubMed

    Loree, Amy M; Ondersma, Steven J; Grekin, Emily R

    2017-05-01

    Although effective treatments exist, most women who smoke during pregnancy neither seek nor receive treatment. Complementary and alternative medicine (CAM) treatments (eg, mindfulness, yoga, and acupuncture) may be attractive, low-cost options that can be used to assist a large proportion of pregnant women with smoking cessation. This study examined participant characteristics and treatment utilization among pregnant smokers in the National Survey on Drug Use and Health (NSDUH) and the National Health Interview Survey (NHIS) in order to explore the prevalence and predictors of CAM use for any purpose within this population. Results indicated that a considerable proportion (6.9%-29.1%) of pregnant smokers are already accessing CAM, particularly Whites and those of greater socioeconomic status. Use of yoga, meditation, and massage increased across study waves. NSDUH participants were most likely to report seeking chiropractic or massage therapy; NHIS participants most frequently reported use of herbs/supplements, deep breathing, and meditation. Up to roughly a quarter of women endorsed traditional/conventional and CAM treatment use, suggesting that some pregnant smokers are open to trying a variety of approaches to promote health. Further research is needed to validate CAM treatments for smoking cessation and to guide safety and treatment recommendations during pregnancy. CAM treatments may be an attractive treatment alternative for pregnant smokers. However, no previous investigations have examined whether pregnant smokers seek out these treatments. Using nationally representative survey data, the present study aimed to explore whether pregnant smokers use CAM treatments. We found that approximately 7%-29% of pregnant smokers reported using a variety of CAM methods, suggesting the need for further investigation into the efficacy and dissemination of CAM for smoking in pregnancy. Published by Oxford University Press on behalf of the Society for Research on Nicotine

  2. Use of tannery wastewater as an alternative substrate and a pre-treatment medium for biogas production.

    PubMed

    Vazifehkhoran, Ali Heidarzadeh; Shin, Seung Gu; Triolo, Jin M

    2018-06-01

    This study investigated biogas production as an alternative treatment of tannery wastewater (TWW) and its use as a pre-treatment medium to increase CH 4 yield from anaerobic digestion (AD) of wheat straw. The TWW had high levels of sulfate and chloride, so biochemical CH 4 potential could be estimated only when the TWW was diluted. Untreated straw yielded 255 NL CH 4 (kg VS) -1 , whereas straw that had been pre-treated with TWW yielded 314 NL CH 4 (kg VS) -1 (35% increase). Treatment of TWW by AD with a co-substrate might be possible using a controlled feedstock mixing ratio. Use of TWW as a pre-treatment medium by simple co-storage before AD would be beneficial as an inexpensive treatment of lignocellulosic biomass. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Design and development of a smart knee pain relief pad based on vibration and alternate heating and cooling treatments.

    PubMed

    Priya, L; Krishnan, V; Vignesh, V; Ajeesh, R P

    2018-03-28

    Knee pain is one of the main health issue faced by different people in the different parts of the world. Over one fourth of the people above the age of fifty suffer from knee pain. Though there are several physiotherapy treatments for treating knee pain they are not self-applicable and those which are self-applicable by the patient are not highly efficient. This paper deals with an approach towards the use of combining two effective physiotherapy treatments which includes vibrations at acupressure points on knee and alternate heating and cooling treatments. These treatments are controlled using a smart phone in which the user can choose their setting depending on intensity and places of pain. The knee pad controlled using the smart phone serves as a self-applicable and effective knee pain treatment especially for the elderly. Heating and cooling combination therapy will be a suitable alternative for treatment of musculoskeletal diseases, decrease muscle spasms, muscular pain/tension and also increase the speed of nerve conduction, thus improving range of motion. This methodology also helps to relief the sinusitis pain, chronic low back pain and muscular sprain in athletes.

  4. First-line treatment: a critical appraisal of cognitive behavioral therapy developments and alternatives.

    PubMed

    Arch, Joanna J; Craske, Michelle G

    2009-09-01

    In this article, the authors assess the successes, remaining challenges, and new developments in cognitive behavioral therapy (CBT) for anxiety disorders. They define CBT, examine treatment components, review treatment efficacy, and discuss the challenges of attrition, long-term follow-up, co-occurring/comorbid disorders, limited treatment comparisons, treatment mediators, and broader implementation. In addition, they present recent developments in cognitive behavioral therapy for anxiety disorders, including linking exposure therapy to basic science, mindfulness and acceptance-based treatments, and unified or transdiagnostic treatment protocols.

  5. Correlation between viral load of cytomegalovirus and tacrolimus and sirolimus levels in transplanted pediatric patients.

    PubMed

    Reyes-Pérez, Herlinda; Sánchez-Huerta, José Luis; Varela-Fascinetto, Gustavo; Romo-Vázquez, José Carlos; Morales-Sánchez, Abigail; Fuentes-Pananá, Ezequiel M; Parra-Ortega, Israel; Ramírez-Ramírez, Graciela; López-Martínez, Briceida

    Survival of transplant patients and grafts depends largely on the use of immunosuppressive drugs. However, a balance remains to be established among immunosuppression, transplant rejection and cytomegalovirus (CMV) infection, which results in a high rate of morbidity and mortality. The aim of this study was to define a better strategy for monitoring transplanted patients based on the analysis of the blood concentration of sirolimus and tacrolimus and the burden of CMV. Fifty five post-transplant (kidney and liver) pediatric patients, nine treated with sirolimus and 46 treated with tacrolimus, were included. A total of 541 measurements were obtained. In each measurement the concentration of immunosuppressant in whole blood and CMV viral load in plasma and whole blood was quantified by real-time PCR. Pearson correlation coefficient (r) was estimated. Values of r ≤0.0747 were found for the relationship between dose and concentration of immunosuppressant; r = 0.9406 for the relationship between viral load in whole blood and plasma, and r ≤0.4616 for the relationship between concentration of immunosuppressant and viral load. These data support that the doses of immunosuppressive drugs do not correlate with the levels of the same in whole blood. Therefore, systemic levels of immunosuppressant should be constantly monitored together with CMV load. Meanwhile, a high correlation between viral load measured in whole blood and plasma was found. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  6. Evaluation of the Crystallization Tendency of Commercially Available Amorphous Tacrolimus Formulations Exposed to Different Stress Conditions.

    PubMed

    Trasi, Niraj S; Purohit, Hitesh S; Taylor, Lynne S

    2017-10-01

    Tacrolimus, an immunosuppressant, is a poorly water soluble compound whereby the commercially available capsule formulations contain the drug in amorphous form. The goal of this study was to evaluate the robustness of the innovator product and five generic formulations to crystallization following storage at stress conditions. Products were purchased from a pharmacy and stored at 40°C/75% relative humidity (RH), open dish conditions. Crystallinity was determined using X-ray diffraction. The quantity of the ingredients in the formulations were determined using different approaches and the various factors that might cause instability in the formulations were studied. After 4 weeks of open dish storage at 40°C/75% RH, one of the generic formulations showed evidence of tacrolimus crystallization. Further investigations revealed batch-to-batch variations in crystallization tendency with the extent of crystallinity varying between 50 and 100% for different batches. Crystallization was also observed at lower storage temperatures (30°C) when the RH was maintained at 75%. It was found that crystallization could be induced in a model formulation by wet granulating an ethanolic solution of the drug with lactose and drying at 60-70°C followed by exposure to stress conditions. It seems probable that the generic that was susceptible to crystallization contains amorphous drug physically mixed with polymeric excipients, rather than as an amorphous solid dispersion. This study highlights the importance of considering the manufacturing process on the stability of the resultant amorphous product.

  7. [Application of Fourier amplitude sensitivity test in Chinese healthy volunteer population pharmacokinetic model of tacrolimus].

    PubMed

    Guan, Zheng; Zhang, Guan-min; Ma, Ping; Liu, Li-hong; Zhou, Tian-yan; Lu, Wei

    2010-07-01

    In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

  8. Seeking alternatives to probit 9 when developing treatments for wood packaging materials under ISPM No. 15

    Treesearch

    R.A. Haack; A. Uzunovic; K. Hoover; J.A. Cook

    2011-01-01

    ISPM No. 15 presents guidelines for treating wood packaging material used in international trade. There are currently two approved phytosanitary treatments: heat treatment and methyl bromide fumigation. New treatments are under development, and are needed given that methyl bromide is being phased out. Probit 9 efficacy (100% mortality of at least 93 613 test organisms...

  9. Cost Differentials and the Treatment of Equipment Assets: An Analysis of Alternatives.

    ERIC Educational Resources Information Center

    Frohreich, Lloyd E.

    This paper is a discussion of alternative state approaches to aiding and costing capital outlay programs, particularly equipment purchases for vocational programs. Equipment costs for vocational programs tend to be a larger proportion of the total costs than in other programs. The paper includes a discussion of such topics as the magnitude of…

  10. Brain Games as a Potential Nonpharmaceutical Alternative for the Treatment of ADHD

    ERIC Educational Resources Information Center

    Wegrzyn, Stacy C.; Hearrington, Doug; Martin, Tim; Randolph, Adriane B.

    2013-01-01

    Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed childhood neurobehavioral disorder, affecting approximately 5.5 million children, of which approximately 66% take ADHD medication daily. This study investigated a potential nonpharmaceutical alternative to address the academic engagement of 5th through 11th grade…

  11. The Churchill School: An Alternative to Drug Treatment for Hyperactive Children.

    ERIC Educational Resources Information Center

    Krippner, Stanley

    This paper is a discussion of The Churchill School, founded in 1972 as an alternative approach to serving the educational needs of children diagnosed as hyperactive, hyperkinetic, brain damaged, neurologically impaired, or suffering from minimal brain dysfunction. The school has a student body of 65, ranging between 6 and 13 years of age. The…

  12. Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.

    PubMed

    Woodworth, Michael H; Kraft, Colleen S; Meredith, Erika J; Mehta, Aneesh K; Wang, Tiffany; Mamo, Yafet T; Dhere, Tanvi; Sitchenko, Kaitlin L; Patzer, Rachel E; Friedman-Moraco, Rachel J

    2018-04-01

    Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Immunophenotype of infiltrating cells in protocol renal allograft biopsies from tacrolimus-versus cyclosporine-treated patients.

    PubMed

    Serón, Daniel; O'Valle, Francisco; Moreso, Francesc; Gomà, Montse; Hueso, Miguel; Grinyó, Josep M; Garcia del Moral, Raimundo

    2007-03-15

    The prevalence of subclinical rejection is lower in patients receiving tacrolimus than in patients treated with cyclosporine. However, it is not known whether this difference is related to the modulation of a specific cell immunophenotype. We perform a two case-one control study in patients treated with tacrolimus (n=44) or cyclosporine (n=22) with a protocol biopsy performed at 4 to 6 months. Immunophenotype of infiltrating cells was evaluated with monoclonal antibodies directed against CD45 (all leukocytes), CD3 (T lymphocytes), CD68 (monocytes/macrophages), and CD20 (B lymphocytes) and expressed as interstitial positive cells/mm(2). The number of interstitial CD45 (290+/-209 vs. 696+/-560; P<0.01), CD3 (121+/-84 vs. 208+/-104; P<0.01), and CD68 (155+/-232 vs. 242+/-280; P<0.05) but not CD20 (137+/-119 vs. 197+/-154) positive cells was lower in tacrolimus-treated patients. T lymphocytes and macrophages interstitial infiltration was reduced in tacrolimus treated patients evaluated with protocol biopsies in comparison to cyclosporine-treated patients.

  14. High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients

    PubMed Central

    Goodall, Dawn L.; Willicombe, Michelle; McLean, Adam G.; Taube, David

    2017-01-01

    Background Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol. Methods We retrospectively analyzed the outpatient tacrolimus levels of kidney-only transplant patients taken between 6 and 12 months posttransplant. IPV was determined using the coefficient of variance. Results Six hundred twenty-eight patients with a mean number of 8.98 ± 3.81 tacrolimus levels and a mean follow-up of 4.72 ± 2.19 years were included. Multivariate analysis showed death was associated with increasing age (1.04 [1.01-1.07], P = 0.0055), diabetes at time of transplant (2.79 [1.44-5.41], P = 0.0024), and rejection (2.34 [1.06-5.19], P = 0.036). Variables associated with graft loss included the highest variability group (2.51 [1.01-6.27], P = 0.048), mean tacrolimus level less than 5 ng/mL (4.32 [1.94-9.63], P = 0.0003), a high clinic nonattendance rate (1.10 [1.01-1.20], P = 0.03), and rejection (9.83 [4.62-20.94], P < 0.0001). Independent risk factors for rejection were de novo donor-specific antibody (3.15 [1.84-5.39], P < 0.0001), mean tacrolimus level less than 5 ng/mL (2.57 [1.27-5.19], P = 0.00860, and a high clinic nonattendance rate (1.11 [1.05-1.18], P = 0.0005). Conclusions This study shows that high tacrolimus IPV and clinic nonattendance are associated with inferior allograft survival. Interventions to minimize the causes of high variability, particularly nonadherence are essential to improve long-term allograft outcomes. PMID:28795143

  15. Incidence of Posttransplantation Diabetes Mellitus in De Novo Kidney Transplant Recipients Receiving Prolonged-Release Tacrolimus-Based Immunosuppression With 2 Different Corticosteroid Minimization Strategies: ADVANCE, A Randomized Controlled Trial

    PubMed Central

    Mourad, Georges; Glyda, Maciej; Albano, Laetitia; Viklický, Ondrej; Merville, Pierre; Tydén, Gunnar; Mourad, Michel; Lõhmus, Aleksander; Witzke, Oliver; Christiaans, Maarten H. L.; Brown, Malcolm W.; Undre, Nasrullah; Kazeem, Gbenga; Kuypers, Dirk R. J.

    2017-01-01

    Background ADVANCE (NCT01304836) was a phase 4, multicenter, prospectively randomized, open-label, 24-week study comparing the incidence of posttransplantation diabetes mellitus (PTDM) with 2 prolonged-release tacrolimus corticosteroid minimization regimens. Methods All patients received prolonged-release tacrolimus, basiliximab, mycophenolate mofetil and 1 bolus of intraoperative corticosteroids (0-1000 mg) as per center policy. Patients in arm 1 received tapered corticosteroids, stopped after day 10, whereas patients in arm 2 received no steroids after the intraoperative bolus. The primary efficacy variable was the diagnosis of PTDM as per American Diabetes Association criteria (2010) at any point up to 24 weeks postkidney transplantation. Secondary efficacy variables included incidence of composite efficacy failure (graft loss, biopsy-proven acute rejection or severe graft dysfunction: estimated glomerular filtration rate (Modification of Diet in Renal Disease-4) <30 mL/min per 1.73 m2), acute rejection and graft and patient survival. Results The full-analysis set included 1081 patients (arm 1: n = 528, arm 2: n = 553). Baseline characteristics and mean tacrolimus trough levels were comparable between arms. Week 24 Kaplan–Meier estimates of PTDM were similar for arm 1 versus arm 2 (17.4% vs 16.6%; P = 0.579). Incidence of composite efficacy failure, graft and patient survival, and mean estimated glomerular filtration rate were also comparable between arms. Biopsy-proven acute rejection and acute rejection were significantly higher in arm 2 versus arm 1 (13.6% vs 8.7%, P = 0.006 and 25.9% vs 18.2%, P = 0.001, respectively). Tolerability profiles were comparable between arms. Conclusions A prolonged-release tacrolimus, basiliximab, and mycophenolate mofetil immunosuppressive regimen is efficacious, with a low incidence of PTDM and a manageable tolerability profile over 24 weeks of treatment. A lower incidence of biopsy-proven acute rejection was seen in patients

  16. Everolimus Is Associated With Less Weight Gain Than Tacrolimus 2 Years After Liver Transplantation: Results of a Randomized Multicenter Study

    PubMed Central

    Charlton, Michael; Rinella, Mary; Patel, Dharmesh; McCague, Kevin; Heimbach, Julie; Watt, Kymberly

    2017-01-01

    Background Weight gain early after transplant is a risk factor for posttransplant metabolic syndrome (PTMS), cardiovascular events, and renal insufficiency. The impact of mammalian target of rapamycin inhibition on posttransplant weight gain and the development of PTMS components postliver transplantation were examined in a randomized, controlled study. Methods After a run-in period, patients (N = 719) were randomized at 30 ± 5 days posttransplant in a 1:1:1 ratio to 3 treatment groups: (i) everolimus (EVR) + reduced tacrolimus (TAC) (n = 245); (ii) TAC control (n = 243) or (iii) TAC elimination (n = 231). In this post hoc analysis, weight change at 12 and 24 months was compared between groups. Vital signs, lipids, and laboratory parameters at 12 and 24 months and rates of PTMS were assessed. Results Mean increase in weight from baseline was higher at month 12 in the TAC control arm (8.15 ± 9.27 kg) than in the EVR + reduced TAC (5.88 ± 12.60 kg, P = 0.056) and the TAC elimination arms (4.76 ± 9.94 kg, P = 0.007). At month 24, the TAC control arm displayed a significantly greater weight increase (9.54 ± 10.21 kg) than either the EVR + reduced TAC (6.69 ± 8.37 kg, P = 0.011) or the TAC elimination groups (6.01 ± 9.98 kg, P = 0.024). Rates of PTMS were similar for the EVR + reduced TAC (71.8%), TAC elimination (70.3%) and TAC control (67.4%) arms (P = NS). Conclusions EVR with reduced-exposure TAC attenuated weight gain at 1 and 2 years posttransplant compared with a standard TAC immunosuppression regimen. Rates of PTMS were comparable between EVR-containing and TAC control regimens. PMID:28817434

  17. Alternative Techniques for Treatment of Complex Below-the Knee Arterial Occlusions in Diabetic Patients With Critical Limb Ischemia

    SciTech Connect

    Gandini, Roberto; Uccioli, Luigi; Spinelli, Alessio

    The purpose of this study was to describe alternative endovascular (EV) techniques and assess their feasibility and efficacy in minimizing failure rates in limb salvage for the treatment of complex below-the knee (BTK) occlusions that could not be crossed with a conventional antegrade access. Between December 2007 and November 2010, 1,035 patients (557 male) underwent EV treatment for critical limb ischemia in our institution. In 124 (12% [83 male], mean age 68.2 {+-} 0.5 years) patients, transfemoral antegrade revascularization attempt failed, and an alternative approach was used. Follow-up was performed at 1 and 6 months. Results were compared with 56more » patients treated between November 2002 and November 2007, in whom conventional technique was unsuccessful and unconventional techniques were not adopted. Technical success was achieved in 119 (96%) patients. The limb-salvage rates were 96.8% and 83% at 1- and 6-month follow-up, respectively. Sixteen (12.9%) and 33 (26.6%) patients underwent reintervention at 1- and 6-month follow-up, respectively. Transcutaneous oxygen tension increased at 1 month (44.7 {+-} 1.1 vs. 15.7 {+-} 0.8 mmHg; p < 0.001) and remained stable at follow-up. Twenty (16.1%) patients required major amputation. Thirteen (10.4%) patients died during follow-up. In our previous experience, percutaneous transluminal angioplasty failure, amputation, and death rates were 10.9, 39.2, and 23.2%, respectively. Alternative techniques allowed a significant decrease of major amputation and death rates (p = 0.0001 and p = 0.02, respectively). The use of alternative techniques seems feasible in case of a failed antegrade BTK revascularization attempt and could minimize failure rates in the treatment of complex occlusions while providing satisfying clinical success rates at 6 months.« less

  18. Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region

    PubMed Central

    Qin, Xuzhen; Rui, Jianzhong; Xia, Yong; Mu, Hong; Song, Sang Hoon; Raja Aziddin, Raja Elina; Miles, Gabrielle; Sun, Yuli

    2018-01-01

    Background The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). Methods This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). Results Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. Conclusions The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types. PMID:29214751

  19. The impact of conversion from prograf to generic tacrolimus in liver and kidney transplant recipients with stable graft function.

    PubMed

    Momper, J D; Ridenour, T A; Schonder, K S; Shapiro, R; Humar, A; Venkataramanan, R

    2011-09-01

    Bioequivalence of the recently available generic tacrolimus formulation, manufactured by Sandoz, to the reference product (Prograf; Astellas Pharma, Tokyo, Japan) has been demonstrated in healthy subjects. However, the safety and efficacy of substitution with generic tacrolimus in transplant patients have not been evaluated. Tacrolimus trough concentrations and indices of liver and kidney function were recorded before and after generic substitution in 48 liver and 55 kidney transplant recipients. In liver transplant patients, the mean tacrolimus concentration/dose (C/D) ratio (± SD) was 184.1 (± 123.2) ([ng/mL]/[mg/kg/day]) for the reference product and 154.7 (± 87.8) ([ng/mL]/[mg/kg/day]) for the generic product (p < 0.05). The mean C/D-ratios in kidney transplant patients were 125.3 (± 92.7) and 110.4 (± 79.2) ([ng/mL]/[mg/kg/day]) for the reference and generic products, respectively (p < 0.05). Actual trough concentrations declined by an average of 1.98 ng/mL in liver and 0.87 ng/mL in kidney transplant patients following the switch, after accounting for all significant covariates. No change was observed in biochemical indices of liver or kidney function and no cases of acute rejection occurred following the substitution. These results suggest that transplant patients currently taking the reference tacrolimus formulation may be safely switched to the Sandoz-generic product provided trough concentrations are closely monitored following the substitution. © 2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. Benefits and risks of emerging technologies: integrating life cycle assessment and decision analysis to assess lumber treatment alternatives.

    PubMed

    Tsang, Michael P; Bates, Matthew E; Madison, Marcus; Linkov, Igor

    2014-10-07

    Assessing the best options among emerging technologies (e.g., new chemicals, nanotechnologies) is complicated because of trade-offs across benefits and risks that are difficult to quantify given limited and fragmented availability of information. This study demonstrates the integration of multicriteria decision analysis (MCDA) and life cycle assessment (LCA) to address technology alternative selection decisions. As a case study, prioritization of six lumber treatment alternatives [micronized copper quaternary (MCQ); alkaline copper quaternary (ACQ); water-borne copper naphthenate (CN); oil-borne copper naphthenate (CNo); water-borne copper quinolate (CQ); and water-borne zinc naphthenate (ZN)] for military use are considered. Multiattribute value theory (MAVT) is used to derive risk and benefit scores. Risk scores are calculated using a cradle-to-gate LCA. Benefit scores are calculated by scoring of cost, durability, and corrosiveness criteria. Three weighting schemes are used, representing Environmental, Military and Balanced stakeholder perspectives. Aggregated scores from all three perspectives show CQ to be the least favorable alterative. MCQ is identified as the most favorable alternative from the Environmental stakeholder perspective. From the Military stakeholder perspective, ZN is determined to be the most favorable alternative, followed closely by MCQ. This type of scoring and ranking of multiple heterogeneous criteria in a systematic and transparent way facilitates better justification of technology selection and regulation.

  1. Evaluation of Amphotericin B and Chloramphenicol as Alternative Drugs for Treatment of Chytridiomycosis and Their Impacts on Innate Skin Defenses

    PubMed Central

    Holden, Whitney M.; Ebert, Alexander R.; Canning, Peter F.

    2014-01-01

    Chytridiomycosis, an amphibian skin disease caused by the emerging fungal pathogen Batrachochytrium dendrobatidis, has been implicated in catastrophic global amphibian declines. The result is an alarming decrease in amphibian diversity that is a great concern for the scientific community. Clinical trials testing potential antifungal drugs are needed to identify alternative treatments for amphibians infected with this pathogen. In this study, we quantified the MICs of chloramphenicol (800 μg/ml), amphotericin B (0.8 to 1.6 μg/ml), and itraconazole (Sporanox) (20 ng/ml) against B. dendrobatidis. Both chloramphenicol and amphotericin B significantly reduced B. dendrobatidis infection in naturally infected southern leopard frogs (Rana [Lithobates] sphenocephala), although neither drug was capable of complete fungal clearance. Long-term exposure of R. sphenocephala to these drugs did not inhibit antimicrobial peptide (AMP) synthesis, indicating that neither drug is detrimental to this important innate skin defense. However, we observed that chloramphenicol, but not amphotericin B or itraconazole, inhibited the growth of multiple R. sphenocephala skin bacterial isolates in vitro at concentrations below the MIC against B. dendrobatidis. These results indicate that treatment with chloramphenicol might dramatically alter the protective natural skin microbiome when used as an antifungal agent. This study represents the first examination of the effects of alternative antifungal drug treatments on amphibian innate skin defenses, a crucial step to validating these treatments for practical applications. PMID:24771024

  2. An Economic comparison of sludge irradiation and alternative methods of municipal sludge treatment

    SciTech Connect

    Ahlstrom, S.B.; McGuire, H.E.

    1977-11-01

    The relative economics of radiation treatment and other sludge treatment processes are reported. The desirability of radiation treatment is assessed in terms of cost and the quality of the treated sludge product. The major conclusions of this study are: radiation treatment is a high-level disinfection process. Therefore, it should only be considered if high levels of disinfection are required for widespread reuse of the sludge; the handling, transporting and pathogen growback problems associated with disinfected wet sludge makes it less attractive for reuse than dry sludge; radiation of composted sludge produces a product of similar quality at less cost thanmore » any thermal treatment and/or flash drying treatment option for situations where a high degree of disinfection is required; and heavy metal concerns, especially cadmium, may limit the reuse of sludge despite high disinfection levels. It is recommended that radiation treatment of sludge, particularly dry sludge, continue to be studied. A sensitivity analysis investigating the optimal conditions under which sludge irradiation operates should be instigated. Furthermore, costs of adding sludge irradiation to existing sludge treatment schemes should be determined.« less

  3. Attention Deficit Hyperactive Disorder: Alternative Treatment Plans for School Age Children Diagnosed with ADHD.

    ERIC Educational Resources Information Center

    Carbonell, Claudia L.

    This literature review of attention deficit hyperactivity disorder (ADHD) reviews the diagnosis and treatment options for children diagnosed with ADHD. It describes the complexity of ADHD, its symptoms, treatments, and implications on a child's social and academic development as well as strategies for assisting such children. Individual sections…

  4. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 5. Complementary and Alternative Medicine Treatments.

    PubMed

    Ravindran, Arun V; Balneaves, Lynda G; Faulkner, Guy; Ortiz, Abigail; McIntosh, Diane; Morehouse, Rachel L; Ravindran, Lakshmi; Yatham, Lakshmi N; Kennedy, Sidney H; Lam, Raymond W; MacQueen, Glenda M; Milev, Roumen V; Parikh, Sagar V

    2016-09-01

    The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals. Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Complementary and Alternative Medicine Treatments" is the fifth of six sections of the 2016 guidelines. Evidence-informed responses were developed for 12 questions for 2 broad categories of complementary and alternative medicine (CAM) interventions: 1) physical and meditative treatments (light therapy, sleep deprivation, exercise, yoga, and acupuncture) and 2) natural health products (St. John's wort, omega-3 fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate, Crocus sativus, and others). Recommendations were based on available data on efficacy, tolerability, and safety. For MDD of mild to moderate severity, exercise, light therapy, St. John's wort, omega-3 fatty acids, SAM-e, and yoga are recommended as first- or second-line treatments. Adjunctive exercise and adjunctive St. John's wort are second-line recommendations for moderate to severe MDD. Other physical treatments and natural health products have less evidence but may be considered as third-line treatments. CAM treatments are generally well tolerated. Caveats include methodological limitations of studies and paucity of data on long-term outcomes and drug interactions. © The Author(s) 2016.

  5. Treatment of fibromyalgia syndrome: recommendations of recent evidence-based interdisciplinary guidelines with special emphasis on complementary and alternative therapies.

    PubMed

    Ablin, Jacob; Fitzcharles, Mary-Ann; Buskila, Dan; Shir, Yoram; Sommer, Claudia; Häuser, Winfried

    2013-01-01

    Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS). First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques).

  6. Treatment of eight dogs with nasal tumours with alternating doses of doxorubicin and carboplatin in conjunction with oral piroxicam.

    PubMed

    Langova, V; Mutsaers, A J; Phillips, B; Straw, R

    2004-11-01

    To determine the efficacy and toxicity of chemotherapy in the treatment of canine nasal tumours. Retrospective clinical study Eight dogs with histologically confirmed nasal tumours were staged by means of complete blood count, serum biochemical analysis, cytological analysis of fine needle aspirate of the regional lymph nodes, thoracic radiographs and computed tomography scan of the nasal cavity. All dogs were treated with alternating doses of doxorubicin, carboplatin and oral piroxicam. All dogs were monitored for side effects of chemotherapy and evaluated for response to treatment by computed tomography scan of the nasal cavity after the first four treatments. Complete remission was achieved in four dogs, partial remission occurred in two dogs and two had stable disease on the basis of computed tomography evaluation. There was resolution of clinical signs after one to two doses of chemotherapy in all dogs. This chemotherapy protocol was efficacious and well tolerated in this series of eight cases of canine nasal tumours.

  7. The effectiveness of alternative planned durations of residential drug abuse treatment.

    PubMed Central

    McCusker, J; Vickers-Lahti, M; Stoddard, A; Hindin, R; Bigelow, C; Zorn, M; Garfield, F; Frost, R; Love, C; Lewis, B

    1995-01-01

    Randomized controlled trials were conducted at two residential drug abuse treatment facilities to compare programs that differed in planned duration. One trial compared a 6-month and a 12-month therapeutic community program (n = 184), and the second compared a 3-month and a 6-month relapse prevention program (n = 444). Retention rates over comparable time periods differed minimally by planned treatment duration, and the longer programs had lower completion rates. There was no effect in either trial of planned treatment duration on changes in psychosocial variables between admission and exit or on rates or patterns of drug use at follow-up between 2 and 6 months after exit. PMID:7573630

  8. Laryngeal debridement: an alternative treatment for a laryngopyocele presenting with severe airway obstruction.

    PubMed

    Fraser, L; Pittore, B; Frampton, S; Brennan, P; Puxeddu, R

    2011-04-01

    The laryngocele is an abnormal saccular dilatation of the ventricle of Morgagni, which maintains its communication with the laryngeal vestibule. Three types of laryngoceles have been described: internal, external, and combined or mixed in relation to the position of the sac with respect to the thyrohyoid membrane. If the laryngocele becomes obstructed and infected it leads to the so-called laryngopyocele which, although a rare disease (8% of laryngoceles), can become an emergency causing severe airway obstruction needing urgent management, even tracheostomy. An alternative method is presented of emergency management of an internal laryngopyocele causing severe airway obstruction using a laryngeal microdebrider and avoiding tracheostomy.

  9. A historical overview of bacteriophage therapy as an alternative to antibiotics for the treatment of bacterial pathogens

    PubMed Central

    Wittebole, Xavier; De Roock, Sophie; Opal, Steven M

    2014-01-01

    The seemingly inexorable spread of antibiotic resistance genes among microbial pathogens now threatens the long-term viability of our current antimicrobial therapy to treat severe bacterial infections such as sepsis. Antibiotic resistance is reaching a crisis situation in some bacterial pathogens where few therapeutic alternatives remain and pan-resistant strains are becoming more prevalent. Non-antibiotic therapies to treat bacterial infections are now under serious consideration and one possible option is the therapeutic use of specific phage particles that target bacterial pathogens. Bacteriophage therapy has essentially been re-discovered by modern medicine after widespread use of phage therapy in the pre-antibiotic era lost favor, at least in Western countries, after the introduction of antibiotics. We review the current therapeutic rationale and clinical experience with phage therapy as a treatment for invasive bacterial infection as novel alternative to antimicrobial chemotherapy. PMID:23973944

  10. Implications of the Emergency Medical Treatment and Labor Act (EMTALA) during public health emergencies and on alternate sites of care.

    PubMed

    Roszak, Andrew R; Jensen, Frances R; Wild, Richard E; Yeskey, Kevin; Handrigan, Michael T

    2009-12-01

    Hospitals throughout the country are using innovative strategies to accommodate the surge of patients brought on by the novel H1N1 virus. One strategy has been to help decompress the amount of patients seeking care within emergency departments by using alternate sites of care, such as tents, parking lots, and community centers as triage, staging, and screening areas. As at any other time an individual presents on hospital property, hospitals and providers must be mindful of the requirements of the Emergency Medical Treatment and Labor Act. In this article we review the act and its implications during public health emergencies, with a particular focus on its implications on alternative sites of care.

  11. Cost-effectiveness analysis of treatment alternatives for beef bulls with preputial prolapse.

    PubMed

    Kasari, T R; McGrann, J M; Hooper, R N

    1997-10-01

    To develop an economic model for comparing cost-effectiveness of medical and surgical treatment versus replacement of beef bulls with preputial prolapse. Economic analysis. Estimates determined from medical records of bulls treated for preputial prolapse at our hospital and from information about treatment of bulls published elsewhere. Annual depreciation cost for treatment (ADC(T)) and replacement (ADC(R)) were calculated. Total investment for an injured bull equaled the sum of salvage value, maintenance cost, and expected cost of the treatment option under consideration. Total investment for a replacement bull was purchase price. Net present value of cost was calculated for each year of bull use. Sensitivity analyses were constructed to determine the value that would warrant treatment of an injured bull. The decision to treat was indicated when ADC(T) was less than ADC(R). In our example, it was more cost-effective for owners to cull an injured bull. The ADC(R) was $97 less than ADC(T) for medical treatment ($365 vs $462) and $280 less than ADC(T) for surgical treatment ($365 vs $645). Likewise, net present value of cost values indicated that it was more cost-effective for owners to cull an injured bull. Sensitivity analysis indicated treatment decisions were justified on the basis of replacement value or planned number of breeding seasons remaining for the bull. The model described here can be used by practitioners to provide an objective basis to guide decision making of owners who seek advice on whether to treat or replace bulls with preputial prolapse.

  12. Applicability of bacterial cellulose as an alternative to paper points in endodontic treatment.

    PubMed

    Yoshino, Aya; Tabuchi, Mari; Uo, Motohiro; Tatsumi, Hiroto; Hideshima, Katsumi; Kondo, Seiji; Sekine, Joji

    2013-04-01

    Dental root canal treatment is required when dental caries progress to infection of the dental pulp. A major goal of this treatment is to provide complete decontamination of the dental root canal system. However, the morphology of dental root canal systems is complex, and many human dental roots have inaccessible areas. In addition, dental reinfection is fairly common. In conventional treatment, a cotton pellet and paper point made from plant cellulose is used to dry and sterilize the dental root canal. Such sterilization requires a treatment material with high absorbency to remove any residue, the ability to improve the efficacy of intracanal medication and high biocompatibility. Bacterial cellulose (BC) is produced by certain strains of bacteria. In this study, we developed BC in a pointed form and evaluated its applicability as a novel material for dental canal treatment with regard to solution absorption, expansion, tensile strength, drug release and biocompatibility. We found that BC has excellent material and biological characteristics compared with conventional materials, such as paper points (plant cellulose). BC showed noticeably higher absorption and expansion than paper points, and maintained a high tensile strength even when wet. The cumulative release of a model drug was significantly greater from BC than from paper points, and BC showed greater compatibility than paper points. Taken together, BC has great potential for use in dental root canal treatment. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Treatment of clinical solid waste using a steam autoclave as a possible alternative technology to incineration.

    PubMed

    Hossain, Md Sohrab; Balakrishnan, Venugopal; Rahman, Nik Norulaini Nik Ab; Sarker, Md Zaidul Islam; Kadir, Mohd Omar Ab

    2012-03-01

    A steam autoclave was used to sterilize bacteria in clinical solid waste in order to determine an alternative to incineration technology in clinical solid waste management. The influence of contact time (0, 5, 15, 30 and 60 min) and temperature (111 °C, 121 °C and 131 °C) at automated saturated steam pressure was investigated. Results showed that with increasing contact time and temperature, the number of surviving bacteria decreased. The optimum experimental conditions as measured by degree of inactivation of bacteria were 121 °C for 15 minutes (min) for Gram negative bacteria, 121 °C and 131 °C for 60 and 30 min for Gram positive bacteria, respectively. The re-growth of bacteria in sterilized waste was also evaluated in the present study. It was found that bacterial re-growth started two days after the inactivation. The present study recommends that the steam autoclave cannot be considered as an alternative technology to incineration in clinical solid waste management.

  14. Complementary and alternative medicine for the treatment of type 2 diabetes

    PubMed Central

    Nahas, Richard; Moher, Matthew

    2009-01-01

    ABSTRACT OBJECTIVE To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. QUALITY OF EVIDENCE MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. MAIN MESSAGE Chromium reduced glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA1c levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA1c are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA1c or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. CONCLUSION Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes. PMID:19509199

  15. Development of the Use of Alternative Cements for the Treatment of Intermediate Level Waste

    SciTech Connect

    Hayes, M.; Godfrey, I.H.

    2007-07-01

    This paper describes initial development studies undertaken to investigate the potential use of alternative, non ordinary Portland cement (OPC) based encapsulation matrices to treat historic legacy wastes within the UK's Intermediate Level Waste (ILW) inventory. Currently these wastes are encapsulated in composite OPC cement systems based on high replacement with blast furnace slag of pulverised fuel ash. However, the high alkalinity of these cements can lead to high corrosion rates with reactive metals found in some wastes releasing hydrogen and forming expansive corrosion products. This paper therefore details preliminary results from studies on two commercial products, calcium sulfo-aluminate (CSA) andmore » magnesium phosphate (MP) cement which react with a different hydration chemistry, and which may allow wastes containing these metals to be encapsulated with lower reactivity. The results indicate that grouts can be formulated from both cements over a range of water contents and reactant ratios that have significantly improved fluidity in comparison to typical OPC cements. All designed mixes set in 24 hours with zero bleed and the pH values in the plastic state were in the range 10-11 for CSA and 5-7 for MP cements. In addition, a marked reduction in aluminium corrosion rate has been observed in both types of cements compared to a composite OPC system. These results therefore provide encouragement that both cement types can provide a possible alternative to OPC in the immobilisation of reactive wastes, however further investigation is needed. (authors)« less

  16. Life cycle comparison of waste-to-energy alternatives for municipal waste treatment in Chilean Patagonia.

    PubMed

    Bezama, Alberto; Douglas, Carla; Méndez, Jacqueline; Szarka, Nóra; Muñoz, Edmundo; Navia, Rodrigo; Schock, Steffen; Konrad, Odorico; Ulloa, Claudia

    2013-10-01

    The energy system in the Region of Aysén, Chile, is characterized by a strong dependence on fossil fuels, which account for up to 51% of the installed capacity. Although the implementation of waste-to-energy concepts in municipal waste management systems could support the establishment of a more fossil-independent energy system for the region, previous studies have concluded that energy recovery systems are not suitable from an economic perspective in Chile. Therefore, this work intends to evaluate these technical options from an environmental perspective, using life cycle assessment as a tool for a comparative analysis, considering Coyhaique city as a case study. Three technical alternatives were evaluated: (i) landfill gas recovery and flaring without energy recovery; (ii) landfill gas recovery and energy use; and (iii) the implementation of an anaerobic digestion system for the organic waste fraction coupled with energy recovery from the biogas produced. Mass and energy balances of the three analyzed alternatives have been modeled. The comparative LCA considered global warming potential, abiotic depletion and ozone layer depletion as impact categories, as well as required raw energy and produced energy as comparative regional-specific indicators. According to the results, the use of the recovered landfill gas as an energy source can be identified as the most environmentally appropriate solution for Coyhaique, especially when taking into consideration the global impact categories.

  17. Complementary and alternative medicine for the treatment of type 2 diabetes.

    PubMed

    Nahas, Richard; Moher, Matthew

    2009-06-01

    To review clinical evidence supporting complementary and alternative medicine interventions for improving glycemic control in type 2 diabetes mellitus. MEDLINE and EMBASE were searched from January 1966 to August 2008 using the term type 2 diabetes in combination with each of the following terms for specific therapies selected by the authors: cinnamon, fenugreek, gymnema, green tea, fibre, momordica, chromium, and vanadium. Only human clinical trials were selected for review. Chromium reduced glycosylated hemoglobin (HbA(1c)) and fasting blood glucose (FBG) levels in a large meta-analysis. Gymnema sylvestre reduced HbA(1c) levels in 2 small open-label trials. Cinnamon improved FBG but its effects on HbA(1c) are unknown. Bitter melon had no effect in 2 small trials. Fibre had no consistent effect on HbA(1c) or FBG in 12 small trials. Green tea reduced FBG levels in 1 of 3 small trials. Fenugreek reduced FBG in 1 of 3 small trials. Vanadium reduced FBG in small, uncontrolled trials. There were no trials evaluating microvascular or macrovascular complications or other clinical end points. Chromium, and possibly gymnema, appears to improve glycemic control. Fibre, green tea, and fenugreek have other benefits but there is little evidence that they substantially improve glycemic control. Further research on bitter melon and cinnamon is warranted. There is no complementary and alternative medicine research addressing microvascular or macrovascular clinical outcomes.

  18. Treatment of Clinical Solid Waste Using a Steam Autoclave as a Possible Alternative Technology to Incineration

    PubMed Central

    Hossain, Md. Sohrab; Balakrishnan, Venugopal; Rahman, Nik Norulaini Nik Ab; Sarker, Md. Zaidul Islam; Kadir, Mohd Omar Ab

    2012-01-01

    A steam autoclave was used to sterilize bacteria in clinical solid waste in order to determine an alternative to incineration technology in clinical solid waste management. The influence of contact time (0, 5, 15, 30 and 60 min) and temperature (111 °C, 121 °C and 131 °C) at automated saturated steam pressure was investigated. Results showed that with increasing contact time and temperature, the number of surviving bacteria decreased. The optimum experimental conditions as measured by degree of inactivation of bacteria were 121 °C for 15 minutes (min) for Gram negative bacteria, 121 °C and 131 °C for 60 and 30 min for Gram positive bacteria, respectively. The re-growth of bacteria in sterilized waste was also evaluated in the present study. It was found that bacterial re-growth started two days after the inactivation. The present study recommends that the steam autoclave cannot be considered as an alternative technology to incineration in clinical solid waste management. PMID:22690168

  19. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. V. Complementary and alternative medicine treatments.

    PubMed

    Ravindran, Arun V; Lam, Raymond W; Filteau, Marie J; Lespérance, François; Kennedy, Sidney H; Parikh, Sagar V; Patten, Scott B

    2009-10-01

    In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. There is widespread interest in complementary and alternative medicine (CAM) therapies in the treatment of major depressive disorder (MDD). The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included evidence and expert clinical support. This section on "Complementary and Alternative Medicine Treatments" is one of 5 guideline articles. There is Level 1 evidence to support light therapy in seasonal MDD and St. John's wort in mild to moderate MDD. There is also some evidence for the use of exercise, yoga and sleep deprivation, as well as for omega-3 fatty acids and SAM-e . Support for other natural health products and therapies is still limited. The evidence base remains limited and studies often have methodological problems, including small samples, variability in dose, short duration of treatment, unknown quality of the agent and limited long-term data. Safety data are also sparse with little information about drug interactions. Some CAM treatments have evidence of benefit in MDD. However, problems with standardization and safety concerns may limit their applicability in clinical practice.

  20. A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

    PubMed

    Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

    2013-10-01

    The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

  1. Synergistic effects of Isatis tinctoria L. and tacrolimus in the prevention of acute heart rejection in mice.

    PubMed

    Wang, Yongzhi; Qin, Qing; Chen, Jibing; Kuang, Xiaocong; Xia, Junjie; Xie, Baiyi; Wang, Feng; Liang, Hua; Qi, Zhongquan

    2009-12-01

    Although immunosuppressive treatments are available for acute cardiac rejection no viable treatment exists for long-term cardiac graft failure. Moreover, the extended use of calcineurin inhibitor immunosuppressants, the mainstay of current treatment for cardiac transplantation, leads to significant side effects such as nephrotoxicity and an increased risk of cardiac disease. Because some agents used in Traditional Chinese Medicine (TCM) have strong immunosuppressive effects coupled with low toxicity, we investigated the effect of Compound K (K), the synthesized analogue of highly unsaturated fatty acids from Isatis tinctoria L., either as a single treatment or combined with tacrolimus (FK-506) on acute cardiac allograft rejection. We compared the ability of K alone, or in combination with FK-506, to inhibit acute heart transplant rejection both in vitro and in vivo. We found that the inhibition of lymphocyte proliferation was positively correlated with K concentration. K significantly reduced IL-2 and IFN-gamma expression levels and significantly inhibited lymphocyte proliferation in both a lymphocyte transformation test and a mixed lymphocyte reaction (MLR). We also found that the inhibitory effect of a combination of K and a sub-therapeutic dose of FK-506 (SubFK-506) was stronger than that of full-dose FK-506 alone. Oral administration of K reduced acute cardiac allograft rejection in mice and had no apparent toxicity. In vivo, the immunosuppressive effect of K combined with a half-dose of FK-506 was equivalent to that of a full-dose of FK-506 alone. K combined with a half-dose of FK-506 reduced the expression levels of IL-2 and IFN-gamma (both within the graft and in the recipients' serum) more effectively than a full-dose of FK-506. These results show that K has significant immunosuppressive effects both in vitro and in vivo. When used as a combination therapy with FK-506 we see a powerful inhibition of rejection with no obvious toxic side effects. The

  2. Economic evaluation of alternative wastewater treatment plant options for pulp and paper industry.

    PubMed

    Buyukkamaci, Nurdan; Koken, Emre

    2010-11-15

    Excessive water consumption in pulp and paper industry results in high amount of wastewater. Pollutant characteristics of the wastewater vary depending on the processes used in production and the quality of paper produced. However, in general, high organic material and suspended solid contents are considered as major pollutants of pulp and paper industry effluents. The major pollutant characteristics of pulp and paper industry effluents in Turkey were surveyed and means of major pollutant concentrations, which were grouped in three different pollution grades (low, moderate and high strength effluents), and flow rates within 3000 to 10,000m(3)/day range with 1000m(3)/day steps were used as design parameters. Ninety-six treatment plants were designed using twelve flow schemes which were combinations of physical treatment, chemical treatment, aerobic and anaerobic biological processes. Detailed comparative cost analysis which includes investment, operation, maintenance and rehabilitation costs was prepared to determine optimum treatment processes for each pollution grade. The most economic and technically optimal treatment processes were found as extended aeration activated sludge process for low strength effluents, extended aeration activated sludge process or UASB followed by an aeration basin for medium strength effluents, and UASB followed by an aeration basin or UASB followed by the conventional activated sludge process for high strength effluents. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Granulosis rubra nasi: a rare condition treated successfully with topical tacrolimus.

    PubMed

    Kumar, Piyush; Gosai, Anubhav; Mondal, Ashim Kumar; Lal, Niharika Ranjan; Gharami, Ramesh Chandra

    2012-01-02

    A 20 years-old girl presented with multiple asymptomatic reddish vesicles on face for four years. It used to get worse in summer and was associated with localized hyperhidrosis. The lesions were notable for disappearance on diascopy. Histopathology from the vesicle showed mononuclear cell infiltration in the upper dermis, especially around eccrine sweat apparatus, along with dilatation of superficial capillaries and lymphatics. Based on clinical presentation and histopathology, diagnosis of Granulosis rubra nasi (GRN) was made. GRN usually resolves at puberty; however, rarely it may persist in adulthood. We here report a case of GRN having lesions persisting in adulthood. Moreover, she showed excellent response to topical tacrolimus, a finding not observed in literature.

  4. Lactoferricin/verbascoside topical emulsion: a possible alternative treatment for atopic dermatitis in dogs.

    PubMed

    Biasibetti, Elena; Bruni, Natascia; Bigliati, Mauro; Capucchio, Maria Teresa

    2017-08-28

    Atopic dermatitis affects 3-15% of the general dog population and it has been diagnosed by veterinarians up to 58% of dogs affected with skin disease. It is usually a life-long pathology which can be controlled, but it can be seldom cured. The present investigation describes a case study in which lactoferricin and verbascoside are part of a formulation to obtain a dermatological lotion for canine dermatitis treatment. The study was an open-label trial design of two-week treatment. Thirty-eight dogs (23 females and 15 males), with atopic dermatitis and secondary bacterial or yeast overgrowth have been included. During treatment period the total clinical score progressively decreased associated with an improvement in clinical signs. No adverse effects were reported in any of the treated dogs. The present research suggests that daily applications of tested emulsion are effective in reducing bacterial overgrowth and clinical signs in skin folds and atopic dermatitis.

  5. Economic Evaluation of Munitions Manufacturing Pink Wastewater Treatment Alternatives Using a Present Value-Unit Cost Methodology

    DTIC Science & Technology

    1982-02-01

    BACKGROUND 1 1.2 TECHNICAL APPROACH 3 1.3 OBJECTIVES 3 2.0 INVESTIGATION 5 2.1 LITERATURE SEARCH 5 2.2 SITE ViSITS 6 2.3 PINK WATER SOURCES AND...Scale 10 5 and 106 GPD Plant Designs 13 3.1 Matrix of Pink Water Treatment Systems Compared on a PVUC Basis 28 3.2 Calculated Capital & Annual... 5 Year Planning Horizon 109 3.6 Calculated PVUC ($/K-GAL) for Each Alternative - 1,000,000 GPD - 5 Year Planning Horizon 110 3.7 Calculated Annual

  6. Resolving bacterial contamination of fuel ethanol fermentations with beneficial bacteria - An alternative to antibiotic treatment.

    PubMed

    Rich, Joseph O; Bischoff, Kenneth M; Leathers, Timothy D; Anderson, Amber M; Liu, Siqing; Skory, Christopher D

    2018-01-01

    Fuel ethanol fermentations are not performed under aseptic conditions and microbial contamination reduces yields and can lead to costly "stuck fermentations". Antibiotics are commonly used to combat contaminants, but these may persist in the distillers grains co-product. Among contaminants, it is known that certain strains of lactic acid bacteria are capable of causing stuck fermentations, while other strains appear to be harmless. However, it was not previously known whether or how these strains interact one with another. In this study, more than 500 harmless strains of lactic acid bacteria were tested in a model system in combination with strains that cause stuck fermentations. Among these harmless strains, a group of beneficial strains was identified that restored ethanol production to near normal levels. Such beneficial strains may serve as an alternative approach to the use of antibiotics in fuel ethanol production. Published by Elsevier Ltd.

  7. Alternative approaches to Hsp90 modulation for the treatment of cancer

    PubMed Central

    Hall, Jessica A; Forsberg, Leah K; Blagg, Brian SJ

    2015-01-01

    Hsp90 is responsible for the conformational maturation of newly synthesized polypeptides (client proteins) and the re-maturation of denatured proteins via the Hsp90 chaperone cycle. Inhibition of the Hsp90 N-terminus has emerged as a clinically relevant strategy for anticancer chemotherapeutics due to the involvement of clients in a variety of oncogenic pathways. Several immunophilins, co-chaperones and partner proteins are also necessary for Hsp90 chaperoning activity. Alternative strategies to inhibit Hsp90 function include disruption of the C-terminal dimerization domain and the Hsp90 heteroprotein complex. C-terminal inhibitors and Hsp90 co-chaperone disruptors prevent cancer cell proliferation similar to N-terminal inhibitors and destabilize client proteins without induction of heat shock proteins. Herein, current Hsp90 inhibitors, the chaperone cycle, and regulation of this cycle will be discussed. PMID:25367392

  8. Influence of ABCB1 polymorphisms and haplotypes on tacrolimus nephrotoxicity and dosage requirements in children with liver transplant

    PubMed Central

    Hawwa, Ahmed F; McKiernan, Patrick J; Shields, Michael; Millership, Jeff S; Collier, Paul S; McElnay, James C

    2009-01-01

    AIMS The aim of this study was to investigate the influence of genetic polymorphisms in ABCB1 on the incidence of nephrotoxicity and tacrolimus dosage-requirements in paediatric patients following liver transplantation. METHODS Fifty-one paediatric liver transplant recipients receiving tacrolimus were genotyped for ABCB1 C1236>T, G2677>T and C3435>T polymorphisms. Dose-adjusted tacrolimus trough concentrations and estimated glomerular filtration rates (EGFR) indicative of renal toxicity were determined and correlated with the corresponding genotypes. RESULTS The present study revealed a higher incidence of the ABCB1 variant-alleles examined among patients with renal dysfunction (≥30% reduction in EGFR) at 6 months post-transplantation (1236T allele: 63.3% vs 37.5% in controls, P= 0.019; 2677T allele: 63.3% vs. 35.9%, p = 0.012; 3435T allele: 60% vs. 39.1%, P= 0.057). Carriers of the G2677->T variant allele also had a significant reduction (%) in EGFR at 12 months post-transplant (mean difference = 22.6%; P= 0.031). Haplotype analysis showed a significant association between T-T-T haplotypes and an increased incidence of nephrotoxicity at 6 months post-transplantation (haplotype-frequency = 52.9% in nephrotoxic patients vs 29.4% in controls; P= 0.029). Furthermore, G2677->T and C3435->T polymorphisms and T-T-T haplotypes were significantly correlated with higher tacrolimus dose-adjusted pre-dose concentrations at various time points examined long after drug initiation. CONCLUSIONS These findings suggest that ABCB1 polymorphisms in the native intestine significantly influence tacrolimus dosage-requirement in the stable phase after transplantation. In addition, ABCB1 polymorphisms in paediatric liver transplant recipients may predispose them to nephrotoxicity over the first year post-transplantation. Genotyping future transplant recipients for ABCB1 polymorphisms, therefore, could have the potential to individualize better tacrolimus immunosuppressive therapy and

  9. Analysis of tacrolimus and creatinine from a single dried blood spot using liquid chromatography tandem mass spectrometry.

    PubMed

    Koop, Dennis R; Bleyle, Lisa A; Munar, Myrna; Cherala, Ganesh; Al-Uzri, Amira

    2013-05-01

    Long term therapeutic drug monitoring and assessment of renal function are required in renal transplant recipients on immunosuppressant therapy such as tacrolimus. Dry blood spots (DBS) have been used successfully in the clinic for many years and offers a convenient, simple and non-invasive method for repeated blood tests. We developed and performed a preliminary validation of a method for the analysis of tacrolimus and creatinine from a single DBS using liquid chromatography-tandem mass spectrometric (LC-MS/MS). Tacrolimus and creatinine were extracted from a 6mm punch with a mixture of methanol/acetonitrile containing ascomycin and deuterated creatinine as internal standards. A 10 μl aliquot of the extract was analyzed directly after dilution for creatinine with normal phase high performance liquid chromatography and multiple reaction monitoring. The remainder of the extract was processed and analyzed for tacrolimus. The lower limit of quantification for tacrolimus was 1 ng/ml with accuracy of 0.34% bias and precision (CV) of 11.1%. The precision ranged from 1.33% to 7.68% and accuracy from -4.44% to 11.6% bias for the intra- and inter-day analysis. The lower limit of quantification of creatinine was 0.01 mg/dL with precision of 7.94%. Accuracy was based on recovery of additional creatinine spiked into whole blood samples and ranged from -2.45% bias at 5 mg/dL to 3.75% bias at 0.5 mg/dL. Intra- and inter-day precision was from 3.48 to 4.11%. The assay was further validated with DBS prepared from pediatric renal transplant recipients. There was excellent correlation between the levels of tacrolimus and creatinine obtained from the clinical laboratory and the DBS method developed. After additional validation, this assay may have a significant impact on compliance with medication intake as well as potentially lowering the cost associated with intravenous blood draws in clinical laboratories. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Healing Childhood Ear Infections: Prevention, Home Care, and Alternative Treatment. 2nd Edition.

    ERIC Educational Resources Information Center

    Schmidt, Michael A.

    This book describes current controversy in medical journals over existing treatments for chronic childhood earaches. It suggests that the causes of otitis media are a series of events which flourish when poor nutrition occurs, noting that careful attention to diet and nutrition to prevent food allergies, and the use of acupressure, homeopathic…

  11. Sanitizing with peracetic acid (PAA)- An alternative treatment to use in aquaculture ...?

    USDA-ARS?s Scientific Manuscript database

    Because of the lack of approved treatments for fish disease, disinfectants were tested to treat fish pathogens. One of these substances is peracetic acid (PAA). PAA is an agent used for disinfection in aquaculture, but it must be investigated thoroughly in order to mitigate diseases without harmful ...

  12. 40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... treatment standards for contaminated soil. (a) Applicability. You must comply with LDRs prior to placing soil that exhibits a characteristic of hazardous waste, or exhibited a characteristic of hazardous...

  13. 40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... treatment standards for contaminated soil. (a) Applicability. You must comply with LDRs prior to placing soil that exhibits a characteristic of hazardous waste, or exhibited a characteristic of hazardous...

  14. 40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... treatment standards for contaminated soil. (a) Applicability. You must comply with LDRs prior to placing soil that exhibits a characteristic of hazardous waste, or exhibited a characteristic of hazardous...

  15. 40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... treatment standards for contaminated soil. (a) Applicability. You must comply with LDRs prior to placing soil that exhibits a characteristic of hazardous waste, or exhibited a characteristic of hazardous...

  16. 40 CFR 268.49 - Alternative LDR treatment standards for contaminated soil.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for contaminated soil. 268.49 Section 268.49 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... treatment standards for contaminated soil. (a) Applicability. You must comply with LDRs prior to placing soil that exhibits a characteristic of hazardous waste, or exhibited a characteristic of hazardous...

  17. Effects of alternative treatments on canopy fuel characteristics in five conifer stands

    Treesearch

    Joe H. Scott; Elizabeth D. Reinhardt

    2007-01-01

    A detailed study of canopy fuel characteristics in five different forest types provided a unique dataset for simulating the effects of various stand manipulation treatments on canopy fuels. Low thinning, low thinning with commercial dbh limit, and crown thinning had similar effects on canopy bulk density (CBD) and canopy fuel load (CFL...

  18. Alternative timing of carbaryl treatments for protecting lodgepole pine from mortality attributed to mountain pine beetle

    Treesearch

    Christopher J. Fettig; A.Steve Munson; Kenneth E. Gibson

    2015-01-01

    Carbaryl is regarded among the most effective, economically viable, and ecologically-compatible insecticides available for protecting conifers from bark beetle attack in the western United States. Treatments are typically applied in spring prior to initiation of bark beetle flight for that year. We evaluated the efficacy of spring and fall applications for protecting...

  19. Alternative Funding Resources Manual for Drug Abuse and Alcohol Treatment and Rehabilitation Programs.

    ERIC Educational Resources Information Center

    Bertagnoli, Cliff

    The purpose of this manual is to guide and assist alcohol and other drug abuse treatment programs to maximize cost recovery from third party reimbursements. It is intended to be a guide for planning and decision making rather than a resource manual. The text is based on the experiences of agencies in six states participating in a demonstration…

  20. Nitrogen Control Through Decentralized Wastewater Treatment: Process Performance and Alternative Management Strategies

    EPA Science Inventory

    Decentralized or onsite wastewater treatment (OWT) systems have long been implicated in being a major source of N inputs to surface and ground waters and numerous regulatory bodies have promulgated strict total N (TN) effluent standards in N-sensitive areas. These standards, howe...

  1. Sequenced treatment alternatives to relieve depression (STAR*D): rationale and design.

    PubMed

    Rush, A John; Fava, Maurizio; Wisniewski, Stephen R; Lavori, Philip W; Trivedi, Madhukar H; Sackeim, Harold A; Thase, Michael E; Nierenberg, Andrew A; Quitkin, Frederic M; Kashner, T Michael; Kupfer, David J; Rosenbaum, Jerrold F; Alpert, Jonathan; Stewart, Jonathan W; McGrath, Patrick J; Biggs, Melanie M; Shores-Wilson, Kathy; Lebowitz, Barry D; Ritz, Louise; Niederehe, George

    2004-02-01

    STAR*D is a multisite, prospective, randomized, multistep clinical trial of outpatients with nonpsychotic major depressive disorder. The study compares various treatment options for those who do not attain a satisfactory response with citalopram, a selective serotonin reuptake inhibitor antidepressant. The study enrolls 4000 adults (ages 18-75) from both primary and specialty care practices who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode. After receiving citalopram (level 1), participants without sufficient symptomatic benefit are eligible for randomization to level 2 treatments, which entail four switch options (sertraline, bupropion, venlafaxine, cognitive therapy) and three citalopram augment options (bupropion, buspirone, cognitive therapy). Those who receive cognitive therapy (switch or augment options) at level 2 without sufficient improvement are eligible for randomization to one of two level 2A switch options (venlafaxine or bupropion). Level 2 and 2A participants are eligible for random assignment to two switch options (mirtazapine or nortriptyline) and to two augment options (lithium or thyroid hormone) added to the primary antidepressant (citalopram, bupropion, sertraline, or venlafaxine) (level 3). Those without sufficient improvement at level 3 are eligible for level 4 random assignment to one of two switch options (tranylcypromine or the combination of mirtazapine and venlafaxine). The primary outcome is the clinician-rated, 17-item Hamilton Rating Scale for Depression, administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments. Secondary outcomes include self-reported depressive symptoms, physical and mental function, side-effect burden, client satisfaction, and health care utilization and cost. Participants with an adequate symptomatic response may enter the 12-month

  2. The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

    PubMed

    van Gestel, Aukje; Webers, Carroll A; Severens, Johan L; Beckers, Henny J; Jansonius, Nomdo M; Hendrikse, Fred; Schouten, Jan S

    2012-02-01

    To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a β-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

  3. Tacrolimus Injection

    MedlinePlus

    ... of the transplanted organ by the transplant recipient's immune system) in people who have received kidney, liver, or ... It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

  4. Optimizing clinical benefit with targeted treatment in mRCC: "Tumor growth rate" as an alternative clinical endpoint.

    PubMed

    Milella, Michele

    2016-06-01

    Tumor growth rate (TGR), usually defined as the ratio between the slope of tumor growth before the initiation of treatment and the slope of tumor growth during treatment, between the nadir and disease progression, is a measure of the rate at which tumor volume increases over time. In patients with metastatic renal cell carcinoma (mRCC), TGR has emerged as a reliable alternative parameter to allow a quantitative and dynamic evaluation of tumor response. This review presents evidence on the correlation between TGR and treatment outcomes and discusses the potential role of this tool within the treatment scenario of mRCC. Current evidence, albeit of retrospective nature, suggests that TGR might represent a useful tool to assess whether treatment is altering the course of the disease, and has shown to be significantly associated with progression-free survival and overall survival. Therefore, TGR may represent a valuable endpoint for clinical trials evaluating new molecularly targeted therapies. Most importantly, incorporation of TGR in the assessment of individual patients undergoing targeted therapies may help clinicians decide if a given agent is no longer able to control disease growth and whether continuing therapy beyond RECIST progression may still produce clinical benefit. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Pharmacological Alternatives for the Treatment of Neurodegenerative Disorders: Wasp and Bee Venoms and Their Components as New Neuroactive Tools

    PubMed Central

    Silva, Juliana; Monge-Fuentes, Victoria; Gomes, Flávia; Lopes, Kamila; dos Anjos, Lilian; Campos, Gabriel; Arenas, Claudia; Biolchi, Andréia; Gonçalves, Jacqueline; Galante, Priscilla; Campos, Leandro; Mortari, Márcia

    2015-01-01

    Neurodegenerative diseases are relentlessly progressive, severely impacting affected patients, families and society as a whole. Increased life expectancy has made these diseases more common worldwide. Unfortunately, available drugs have insufficient therapeutic effects on many subtypes of these intractable diseases, and adverse effects hamper continued treatment. Wasp and bee venoms and their components are potential means of managing or reducing these effects and provide new alternatives for the control of neurodegenerative diseases. These venoms and their components are well-known and irrefutable sources of neuroprotectors or neuromodulators. In this respect, the present study reviews our current understanding of the mechanisms of action and future prospects regarding the use of new drugs derived from wasp and bee venom in the treatment of major neurodegenerative disorders, including Alzheimer’s Disease, Parkinson’s Disease, Epilepsy, Multiple Sclerosis and Amyotrophic Lateral Sclerosis. PMID:26295258

  6. Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

    PubMed

    Sauer, Harald; Wollny, Caroline; Oster, Isabel; Tutdibi, Erol; Gortner, Ludwig; Gottschling, Sven; Meyer, Sascha

    2015-05-01

    The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. Case report. We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

  7. Increased alternative lengthening of telomere phenotypes of telomerase-negative immortal cells upon trichostatin--a treatment.

    PubMed

    Jung, A Ra; Yoo, Jeong Eun; Shim, Yhong-Hee; Choi, Ye-Na; Jeung, Hei-Cheul; Chung, Hyun Cheol; Rha, Sun Young; Oh, Bong-Kyeong

    2013-03-01

    Human immortal cells maintain their telomeres either by telomerase or by alternative lengthening of telomeres (ALT) that is based on homologous telomeric recombination. Previous studies showed that the ALT mechanism is activated in non-ALT cells when heterochromatic features are reduced. In this study, we examined the ALT phenotypes of ALT cells after treatment with trichostatin-A (TSA), which is an inhibitor of histone deacetylases and causes global chromatin decondensation. The ALT cells remained telomerase-negative after TSA treatment. ALT-associated promyelocytic leukemia (PML) nuclear bodies and telomere sister chromatid exchanges, typical ALT phenotypes, markedly increased in the TSA-treated cells, while the telomere length remained unchanged. In addition, telomerase expression in the ALT cells suppressed TSA-mediated ALT phenotype enhancement. Our results show that certain ALT phenotypes become more pronounced when chromatin is decondensed, and also suggest that the ALT mechanism may compete with telomerase for telomere maintenance in cells that lack heterochromatin.

  8. Pregnancy- and lactation-associated osteoporosis with severe vertebral deformities: can strontium ranelate be a new alternative for the treatment?

    PubMed

    Tanriover, Mine Durusu; Oz, S Gul; Sozen, Tumay; Kilicarslan, Alpaslan; Guven, Gulay Sain

    2009-04-01

    Pregnancy- and lactation-associated osteoporosis is an uncommon condition that may be a consequence of preexisting low bone density, loss of bone mineral content during pregnancy, and increased bone turnover. To present a case of severe osteoporosis associated with pregnancy and lactation and its treatment protocol. A tertiary care hospital. A young female after twin pregnancy presenting with severe osteoporosis. The diagnosis was done on the basis of bone mineral density (BMD) measurement. The patient was treated with first alendronate and then strontium ranelate. She was considered as a candidate for kyphoplasty. A dramatic increase in the BMD and palliation of back pain were observed. Strontium ranelate may be a new alternative in the treatment of pregnancy- and lactation-associated osteoporosis.

  9. Behaviors of providers of traditional korean medicine therapy and complementary and alternative medicine therapy for the treatment of cancer patients.

    PubMed

    Yu, Jun-Sang; Kim, Chun-Bae; Kim, Ki-Kyong; Lee, Ji-Eun; Kim, Min-Young

    2015-03-01

    In Korea, cancer is one of the most important causes of death. Cancer patients have sought alternative methods, like complementary and alternative medicine (CAM) together with Western medicine, to treat cancer. Also, there are many kinds of providers of CAM therapy, including providers of Korean oriental medicine therapy. The purpose of this study is to identify the behaviors of Korean oriental medicine therapy and CAM therapy providers who treat cancer patients and to provide background knowledge for establishing a new policy with the management and quality control of CAM. Structured and well organized questionnaires were made, and 350 persons were surveyed concerning the providers of CAM or Korean oriental medicine. The questionnaires were collected and analyzed. The questionnaires (182) were collected. The questionnaires identified a total of 73 known providers, such as medicinal professionals or other providers of CAM suppliers, 35.6% of whom had had experience with treating cancer patients (52.6% vs. 29.6%). The treatment methods were a little different: alternative therapy and nutritional therapy being preferred by medicinal professionals and mind body modulation therapy and alternative therapy being preferred by other CAM providers. Four patients (7.4%) experienced side effects, and 6 patients (12.5%) experienced legal problems. As the method for managing the therapy, CAM providers, medicinal professionals, and other CAM providers had different viewpoints. For example, some CAM providers stated that both legislation and an official education on CAM or a national examination were needed as a first step to establish the provider's qualifications and that as a second step, a license test was needed for quality control. To the contrary, medicinal professionals stated that a license test was needed before legislation. Adequate management and quality control of CAM providers is thought to involve both education and legislation.

  10. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment.

    PubMed

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J; Olliaro, Piero L; Millet, Pascal

    2012-10-15

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic - specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment

    PubMed Central

    Kauss, Tina; Gaudin, Karen; Gaubert, Alexandra; Ba, Boubakar; Tagliaferri, Serena; Fawaz, Fawaz; Fabre, Jean-Louis; Boiron, Jean-Michel; Lafarge, Xavier; White, Nicholas J.; Olliaro, Piero L.; Millet, Pascal

    2012-01-01

    The aim of this study was to identify a candidate formulation for further development of a home or near-home administrable paediatric rectal form of a broad-spectrum antibiotic – specially intended for (emergency) use in tropical rural settings, in particular for children who cannot take medications orally and far from health facilities where injectable treatments can be given. Azithromycin, a broad-spectrum macrolide used orally or intravenously for the treatment of respiratory tract, skin and soft tissue infections, was selected because of its pharmacokinetic and therapeutic properties. Azithromycin in vitro solubility and stability in physiologically relevant conditions were studied. Various pharmaceutical forms, i.e. rectal suspension, two different rectal gels, polyethylene glycol (PEG) suppository and hard gelatin capsule (HGC) were assessed for in vitro dissolution and in vivo bioavailability in the rabbit. Azithromycin PEG suppository appears to be a promising candidate. PMID:22868232

  12. Effects of dimethyl dicarbonate (DMDC) on the fermentation of litchi juice by Lactobacillus casei as an alternative of heat treatment.

    PubMed

    Yu, Yuanshan; Xiao, Gengsheng; Xu, Yujuan; Wu, Jijun; Wen, Jing

    2014-05-01

    This study investigated the effects of dimethyl dicarbonate (DMDC) on the fermentation of litchi juice by Lactobacillus casei as an alternative of heat treatment that may have undesirable effect on the juice. Quality attributes and products stability of both the fermented heat- and DMDC-treated litchi juice by L. casei were compared. It was found that residual indigenous microorganisms in both the heat- and DMDC-treated litchi juice cannot grow into dominant bacteria during further fermentation of litchi juice by L. casei. Compared with fermented heat-treated litchi juice, fermented DMDC-treated litchi juice showed a better color, flavor, and overall acceptance, and also retained more total phenolics and antioxidant capacity. The viability counts of L. casei in both the heat- and DMDC-treated litchi juice were more 8.0 lg CFU/mL after 4 wk of storage at 4 °C. Also, some quality attributes in both the fermented heat- and DMDC-treated litchi juices, including pH, total phenolics, ascorbic acid, antioxidant capacity, and so on, showed the tendency to slow decrease during storage at 4 °C, but the scores of overall acceptance showed no reduction after the storage of 4 wk at 4 °C. On the whole, the application of DMDC treatment could be an ideal alternative of heat treatment to ensure the microbial safety, consistent sensory, and nutritional quality of fermented litchi juice prior to fermentation. The pasteurization treatment is often recommended prior to fermentation of fruit juice by probiotics, as it would lead to a rapid inactivation and inhibition of spoilage and pathogenic bacteria, and ensure the fermented products with consistent sensory and nutritional quality. Dimethyl dicarbonate (DMDC) is a powerful antimicrobial agent, which was approved for use as a microbial control agent in juice beverages by FDA. This study provides a scientific basis for the application of DMDC prior to fermentation of litchi juice. © 2014 Institute of Food Technologists®

  13. Embolization of Rectal Arteries: An Alternative Treatment for Hemorrhagic Shock Induced by Traumatic Intrarectal Hemorrhage

    SciTech Connect

    Pichon, Nicolas, E-mail: nicolas.pichon@unilim.fr, E-mail: nicolas.pichon@chu-limoges.fr; Francois, Bruno; Pichon-Lefievre, Florence

    2005-05-15

    Rectal injuries caused by foreign bodies or iatrogenic insertions may lead to severe complications whose therapeutic management remains controversial. At times, both the rapid identification and treatment of subsequent active rectal bleeding may be challenging, especially when endoscopy fails to locate and control the arterial hemorrhage. We present the first two successful cases of middle rectal artery embolization in patients presenting with sustained bleeding and hemorrhagic shock.

  14. Technique of antroduodenectomy without ulcer excision as a safe alternative treatment for bleeding chronic duodenal ulcers.

    PubMed

    Guinier, David; Destrumelle, Nicolas; Denue, Pierre Olivier; Mathieu, Pierre; Heyd, Bruno; Mantion, Georges Andre

    2009-05-01

    The treatment of a bleeding chronic posterior duodenal ulcer, with bleeding recurrence or persistence despite endoscopic therapy, requires surgical treatment and constitutes a challenge for the surgeon; furthermore such chronic ulcers are often wide and sclerotic, so the surgeon needs to avoid the risk of recurrent bleeding if conservative surgery is applied. If radical surgery must be performed, the greater risk involves duodenal leakage, hepatic hilar injury, or pancreatic injury. This study aimed to evaluate the efficacy and complications arising from a surgical procedure, described by Dubois in 1971 (Gastrectomy and gastroduodenal anastomosis for post-bulbar ulcers and peptic ulcers of the second part of the duodenum. J Chir 101:177-186). This operation involves antroduonectomy with gastroduodenal anastomosis. It is similar to a Billroth I gastrectomy but without dissection of the ulcer. We retrospectively studied the medical data of patients who underwent this procedure for the treatment of bleeding chronic posterior duodenal ulcers during the past 20 years. There were 28 such patients admitted to our institution for emergency surgery, who went on to be treated by the Dubois procedure. Ulcerous disease was efficiently treated